Neurocognitive profile and cognitive intervention in Alzheimer's disease

Tese de Doutoramento em Psicologia (Especialidade de Psicologia Clínica)

Análise do ciclo de vida usando Lourenço modelo: caso da cidade de Damasco (1960-2015)

Dissertação de mestrado Internacional em Ambiente Construído Sustentável

Programas metacognitivos com enfoque em cognição social na reabilitação da esquizofrenia: uma revisão sistemática

OBJETIVO: Revisar sistematicamente a literatura sobre programas psicoterapêuticos para a esquizofrenia com enfoque em CS, cujos métodos envolvam estratégias metacognitivas. MÉTODOS: Foi realizada uma busca na base MedLine, por trabalhos publicados em inglês ou português utilizando a frase "Social cognition" AND "Schizophrenia" [Mesh] AND "Psychotherapy" [Mesh] e os limitadores "Humans", "Clinical Trial", "Meta-Analysis" e "Randomized Controlled Trial". Adicionalmente, foram elaborados critérios de inclusão para selecionar os trabalhos com abordagem metacognitiva. RESULTADOS: Dezessete estudos foram selecionados, abrangendo essencialmente programas de reconhecimento do afeto facial e de emoções, Teoria da Mente (ToM), imitação e tomada de perspectiva em situações sociais. CONCLUSÃO: A maior parte dos estudos mostrou que seus programas são eficazes para melhorar medidas de psicopatologia, CS e funcionamento social. Futuras pesquisas deverão esclarecer sobre segurança, especificidade e durabilidade dessas intervenções.

Avaliação externa de escolas e avaliação externa de aprendizagens no contexto institucional: um estudo paralelo sobre Brasil e Portugal

Dissertação de mestrado em Ciências da Educação (área de especialização em Desenvolvimento Curricular e Inovação Educativa)

Emotional and behavioral problems in preschoolers: risk factors and assessment Issues

Tese de Doutoramento em Psicologia Aplicada.

Marcadores inflamatórios da doença cardiovascular em idosos

A maior parte das informações sobre o papel dos marcadores inflamatórios como preditores de doença cardiovascular envolve apenas indivíduos de meia-idade. Nesta revisão foi avaliado o papel dos marcadores inflamatórios como preditores de doença cardiovascular em idosos. Foram consultadas as bases de dados do Medline (Pubmed) e a base de dados da Cochrane, utilizando as palavras-chave. Após o acréscimo dos seguintes filtros: Limits: Aged 65+ years, Humans, Randomized Controlled Trial, Meta-Analysis, Review, Clinical Trials, foram encontrados 554 artigos. Desses, foram selecionados 120 artigos e avaliados quanto à sua força de evidência (classificação de Oxford Centre for Evidence Based Medicine). Nos pacientes com >65 anos, a interleucina 6 (IL-6), fator de necrose tumoral alfa (TNF α) e interleucina-10 (IL-10) têm se mostrado bons preditores de desfechos cardiovasculares. Em relação à proteína C-reativa (PCR), os dados são inconsistentes e ela parece ter menor poder como preditor em idosos, quando comparada aos indivíduos de meia-idade. Níveis de fibrinogênio parecem ser preditores de mortalidade, porém de uma forma não específica, ou seja, não apenas para mortalidade cardiovascular. Além disso, os marcadores inflamatórios também são indicadores de declínio funcional e mortalidade, independentemente da presença de doença cardiovascular. As evidências atuais são insuficientes para uso rotineiro dos marcadores inflamatórios, em idosos, já que existem poucos estudos nessa faixa etária, sendo a maioria deles de curta duração e com número reduzido de marcadores inflamatórios. A solicitação desses marcadores, de rotina, deve ser considerada individualmente.

Long-term Outcomes of Drug-eluting versus Bare-metal stent for ST-elevation Myocardial Infarction

Background:Long-term outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI) remain uncertain.Objective:To investigate long-term outcomes of drug-eluting stents (DES) versus bare-metal stents (BMS) in patients with ST-segment elevation myocardial infarction (STEMI).Methods:We performed search of MEDLINE, EMBASE, the Cochrane library, and ISI Web of Science (until February 2013) for randomized trials comparing more than 12-month efficacy or safety of DES with BMS in patients with STEMI. Pooled estimate was presented with risk ratio (RR) and its 95% confidence interval (CI) using random-effects model.Results:Ten trials with 7,592 participants with STEMI were included. The overall results showed that there was no significant difference in the incidence of all-cause death and definite/probable stent thrombosis between DES and BMS at long-term follow-up. Patients receiving DES implantation appeared to have a lower 1-year incidence of recurrent myocardial infarction than those receiving BMS (RR = 0.75, 95% CI 0.56 to 1.00, p= 0.05). Moreover, the risk of target vessel revascularization (TVR) after receiving DES was consistently lowered during long-term observation (all p< 0.01). In subgroup analysis, the use of everolimus-eluting stents (EES) was associated with reduced risk of stent thrombosis in STEMI patients (RR = 0.37, p=0.02).Conclusions:DES did not increase the risk of stent thrombosis in patients with STEMI compared with BMS. Moreover, the use of DES did lower long-term risk of repeat revascularization and might decrease the occurrence of reinfarction.

Impact of Physical Activity Interventions on Blood Pressure in Brazilian Populations

Background:High blood pressure is associated with cardiovascular disease, which is the leading cause of mortality in the Brazilian population. Lifestyle changes, including physical activity, are important for lowering blood pressure levels and decreasing the costs associated with outcomes.Objective:Assess the impact of physical activity interventions on blood pressure in Brazilian individuals.Methods:Meta-analysis and systematic review of studies published until May 2014, retrieved from several health sciences databases. Seven studies with 493 participants were included. The analysis included parallel studies of physical activity interventions in adult populations in Brazil with a description of blood pressure (mmHg) before and after the intervention in the control and intervention groups.Results:Of 390 retrieved studies, eight matched the proposed inclusion criteria for the systematic review and seven randomized clinical trials were included in the meta-analysis. Physical activity interventions included aerobic and resistance exercises. There was a reduction of -10.09 (95% CI: -18.76 to -1.43 mmHg) in the systolic and -7.47 (95% CI: -11.30 to -3.63 mmHg) in the diastolic blood pressure.Conclusions:Available evidence on the effects of physical activity on blood pressure in the Brazilian population shows a homogeneous and significant effect at both systolic and diastolic blood pressures. However, the strength of the included studies was low and the methodological quality was also low and/or regular. Larger studies with more rigorous methodology are necessary to build robust evidence.

Biomedical risk assessment as an aid for smoking cessation.

BACKGROUND: A possible strategy for increasing smoking cessation rates could be to provide smokers who have contact with healthcare systems with feedback on the biomedical or potential future effects of smoking, e.g. measurement of exhaled carbon monoxide (CO), lung function, or genetic susceptibility to lung cancer. OBJECTIVES: To determine the efficacy of biomedical risk assessment provided in addition to various levels of counselling, as a contributing aid to smoking cessation. SEARCH STRATEGY: We systematically searched the Cochrane Collaboration Tobacco Addiction Group Specialized Register, Cochrane Central Register of Controlled Trials 2008 Issue 4, MEDLINE (1966 to January 2009), and EMBASE (1980 to January 2009). We combined methodological terms with terms related to smoking cessation counselling and biomedical measurements. SELECTION CRITERIA: Inclusion criteria were: a randomized controlled trial design; subjects participating in smoking cessation interventions; interventions based on a biomedical test to increase motivation to quit; control groups receiving all other components of intervention; an outcome of smoking cessation rate at least six months after the start of the intervention. DATA COLLECTION AND ANALYSIS: Two assessors independently conducted data extraction on each paper, with disagreements resolved by consensus. Results were expressed as a relative risk (RR) for smoking cessation with 95% confidence intervals (CI). Where appropriate a pooled effect was estimated using a Mantel-Haenszel fixed effect method. MAIN RESULTS: We included eleven trials using a variety of biomedical tests. Two pairs of trials had sufficiently similar recruitment, setting and interventions to calculate a pooled effect; there was no evidence that CO measurement in primary care (RR 1.06, 95% CI 0.85 to 1.32) or spirometry in primary care (RR 1.18, 95% CI 0.77 to 1.81) increased cessation rates. We did not pool the other seven trials. One trial in primary care detected a significant benefit of lung age feedback after spirometry (RR 2.12; 95% CI 1.24 to 3.62). One trial that used ultrasonography of carotid and femoral arteries and photographs of plaques detected a benefit (RR 2.77; 95% CI 1.04 to 7.41) but enrolled a population of light smokers. Five trials failed to detect evidence of a significant effect. One of these tested CO feedback alone and CO + genetic susceptibility as two different intervention; none of the three possible comparisons detected significant effects. Three others used a combination of CO and spirometry feedback in different settings, and one tested for a genetic marker. AUTHORS' CONCLUSIONS: There is little evidence about the effects of most types of biomedical tests for risk assessment. Spirometry combined with an interpretation of the results in terms of 'lung age' had a significant effect in a single good quality trial. Mixed quality evidence does not support the hypothesis that other types of biomedical risk assessment increase smoking cessation in comparison to standard treatment. Only two pairs of studies were similar enough in term of recruitment, setting, and intervention to allow meta-analysis.

Extent of non-publication in cohorts of studies approved by research ethics committees or included in trial registries

BACKGROUND: The synthesis of published research in systematic reviews is essential when providing evidence to inform clinical and health policy decision-making. However, the validity of systematic reviews is threatened if journal publications represent a biased selection of all studies that have been conducted (dissemination bias). To investigate the extent of dissemination bias we conducted a systematic review that determined the proportion of studies published as peer-reviewed journal articles and investigated factors associated with full publication in cohorts of studies (i) approved by research ethics committees (RECs) or (ii) included in trial registries. METHODS AND FINDINGS: Four bibliographic databases were searched for methodological research projects (MRPs) without limitations for publication year, language or study location. The searches were supplemented by handsearching the references of included MRPs. We estimated the proportion of studies published using prediction intervals (PI) and a random effects meta-analysis. Pooled odds ratios (OR) were used to express associations between study characteristics and journal publication. Seventeen MRPs (23 publications) evaluated cohorts of studies approved by RECs; the proportion of published studies had a PI between 22% and 72% and the weighted pooled proportion when combining estimates would be 46.2% (95% CI 40.2%-52.4%, I2 = 94.4%). Twenty-two MRPs (22 publications) evaluated cohorts of studies included in trial registries; the PI of the proportion published ranged from 13% to 90% and the weighted pooled proportion would be 54.2% (95% CI 42.0%-65.9%, I2 = 98.9%). REC-approved studies with statistically significant results (compared with those without statistically significant results) were more likely to be published (pooled OR 2.8; 95% CI 2.2-3.5). Phase-III trials were also more likely to be published than phase II trials (pooled OR 2.0; 95% CI 1.6-2.5). The probability of publication within two years after study completion ranged from 7% to 30%. CONCLUSIONS: A substantial part of the studies approved by RECs or included in trial registries remains unpublished. Due to the large heterogeneity a prediction of the publication probability for a future study is very uncertain. Non-publication of research is not a random process, e.g., it is associated with the direction of study findings. Our findings suggest that the dissemination of research findings is biased.

SUCLG2 identified as both a determinator of CSF Aβ1-42 levels and an attenuator of cognitive decline in Alzheimer's disease.

Cerebrospinal fluid amyloid-beta 1-42 (Aβ1-42) and phosphorylated Tau at position 181 (pTau181) are biomarkers of Alzheimer's disease (AD). We performed an analysis and meta-analysis of genome-wide association study data on Aβ1-42 and pTau181 in AD dementia patients followed by independent replication. An association was found between Aβ1-42 level and a single-nucleotide polymorphism in SUCLG2 (rs62256378) (P = 2.5×10(-12)). An interaction between APOE genotype and rs62256378 was detected (P = 9.5 × 10(-5)), with the strongest effect being observed in APOE-ε4 noncarriers. Clinically, rs62256378 was associated with rate of cognitive decline in AD dementia patients (P = 3.1 × 10(-3)). Functional microglia experiments showed that SUCLG2 was involved in clearance of Aβ1-42.

Alcohol Brief Intervention in Primary Care: A Systematic Review

BACKGROUND: The purpose of the present review was to evaluate the evidence of the effectiveness of brief interventions aimed at reducing chronic alcohol use and harm related to alcohol consumption, conducted among individuals actively attending primary care but who were not seeking help for alcohol problems. METHODS: Randomised trials reporting at-least one outcome related to alcohol consumption and conducted in outpatients who were actively attending primary care centre or provider were selected using Cochrane Central Register of Controlled Trials, MEDLINE, PsycINFO, ISI Web of Science, ETOH database, and bibliographies of the retrieved references and previous reviews. Selection and data abstraction were performed independently and in duplicate. We assessed validity of the studies and performed a meta-analysis for studies reporting alcohol consumption at 6 or 12 months follow up. RESULTS: We included 24 reports, reporting results of 19 trials and including 5,639 individuals. Seventeen trials reported a measure of alcohol consumption, eight reporting a significant effect of intervention. The meta-analysis showed a mean pooled difference of -41 (95% CI: −54; −28) g of pure ethanol per week in favour of brief intervention group. Evidences for other outcomes (laboratory values, health related quality of life, morbidity and mortality, health care utilisation) were inconclusive. CONCLUSION: Our systematic review indicated that brief intervention might be effective for both men and women in reducing alcohol consumption compared to a controlled intervention, in a primary health care population. The meta-analysis confirmed the reduction in alcohol consumption at 6 and 12 month. Further research should precise the components of effectiveness of brief intervention and the evidence of effects on morbidity, mortality, and quality of life related outcomes.

Remains of the day: Biliary complications related to single-port laparoscopic cholecystectomy.

AIM: To assesse the rate of bile duct injuries (BDI) and overall biliary complications during single-port laparoscopic cholecystectomy (SPLC) compared to conventional laparoscopic cholecystectomy (CLC). METHODS: SPLC has recently been proposed as an innovative surgical approach for gallbladder surgery. So far, its safety with respect to bile duct injuries has not been specifically evaluated. A systematic review of the literature published between January 1990 and November 2012 was performed. Randomized controlled trials (RCT) comparing SPLC versus CLC reporting BDI rate and overall biliary complications were included. The quality of RCT was assessed using the Jadad score. Analysis was made by performing a meta-analysis, using Review Manager 5.2. This study was based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. A retrospective study including all retrospective reports on SPLC was also performed alongside. RESULTS: From 496 publications, 11 RCT including 898 patients were selected for meta-analysis. No studies were rated as high quality (Jadad score ≥ 4). Operative indications included benign gallbladder disease operated in an elective setting in all studies, excluding all emergency cases and acute cholecystitis. The median follow-up was 1 mo (range 0.03-18 mo). The incidence of BDI was 0.4% for SPLC and 0% for CLC; the difference was not statistically different (P = 0.36). The incidence of overall biliary complication was 1.6% for SPLC and 0.5% for CLC, the difference did not reached statistically significance (P = 0.21, 95%CI: 0.66-15). Sixty non-randomized trials including 3599 patients were also analysed. The incidence of BDI reported then was 0.7%. CONCLUSION: The safety of SPLC cannot be assumed, based on the current evidence. Hence, this new technology cannot be recommended as standard technique for laparoscopic cholecystectomy.

Simulation-based systematic review of imatinib population pharmacokinetics and PK-PD relationships in chronic myeloid leukemia (CML) patients

Objectives: Several population pharmacokinetic (PPK) and pharmacokinetic-pharmacodynamic (PK-PD) analyses have been performed with the anticancer drug imatinib. Inspired by the approach of meta-analysis, we aimed to compare and combine results from published studies in a useful way - in particular for improving the clinical interpretation of imatinib concentration measurements in the scope of therapeutic drug monitoring (TDM). Methods: Original PPK analyses and PK-PD studies (PK surrogate: trough concentration Cmin; PD outcomes: optimal early response and specific adverse events) were searched systematically on MEDLINE. From each identified PPK model, a predicted concentration distribution under standard dosage was derived through 1000 simulations (NONMEM), after standardizing model parameters to common covariates. A "reference range" was calculated from pooled simulated concentrations in a semi-quantitative approach (without specific weighting) over the whole dosing interval. Meta-regression summarized relationships between Cmin and optimal/suboptimal early treatment response. Results: 9 PPK models and 6 relevant PK-PD reports in CML patients were identified. Model-based predicted median Cmin ranged from 555 to 1388 ng/ml (grand median: 870 ng/ml and inter-quartile range: 520-1390 ng/ml). The probability to achieve optimal early response was predicted to increase from 60 to 85% from 520 to 1390 ng/ml across PK-PD studies (odds ratio for doubling Cmin: 2.7). Reporting of specific adverse events was too heterogeneous to perform a regression analysis. The general frequency of anemia, rash and fluid retention increased however consistently with Cmin, but less than response probability. Conclusions: Predicted drug exposure may differ substantially between various PPK analyses. In this review, heterogeneity was mainly attributed to 2 "outlying" models. The established reference range seems to cover the range where both good efficacy and acceptable tolerance are expected for most patients. TDM guided dose adjustment appears therefore justified for imatinib in CML patients. Its usefulness remains now to be prospectively validated in a randomized trial.