Dans les essais cliniques randomisés (ECR) en cancérologie, un critère de substitution est une mesure biologique utilisée à la place d’un critère cliniquement pertinent pour le patient, par exemple la survie globale (SG), qui doit permettre de prédire l’effet attendu du traitement. Des critères alternatifs à la SG, par exemple la survie sans progression, sont de plus en plus fréquemment utilisés en tant que critère de jugement principal dans les ECR. En pratique cependant, les capacités de substitution à la SG de ces critères ne sont pas systématiquement évaluées. Nous avons dressé un état des lieux des critères de substitution validés en cancérologie à partir d’une revue systématique de la littérature. Par la suite, nous avons évalué par une approche méta-analytique des critères de substitution dans le contexte des sarcomes des tissus mous en situation avancée et du cancer du sein en situation adjuvante. Les résultats n’ont pas permis de définitivement valider de critères de substitution à la SG dans ces indications. La SG doit donc rester le critère de jugement principal des ECR, même si certains critères alternatifs restent informatifs dans des évaluations plus précoces (phase II, analyse de futilité), sous réserve que les données de survie continuent à être recueillies. Ce travail fournit des informations clés pour le développement des ECR en cancérologie afin notamment de sélectionner au mieux les critères de jugement de l’efficacité thérapeutique. / In cancer randomized controlled trials (RCT), a surrogate endpoint is intended to substitute a clinically relevant endpoint, e.g. overall survival (OS), and it is supposed to predict treatment effect. Alternative endpoints, for example progression-free survival, are increasingly being used in place of OS as primary efficacy endpoints in RCTs. In practice however, the surrogate properties of these endpoints are not systematically assessed. We performed a systematic literature review to identify surrogate endpoints validated in oncology. We next conducted MAs to evaluate surrogate endpoints in two cancer settings: advanced soft-tissue sarcoma and adjuvant breast cancer. Results could not definitely validate surrogate endpoints in these indications. OS must remain the primary efficacy endpoint in these settings, even though alternative endpoints may provide valuable input in earlier phase studies (phase II trials, futility analyses). This work provides key information for the design of cancer RCTs, in particular for the choice of primary endpoints to assess treatment efficacy.

Introdução: O zumbido é um sintoma que acomete cerca de 10% da população e pode prejudicar bastante a qualidade de vida, sendo considerado um importante problema de saúde pública mundial. Os modelos fisiopatológicos atuais do zumbido consideram que a compensação da perda auditiva poderia prevenir ou reverter mudanças no córtex auditivo central acerca do zumbido. Próteses auditivas com gerador de som integrado têm sido utilizadas como alternativa para potencializar o tratamento do zumbido nos pacientes com perda auditiva associada. Contudo, não existe evidência científica suficiente para suportar a superioridade do uso combinado de ferramentas em relação à amplificação convencional. Objetivo: verificar se o uso combinado de amplificação e gerador de som é mais eficaz do que somente amplificação na redução do incômodo com o zumbido em pacientes com zumbido e perda auditiva neurossensorial bilateral simétrica de grau leve a moderado. Métodos: 49 pacientes com zumbido e perda auditiva participaram de um ensaio clínico cego randomizado. Um grupo foi adaptado bilateralmente com uso combinado de amplificação e gerador de som e o outro grupo foi adaptado somente com amplificação. O incômodo com o zumbido foi medido pelo THI e escala numérica. As medidas psicoacústicas do zumbido também foram realizadas. As avaliações inicial e final foram realizadas por um avaliador cego. Resultados: Após três meses, no grupo da adaptação combinada, 62,5% dos pacientes apresentaram redução do incômodo com o zumbido e no grupo da adaptação simples, 78%, sem diferença estatisticamente significante entre os grupos. Para o THI, escala numérica e intensidade sonora de zumbido, detectou-se efeito do nível mínimo de mascaramento, em que maiores valores de nível mínimo de mascaramento estão associados a maior incômodo e maior intensidade do zumbido. Conclusão: O uso combinado de amplificação e gerador de som e o uso de amplificação convencional foram igualmente eficazes na redução do incômodo com o zumbido / Introduction: Tinnitus is a symptom that affects about 10% of the population and can greatly impair the quality of life. In fact, it is considered as an important public health problem worldwide. The current pathophysiological models of tinnitus consider that the compensation of hearing loss could prevent or reverse changes in the auditory cortex. Hearing aids with an integrated sound generator have been used as an alternative to enhance the treatment of tinnitus in patients with hearing loss. However, there is no sufficient scientific evidence to support the superiority of the combined use of sound generator and amplification compared to conventional amplification alone. Objective: to verify whether the combined use of amplification and sound generator is more effective than amplification alone in reducing bothersome tinnitus in patients with mild to moderate bilaterally symmetrical sensorineural hearing loss. Methods: 49 patients with tinnitus and hearing loss underwent a blind randomized clinical trial. One group was bilaterally fitted with the combined use of amplification and sound generator, and the other group was fitted with amplification alone. The tinnitus annoyance was measured by THI and numerical scale. Psychoacoustic measurements of tinnitus were also performed. The initial and final assessments were performed by a blinded evaluator. Results: After 3 months, 62.5% of patients showed a reduction in tinnitus annoyance in the group of the combined use of amplification and sound generator, and 78% in the group with amplification alone, with no significant difference between the groups. For THI, numeric scale and tinnitus loudness, it was detected an effect of the MML, where higher values of MML are associated with greater discomfort due to tinnitus. Conclusion: The combined use of amplification and sound generator and the use of conventional amplification alone were equally effective in reducing tinnitus annoyance

En économie du développement, la culture d’évaluation s’est renforcée pour mieux orienter l’aide vers les actions qui ont démontré la preuve de leur efficacité. Dans ce contexte aux pratiques renouvelées, un essor des méthodes expérimentales s’est fait jour dans le domaine de l’évaluation, notamment à travers la méthode des évaluations aléatoires qui est fortement promue par le laboratoire J-PAL, et notamment par Esther Duflo. Contribuant empiriquement à la constitution d’un « fonds scientifique capitalisable » grâce aux connaissances mises à jour, mais comportant des failles persistantes, nous procédons dans cette thèse à une analyse critique de la méthode, avec l’appui d’une récente littérature économique française et anglophone.De plus, nous avons mené une enquête par questionnaire auprès de parents d’élèves du primaire à Madagascar, notre terrain d’étude. Pour la réaliser, nous nous sommes basés sur une évaluation aléatoire qui avait été menée dans ce pays par une doctorante affiliée au J-PAL, et qui concluait à un impact positif d’un traitement à base d’information statistique sur les rendements de l’éducation, délivrée aux parents d’élèves du primaire. En reproduisant ce traitement dans notre enquête, nous avons voulu savoir si l’on pouvait aboutir à des résultats similaires bien que la méthode employée varie. Nous retrouvons globalement les conclusions de l’auteure de l’évaluation aléatoire, bien que nous utilisions une méthode moins purement quantitative. / In development economics, the culture of evaluation is being strengthened to specify which development actions could be effective, and thus allows a better targeting of aid on the actions that have proven their effectiveness. Within this context of renewed practices, an expansion of experimental methods in the evaluation field has emerged, in particular through the method of randomized evaluations strongly promoted by the J-PAL laboratory, particularly by the emblematic figure of Esther Duflo. Contributing empirically to the composition of a « scientific capitalizable fund » thanks to the updated knowledge, but still including persistent limits, we set into this thesis about a critical analysis of this method, with the mobilization of some recent French and English economic literature.Moreover, we conducted a questionnaire survey to primary school pupils’ parents in Madagascar, our field study. To carry out it, we used a randomized evaluation that had been conducted in this country by a PhD student affiliated with the J-PAL and whose finding was the positive effect of some statistical information treatment on returns to education towards primary school pupils’ parents. By reproducing this treatment in our study, we wanted to know whether it was possible to achieve similar results even though the applied method varies. It’s globally matching up with the conclusions of the author of the randomized evaluation, even if we use a less purely quantitative method.

Most statistical methods to design and analyze randomized controlled trials with time-to-event data, and synthesize their results in meta-analyses, use the hazard ratio (HR) as the measure of treatment effect. However, the HR relies on the proportional hazard assumption which is often violated, especially in cancer trials. In addition, the HR might be challenging to interpret and is frequently misinterpreted as a risk ratio (RR). In meta-analysis, conventional methods ignore that HRs are estimated over different time supports when the component trials have different follow-up durations. These issues also pertain to advanced statistical methods, such as network meta-analysis and surrogate endpoints validation. Novel methods that rely on the difference in restricted mean survival times (RMST) would help addressing these issues. In this dissertation, I first developed a Bayesian network meta-analysis model using the difference in RMST. This model synthesizes all the available evidence from multiple time points and treatment comparisons simultaneously through within-study covariance and between-study covariance for the differences in RMST. I proposed an estimator of the within-study covariance and estimated the model under the Bayesian framework. The simulation studies showed adequate performance in terms of mean bias and mean squared error. I illustrated the model on a network of randomized trials of second-line treatments of advanced non-small-cell lung cancer. Second, I introduced a novel two-stage meta-analytical model to evaluate trial-level surrogacy. I measured trial-level surrogacy by the coefficient of determination at multiple time points based on the differences in RMST. The model borrows strength across data available at multiple time points and enables assessing how the strength of surrogacy changes over time. Simulation studies showed that the estimates of coefficients of determination are unbiased and have high precision in almost all of the scenarios we examined. I demonstrated my model in two individual patient data meta-analyses in gastric cancer. Both methods, for network meta-analysis and surrogacy evaluation, have the advantage of not involving extrapolation beyond the observed time support in component trials and of not relying on the proportional hazard assumption. Finally, motivated by the common misinterpretation of the HR as a RR, I investigated the theoretical relationship between the HR and the RR and compared empirically the treatment effects measured by the HR and the RR in a large sample of oncology RCTs. When there is evidence of superiority for experimental group, misinterpreting the HR as the RR leads to overestimating the benefits by about 20%. / 2026-02-08T00:00:00Z

Bakgrund: Sömnsvårigheter är vanliga hos barn och ungdomar med AST (autismspektrumtillstånd) och ADHD (attention deficit hyperactivity disorder). Fysisk aktivitet kan vara en intervention som förbättrar sömnen hos denna population. Syfte: Att sammanställa aktuell forskning på fysisk aktivitet som fysioterapeutisk behandlingsform för och dess effekter på sömnsvårigheter hos barn och ungdomar med AST/ADHD.  Metod: Systematisk litteraturöversikt med databasen PubMed, med randomiserade kontrollerade studier på engelska i fulltext publicerade 2012–2023. Studierna inkluderade barn och ungdomar 2–18 år med AST/ADHD och jämförde fysisk aktivitet som behandlingsform med en kontrollgrupp utan behandling. Granskning gjordes avseende risk för snedvridning (PEDro-skalan) samt tillförlitlighet till sammanvägt resultat (GRADEstud). Resultat: Fem studier inkluderades och kvalitetsgranskades med PEDro-skalan. Tre ingick i det sammanvägda resultatet. Dessa studerade effekten av fysisk aktivitet på sömneffektivitet, sömnduration och vakentid efter insomning, och två av studierna undersökte effekten på sömnlatens. Tillförlitligheten till det sammanvägda resultatet (tre studier) bedömdes vara låg på grund av bristande samstämmighet och precision. Det sammanvägda resultatet visade signifikant förbättring hos interventionsgruppen på de flesta utfallsmått, och en av studierna visade signifikanta mellangruppsskillnader på de flesta utfallsmått. Konklusion: Det vetenskapliga underlaget för effekt av fysisk aktivitet på sömnsvårigheter hos den ovannämnda populationen är för begränsat för att dra starka slutsatser. Det kan vara en lovande behandlingsform, men mer forskning krävs för att stärka evidensen. Fysisk aktivitet som en del av fysioterapeutisk behandling skulle kunna förbättra sömnkvalitet och främja övergripande hälsa och livskvalitet hos populationen. / Background: Sleep difficulties are common in children and adolescents with ASD (Autism Spectrum Disorder) or ADHD (Attention Deficit Hyperactivity Disorder). Physical activity may be an intervention that improves sleep in this population. Purpose: To compile current research on physical activity as a physiotherapeutic treatment for and its effects sleep difficulties in children and adolescents with ASD/ADHD. Method: Systematic literature review utilizing PubMed database, encompassing full-text randomized controlled trials in English from 2012–2023. The studies included children and adolescents aged 2–18 with ASD/ADHD, comparing physical activity treatment with a control group. The review was conducted regarding the risk of bias (PEDro-scale) and the reliability of the pooled results (GRADEstud). Results: Five studies were assessed for quality using the PEDro scale, with three contributing to the pooled results. These studies investigated various physical activities' effects on sleep, including efficiency, duration, wake time after onset, and two also looked at sleep latency. Due to inconsistency and lack of precision, the pooled results' reliability (from three studies) was low. However, they showed significant improvements in most outcome measures for the intervention group, with only one study revealing intergroup differences. Conclusion: The scientific evidence regarding the effect of physical activity on sleep difficulties in the above-mentioned population is too limited to draw strong conclusions. Physical activity shows promise as a potential treatment, though additional research is needed to strengthen the evidence. The incorporation of physical activity into physiotherapeutic treatment could enhance sleep quality and promote overall health and quality of life in this population.

No / There is a substantial body of evidence that prescribing for care home residents is suboptimal and requires improvement. Consequently, there is a need to identify effective interventions to optimise prescribing and resident outcomes in this context. OBJECTIVES: The objective of the review was to determine the effect of interventions to optimise prescribing for older people living in care homes. SEARCH METHODS: We searched the Cochrane Effective Practice and Organisation of Care (EPOC) Group Specialised Register; Cochrane Central Register of Controlled Trials (CENTRAL), The Cochrane Library (Issue 11, 2012); Cochrane Database of Systematic Reviews, The Cochrane Library (Issue 11, 2012); MEDLINE OvidSP (1980 on); EMBASE, OvidSP (1980 on); Ageline, EBSCO (1966 on); CINAHL, EBSCO (1980 on); International Pharmaceutical Abstracts, OvidSP (1980 on); PsycINFO, OvidSP (1980 on); conference proceedings in Web of Science, Conference Proceedings Citation Index - SSH & Science, ISI Web of Knowledge (1990 on); grey literature sources and trial registries; and contacted authors of relevant studies. We also reviewed the references lists of included studies and related reviews (search period November 2012). We included randomised controlled trials evaluating interventions aimed at optimising prescribing for older people (aged 65 years or older) living in institutionalised care facilities. Studies were included if they measured one or more of the following primary outcomes, adverse drug events; hospital admissions;mortality; or secondary outcomes, quality of life (using validated instrument); medication-related problems; medication appropriateness (using validated instrument); medicine costs. Two authors independently screened titles and abstracts, assessed studies for eligibility, assessed risk of bias and extracted data. A narrative summary of results was presented. The eight included studies involved 7653 residents in 262 (range 1 to 85) care homes in six countries. Six studies were cluster-randomised controlled trials and two studies were patient-randomised controlled trials. The interventions evaluated were diverse and often multifaceted. Medication review was a component of seven studies, three studies involved multidisciplinary case-conferencing, two studies involved an educational element for care home staff and one study evaluated the use of clinical decision support technology. Due to heterogeneity, results were not combined in a meta-analysis. There was no evidence of an effect of the interventions on any of the primary outcomes of the review (adverse drug events, hospital admissions and mortality). No studies measured quality of life. There was evidence that the interventions led to the identification and resolution of medication-related problems. There was evidence from two studies that medication appropriateness was improved. The evidence for an effect on medicine costs was equivocal. Robust conclusions could not be drawn from the evidence due to variability in design, interventions, outcomes and results. The interventions implemented in the studies in this review led to the identification and resolution of medication-related problems, however evidence of an effect on resident-related outcomes was not found. There is a need for high-quality cluster-randomised controlled trials testing clinical decision support systems and multidisciplinary interventions that measure well-defined, important resident-related outcomes.

Thesis (MSc)--Stellenbosch University, 2013. / ENGLISH ABSTRACT: Adolescents are regarded as a high risk group in South Africa with the highest human immunodeficiency virus (HIV) incidence occurring in this group. Prevention among adolescents is therefore a key in decreasing the HIV burden. This thesis aims to assist in the design of trials by simulating the potential outcomes of a combination prevention trial in adolescents. We develop a stochastic individual-based model stratified by sex and age. We then use this model to determine the impact of various prevention packages on HIV incidence among adolescents participating in a hypothetical trial over a three year period. The trial that is simulated involves an intervention arm, in which adolescents are offered a choice of a prevention methods (including medical male circumcision (MMC), oral pre-exposure prophylaxis (PrEP) and antiretroviral-based vaginal microbicides (ARV-VM)), and a control arm. We predict that the impact of a full prevention package on HIV incidence would be a 46% per personyear( PPY) (95% CI 45–47%) risk reduction. The combination of MMC and PrEP has a substantial impact on HIV incidence in males, with a 51% PPY (95% CI 49–53%) relative risk of HIV infection. Offering women the choice of PrEP, a microbicide gel or a microbicide in the form of a vaginal ring would be less effective, with a 57% PPY (95% CI 56–58%) relative risk of HIV acquisition. This is not substantially different from the relative risk estimated when the vaginal ring alone is offered, as the ring is assumed to be the most accept able of the three prevention methods. We determine a sample size requirement of approximately 1013 in each arm of a trial would achieve 80% power to detect a statistically significant reduction in HIV risk. We find that the relative risk is sensitive to the assumed degree of correlation between condom use and the acceptability of the prevention method. We also find that the most efficient trial design may be to offer both MMC and PrEP to males but to offer only a microbicide ring to females. Further work is required to better understand the processes by which adolescent prevention method choices are made. / AFRIKAANSE OPSOMMING: Adolessente word beskou as ‘n hoe risiko groep in Suid Afrika, met die hoogste menslike immuniteitsgebrekvirus (MIV) insidensie in hierdie groep. Voorkoming van MIV onder adolessente is daarom noodsaaklik om die MIV las te verminder. Die doel van hierdie tesis is om te help met die ontwerp van studies deur die moontlike uitkomste van ‘n kombinasie-voorkoming studie in adolessente te simuleer. Ons het ‘n stogastiese individu-gebaseerde model, gestratifiseer met betrekking tot seks en ouderdom, ontwikkel. Ons het toe die model gebruik om die impak van ‘n verskeinheid van voorkomingspakette op MIV insidensie onder adolessente wat deelneem aan ‘n hipotetiese proef oor ‘n drie jaar periode, te bepaal. Die proef wat gesimuleer word behels a intervensie groep, waarin die jong volwassenes ‘n keuse van voorbehoedings metodes (insluitende mediese manlike besnydenis (MMB), pre-blootstelling profilakse (PrBP) en anti-retrovirale vaginale mikrobisiedes (ARV-VM)) aangebied word, en ‘n kontrole groep. Ons voorspel dat die impak van ‘n volle voorkomingspaket op MIV insidensie ‘n 46% per persoon-jaar (PPJ) (95% VI 47–47%) risiko vermindering sal wees. Die kombinasie van MMB en PrBP het ‘n substansiele impak op MIV insidensie onder mans, met ‘n relatiewe risiko van MIV infeksie van 51% PPJ (95% VI 49–53%). Om die keuse van PrBP, ‘n mikrobisiede gel of ‘n mikrobisiede in die vorm van ‘n vaginale ring aan vrouens te bied, is minder effektief, met ‘n relatiewe risiko van MIV infeksie van 57% PPJ (95% VI 56%–58%). Hierdie verskil nie substansieel van die beraamde relatiewe risiko in die geval waar slegs die vaginale ring gebied word nie, aangesien daar aanvaar word dat die ring die mees aanvaarde van die drie voorkomingsmetodes is. Ons het bepaal dat ‘n steekproef van ongeveer 1013 individue in elke arm van die proef nodig is om ‘n 80% kans te he om ‘n statisties betekenisvolle afname in MIV-risiko te bespeur. Ons vind dat die relatiewe risiko sensitief is tot die aanvaarde graad van die korrelasies tussen kondoom-gebruik en die aanvaarding van die voorkomings metodes. Ons het ook gevind dat dit mag wees dat die mees doeltreffende proef ontwerp is om beide MMB en PrBP vir mans en slegs ‘n mikrobisiede ring vir vrouens te bied. Verdere werk word benodig om die prosesse waarby jong volwassenes keuses maak oor voorkomingsmetodes te verstaan.

O cateter irrigado foi comparado com o de 8 mm para ablação com radiofrequência do istmo cavo-tricuspídeo(Ist-CT). Foram randomizados 52 pacientes portadores de flutter atrial típico para ablação com cateter irrigado(grupoI) ou com cateter de 8 mm(grupo II). O bloqueio do Ist-CT foi obtido em 51 pacientes. Não houve diferença estatística em relação aos parâmetros de aplicação de RF entre os dois grupos. A ablação do Ist-CT com cateter irrigado versus cateter de 8mm foi igualmente eficaz e segura no controle do flutter atrial típico. / A 4-mm cooled tip catheter was compared to an 8-mm tip catheter to cavotricuspid isthmus(CTI) ablation. This prospective study enrolled 52 patients with typical atrial flutter to ablation with a closed cooled-tip catheter(group1) or an 8-mm tip catheter. Radiofrequency(RF) applications were performed to achieve complete CTI block wich was achieved in 51 patients. No significant differences were found in the procedure parameters. CTI ablation with an irrigated tip catheter versus an 8-mm tip catheter was equally effective and satisfactorily safe for ablation of typical atrial flutter.

O objetivo desta pesquisa é comparar a eficiência clínica dos métodos convencional ou piggyback de transplante de fígado (Tx) na reconstrução do efluxo venoso do enxerto. Adicionalmente, pretende-se comparar a eficácia da drenagem venosa do enxerto hepático em diferentes modalidades do método piggyback. Foram estudados 32 pacientes submetidos a Tx pelo método convencional (n=15) ou piggyback (n=17). A pressão da veia hepática livre (PVHL) foi medida por catéter introduzido na veia hepática direita (VHD) do enxerto e a pressão venosa central (PVC) por catéter de Swan-Ganz. As medidas de pressão foram realizadas após a revascularização do enxerto. Gradiente PVHL-PVC superior a 3 mm Hg foi encontrado em 26,7% (4/15) no grupo convencional e 17,6% (3/17) no grupo piggyback (p=0,678). A mediana do gradiente PVC-PVHL foi de 2 mm Hg (0-8 mm Hg) no grupo convencional e 3 mm Hg (0-7 mm Hg) no piggyback (p=0,734). A creatinina sérica (Cr) foi medida no pré-operatório, do 1º ao 7º dia pós-operatório (PO) e no 14º, 21º e 28º PO. A Cr global pós-operatória, calculada pela área sob a curva da Cr vs tempo, foi significativamente maior no grupo convencional (2,04 ± 0,89 vs. 1,41 ± 0,44 mg/dL; p=0,02). Não houve diferença estatisticamente significante entre os grupos quanto à ocorrência de insuficiência renal aguda (p=0,120), definida como Cr maior ou igual a 2,0 mg/dL, quanto ao desenvolvimento de ascite maciça (p=1,000) e em relação à sobrevida dos pacientes (p=0,316). O gradiente PVHL-PVC foi significativamente menor nos casos em que o óstio da VHD é utilizado para reconstrução da via de drenagem venosa no Tx piggyback (1,4 ± 1,4 mm Hg vs. 3,9 ± 1,7 mm Hg; p=0,005). Conclui-se que pacientes submetidos a Tx pelos métodos convencional e piggyback apresentam resultados semelhantes em relação à drenagem venosa do enxerto, ao desenvolvimento de ascite e à sobrevida. Os valores de Cr no PO imediato são significantemente maiores no método convencional. Nos pacientes submetidos a Tx pelo método piggyback, o gradiente PVHL-PVC é menor nos casos em que o óstio da VHD do receptor é incluído para implantação da VCI do enxerto. / The aim of this study is to compare the clinical efficiency of hepatic venous outflow reconstruction in conventional and piggyback method of liver transplantation (LTx). The efficacy of the different types of reconstruction of venous drainage in the piggyback liver transplantation was analyzed by a second purpose. Thirty two patients submitted to LTx by conventional method (n=15) or piggyback method (n=17) were studied. Free hepatic venous pressure (FHVP) was measured using a catheter introduced in right hepatic vein (RHV). Central venous pressure (CVP) was obtained through Swan-Ganz catheter. Pressure measurements were performed after graft reperfusion. A FHVP-CVP gradient higher than 3 mm Hg was observed in 26.7% (4/15) of the conventional and in 17.6% (3/17) of the piggyback patients (p=0.678). Median FHVP-CPV gradient value was 2 mm Hg (0-8 mm Hg) in the conventional and 3 mm Hg (0-7 mm Hg) in the piggyback group (p=0.734). Serum creatinine (Cr) was measured on postoperative days 1 to 7, 14, 21 and 28. Postoperative overall Cr, calculated by area under the curve of Cr vs. time, was significantly higher in conventional group (2.04 ± 0.89 vs. 1.41 ± 0.44 mg/dL; p=0.02). There is no significant difference between the groups regarding occurrence of acute renal failure (p=0,120), defined by Cr maior ou igual a 2,0 mg/dL, development of massive ascites (p=1,000) and patient survival (p=0,316). In piggyback LTx patients, FHVP-CVP gradient was significantly lower when the ostium of the RHV of the recipient is used for venous drainage reconstruction (1.4 ± 1.4 mm Hg vs. 3.9 ± 1.7 mm Hg; p=0.005). In conclusion, patients submitted to conventional or piggyback method of LTx have similar results regarding venous outflow, development of ascites and survival. The postoperative Cr values are significantly higher in conventional method. Patients submitted to piggyback LTx present a lower FHVP-CVP gradient when the ostium of the RHV of the recipient is included for implantation of the graft inferior vena cava.

Introdução: Estudos anteriores sugerem possível benefício do uso perioperatório das estatinas para redução de eventos cardiovasculares pósoperatórios. Metanálise previamente publicada demonstra que as estatinas reduzem mortalidade e infarto perioperatório em pacientes submetidos a cirurgia não-cardíaca. Entretanto, novas evidências em cirurgia cardíaca sugerem efeitos neutros ou mesmo deletérios das estatinas, sendo que metanálise recente demonstrou aumento da incidência de insuficiência renal aguda e tendência a maior mortalidade pós-operatória. Devido aos resultados conflitantes e escassez de evidências definitivas, foi realizada uma revisão sistemática e metanálise de estudos randomizados para avaliar os efeitos do uso perioperatório das estatinas em cirurgia cardíaca e nãocardíaca. Objetivo: Avaliar em pacientes adultos submetidos à cirurgia cardíaca e não-cardíaca a associação entre o uso perioperatório de estatinas e a incidência pós-operatória de infarto agudo do miocárdio, acidente vascular cerebral, insuficiência renal aguda e mortalidade. Metodologia: As bases de dados Pubmed, EMBASE e Cochrane foram avaliadas por 2 pesquisadores independentes até 1º de maio de 2018 para busca de artigos apropriados. Foram incluídos estudos randomizados que avaliaram o uso perioperatório de estatinas comparadas a placebo ou a nenhum tratamento em pacientes submetidos a cirurgia cardíaca e nãocardíaca. Foram calculados o risco relativo (RR) ou razão de chances (odds ratio, OR) e intervalo de confiança 95% (IC 95%) por meio de metanálise de efeitos fixos. Foi realizada a análise sequencial dos estudos (trial sequential analysis, TSA) para quantificar a confiabilidade estatística dos dados. A metodologia Cochrane foi utilizada. Os desfechos primários foram definidos como infarto agudo do miocárdio, acidente vascular cerebral, insuficiência renal aguda e mortalidade no período pós-operatório. Resultados: Foram incluídos 35 estudos randomizados totalizando 8200 pacientes. O uso de estatina comparado ao controle foi associado a menor incidência de infarto em pacientes submetidos a cirurgia não-cardíaca (OR=0,44 [IC 95%, 0,30 a 0,64], p < 0,0001), mas não em pacientes submetidos a cirurgia cardíaca (OR=0,93 [IC 95%, 0,70 a 1,24], p=0,61). O uso da estatina foi associado a maior incidência de insuficiência renal aguda em cirurgia cardíaca (RR=1,15 [IC 95%, 1,00 a 1,31], p=0,05), mas não em cirurgia não-cardíaca (RR=1,52 [IC 95%, 0,71 a 3,26], p=0,28). Não foi observado impacto do uso das estatinas na ocorrência de acidente vascular cerebral e mortalidade em ambos os grupos cirúrgicos. No entanto, a análise dos estudos com baixo risco de viés em cirurgia cardíaca demonstrou maior mortalidade com o uso de estatinas comparadas a placebo (OR=3,71 [IC 95%, 1,03 a 13,34], p=0,04). A análise sequencial dos estudos (TSA) não sugeriu conclusões definitivas sobre o assunto. Conclusão: As estatinas parecem ter efeito protetor contra infarto pós-operatório em cirurgia não-cardíaca, mas estão associadas a maior risco de insuficiência renal aguda em cirurgia cardíaca. Possíveis efeitos positivos ou negativos sobre a mortalidade não podem ser excluídos. Os dados dos estudos randomizados disponíveis até o momento ainda são insuficientes para conclusões definitivas sobre o uso perioperatório das estatinas. Estudos randomizados adicionais são necessários para avaliar o perfil de segurança e possíveis efeitos benéficos destas medicações nos desfechos pós-operatórios / Introduction: Previous studies supported potential beneficial effects of perioperative statin therapy to reduce postoperative complications. Accordingly, previous meta-analysis concluded that statin treatment decreases the perioperative incidence of mortality and myocardial infarction in non-cardiac surgery. In contrast, growing evidences on perioperative statins administration in cardiac surgery setting suggested neutral or even detrimental results. A recent systematic review and meta-analysis found that perioperative statin therapy in this population was associated with an increased incidence of postoperative acute kidney injury and a trend toward increased mortality. Due to the contrasting results and lack of definitive evidence, we performed a systematic review and meta-analysis of randomized controlled trials to examine the effects of perioperative statin therapy on postoperative outcomes in adult cardiac and non-cardiac surgery patients. Objective: To assess the association between perioperative statin therapy and postoperative myocardial infarction, stroke, acute kidney injury and mortality in patients submitted to cardiac and non-cardiac surgery. Methods: Pubmed, EMBASE, and Cochrane databases were searched through May 1st, 2018 for appropriate articles. Articles were independently assessed by 2 reviewers. Randomized controlled trials evaluating adult cardiac and non-cardiac surgery patients comparing perioperative statin therapy versus placebo or no treatment were included. Risk ratio (RR) or odds ratio (OR) and 95% confidence interval (CI) were obtained using fixedeffects meta-analyses. Trial sequential analysis (TSA) was performed to quantify the statistical reliability of data. The Cochrane methodology was used. Main outcomes were postoperative myocardial infarction, stroke, acute kidney injury, and mortality. Results: Data from 35 randomized controlled trials involving 8200 patients were included. Perioperative statin therapy was associated with lower incidence of postoperative myocardial infarction in noncardiac surgery compared to control (OR=0.44 [95% CI, 0.30 a 0.64], p < 0.0001), but not in cardiac surgery OR=0.93 [95% CI, 0.70 a 1.24], p=0.61). Higher incidence of acute kidney injury was evident in cardiac surgery patients receiving perioperative statins (RR=1.15 [95% CI, 1.00 a 1.31], p=0.05), but not in the non-cardiac surgery population (RR=1.52 [95% CI, 0.71 a 3.26], p=0.28). No difference in postoperative stroke and mortality was present in patients undergoing either cardiac or non-cardiac surgery. However, low risk of bias trials performed in cardiac surgery showed a higher mortality with statins versus placebo (OR=3.71 [95% CI, 1.03 a 13.34], p=0.04). Trial sequential analysis suggested no firm conclusions on the topic. Conclusions: Statins appear to be protective against postoperative myocardial infarction in non-cardiac surgery and associated with an increased risk of acute kidney injury in cardiac surgery. Possible positive or even negative effects on mortality could not be excluded. There is still insufficient randomized data for firm conclusions on perioperative statin therapy. Further randomized controlled trials should evaluate both the safety profile and possible effects on patients\' outcomes