The aims of this thesis were to investigate the utility of in vitro drug sensitivity testing to optimize the use of cancer chemotherapy and to assess the properties of a new cancer drug in a phase I clinical trial. Tumour cells from patients were analysed with the short-term Fluorometric Microculture Cytotoxicity Assay (FMCA). In samples from a wide spectrum of tumour types, the effect of the drug combination FEC (5Fu-epirubicin-cyclophosphamide) was generally appropriately predicted from the effect of the best component drug. However, of samples intermediately sensitive to the best single drug, 45% converted to sensitive when testing the combination. Thus, combination testing may identify advantageous interactions and improve in vitro test performance. In tumour samples from peritoneal carcinomatosis, significant differences in drug sensitivity between diagnoses were observed, cross-resistance between most drugs was modest or absent, and the concentration-effect relationships for two drugs in individual samples varied considerably. Thus, for optimal selection of drugs for intraperitoneal chemotherapy, differences in drug sensitivity at the diagnosis and individual patient level should be considered. In samples from patients with ovarian carcinoma, drug sensitivity was related to tumour grade, histologic subtype and patient treatment status. In a homogeneous subset of patients, the FMCA predicted individual patient tumour response with high sensitivity and specificity. Thus, if carefully interpreted in the context of important clinical variables, in vitro testing could be of value for individualizing chemotherapy in ovarian cancer. Employing a once weekly dosing schedule in a phase I trial, the mechanistically new and preclinically promising NAD depleting drug CHS 828 produced dose limiting thrombocytopenia and gastrointestinal toxicity without clear evidence of anti-tumour efficacy. It is concluded that in vitro drug sensitivity testing could be a way to optimize the use of chemotherapy and that successful development of new cancer drugs needs improved strategies.

Thesis (M.A.)--Indiana University, 2008. / Title from screen (viewed on June 2, 2009). Department of Philosophy, Indiana University-Purdue University Indianapolis (IUPUI). Advisor(s): Eric Mark Meslin, John J. Tilley, Timothy D. Lyons. Includes vita. Includes bibliographical references (leaves 48-52).

Orientador: Eliana Mara Braga / Abstract: The World Health Organization acknowledges the importance of integrative and complementary health practices and recommends that studies are carried out to advance them, using, for example, randomized clinical trials, powerful tool to evaluate health interventions. Among these practices, floral therapy emerges in the field of vibrational therapies, with simple and natural non-invasive characteristics that heals and harmonizes without side-effects or incompatibility to other treatments. Thus, the objective of this study was to understand the experience of overweight or obese anxious individuals in participating of a clinical research trial that used floral therapy as health intervention. This is a qualitative study linked to the project entitled "Effectiveness of floral therapy on anxiety of overweight or obese adults". Forty-two overweight and obese individuals of both sexes were enrolled in this study between June and November of 2016 for a semi-structured interview after termination of the primary clinical trial conducted in an institute of public health. Data collected from interviews were qualitatively organized and analyzed according to Content Analysis from Bardin, separated in two categories that emerged from participants' speeches: “Meaning of participating in a clinical research trial” and “Perception of the action of the therapy used”. Publications from Edward Bach were used as theoretical basis for this study. Results showed that overweight or obese anxious individu... (Complete abstract click electronic access below) / Resumo: A Organização Mundial da Saúde reconhece a importância das práticas integrativas e complementares em saúde e recomenda que estudos sejam realizados para o avanço deste modo de cuidar, como é o caso do ensaio clínico randomizado, uma poderosa ferramenta para avaliação de intervenções na área da saúde. Dentre as práticas, surge a terapia floral como parte de um campo de terapias vibracionais, de características não invasivas, simples e naturais, que atuam curando e harmonizando sem que haja a possibilidade de efeitos colaterais e incompatibilidade com outros tratamentos. Desta forma, o objetivo desse estudo é compreender a experiência do participante de uma pesquisa clínica, que teve como intervenção a terapia floral, para ansiedade de indivíduos com sobrepeso ou obesidade. Trata-se de um estudo de abordagem qualitativa, vinculado ao projeto intitulado “Efetividade da terapia floral na ansiedade de adultos com sobrepeso ou obesidade”. A pesquisa foi realizada em uma Instituição Pública de Saúde com 42 indivíduos de ambos os sexos, no período de junho a novembro de 2016. A coleta de dados foi realizada após o término da participação na pesquisa clínica originária, por meio de uma entrevista semiestruturada. O referencial teórico que alicerça essa pesquisa são as publicações de Edward Bach. Para organização e análise dos dados qualitativos foi adotado como referencial metodológico a Análise de Conteúdo segundo Bardin, resultando em duas categorias que emergiram dos discursos dos ... (Resumo completo, clicar acesso eletrônico abaixo) / Mestre

Cette thèse est consacrée au travail dans un essai médical à caractère préventif sur la maladie d’Alzheimer en France. L’enquête s’est déroulée essentiellement au sein de deux Centres mémoire de ressources et de recherches (CMRR), lesquels ont été parmi les principaux recruteurs du protocole de recherche. Elle a surtout reposé sur la volonté de donner à voir les multiples formes d’incertitude entourant l’essai clinique, depuis le travail de recrutement jusqu’à celui de gestion des participants. Plus précisément, le présent travail a pour objectif d’examiner empiriquement, d’une part, dans quelle mesure certaines propriétés sociales des travailleurs influent sur les logiques professionnelles et scientifiques et quels sont, d’autre part, les facteurs qui ont conduit au départ de nombreux participants de l’essai clinique multi-sites. / This thesis is devoted to work in a preventive medical trial on Alzheimer's disease in France. The survey was carried out mainly at two “Centres Mémoire de Ressources et de Recherches” (CMRR) which were among the main recruiters of the research protocol. Above all, it sought to highlight the many forms of uncertainty surrounding the clinical trial, from the recruitment work to the management of the participants. More precisely, this work aims to lookat, on the one hand, the extent to which certain social properties of workers influence the professional and scientific logics and, on the other hand, what factors led to the departure of many participants in the multi-site clinical trial.

Made available in DSpace on 2015-05-14T12:56:02Z (GMT). No. of bitstreams: 1 arquivototal.pdf: 1778703 bytes, checksum: fdc31d949eee563ab3213db7eec3ac95 (MD5) Previous issue date: 2014-02-26 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / The Cinnamomum zeylanicum Blume leaf (Cinnamon) essential oil has been reported in the literature by presenting antifungal activity against Candida species. This study aimed to verify the in vitro antifungal activity of a Cinnamomum zeylanicum Blume leaf essential oil based mouthwash, in addition to changes in roughness and hardness caused by it in thermopolymerizable acrylic resin. Further evaluation of the safety and tolerability of the test product was seeked through a phase I clinical trial involving users of removable dentures. For this to happen, the determination of the Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC) on twelve strains of Candida, using the technique of Sabouraud Dextrose Broth microdilution (CSD) and subculture on Sabouraud Dextrose Agar (SDA), respectively. For microhardness tests and surface roughness, 30 specimens were made in thermopolymerizable acrylic resin (Vip Flash, Ltda. São Paulo, SP, Brazil), divided into three groups of n = 10. Group I remained in artificial saliva during the test, while groups II and III remained for 1 minute, 3 times a day, in their corresponding solutions (mouthwash and nystatin, respectively), returning to neutral artificial saliva during 15 days. Roughness measurements (SJ-201 Minutayo, Kawasaki, Japan) and microhardness (Shimadzu, Kyoto, Japan) were performed (24 hours before and 24 hours after the start and end of the test) to obtain data on the roughness and microhardness (25g / 30s), which were submitted to ANOVA and followed by Tukey post-test (&#945; = 5%). For the phase I clinical trial, 15 healthy patients using a C. zeylanicum mouthwash in CIM (15 days, 3 times a day) were submitted to clinical and mycological examinations before and after the intervention. The essential oil of C. zeylanicum showed anti-Candida activity on the 12 strains tested, with an MIC = 625.0&#956;g/mL equivalent to CFM. All groups experienced an increase in roughness after the intervention (p <0.0001). The test product group (GII) suffered alteration (&#916;Ra) of 0.40&#956;m, not statistically different from the group that remained immersed in saliva (GI) whose value was &#916;Ra 0.39&#956;m. Nystatin (GIII) showed the largest increase in roughness (&#916;Ra = 0.50&#956;m) compared to GI and GII (p <0.0001). Regarding hardness, nystatin also promoted a greater decrease (&#916;M = -3.62VHN) compared to saliva (&#916;M = -2.57VHN) and mouthwash, which promoted change of -2.12VHN (p <0.0001). Regarding the clinical stage of phase 1, there were no adverse clinical signs after the intervention, or relevant reports indicating that suspension of use. The mouthwash showed antifungal activity against all tested strains and promoted minor variation of roughness and hardness of acrylic resin compared to positive control (nystatin). These factors combined with the absence of adverse effects in humans make it possible to consider, in this study, satisfactory safety and tolerability of the tested substance, supporting new advances involving the clinical use of C. zeylanicum Blume essential oil. / O óleo essencial das folhas de Cinnamomum zeylanicum Blume (Canela) tem sido reportado pela literatura por apresentar atividade antifúngica sobre espécies de Candida. Objetivou-se verificar, in vitro, a atividade antifúngica de um enxaguatório bucal a base do óleo essencial das folhas de Cinnamomum zeylanicum Blume, além de alterações de rugosidade e microdureza provocadas pelo mesmo em resina acrílica termopolimerizável. Buscou-se ainda avaliar a segurança e tolerabilidade do produto-teste através de um ensaio clínico fase I envolvendo usuários de próteses removíveis. Para tal procedeu-se com a determinação da Concentração Inibitória Mínima (CIM) e da Concentração Fungicida Mínima (CFM) sobre doze cepas de Candida, utilizando-se a técnica da microdiluição em Caldo Sabouraud Dextrose (CSD) e subcultivo em Ágar Sabouraud Dextrose (ASD), respectivamente. Para os ensaios de microdureza e rugosidade superficial foram confeccionados 30 corpos de prova em resina acrílica termopolimerizável (Vip Flash, Ltda. São Paulo, SP, Brasil), divididos em três grupos de n=10. O grupo I manteve-se em saliva artificial durante o ensaio, enquanto os grupos II e III, permaneceram durante 1 minuto, 3 vezes ao dia, em suas soluções correspondentes (enxaguatório bucal e nistatina, respectivamente), retornando à saliva artificial neutra, durante 15 dias. Medições em rugosímetro (SJ-201 Minutayo, Kawasaky,Japão) e microdurômetro (Shimadzu, Kyoto, Japão) foram realizadas (24h antes e 24h após o início e término do ensaio) para obtenção dos dados relativos à rugosidade e microdureza Vickers (25g/30s), os quais foram submetidos à análise de variância ANOVA e pós-teste de Tukey (&#945;=5%). Para o ensaio clínico fase I, 15 pacientes saudáveis utilizaram um enxaguatório bucal de C. zeylanicum na CIM (15 dias, 3 vezes ao dia) sendo submetidos à exames clínico e micológico antes e após a intervenção. O óleo essencial de C. zeylanicum apresentou atividade anti-Candida sobre as 12 cepas testadas, sendo a CIM = 625,0&#956;g/mL equivalente à CFM. Todos os grupos sofreram aumento da rugosidade após a intervenção (p<0,0001). O grupo referente ao produto-teste (GII) sofreu alteração (&#916;Ra) de 0,40&#956;m, não diferindo estatisticamente do grupo que permaneceu imerso em saliva (GI) cujo valor de &#916;Ra foi de 0,39&#956;m. A nistatina (GIII) promoveu maior aumento da rugosidade (&#916;Ra=0,50&#956;m), quando comparada a GI e GII (p<0,0001). Em relação à microdureza, a nistatina também promoveu uma maior diminuição (&#916;M=-3,62VHN), quando comparada à saliva (&#916;M=-2,57VHN) e ao enxaguatório, que promoveu alteração de - 2,12VHN (p<0,0001). Em relação à etapa clínica de fase I, não houve sinais clínicos adversos após a intervenção, nem relatos relevantes que indicassem suspensão do uso. O enxaguatório apresentou atividade antifúngica sobre todas as cepas testadas e promoveu menor alteração de rugosidade e microdureza em resina acrílica se comparada ao controle positivo (nistatina). Tais fatores aliados à ausência de efeitos adversos em humanos permitem considerar, neste estudo, a segurança e a tolerabilidade da substância testada satisfatórias, subsidiando novos avanços envolvendo a utilização clínica do óleo essencial da C. zeylanicum Blume.

The objective of the work presented in this thesis was to explore the role of potential alternatives to platelet transfusions and specifically to investigate whether desmopressin could be used for treatment of thrombocytopenia or platelet dysfunction. Patients with thrombocytopenia or platelet dysfunction are often treated with platelet transfusions to treat or prevent bleeding. However the evidence for the efficacy of platelet transfusion is limited and there is some evidence of harm. I have focused on thrombocytopenic patients with haematological malignancies or critically ill patients, who are amongst the groups most commonly treated with platelet transfusions. The aims of this research were to determine: 1. If levels of Von Willebrand factor (VWF) or other measures of haemostasis are predictive of bleeding in severe thrombocytopenia; 2. Whether VWF compensates for thrombocytopenia in vitro; 3. The evidence for the efficacy of desmopressin in all patients undergoing surgery or invasive procedures; 4. The evidence for desmopressin for platelet dysfunction or thrombocytopenia; 5. If it is feasible to use desmopressin to treat critically ill thrombocytopenic patients in a clinical trial. To identify derangements of haemostasis that may signify candidates for alternatives to platelet transfusions, I analysed blood samples from an observational trial of fifty patients with haematological malignancies and profound thrombocytopenia due to intensive chemotherapy. I used a panel of tests to investigate measures of primary haemostasis, thrombin generation, cross-linked fibrin formation and fibrinolysis. Using multivariable logistic regression, I found no consistent correlation between any measures of haemostasis and the risk of clinically significant bleeding. VWF antigen levels were the best predictor of clinically significant bleeding on the same day (odds ratio 0.31, 95% confidence interval 0.10 to 0.98, p=0.047) but were not predictive of severe bleeding over the 24 hours after the test (odds ratio 0.48, 95% confidence interval 0.10 to 2.34, p=0.36). In a separate set of experiments, I evaluated thrombus formation under flow in thrombocytopenia. This technique was sensitive to the platelet count . Addition of exogenous VWF to thrombocytopenic blood resulted in improvement in thrombus formation, suggesting that agents that affect or influence VWF pathways might have a role. Desmopressin can be used to increase VWF levels, so leading on from my laboratory experiments; I used systematic reviews and meta-analyses to assess whether desmopressin could be used in unselected patients to reduce bleeding peri-operatively. I identified 62 randomised controlled trials. Overall there was no evidence of benefit for administering desmopressin to unselected patients. However further analysis of eleven randomised controlled trials that focused on patients with platelet dysfunction found that desmopressin resulted in transfusion of fewer units of red cells (equivalent to a 25% reduction compared to control), less blood loss (equivalent to a 23% reduction compared to control) and a lower risk of requiring a re-operation due to bleeding (Peto odds ratio 0.39, 95% confidence interval 0.18 to 0.84). There was no evidence for an increase in thrombotic events. There was no randomised controlled trial evidence for perioperative desmopressin for patients with thrombocytopenia. These specific research gaps were addressed by designing new clinical trials. I have commenced a randomised controlled feasibility trial of desmopressin versus placebo for critically ill patients with thrombocytopenia undergoing invasive procedures. This trial is ongoing and is the first randomised trial evaluating peri-procedural desmopressin in thrombocytopenia. The programme of work arising from this research has the potential to benefit a large number of patients by preventing bleeding and reducing exposure to allogeneic blood components such as platelets. The results presented in this thesis are exploratory but are an important step on a path towards larger trials using desmopressin as an alternative, or adjunct to platelet transfusion.

Orientador: José Carlos de Figueiredo Pantoja / Resumo: O objetivo deste estudo foi avaliar novas estratégias de identificação e tratamento de mastite subclínica causada por Streptococcus agalactiae. Dois estudos foram conduzidos para alcançar os objetivos propostos: 1) um ensaio clínico randomizado, para avaliar a eficácia do tratamento de S. agalactiae com cloxacilina intramamária (CLOXIMM), cefquinoma intramamária (CEFIMM) e cefquinoma intramuscular (CEFIM); e avaliar a não-inferioridade da CLOXIMM em relação a CEFIMM. E, 2) um estudo de acurácia diagnóstica, para estimar a acurácia do Somaticell, California Mastitis Test (CMT) e do exame microbiológico do leite composto (leite dos quatro quartos) na detecção de quartos e animais infectados com S. agalactiae. Os resultados indicaram que quartos tratados com CEFIM apresentaram menor taxa de cura bacteriológica (55%) do que aqueles tratados com CLOXIMM (86%) ou CEFIMM (98%). A diferença na proporção de cura bacteriológica entre CEFIMM e CLOXIMM foi de 0,121 (intervalo de confiança de 95%: 0,056 - 0,184). A CLOXIMM foi considerada não inferior a CEFIMM quando margens de não inferioridade de 0,20 e 0,25 foram utilizadas. Contudo, a determinação da não inferioridade foi inconclusiva para margens de 0,10 e 0,15. A cultura do leite composto apresentou acurácia diagnóstica satisfatória (95,7%) quando comparada a cultura individual por quarto. Para identificação dos quartos infectados com S. agalactiae, o ponto de corte considerado mais adequado foi de 205.000 células/mL para o teste So... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The objective of the present study was to assess new strategies to identify and treat Streptococcus agalactiae subclinical mastitis. Two studies were conducted to achieve the proposed objectives: 1) a randomized clinical trial, to assess the efficacy of intramammary cloxacillin (CLOXIMM), intramammary cefquinome (CEFIMM), and intramuscular cefquinome (CEFIM), to treat S. agalactiae intramammary infections (IMI); and assess whether CLOXIMM was non-inferior to CEFIMM to treat S. agalactiae IMI. And, 2) a diagnostic accuracy study, to estimate the accuracy of the Somaticell, California Mastitis Test (CMT), and the composite milk microbiological examination of milk to detect S. agalactiae IMI. Results indicated that the bacteriological cure rate was lower for quarters treated with CEFIM (55%), as compared with CLOXIMM (86%) or CEFIMM (98%). The bacteriological cure difference between CEFIMM and CLOXIMM was 0.121 (95% confidence interval: 0.056 - 0.184). The CLOXIMM was considered non-inferior to CEFIMM when the non-inferiority margins of 0.20 and 0.25 were considered. Nevertheless, determination of non-inferiority was inconclusive for margins of 0.10 and 0.15. Microbiological examination of composite milk was of high accuracy (95.7%), as compared with microbiological examination of quarter milk samples. The thresholds of 205,000 cells/mL for the Somaticell and of score 1 for the CMT can be considered the most appropriate for diagnosing S. agalactiae IMI. The higher sensitivity an... (Complete abstract click electronic access below) / Mestre

The adverse effects of maternal smoking on infant mortality and morbidity has been well documented in the literature. Maternal tobacco use is causally associated with fetal growth restriction and correlates negatively with folate intake and metabolism. Studies have examined the association between smoking and folate levels during pregnancy, but very few have assessed this relationship using objective and accurate measures of both variables. Furthermore, despite evidence of a causal association between smoking in pregnancy and intrauterine growth restriction, and a plausible relationship between tobacco use and low maternal folate which is required for optimal fetal growth, no experimental study has investigated the potential benefit of folic acid in mitigating the adverse effects of maternal smoking on fetal outcomes. The objectives of this study were to investigate the relationship between maternal smoking and folate levels and examine the efficacy of higher-strength folic acid supplementation, in combination with enrollment in a smoking cessation program, in promoting fetal body and brain growth. Our hypothesis was that women who smoke during pregnancy have lower peri-conceptional folic acid reserves than non-smoker pregnant women and that folic acid reserves will decrease with increasing cotinine level. Additionally, smoker pregnant women on higher-strength folic acid (4mg daily) in combination with smoking cessation programs will experience faster fetal brain growth and have infants with larger body size at birth compared to smokers on the standard dose of folic acid (0.8mg daily). Participants were pregnant women (smokers and non-smokers) who received antenatal care between 2010-2014 at the Genesis Clinic of Tampa, a community health center affiliated with the Department of Obstetrics and Gynecology of the University of South Florida (USF). They were aged 18-44 years and had a gestational age of less than 21 weeks at study enrollment. To determine the peri-conceptional folic acid reserves in smoking versus nonsmoking women during pregnancy and associated sociodemographic factors, baseline (crosssectional) data from a double-blinded randomized controlled trial were analyzed using Tobit regression models (n=496). Smoking information was assessed using salivary cotinine, a sensitive and specific tobacco use biomarker. Folate reserve was measured using red blood cell folate. To investigate the efficacy of higher-strength folic acid on fetal body and brain size, baseline and follow-up data from pregnant smokers enrolled in the randomized controlled trial were utilized (n=345). All primary analyses of the clinical trial data were conducted on a modified intention-to-treat basis and included participants who completed the trial with an observed endpoint, irrespective of compliance to protocol. Multilevel modeling, linear regression, and log-binomial regression analyses were conducted. A significant inverse association between salivary cotinine level and periconceptional red blood cell folate concentration was found among pregnant women in the early to midpregnancy period. Smokers on high-dose folate during pregnancy had infants with a 140.38g higher birth weight than infants of their counterparts on standard dose folate (P =0.047). Mothers who received higher strength folate had a 31.0% lower risk of having babies with SGA compared to their mothers on the standard-dose (adjusted relative risk-ARR=0.69, 95% CI: 0.46–1.03; (P =0.073)). High-dose folate had no significant effect on the intrauterine rate of growth in head circumference, and head circumference and brain weight at birth in our trial sample. However, the brain-body ratio of infants of mothers who received high-dose treatment was 0.33 percentage-point lower than that for infants of mothers who received the standard dose of folate (P =0.044). Higher strength folic acid supplementation in pregnant women who smoke might be a cost-effective and safe option to improve birth outcomes and reduce low birth weight and SGA associated infant morbidity and mortality. Future studies with larger sample sizes and diverse populations are indicated to confirm or refute the results of this study. Randomized controlled trials starting during the preconception period and with follow-up until delivery are warranted, to identify the most folate-sensitive period of fetal growth and determine the optimal dose of folic acid supplement. Further research investigating several pathways through which the effects of prenatal smoking on adverse birth outcomes can be mitigated is needed.

Objetivo: Avaliar a eficácia da fisioterapia respiratória como tratamento adjuvante em pacientes pediátricos com pneumonia adquirida na comunidade. Delineamento: Ensaio clínico randomizado Local do estudo: Hospital da Criança Santo Antônio – Complexo Hospitalar Santa Casa, Porto Alegre, Brasil. Participantes e métodos: Foram arroladas crianças com idade entre 1 e 12 anos, com diagnóstico clínico e radiológico confirmado de pneumonia, hospitalizadas no período de setembro de 2001 a setembro de 2002. Os pacientes que preencheram os critérios de inclusão foram randomizados para receber fisioterapia respiratória três vezes ao dia (grupo intervenção) ou para receber, uma vez ao dia, orientações para respirar profundamente, expectorar a secreção e manter preferencialmente o decúbito lateral (grupo controle). As variáveis analisadas na linha de base, no primeiro e no segundo períodos de seguimento e no dia da alta hospitalar foram: escore de gravidade (composto pela freqüência respiratória anormal para a idade, tiragem supra-esternal, intercostal, e subcostal, febre, saturação de oxigênio da hemoglobina e raio-x de tórax), duração da hospitalização, freqüência respiratória, temperatura e saturação do oxigênio. Resultados: Setenta e dois pacientes foram randomizados para os grupos intervenção ou controle. Destes, sete foram retirados devido a complicações como atelectasia ou drenagem pleural. Dentre os 65 pacientes estudados no primeiro seguimento (terceiro dia), a febre foi mais prevalente no grupo intervenção (34,4%) do que no grupo controle (12,5%), bem como o escore de gravidade 9,63 ± 1,62 e 8,71 ± 0,86 pontos, respectivamente. No segundo seguimento, entre o quarto e sexto dia, a diferença entre os grupos teve tendência à significância apenas para febre, 31,6% no grupo intervenção e 6,7% no grupo controle (P= 0,07). A duração média da hospitalização foi de 7,41 ± 6,58 dias para o grupo intervenção e 4,52 ± 2,21 dias para o controle. Conclusão: Neste ensaio clínico, a fisioterapia prolongou a hospitalização e a duração da febre nos pacientes pediátricos com pneumonia adquirida na comunidade. Nestes pacientes, a fisioterapia é prejudicial e não deveria ser prescrita até que evidências de benefício estejam disponíveis. / Objective: To evaluate the efficacy of chest physiotherapy as a supplementary treatment in paediatric patients hospitalised with acute community-acquired pneumonia. Study design: a randomised clinical trial. Setting: Hospital da Criança Santo Antônio, Complexo Hospitalar Santa Casa, Porto Alegre, RS, Brasil. Patients and Methods: Children between 1 and 12 years of age, with confirmed clinical and radiological diagnosis of pneumonia, hospitalised between September 2001 and September 2002 were eligible to the trial. Participants were selected at random to receive respiratory physiotherapy three times daily (intervention group) or to receive once a day orientation to breath deeply, expectorate the sputum and to maintain preferably a lateral body position (control group). The variables analysed at the baseline, the first and second follow-up periods, and at hospital discharge were (1) the severity score (composed of age, respiratory rate, suprasternal, intercostal and subcostal retractions, fever, saturation of the haemoglobin oxygen and thorax x-rays), (2) the duration of hospitalisation, (3) respiratory rate, and (4) temperature. Results: Seventy-two patients were divided randomly into the intervention and control groups. Of these, seven were subsequently withdraw of the study due to complications such as atelectasis at the x-ray or pleural drainage. Amongst the 65 patients examined on the first follow-up (on the third day) fever was more prevalent in the intervention group (34.4%) than in the control group (12.5%) and the severity score showed the same tendency (9.63 ±1.62 and 8.71 ±0.86 points, respectively). At the second follow-up assessment, between the fourth and sixth day, the differences between the groups had a borderline statistical significance for fever (31.6% for the intervention group and 6.7% for the control group; P= 0.07). The average length of hospitalisation was 7.41 ±6.58 days for the intervention group and 4.52 ±2.21 days for the control. Conclusion: In this clinical trial, physiotherapy increased the hospital stay and the duration of fever in patients with acute pneumonia acquired in the community. In such patients physiotherapy may be prejudicial and should not be prescribed until evidence of benefit is available.

As evidências mostram uma redução ou eliminação significativa na quantidade de bactérias viáveis sob selantes e restaurações e consequente diminuição na progressão da cárie quando as bactérias se encontram separadas do meio bucal. O objetivo deste ensaio clínico controlado randomizado foi avaliar a eficácia de duas estratégias de tratamentos: 1) selamento de lesões de cárie oclusal e 2) tratamento restaurador convencional com remoção total da dentina cariada em dentes permanentes. A amostra foi constituída de 52 dentes com lesões de cárie na superfície oclusal (pré-molares e/ou molares) de 47 pacientes com idade entre 8 a 43 anos. Todas as lesões de cárie apresentaram necessidade de tratamento restaurador de acordo com os seguintes critérios: presença de cavidade e impossibilidade de controle do biofilme. A profundidade máxima das lesões foi até a metade externa de dentina avaliada através de radiografias interproximais. Os dentes foram divididos aleatoriamente em um grupo teste - tratamento selante, ou grupo controle - tratamento restaurador convencional. Dados iniciais referentes à experiência de cárie (CPOD) e índice de sangramento gengival (ISG) foram avaliados. Radiografias interproximais foram realizadas após 12 meses para avaliar a integridade das restaurações e a zona radiolúcida (ZR) sob os selantes/restaurações. Os desfechos analisados foram o desempenho clínico dos tratamentos selante e restauração e a prevalência de regressão, inativação e progressão da cárie com exames radiográficos. A presença de dentina terciária também foi observada. Os dados foram avaliados por meio do teste exato de Fisher. Um total de 26 selantes e 26 restaurações foram realizadas. Não houve diferença entre os grupos quanto às características iniciais - idade, sexo, CPOD e ISG. Após um ano, foram avaliados 49 dentes, apresentando taxas de sucesso de 95,8% e 100% nos grupos selante e restauração convencional, respectivamente (p>0,05). Houve uma falha em um dos tratamentos (perda total no grupo selante) observada durante o estudo. A avaliação radiográfica (progressão, inativação, regressão e presença de dentina terciária) não demonstrou diferença entre os grupos. Nenhum dos dentes apresentou progressão de cárie; a regressão foi observada em apenas um caso (grupo do selante) e a presença de dentina terciária foi encontrada em 12,5% da amostra (5 selantes e 1 restauração). Selantes podem ser utilizados como tratamento terapêutico para lesões de cárie incipientes em dentes permanentes, uma vez que impedem a progressão das lesões de cárie, preservando a estrutura do dente, quando comparado ao tratamento restaurador convencional. / There is a significant decrease in the number of viable microorganisms under sealants and restorations and a consequent decrease in caries progression when bacteria are separated from the oral environment. The aim of this randomized controlled clinical trial was to evaluate the efficacy of two treatments strategies: 1) sealing of carious lesions and 2) operative restorative treatment of occlusal carious lesions in permanent teeth. The sample consisted of 52 carious posterior teeth (premolars and molars) from 47 patients aged 8 - 43 years. In all lesions restorative treatment was necessary according to the following current strategies: presence of cavity and impossibility to perform biofilm control. The maximum depth of lesions was halfway through the dentine assessed by bitewing radiograph. The teeth were randomly assigned to test group – sealant treatment or control group - conventional restorative treatment. Baseline caries experience (DMFT) and gingival bleeding index (GBI) was assessed. Bitewing radiographs were performed after 12 months to evaluate the integrity of the restorations and the radiolucent zone (ZR) beneath the sealants/restorations. Outcomes were defined as clinical performance of sealant and restoration and the prevalence of regression, inactivation and progression of carious lesion by radiographic examinations. Presence of tertiary dentine was also evaluated. The data were submitted to Fisher`s exact test. A total of 26 sealants and 26 restorations were performed. There were no differences between the two groups regarding baseline characteristics – age, gender, DMFT and GBI. After one year, 49 evaluations had been performed, showing 95.8% and 100% of success rates in test and control group respectively (p>0.05). There was one therapeutic failure (total loss in the sealant group) observed during the study. No difference in the radiographic evaluation (progression, inactivation, regression and tertiary dentin deposition) was observed between the groups (p>0.05). No teeth showed caries progression; regression was observed in only one case (sealant group) and tertiary dentin was founded in 12.5% of the sample (5 sealants and 1 restoration). Sealants can be used as a therapeutic treatment for incipient carious lesions in permanent teeth, since they prevent the progression of carious lesions, while preserving tooth structure when compared to conventional restorative treatment.