Antiplatelet therapy with clopidogrel is widely used in patients with coronary artery disease, but the recent development of the new P2Y12 receptor antagonists prasugrel and ticagrelor will increase treatment options. An overview of systematic reviews was performed to summarize available evidence on clopidogrel. Current data on prasugrel and ticagrelor were identified by a systematic review and used for an indirect treatment comparison (ITC) of the drugs against each other and versus placebo in the absence of head-to-head clinical trials. Adjusted indirect comparison according to Bucher, Bayesian methods for mixed treatment comparisons using Winbugs, and generalized linear mixed models using SAS were employed for ITC, yielding almost identical results: prasugrel was favored regarding stent thrombosis and ticagrelor regarding major bleeding. However, substantial differences in trial design were identified, demanding caution when interpreting these results. On the basis of the obtained results, a randomized controlled trial was designed within the gap of current evidence.

Human memory systems have been divided into two broad domains, one responsible for 'declarative memory' and the other for 'non-declarative memory'. The evidence for multiple memory systems is reviewed with respect to the human SRT, a sensitive measure of non-declarative memory. A qualitative review of the human SRT literature concludes that damage to extrapyramidal brain systems disrupts SRT performance whereas limbic system neuropathology (LSN) leaves performance intact. However, a meta-analysis of the SRT literature with neuropathological patients revealed unexpectedly that patients with explicit memory disorders are impaired on the SRT task, although less severely than patients with extrapyramidal damage. Other evidence suggested that the apparent SRT impairment in humans with LSN might be due to the additional pathology (eg frontal) often evident in these patients. A brief review of the animal evidence for multiple memory systems concluded that, like humans, animals too have multiple memory systems but none of the animal tasks used to model non-declarative memory make good conceptual or behavioural contact with the corresponding human tasks. Thus a novel animal-analogue of the human-SRT task, the 'fan-maze', was developed. Although rats displayed a reasonable ability to perform the fan-maze SRT task it was abandoned due to technical and conceptual problems in favour of a better design. The second new SRT task used intra-cranial self-stimulation to promote prolonged, rapid and continuous responding. A control study determined that the optimal conditions for sequence learning was a single large (2820 trial) session. Intact rats that experienced a switch from the repeating to a random sequence under these conditions demonstrated a clear interference effect, the primary measure of SRT performance. A lesion study used these optimal conditions and showed that small caudate lesions impaired, whereas small hippocampal lesions facilitated, rat-SRT performance. Hence, this second task has proven to be a valid animal-analogue of the human SRT task, as rats performed it in a manner similar to that shown by humans and relied on the same neural substrate to perform the task as humans. In addition, this second task resolved the discrepancy of the LSN meta-analysis. Quantitative findings are reviewed in light of theories and studies presented earlier in the thesis. Limitations of the thesis are identified and suggestions are made as to future SRT research in animals or humans.

PhD / Introduction Kidney transplantation confers both survival and quality of life advantages over dialysis for most people with end-stage kidney disease (ESKD). The mortality rate on dialysis is 10-15% per year, compared with 2-4% per year post-transplantation. Short-term graft survival is related to control of the acute rejection process, requiring on-going immunosuppression. Most current immunosuppressive algorithms include one of the calcineurin inhibitors (CNI: cyclosporin or tacrolimus), an anti-metabolite (azathioprine or mycophenolate) and corticosteroids, with or without antibody induction agents (Ab) given briefly peri-transplantation. Despite this approach, between 15-35% of recipients undergo treatment for an episode of acute rejection (AR) within one year of transplantation. Transplantation is not without risk, and relative mortality rates for kidney recipients after the first post-transplant year remain 4-6 times that of the general population. Longer-term transplant and recipient survival are related to control of chronic allograft nephropathy (rooted in the interplay of AR, non-immunological factors, and the chronic nephrotoxicity of CNI) and limitation of the complications of chronic ESKD and long-term immunosuppression: cardiovascular disease, cancer and infection, which are responsible for 22%, 39% and 21% of deaths respectively. This thesis is presented as published works on the theme of immunosuppression and cancer after kidney transplantation. The work presented in the first chapters of this thesis has striven to identify, evaluate, synthesise and distil the entirety of evidence available of new and established immunosuppressive drug agents through systematic review of randomised trial data, with particular emphasis on quantifying harms of treatment. The final chapters use inception cohort data from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA), which is first validated then used to explore the risk of cancer in more detail than was possible from trial data alone. Interleukin 2 receptor antagonists Interleukin-2 receptor antagonists (IL2Ra, commercially available as basiliximab and daclizumab) are humanised or chimeric IgG monoclonal antibodies to the alpha subunit of the IL2 receptor present only on activated T lymphocytes, and the rationale for their use has been as induction agents peri-transplantation. Introduced in the mid-1990s, IL2Ra use has increased globally, and by 2003 38% of new kidney transplant recipients in the United States and 25% in Australasia received an IL2Ra. This study aimed to systematically identify and synthesise the evidence of effects of IL2Ra as an addition to standard therapy, or as an alternative to other induction agents. We identified 117 reports from 38 randomised trials involving 4893 participants. Where IL2Ra were compared with placebo (17 trials; 2786 patients), graft loss was not different at one (Relative Risk -RR 0.84; 0.64 to 1.10) or 3 years (RR 1.08; 0.71 to1.64). AR was reduced at 6 months (RR 0.66; 0.59 to 0.74) and at 1 year (RR 0.66; 0.59 to 0.74) but cytomegalovirus (CMV) disease (RR 0.82; CI 0.65 to 1.03) and malignancy (RR 0.67; 0.33 to1.36) were not different. Where IL2Ra were compared with other antibody therapy no significant differences in treatment effects were demonstrated, but IL2Ra had significantly fewer side effects. Given a 40% risk of rejection, 7 patients would need treatment with IL2Ra in addition to standard therapy, to prevent 1 patient having rejection, with no definite improvement in graft or patient survival. There was no apparent difference between basiliximab and daclizumab. Tacrolimus versus cyclosporin for primary immunosuppression There are pronounced global differences in CNI use; 63% of new kidney transplant recipients in the USA but only 22% in Australia receive tacrolimus as part of the initial immunosuppressive regimen. The side effects of CNI differ: tacrolimus is associated more with diabetes and neurotoxicity, but less with hypertension and dyslipidaemia than cyclosporin, with uncertainty about equivalence of nephrotoxicity or how these relate to patient and graft survival, or impact on patient compliance and quality of life. This study aimed to systematically review and synthesise the positive and negative effects of tacrolimus and cyclosporin as initial therapy for renal transplant recipients. We identified 123 reports from 30 randomised trials involving 4102 participants. At 6 months graft loss was reduced in tacrolimus-treated recipients (RR 0•56; 0•36 to 0•86), and this effect persisted for 3 years. The relative reduction in graft loss with tacrolimus diminished with higher levels of tacrolimus (P=0.04), but did not vary with cyclosporin formulation (P=0.97) or cyclosporin level (P=0.38). At 1 year, tacrolimus patients suffered less AR (RR 0•69; 0•60 to 0•79), and less steroid-resistant AR (RR 0•49; 0•37 to 0•64), but more insulin-requiring diabetes (RR 1•86; 1•11 to 3•09), tremor, headache, diarrhoea, dyspepsia and vomiting. The relative excess in diabetes increased with higher levels of tacrolimus (P=0.003). Cyclosporin-treated recipients experienced significantly more constipation and cosmetic side-effects. We demonstrated no differences in infection or malignancy. Treating 100 recipients with tacrolimus instead of cyclosporin for the 1st year post-transplantation avoids 12 suffering acute rejection and 2 losing their graft but causes an extra 5 to become insulin dependent diabetics, thus optimal drug choice may vary among patients. Target of rapamycin inhibitors for primary immunosuppression Target of rapamycin inhibitors (TOR-I) are among the newest immunosuppressive agents and have a novel mode of action but uncertain clinical role. Sirolimus is a macrocyclic lactone antibiotic and everolimus is a derivative of sirolimus. Both prevent DNA synthesis resulting in arrest of the cell cycle. Animal models suggested TOR-I would provide synergistic immunosuppression when combined with CNI, but early clinical studies demonstrated synergistic nephrotoxicity. Since then diverse trials have explored strategies that avoid this interaction and investigated other potential benefits. The aim of this study was to systematically identify and synthesise available evidence of sirolimus and everolimus when used in initial immunosuppressive regimens for kidney recipients. We identified 142 reports from 33 randomised trials involving 7114 participants, with TOR-I evaluated in four different primary immunosuppressive algorithms: as replacement for CNI, as replacement for antimetabolites, in combination with CNI at low and high dose, and with variable dose of CNI. When TOR-I replaced CNI (8 trials, 750 participants), there was no difference in AR (RR 1.03; 0.74 to 1.44), but creatinine was lower (WMD -18.31 umol/l; -30.96 to -5.67), and bone marrow more suppressed (leucopoenia RR 2.02; 1.12 to 3.66, thrombocytopenia RR 6.97; 2.97 to 16.36, anaemia RR 1.67; 1.27 to 2.20). When TOR-I replaced antimetabolites (11 trials, 3966 participants), AR and CMV were reduced (RR 0.84; 0.71 to 0.99 and RR 0.49; 0.37 to 0.65) but hypercholesterolaemia was increased (RR 1.65; 1.32 to 2.06). When low was compared to high-dose TOR-I, with equal CNI dose (10 trials, 3175 participants), AR was increased (RR 1.23; 1.06 to 1.43) but GFR higher (WMD 4.27 ml/min; 1.12 to 7.41). When low-dose TOR-I and standard-dose CNI were compared to higher-dose TOR-I and reduced CNI AR was reduced (RR 0.67; 0.52 to 0.88), but GFR also reduced (WMD -9.46 ml/min; -12.16 to -6.76). There was no significant difference in mortality, graft loss or malignancy risk demonstrated for TOR-I in any comparison. Generally surrogate endpoints for graft survival favoured TOR-I (lower risk of acute rejection and higher GFR) and surrogate endpoints for patient outcomes were worsened by TOR-I (bone marrow suppression, lipid disturbance). Long-term hard-endpoint data from methodologically robust randomised trials are still needed. Monoclonal and polyclonal antibody therapy for treating acute rejection Strategies for treating AR include pulsed steroids, an antibody (Ab) preparation, the alteration of background immunosuppression, or combinations of these options. In 2002, in the USA 61.4% of patients with AR received steroids, 20.4% received Ab and 18.2% received both. The Ab available for AR are not new: horse and rabbit derived polyclonal antibodies (ATG and ALG) have been used for 35 years, and a mouse monoclonal antibody (muromonab-CD3) became available in the late 1980s. These preparations remove the functional T-cell population from circulation, producing powerful saturation immunosuppression which is useful for AR but which may be complicated by immediate toxicity and higher rates of infection and malignancy. The aim of this study was to systematically evaluate and synthesise all evidence available to clinicians for treating AR in kidney recipients. We identified 49 reports from 21 randomised trials involving 1394 participants. Outcome measures were inconsistent and incompletely defined across trials. Fourteen trials (965 patients) compared therapies for 1st AR episodes (8 Ab versus steroid, 2 Ab versus another Ab, 4 other comparisons). In treating first rejection, Ab was better than steroid in reversing AR (RR 0.57; CI 0.38 to 0.87) and preventing graft loss (RR 0.74; CI 0.58 to 0.95) but there was no difference in preventing subsequent rejection (RR 0.67; CI 0.43 to 1.04) or death (RR 1.16; CI 0.57 to 2.33) at 1 year. Seven trials (422 patients) investigated Ab treatment of steroid-resistant rejection (4 Ab vs another Ab, 1 different doses Ab, 1 different formulation Ab, 2 other comparisons). There was no benefit of muromonab-CD3 over ATG or ALG in reversing rejection (RR 1.32; CI 0.33 to 5.28), preventing subsequent rejection (RR 0.99; CI 0.61 to 1.59), graft loss (RR 1.80; CI 0.29 to 11.23) or death (RR 0.39; CI 0.09 to 1.65). Given the clinical problem caused by AR, comparable data are sparse, and clinically important differences in outcomes between widely used interventions have not been excluded. Standardised reproducible outcome criteria are needed. Validity of cancer data in an end stage kidney disease registry Registries vary in whether the data they collect are given voluntarily or as a requirement of law, the completeness of population coverage, the breadth of data collected and whether data are assembled directly or indirectly through linkage to other databases. Data quality is crucial but difficult to measure objectively. Formal audit of ANZDATA cancer records has not previously taken place. The aim of this study was to assess agreement of records of incident cancer diagnoses held in ANZDATA (voluntary reporting system) with those reported under statute to the New South Wales (NSW) state Central Cancer Registry (CCR), to explore the strengths and weaknesses of both reporting systems, and to measure the impact of any disagreement on results of cancer analyses. From 1980-2001, 9453 residents received dialysis or transplantation in NSW. Records from ANZDATA registrants were linked to CCR using probabilistic matching and agreement between registries for patients with 1 or more cancers, all cancers and site-specific cancer was estimated using the kappa-statistic (κ). ANZDATA recorded 867 cancers in 779 (8.2%) registrants; CCR 867 cancers in 788 (8.3%), with κ =0.76. ANZDATA had sensitivity 77.3% (CI 74.2 to 80.2), specificity 98.1% (CI 97.7 to 98.3) if CCR records were regarded as the reference standard. Agreement was similar for diagnoses whilst receiving dialysis (κ =0.78) or after transplantation (κ =0.79), but varied by cancer type. Melanoma (κ =0.61) and myeloma (κ =0.47) were less good; lymphoma (κ =0.80), leukaemia (κ =0.86) and breast cancer (κ =0.85) were very good. Artefact accounted for 20.8% non-concordance but error and misclassification did occur in both registries. Cancer risk did not differ in any important way whether estimated using ANZDATA or CCR records. Quality of cancer records in ANZDATA are high, differences largely explicable, and seem unlikely to alter results of analyses. Risk of cancer after kidney transplantation Existing data on the magnitude of excess risk of cancer across different kidney recipient groups are sparse. Quantifying an individual transplant candidate’s cancer risk informs both pre-transplant counselling, treatment decisions and has implications for monitoring, screening and follow-up after transplantation. The aims of this study were firstly to establish the risk of cancer in the post-transplant population compared to that experienced by the general population, and secondly to quantify how excess risk varied within the transplanted population, seeking to establish meaningful absolute risk estimates for post-transplant cancer based on unalterable recipient characteristics known a priori at the time of transplantation. 15,183 residents of Australia and New Zealand had a transplant between 1963 and 2004, and were followed for a median of 7.2 years (130,186 person-years), with 1642 (10.8%) developing cancer. Overall, kidney recipients had 3 times the cancer risk, with risk inversely related to age (Standardised Incidence Ratio of 15 to 30 in children reducing to 2 in people > 65 years). Female recipients aged 25 -29 had rates of cancer (779.2/100,000) equivalent to women aged 55 - 59 from the general population. The risk pattern of lymphoma, colorectal and breast cancer was similar to the overall age trend, melanoma showed less variability across ages and prostate cancer showed no risk increase. Within the transplanted population cancer risk was affected by age differently for each sex (P=0.007), and was elevated for recipients with prior non-skin malignancy (Hazard Ratio: HR 1.40; 1.03 to 1.89), of white race (HR 1.36; 1.12 to 1.89), but reduced for those with diabetic ESKD (HR 0.67; 0.50 to 0.89) Rates of cancer in kidney recipients were similar to non-transplanted people 20 -30 years older, but risk differed across patient groups. Men aged 45 - 54 at transplantation with graft function at 10 years had a risk of cancer that varied from 1 in 13 (non-white, diabetic ESKD, no prior cancer) to 1 in 5 (white, prior cancer, ESKD from other causes).

Thesis (Ph. D.)--University of Rhode Island, 2004. / Typescript. Includes bibliographical references (leaves v. 2, 389-428).

Thesis (Ph.D.) - Carleton University, 2007. / Includes bibliographical references (p. 163-172). Also available in electronic format on the Internet.

Thesis (Ph. D.)--Ohio State University, 2006. / Title from first page of PDF file. Includes bibliographical references (p. 136-151).

OBJETIVO Avaliar as evidências quanto à associação entre síndrome metabólica e periodontite através de uma revisão sistemática da literatura e metanálise de estudos observacionais. MATERIAIS E MÉTODOS Os estudos foram acessados através de busca nas bases eletrônicas Medline, EMBASE e Biblioteca Cochrane e de busca manual para identificar estudos, observacionais, originais, realizados com população adulta, que avaliaram a associação entre síndrome metabólica e doença periodontal. Os estudos deveriam mencionar critério de diagnóstico para síndrome metabólica e pelo menos uma medida clínica para o diagnóstico de periodontite e apresentar as medidas de efeito através de razão de chance (OR), risco relativo (RR) ou taxa de prevalência (PR). Os dados foram extraídos por dois investigadores, de maneira independente. A metanálise dos estudos incluídos foi realizada utilizando-se modelos randômicos. RESULTADOS A revisão sistemática incluiu 17 estudos observacionais, que preencheram os critérios de inclusão. Na metanálise foram incluídos 11 estudos, totalizando dados de 38.189 pacientes. Encontrou-se associação entre síndrome metabólica e periodontite com um OR de 1,78 (IC 95% 1,38- 2,30), e heterogeneidade de i2=93%. Para investigar a alta heterogeneidade foram (1) rodadas análises sequenciais, excluindo-se um estudo por vez, (2) metarregressão avaliando-se isoladamente idade, tabagismo, critério de diagnóstico para síndrome metabólica e exame periodontal completo versus parcial, (3) análise de subgrupos analisando-se em separado estudos em população asiática e não asiática e análise de sensibilidade. A heterogeneidade foi reduzida de forma significativa quando subdividiu-se os estudos com origem em população asiática (OR 2,06, IC 95% 1,60– 2,85, i2= 83,1%) e em população não asiática (OR 1,12 IC 95% 1,04- 1,68, i2=65,3%). CONCLUSÃO Os achados deste estudo reportam uma associação significativa entre síndrome metabólica e doença periodontal. A falta de um número suficiente de estudos longitudinais impede que se estabeleça a direção desta associação. Devido a alta heterogeneidade encontrada, estudos de intervenção bem controlados são necessários para que se conheça a magnitude dessa associação. / PURPOSE To investigate the association of metabolic syndrome and periodontitis by means of a systematic review and a meta-analysis of observational studies. RESEARCH DESIGN AND METHODS The electronic databases Medline, EMBASE and The Cochrane Library were searched for observational studies that evaluated the association of Metabolic Syndrome and Periodontitis. Hand search was also done. Data extraction was performed by two reviewers independently. Pooled effect estimates were obtained by using random-effects meta-analysis. RESULTS Systematic review included 17 studies that fulfilled the inclusion criteria. Meta-analysis was done with 11 studies, providing data of 38.189 patients. The results showed that there is an association estimated in an OR of 1,78 (95%IC 1,38- 2,30) between metabolic syndrome and periodontitis. A high heterogeneity was present (i2=93%). To investigate heterogeneity (1) the meta-analysis was re-ran excluding studies one at a time, (2) univariate metaregression was performed analyzing smoke status, metabolic syndrome criteria and parcial versus complete periodontal record, (3) subgroup analysis splitting studies in those performed with Asiatic populations and with non-Asiatic populations and sensitivity analysis. The heterogeneity was reduced significantly when subgroup analysis was done, for Asiatic population an OR of 2,06 (95% IC 1,60-2,85) and i2= 83,1% and for non-Asiatic population an OR of 1,12 (95% IC 1,04- 1,68) and i2=65,3% were found. CONCLUSION This study showed a significant association between metabolic syndrome and periodontitis. The lack of longitudinal studies in this area prevent from setting the direction of this association. Due to the high heterogeneity found, interventional and well controlled studies are encouraged to elucidate the magnitude of this association.

Made available in DSpace on 2015-12-06T23:44:33Z (GMT). No. of bitstreams: 0 Previous issue date: 2006 / Contexto: Mordida aberta anterior (MAA) ocorre quando incisivos superiores não tocam incisivos inferiores. A etiologia é multifatorial, incluindo: hábitos orais, padrão de crescimento desfavorável, aumento de tecidos linfáticos com respiração bucal. Vários tratamentos têm sido propostos para corrigir esta má-oclusão. As intervenções não são suportadas por forte evidência científica. Objetivos: O objetivo desta revisão sistemática foi avaliar tratamentos ortodônticos e ortopédicos para corrigir MAA em crianças. Estratégia de pesquisa: Estratégias de pesquisa foram desenvolvidas para a MEDLINE e elaboradas para as seguintes bases de dados: Cochrane Oral Health Group Trials Register, PubMed (1966-2005); EMBASE (1980-2005); Lilacs (1982-2005); BBO (Biblioteca Brasileira de Odontologia) (1986-2005); SciELO (1997-2005). Revistas chinesas foram manualmente pesquisadas e as bibliografias dos artigos foram checadas. Critérios de Seleção: Todos os ensaios clínicos controlados randomizados ou quasi-randomizados de tratamentos ortodônticos e/ou ortopédicos para correção de MAA em crianças. Coleta de dados e análise: Dois revisores, independentemente, avaliaram a elegibilidade de todos os artigos identificados. RR, NNT e intervalos de confiança de 95% foram calculados para dados dicotômicos. Os resultados expressos em dados contínuos foram apresentados conforme descritos pelo autor. Principais resultados: Vinte e sete estudos foram eleitos, três ensaios clínicos controlados randomizados foram incluídos, comparando: efeitos do Regulador de função de Frankel-4 (RF4) com treinamento de selamento labial versus não tratamento, bite-blocks com magnetos versus bite-blocks; grade palatina associada à mentoneira versus não tratamento. O estudo com bite-blocks magneto versus bite-blocks não pôde ser analisado porque os autores interromperam o tratamento antes do que o planejado em função de efeitos colaterais em quatro dos dez pacientes. RF4 com treinamento de selamento labial e grade palatina associada à mentoneira foram capazes de corrigir MAA. Nenhum estudo descreveu: processo de randomização, cálculo do tamanho da amostra, mascaramento nas análises de dados. Dois estudos avaliaram duas intervenções ao mesmo tempo. Portanto, os resultados devem ser vistos com cautela. Conclusões dos revisores: Há alguma evidência de que as intervenções RF4 com treinamento de selamento labial e grade palatina associada à mentoneira são capazes de corrigir MAA. Os estudos incluídos têm potenciais vieses, portanto, os resultados devem ser vistos com cautela. Mais ensaios clínicos randomizados são necessários para elucidar as intervenções para tratamento de mordida aberta anterior. / Background: Anterior open bite occurs when upper incisors do not touch lower incisors. The aetiology is multifactorial including: oral habits, unfavorable growth pattern, enlarged lymphatic tissue with mouth breathing. Several treatments have been proposed to correct this malocclusion, but interventions are not supported by strong scientific evidence. Objectives: The aim of this systematic review was to evaluate orthodontic and orthopaedic treatments to correct anterior open bite in children Search strategy: Search strategies were developed for MEDLINE and revised appropriately for the following databases: Cochrane Oral Health Group Trials Register; The Cochrane Central Register of Controlled Trials (CENTRAL): The Cochrane Library , current Issue; PubMed (1966 to 2005); EMBASE (1980 to 2005); Lilacs (1982 to 2005); BBO (Bibliografia Brasileira de Odontologia) (1986 to 2005); SciELO (1997 to 2005). Chinese journals were handsearched and the bibliographies from papers were retrieved. Selection criteria: All randomised or quasi-randomised controlled trials of orthodontic and/or orthopaedic treatments to correct anterior open bite in children. Data collection & analysis: Two authors independently assessed the eligibility of all reports identified. Risk ratios, NNT and corresponding 95% confidence intervals were calculated for dichotomous data. The results presented as continuous data were expressed as described by author. Main results: Twenty seven trials were eligible, and only three randomised controlled trial were included comparing: effects of Frankel's functional regulator-4 (RF4) with lip-seal training versus no treatment; repelling-magnet splints versus bite-block; palatal crib associated with high-pull chincup versus no treatment. The study with repelling-magnet splints versus bite-block could not be analysed because the authors interrupted the treatment earlier than planned due to side effects in four of the ten patients. RF4 associated to lip-seal training and removable palatal crib combined with high-pull chincup were able to correct anterior open bite. None study described: randomisation process, size sample calculation, there was no blinding in the cephalometric analysis and the two studies evaluated two interventions at the same time. So, these results should be viewed with caution. Reviewers' conclusions: There is some evidence that the interventions RF4 with lip-seal training and palatal crib associated with high-pull chincup are able to correct anterior open bite. Given that the trials included have potential bias, these results must be viewed with caution. So, recommendations for clinical practice can not be made based only on the results of these trials. More randomised controlled trials are needed to elucidate the interventions for treating anterior open bite. / BV UNIFESP: Teses e dissertações

We analyse the role played by data and specification choices as determinants of the size of the fiscal multipliers obtained using structural vector autoregressive models. The results, based on over twenty million fiscal multiplier estimated for European countries, indicate that many seemingly harmless modelling choices have a significant effect on the size and precision of fiscal multiplier estimates. In addition to the structural shock identification strategy, these modelling choices include the definition of spending and taxes, the national accounts system employed, the use of particular interest rates or inflation measures, or whether data are smoothed prior to estimation. / Series: Department of Economics Working Paper Series

Orientador: Silvana Artioli Schellini / Abstract: Objective: To determine if stents increase the success rate of endoscopic dacryocystorhinostomy (DCR-EN) Method: Systematic review of randomized clinical trials of DCR-EN, comparing surgeries performed with and without stents in children older than 10 years of age and adult patients, with primary lacrimo-nasal duct (LND) obstruction. The outcomes were LND patency and adverse events (complications). We searched the databases of Web of Science, Scopus, Embase, Cochrane, PubMed, Lilacs until May 2018. The RevMan 5.3 software provided by the Cochrane Collaboration was used for meta-analysis. Results: Ten studies involving 887 surgeries were included. Five studies were conducted in India, and each of the others were conducted in Canada, Turkey, Saudi Arabia, China and Finland. Lacrimo-nasal duct patency meta-analysis showed stents did not interfere in the chance of success in relation to non-use of the stents to obtain lacrimal viability (OR 1.62, 95% CI 1.00 to 2.64, I2 = 0%). It was not possible to perform a meta-analysis regarding the adverse effects and a descriptive analysis was made of the general complications and complications due to the stents. Conclusion: The use or no of stents in DCR-EN probably does not make any difference in the NLD patency. Further studies may better define whether there is a trend toward a better success rate with the use of stent. Key words: dacryocystorhinotomy, endoscopic, stent, success, meta-analysis / Resumo: Objetivo: Definir se o uso de stents aumenta a taxa de sucesso da dacriocistorrinostomia endoscópica (DCR-EN). Método: Revisão sistemática de ensaios clínicos randomizados referentes a DCR-EN, comparando as cirurgias realizadas com e sem uso de stents em crianças acima dos 10 anos de idade e adultos, com obstrução adquirida do ducto lacrimo-nasal (DLN). Os desfechos avaliados foram a patência do DLN e os eventos adversos (complicações). Foram pesquisadas as bases de dados: Web of Science, Scopus, Embase, Cochrane, PubMed, Lilacs até maio de 2018. Utilizou-se para metanálise o software RevMan 5.3 fornecido pela Colaboração Cochrane. Resultados: Dez estudos envolvendo 887 cirurgias foram incluidos. Cinco estudos foram realizados na India, um em cada um dos países a seguir: Canada, Turquia, Arabia Saudita, China e Finlândia. A metanálise da patência do DLN mostrou que os stents não interferiram na chance de sucesso em relação ao não uso dos stents para a obtenção de permeabilidade da via lacrimal (OR 1,62, IC 95% 1.00 a 2.64; I2 = 0%). Quanto aos efeitos adversos não foi possível realizar metanálise, tendo sido feita análise descritiva das complicações gerais e complicações dos stents. Conclusão: O uso ou não de stents na DCR-EN provavelmente faz pouca ou nenhuma diferença na patência do DLN. Novos estudos poderão melhor definir se há tendência de melhor taxa de sucesso com o uso de stents. / Mestre