Evidências favoráveis impulsionaram o uso da técnica transradial nos últimos anos. Estudos originais que apresentam o uso dessa prática apontam baixo risco de complicações locais, maior conforto para os pacientes, possibilidade de mobilização e deambulação precoce após procedimento, diminuição do período de internação hospitalar e redução de custos hospitalares. Entre as complicações possíveis, a mais temida é a oclusão da artéria radial (OAR). Embora seja preocupante essa complicação, ainda não há consenso quanto à avaliação rotineira da patência da artéria antes da alta hospitalar e sua relação com o dispositivo hemostático utilizado. Visando preencher essa lacuna do conhecimento, este estudo foi planejado para comparar o efeito de dois dispositivos de hemostasia após cateterismo cardíaco realizado por acesso transradial na ocorrência de OAR. Foi conduzido um ensaio clínico randomizado (ECR) de dois grupos, aberto, no Laboratório de Hemodinâmica (LH) de um hospital público e universitário da região metropolitana de Porto Alegre, Rio Grande do Sul. O período de coleta foi de novembro de 2015 a outubro de 2016. Foram incluídos pacientes adultos ambulatoriais e internados, submetidos a cateterismo cardíaco diagnóstico e/ou terapêutico por acesso transradial, em caráter eletivo e/ou de urgência. Os participantes foram randomizados em dois grupos: Grupo Intervenção (GI) – hemostasia com dispositivo TR Band; e Grupo Controle (GC) – hemostasia com dispositivo de gaze e bandagem elástica adesiva. O desfecho primário foi a OAR imediata ao procedimento e em 30 dias; os desfechos secundários foram a migração dos padrões das curvas após retirada imediata do dispositivo e em 30 dias, a necessidade de tempo a mais para alcance da hemostasia, as demais complicações vasculares relacionadas ao sítio de punção (sangramento e hematoma) e a presença e intensidade de dor. Foram incluídos 600 pacientes: GI (n=301) e GC (n=299), predominantemente do sexo masculino, com média de idade de 63 ± 10 anos; a OAR imediatamente após a remoção do dispositivo ocorreu em 24 (8%) e 19 (6%), no GI e GC, respectivamente; em 30 dias para um terço da amostra foi de 5 (5%) e 7 (6%), no GI e GC, respectivamente. Para estes dois períodos não foram demonstradas diferenças estatísticas; o tempo de hemostasia adicional, assim como o tempo necessário para outro tipo de compressão, foi significativamente maior no GI, p=0,006 e p<0,001, respectivamente; pacientes de ambos os grupos mantiveram um padrão e migração de curvas semelhantes na avaliação pré procedimento, imediatamente após a retirada dos dispositivos e em 30 dias; o sangramento menor foi significativamente maior no GI, quando comparado ao GC, 67 (22%) vs. 40 (13%), respectivamente, p = 0,006; o hematoma foi semelhante entre os dois grupos. O relato de dor foi similar entre os grupos, e a intensidade relatada foi moderada. Os resultados deste estudo permitem concluir que a incidência de OAR foi semelhante entre os grupos TR Band e bandagem elástica adesiva. Os padrões de curva do teste de Barbeau foram semelhantes em todas as avaliações. Pacientes que utilizaram TR Band precisaram de mais tempo adicional de hemostasia assim como mais tempo com outro tipo de compressão. O sangramento menor foi mais incidente no grupo TR Band, enquanto o hematoma foi semelhante entre os grupos. A ocorrência de dor moderada foi semelhante entre os dois grupos. / Favorable evidence increase the use of the transradial technique in recent years. Original studies that address this approach suggest low risk of local complications, greater comfort for patients, the possibility of early mobilization and ambulation after the procedure, a shorter hospital stay and reduced hospital costs. Among the possible complications, the most feared is radial artery occlusion (RAO). Although RAO is of concern, there is still no consensus regarding the routine assessment of radial artery patency before discharge and its relationship to the hemostatic device used. In order to fill this knowledge gap, this study was planned to compare the effect of two hemostasis devices after cardiac catheterization performed by transradial access on the appearance of RAO. A two-group Randomized Clinical Trial (RCT) was conducted at the Hemodynamic Laboratory (HL) of the Hospital de Clínicas of Porto Alegre (HCPA), a public university hospital in the metropolitan region of Porto Alegre, Rio Grande do Sul. The collection period was from November 2015 to October 2016. Adult patients from the outpatient clinic and hospitalized patients undergoing cardiac diagnostic and / or therapeutic catheterization due to transradial access, in an elective and / or emergency manner, were included. Participants were randomized into two groups: intervention group (IG) - hemostasis with TR Band device; Control Group (CG) - hemostasis with gaze device and adhesive elastic bandage. The primary outcome was immediate RAO to the procedure and in 30 days; secondary outcomes were migration of the curvature patterns after immediate device removal and in 30 days, the need for extra time to reach hemostasis other vascular complications related to the puncture site (bleeding and hematoma), and the presence and intensity of pain. A total of 600 patients were included: IG (n=301) and CG (n=299), predominantly males with a mean age of 63 ± 10 years; RAO immediately following device removal occurred in 24 (8%) and 19 (6%), in the IG and CG groups, respectively; in 30 days for a third of the sample was 5 (5%) and 7 (6%) in IG and CG, respectively. For these two periods no statistical difference was demonstrated. The additional hemostasis time, as well as the time required for another type of compression, was significantly higher in IG, p=0.006 and p<0.001, respectively; patients from both groups maintained a pattern of migration of similar curves in the pre-procedure assessment, immediately after the device withdrawal and in 30 days; The lowest bleeding was significantly higher in the IG, compared to the GC, 67 (22%) vs 40 (13%), respectively, p = 0.006; the hematoma was similar between the two groups. The reported pain was similar between the groups, and the reported intensity was moderate. The results of this study allow us to conclude that the incidence of RAO was similar between TR Band groups and adhesive elastic bandage. The standards of the Barbeau test curve were similar in all assessments. Patients who used TR Band required more extra hemostasis time as well as more time with another type of compression. Minor bleeding was more incident in the TR Band group, while the hematoma was similar between the groups. The occurrence of moderate pain was similar between the two groups.

Objetivos: Avaliar o papel da turbinectomia inferior parcial endoscópica (TIPE) na rinosseptoplastia primária sobre os desfechos de qualidade de vida, complicações e tempo cirúrgico. Delineamento: Ensaio clínico pragmático, randomizado, duplo-cego em um centro único e de grupos paralelos. Métodos: Indivíduos maiores de 16 anos, com queixas estéticas e obstrução nasal, candidatos à rinosseptoplastia primária, avaliados entre março de 2014 e maio de 2015, em um Hospital Terciário Universitário no Brasil. Pacientes elegíveis foram randomizados para receberem ou não TIPE concomitantemente à cirurgia. Desfechos: Diferença absoluta dos escores pré e pós-operatórios em qualidade de vida específica, pela aplicação dos questionários Nasal Obstruction Symptom Evaluation Portuguese (NOSE-p) e Rhinoplasty Outcome Evaluation (ROE), e geral, através de aplicação do World Health Organization Quality of Life (WHOQOL)-breve. Os desfechos eram cegados e acessados somente três meses após a cirurgia. O protocolo foi registrado no ClinicalTrials.gov (NCT02231216). Resultados: 50 pacientes foram incluídos, maioria caucasiana com rinite alérgica com sintomas moderados a severos. A média de idade foi 36 (±14,5) anos. Os escores de qualidade de vida específicos e gerais melhoraram independentemente da intervenção TIPE (p < 0,001). ANCOVA foi aplicada para controlar potenciais fatores confundidores. Não houve divergência entre a diferença absoluta nos pacientes submetidos ou não a TIPE nos escores NOSE-p (-50,5 vs. -47,6; p=0,723); ROE (47 vs. 44,8; p= 0,742) e todos os domínios do WHOQOL-breve (p > 0,05). Não houve diferença entre os grupos sobre a presença de complicações. O tempo cirúrgico foi maior no grupo TIPE (212 minutos ± 7,8 vs. 159,1 ± 5,6; p ˂ 0,001). Conclusão: A redução das conchas inferiores através da TIPE durante a rinosseptoplastia primária não melhorou, em curto prazo, a qualidade de vida geral nem específica. O uso de TIPE aumenta o tempo cirúrgico consideravelmente, sem adicionar benefício aos escores avaliados. Não houve diferença na incidência de complicações no pós-operatório, sugerindo a segurança da técnica. / Objectives/Hypothesis: To evaluate the impact of endoscopic partial inferior turbinectomy (EPIT) associated with primary Rhinoseptoplasty on quality of life outcomes (QOL), complications, and surgical duration. Study Design: Randomized clinical trial. Methods: Individuals with nasal obstruction aged ≥ 16 years who were candidates for functional and aesthetics primary Rhinoseptoplasty were evaluated from March 2014 through May 2015 at a tertiary university hospital in Brazil. Eligible participants were randomly allocated to rhinoseptoplasty with or without EPIT. Outcomes: Absolute change (postoperative –preoperative) in the following QOL scores: Nasal Obstruction Symptom Evaluation-Portuguese (NOSE-p), Rhinoplasty Outcome Evaluation (ROE) and World Health Organization Quality of Life (WHOQOL)-bref (to measure general QOL). Outcomes were blindly assessed 3 months postoperatively. The protocol was registered at ClinicalTrials.gov (NCT02231216). Results: Fifty patients were studied. Most were Caucasian and had moderate/severe allergic rhinitis symptoms. Mean age was 36 (±14.5) years. Rhinoseptoplasty was associated with improvement in all QOL scores irrespective of turbinate intervention (P <0.001). ANCOVA was conducted to control for potential confounders. There was no difference between the groups in absolute score changes for NOSE-p (-50.5 vs. -47.6; P=0.723); ROE (47 vs. 44.8; P = 0,742), and all WHOQOL-bref score domains (P >0.05). There were no differences between the groups regarding presence of the complications. Surgical duration was higher in the EPIT group (212 minutes ± 7.8 vs. 159.1 ± 5.6; p ˂ 0.001). Conclusions: Turbinate reduction through EPIT during primary rhinoseptoplasty did not improve short-term general and specific QOL outcomes. The use of EPIT increases surgical time considerably without improving QOL scores. There was no difference in postoperative incidence of complications, suggesting that EPIT is a safe technique.

Esse trabalho objetivou avaliar o perfil genômico de pacientes HIV+ submetidos à imunoterapia com células dendríticas (DC). Os resultados obtidos mostraram que as DC utilizadas na imunoterapia podem ser diferentes em termos de perfil de expressão gênica entre os pacientes selecionados para o ensaio clínico e essas diferenças podem afetar a qualidade do produto administrado ao paciente. Nossos dados não correlacionaram diferenças na ativação das DC com esse perfil de expressão gênica distinto, possivelmente pelo número limitado de amostras disponíveis ou pela escassez de marcadores de ativação adequados. O único paciente que respondeu à imunoterapia mostrou, em leucócitos circulantes, um perfil de expressão específico e relacionado com um melhor controle da carga viral plasmática e com uma resposta imune de tipo Th1 quando comparado com os indivíduos que não responderam ao tratamento. A genotipagem revelou que esse paciente também carrega polimorfismos relacionados a menor progressão à AIDS o que também pode estar relacionado com a boa resposta à imunoterapia. / Aim of this project was the evaluation of genomic profile of HIV+ patients submitted to dendritic cell (DC)-based immunotherapy. Results showed that expression profile of DC used in immunotherapy could be different among patients selected for immunotherapy, and that those differences could affect the quality of final vaccine product, even if our data did not evidence significant difference in DC activation state with regard to expression profile, maybe due to limited size of available samples or to the lack of appropriate DC activation markers. The expression profile of peripheral blood leukocytes from the only good responder of immunotherapy trial was associated with better control of plasma viral load and a Th1 immune response compared to weak or transient responders. Genotyping analysis revealed that the good responder carries polymorphisms associated with a less progression toward AIDS, suggesting that also the genetic background could affect the response to immunotherapy.

A sede é definida como o desejo de beber água. É considerada um sintoma multifatorial, pois o estímulo proporcionado pode ser influenciado pela necessidade de hidratação, ou seja, normalizar os níveis de volemia e osmolaridade plasmática, ou pode ser desencadeado por diferentes fatores pessoais e culturais do indivíduo. O objetivo do estudo foi comparar a intensidade e o desconforto da sede em pacientes no período pré-operatório, após vinte minutos da degustação do picolé mentolado com a sede de pacientes que receberam o cuidado usual. Trata-se de ensaio clínico aleatorizado com tratamento em paralelo, prospectivo e monocêntrico. A amostra do estudo foi composta de 40 pacientes cirúrgicos no período pré-operatório, os quais foram alocados em dois grupos, sendo 20 no grupo controle e 20 no grupo experimental. O paciente alocado no grupo controle (cuidado usual) recebeu as orientações dadas pela equipe de saúde, conforme rotina da instituição de saúde. O paciente alocado no grupo experimental recebeu um picolé mentolado, com, no mínimo, três horas de antecedência do horário programado para o procedimento cirúrgico. Para a coleta de dados elaborou-se instrumento, o qual foi submetido a validação de face e conteúdo por cinco juízes. A intensidade e o desconforto da sede foram os desfechos primários mensurados. A intensidade da sede foi mensurada por meio da Escala Numérica (zero sem sede e dez a pior sede que a pessoa já sentiu), e o desconforto da sede pela Escala de Desconforto da Sede Perioperatória (pontuação varia de zero a 14 pontos, sendo que 14 corresponde ao desconforto mais intenso relacionado com a sede). As médias de intensidade da sede inicial foram diferentes entre os grupos investigados, sendo 5,3 (dp 1,8) para o grupo controle, e 6,6 (dp 1,6) para o grupo experimental (p=0,02). As médias relativas ao desconforto inicial da sede também foram discrepantes, 5,2 (dp 2,9) para o grupo controle, e 8,0 (dp 3,7) para o grupo experimental (p<0,001). Os resultados do ensaio clínico aleatorizado evidenciaram significativamente a diminuição da intensidade e do desconforto da sede de pacientes, após vinte minutos da degustação do picolé mentolado com a sede de pacientes que receberam o cuidado usual (p<0,001 para os dois desfechos). O picolé mentolado mostrou-se como estratégia viável para o manejo da sede em paciente no período pré-operatório. As evidências geradas na condução do estudo podem auxiliar, na tomada de decisão da equipe de saúde, acarretando a melhoria do cuidado prestado ao paciente, por meio da implementação de estratégia de fácil aplicação e barata para o manejo da sede. Outro aspecto relevante consiste na produção de conhecimento sobre a problemática, escasso tanto no cenário nacional, quanto internacional / Thirst is defined as the desire of drinking water. It is also considered a multifactorial symptom for two plausible reasons. The first refers to the provided stimulus that may be influenced for the hydration need. To put it differently, such necessity seeks to balance the volume levels and the plasmatic osmolarity. The second one is justified due to it is initiated by the person\'s various personal and cultural factors. This investigation aimed at comparing the intensity and discomfort that thirst caused in patients. The period analyzed refers to the preoperative twenty minutes after the patients ate the mentholated popsicle in comparison to patients who received the usual assistance. This randomized clinical trial was carried out with a parallel, prospective, and monocentric treatment. The sample had 40 surgical patients within the perioperative period. They were divided into two groups, namely: 20 belonged to the control group and 20 belonged to the experimental one. The patients placed into the former received the expected assistance from the health team. Regarding the patients placed into the latter, they received one mentholated popsicle at least three hours before the surgical arranged time. The data collecting tool developed was submitted to five judges\' face and content validation. The intensity and discomfort of thirst were the measured primary findings. The former was measured by using the Numeral Scale in which the number zero represents no thirst and the number ten, the most intense thirst the patients reported they have ever felt. The latter was evaluated by applying the Discomfort Scale of Preoperative Thirst whose pointing may vary from zero to fourteen. In such scale, the occurrence of fourteen corresponds to the most considerable discomfort the patients reported they have ever experienced. In terms of intensity of thirst, the initial averages were different regarding both investigated groups, scored 5,3 (dp 1,8) to the control one and 6,6 (dp 1,6) to the experimental one (p=0,02). The averages concerning the thirst initial discomfort also presented discrepancy, scored 5,2 (dp 2,9) to the first group and 8,0 (dp 3,7) to the second one (p<0,001). The results of this randomized clinical trial significantly evince the decrease of thirst intensity and discomfort on patients who ate the mentholated popsicle in comparison to the ones who received the usual assistance (p<0,001 to both outcomes). The mentholated popsicle seemed to be a feasible strategy to assist patients in the preoperative period. The evidences produced throughout the investigation may support decision makings by the health team and, consequently, improve the patient\'s given support. It might happen by the implementation of an inexpensive and effortless application of such strategy. Moreover, another relevant aspect concerns to the knowledge production due to the features this study shed lights on, which sparse in both national and international scenarios

Anterior knee pain (AKP) is a common, chronic lower limb musculoskeletal overuse condition that represents substantial morbidity to those affected, and has a significant impact on the health care industry. Health practitioners frequently prescribe foot orthoses in the management of AKP as an alternative or adjunct to multimodal physiotherapy. The primary aim of this thesis was to investigate the clinical efficacy of foot orthoses in AKP, utilising high-quality research methodologies. The two systematic reviews conducted have identified a significant gap in the literature regarding evidence from randomised clinical trials (RCTs) for foot orthoses in AKP and other lower limb overuse conditions. While the best evidence for AKP management was for multimodal physiotherapy, there was insufficient evidence to support or refute the use of foot orthoses in the treatment of lower limb overuse conditions, including AKP. Meta-analysis provided evidence to support the use of foot orthoses in the prevention of the first incidence of lower limb overuse conditions. An interesting finding was evidence from pooled and individual study data of no difference between custom and prefabricated foot orthoses in both treatment and prevention of lower limb overuse conditions, inferring that either type of orthosis may be utilised. Both systematic reviews highlighted substantial methodological flaws of the included studies, and recommended that future studies include larger participant numbers, longer participant follow-up, more consistent use of reliable and valid outcome measures and reporting of outcome data, and utilisation of the CONSORT guidelines in the design and reporting of RCTs. A 12-month prospective RCT investigated the short- and long-term clinical efficacy of prefabricated foot orthoses in the treatment of 179 participants with AKP. Foot orthoses were more effective than flat shoe inserts in the short term, implying that their contoured form has some therapeutic effect. Foot orthoses were not significantly different to multimodal physiotherapy over 12 months, nor was there any benefit in adding foot orthoses to physiotherapy. Considering that all groups experienced clinically meaningful long-term improvements in pain and function, clinicians may prescribe foot orthoses for AKP to hasten recovery. Findings of post-hoc analyses to develop a clinical prediction rule indicate that those of older age and shorter height, who have a lower severity of AKP and a more mobile midfoot, are more than twice as likely to experience a successful outcome with foot orthoses. As a secondary aim, this thesis has provided a more comprehensive profile of AKP as a condition. Baseline data from the RCT participants confirms previous reports of higher rates of AKP in females, and a tendency towards bilaterality and chronicity. This AKP sample did not differ from asymptomatic individuals in terms of body mass index, physical activity level, general and mental health, and foot posture, although they tended to have a more mobile foot under load. These characteristics tend to be homogenous across a number of published RCTs, indicating that the findings of the RCT described above are likely to be generalisable to the broader population with AKP. An additional finding in this group was that those with AKP of long duration, higher pain levels, lower functional levels, and an overall lower score on a specific measure of AKP have a poorer prognosis over 12 months, irrespective of their age, gender or morphometry. These findings suggest that, in order to improve prognosis and the chance of a successful outcome, the primary goals of intervention should be to reduce the severity and duration of AKP, through the use of early intervention with foot orthoses, multimodal physiotherapy, or a combination of the two.

In the present studies we have explored the link between food hypersensitivity and IgA nephropathy (IgAN) and evaluated treatment options in primary and recurrent disease. Approximately one third of our IgAN patients had a rectal mucosal sensitivity to gluten, as demonstrated by increased local mucosal nitric oxide production and/or myeloperoxidase release after gluten challenge. The gluten sensitivity seemed to be an innate immune reaction unrelated to the pathogenesis of celiac disease. Approximately half of the patients had a rectal mucosal sensitivity to soy or cow’s milk (CM). The levels of IgG antibodies to alfa-lactalbumin, beta-lactoglobulin and casein were significantly higher in CM sensitive as compared with non-sensitive IgAN patients, indicating that an adaptive immune response might be involved in addition to the innate immune reaction observed. With the knowledge of gastrointestinal reactivity enteric treatment was considered as a potential new treatment approach of IgAN. A 6-month prospective trial demonstrated proof-of-concept for the use of enteric budesonide targeted to the ileocaecal region of IgAN patients. We observed a modest, but significant reduction in urine albumin, a minor reduction of serum creatinine and a modest increase of eGFR calculated by the MDRD equation. eGFR calculated from the Cockcroft-Gault formula and cystatin C was not changed. In a retrospective study recurrence of IgAN and graft loss was evaluated in Norwegian and Swedish patients having received a primary renal transplant due to IgAN. Adjusting for relevant covariates, a multiple Cox-regression analysis on time to IgAN recurrence showed that use of statins was associated with reduced risk of recurrence and reduced risk of graft loss. The time lag from diagnosis to first transplantation and female gender were also associated with lower risk of recurrence. Improved graft survival was associated with related donor, low donor age and no or low number of acute rejection episodes.

Nasal administration has potential for the treatment of indications requiring a fast onset of effect or for drugs with low oral bioavailability. Liquid nasal sprays are relatively common, but can be associated with suboptimal absorption from the nasal cavity; this thesis shows that nasal absorption can be significantly enhanced with a dry powder formulation. It was shown that interactive mixtures, consisting of fine drug particles adhered to the surface of mucoadhesive carrier particles, could be created in a particle size suitable for nasal administration. Sodium starch glycolate (SSG), a common tablet excipient, was used as carrier material. In vitro evaluation of the formulation indicated that the mucoadhesion of the carrier was unlikely to be affected by the addition of a drug. The powder formulation did not improve the in vitro transfer of dihydroergotamine across porcine nasal mucosa compared with a liquid formulation; however, the results were associated with methodological shortcomings. The binding of model substances to SSG and three other excipients was evaluated. Ion exchange interactions were for example detected between SSG and cationic drugs, but these interactions were most extensive at low salt concentrations and should unlikely affect in vivo bioavailability at physiological salt concentrations. Absorption of the peptide drug desmopressin from the SSG nasal formulation, from a novel sublingual tablet formulation and from a commercial nasal liquid spray was evaluated in a clinical trial. While no improvement over the liquid spray was seen with the sublingual tablet, plasma concentrations after the nasal powder formulation were three times higher than those after the liquid spray. All formulations were well accepted by the volunteers. The use of currently available mucoadhesive carrier particles in interactive mixtures offers potential for a new method of producing nasal powder formulations that should also be applicable to large scale production.

The design of clinical trials is one of the important problems in medical statistics. Its main purpose is to determine the methodology and the sample size required of a testing study to examine the safety and efficacy of drugs. It is also a part of the Food and Drug Administration approval process. In this thesis, we first study the comparison of the efficacy of drugs in clinical trials. We focus on the two-sample comparison of proportions to investigate testing strategies based on two-stage design. The properties and advantages of the procedures from the proposed testing designs are demonstrated by numerical results, where comparison with the classical method is made under the same sample size. A real example discussed in Cardenal et al. (1999) is provided to explain how the methods may be used in practice. Some figures are also presented to illustrate the pattern changes of the power functions of these methods. In addition, the proposed procedure is also compared with the Pocock (1997) and O¡¦Brien and Fleming (1979) tests based on the standardized statistics. In the second part of this work, the operating room scheduling problem is considered, which is also important in medical studies. The national health insurance system has been conducted more than ten years in Taiwan. The Bureau of National Health Insurance continues to improve the national health insurance system and try to establish a reasonable fee ratio for people in different income ranges. In accordance to the adjustment of the national health insurance system, hospitals must pay more attention to control the running cost. One of the major hospital's revenues is generated by its surgery center operations. In order to maintain financial balance, effective operating room management is necessary. For this topic, this study focuses on the model fitting of operating times and operating room scheduling. Log-normal and mixture log-normal distributions are identified to be acceptable statistically in describing these operating times. The procedure is illustrated through analysis of thirteen operations performed in the gynecology department of a major teaching hospital in southern Taiwan. The best fitting distributions are used to evaluate performances of some operating combinations on daily schedule, which occurred in real data. The fitted distributions are selected through certain information criteria and bootstrapping the log-likelihood ratio test. Moreover, we also classify the operations into three different categories as well as three stages for each operation. Then based on the classification, a strategy of efficient scheduling is proposed. The benefits of rescheduling based on the proposed strategy are compared with the original scheduling observed.

Analyses of data with missing values often require assumptions about missingness mechanisms that cannot be assessed empirically, highlighting the need for sensitivity analyses. However, universal recommendations for reporting missing data and conducting sensitivity analyses in empirical studies are scarce. Both steps are often neglected by practitioners due to the lack of clear guidelines for summarizing missing data and systematic explorations of alternative assumptions, as well as the typical attendant complexity of missing not at random (MNAR) models. We propose graphical displays that help visualize and systematize the results of sensitivity analyses, building upon the idea of "tipping-point" analysis for experiments with dichotomous treatment. The resulting "enhanced tipping-point displays" (ETP) are convenient summaries of conclusions drawn from using different modeling assumptions about the missingness mechanisms, applicable to a broad range of outcome distributions. We also describe a systematic way of exploring MNAR models using ETP displays, based on a pattern-mixture factorization of the outcome distribution, and present a set of sensitivity parameters that arises naturally from such a factorization. The primary goal of the displays is to make formal sensitivity analyses more comprehensible to practitioners, thereby helping them assess the robustness of experiments' conclusions. We also present an example of a recent use of ETP displays in a medical device clinical trial, which helped lead to FDA approval. The last part of the dissertation demonstrates another method of sensitivity analysis in the same clinical trial. The trial is complicated by missingness in outcomes "due to death", and we address this issue by employing Rubin Causal Model and principal stratification. We propose an improved method to estimate the joint posterior distribution of estimands of interest using a Hamiltonian Monte Carlo algorithm and demonstrate its superiority for this problem to the standard Metropolis-Hastings algorithm. The proposed methods of sensitivity analyses provide new collections of useful tools for the analysis of data sets plagued with missing values. / Statistics

Patients with bulimia nervosa are at high risk for dental erosion. However, not all bulimic patients suffer from erosion, irrespective of the severity of their eating disorder. It is often speculated that differences in the saliva are important, however, little is known about salivary parameters in bulimic patients, particularly directly after vomiting. The aim of the clinical trial was to compare different salivary parameters of subjects suffering from bulimia with those of healthy controls. Twenty-eight subjects participated (14 patients with bulimia nervosa, 7 of them with erosion; 14 matched healthy controls). Resting and stimulated saliva of all participants was analysed as well as saliva collected from bulimic patients directly and 30 min after vomiting. Parameters under investigation were flow rate, pH, buffering capacity and the enzyme activities of proteases in general, collagenase, pepsin, trypsin, amylase, peroxidase, and lysozyme. Regarding flow rate, pH and buffering capacity only small differences were found between groups; buffering capacity directly after vomiting was significantly lower in bulimic subjects with erosion than in subjects without erosion. Differences in enzymatic activities were more pronounced. Activities of proteases, collagenase and pepsin in resting and proteases in stimulated saliva were significantly higher in bulimic participants with erosion than in controls. Peroxidase activity was significantly decreased by regular vomiting. Proteolytic enzymes seem to be relevant for the initiation and progression of dental erosion directly after vomiting, maybe by both hydrolysis of demineralized dentine structures as well as modulation of the pellicle layer. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.