António Vaz-Carneiro

Caffeine Exposure and the Risk of Parkinson's Disease: A Systematic Review and Meta-Analysis of Observational Studiess

Several studies conducted worldwide report an inverse association between caffeine/coffee consumption and the risk of developing Parkinsons disease (PD). However, heterogeneity and conflicting results between studies preclude a correct estimation of the strength of this association. We conducted a systematic review and meta-analysis of published epidemiological studies to better estimate the effect of caffeine exposure on the incidence of PD. Data sources searched included Medline, LILACS, Scopus, Web of Science and reference lists, up to September 2009. Cohort, case-control and cross-sectional studies were included. Three independent reviewers selected the studies and extracted the data on to standardized forms. Twenty-six studies were included: 7 cohort, 2 nested case-control, 16 case-control, and 1 cross-sectional study. Quantitative data synthesis of the most precise estimates from each study was accomplished through random effects meta-analysis. Heterogeneity was quantified using the I2 statistic. The summary RR for the association between caffeine intake and PD was 0.75 [[95% Confidence Interval (95%CI): 0.68-0.82], with low to moderate heterogeneity (I2= 28.8%). Publication bias for case-control/cross-sectional studies may exist (Eggers test, p=0.053). When considering only the cohort studies, the RR was 0.80 (95%CI: 0.71-90; I2=8.1%). The negative association was weaker when only women were considered (RR=0.86, 95%CI: 0.73-1.02; I2=12.9%). A linear relation was observed between levels of exposure to caffeine and the RR estimates: RR of 0.76 (95%CI: 0.72-0.80; I2= 35.1%) per 300 mg increase in caffeine intake. This study confirm an inverse association between caffeine intake and the risk of PD, which can hardly by explained by bias or uncontrolled confounding.

Caffeine Intake and Dementia: Systematic Review and Meta-Analysis

A recent meta-analysis of 4 studies published up to January 2004 suggests a negative association between coffee consumption and Alzheimers disease, despite important heterogeneity in methods and results. Several epidemiological studies on this issue have been published since then, warranting an update of the insights on this topic. We conducted a systematic review and meta-analysis of published studies quantifying the relation between caffeine intake and cognitive decline or dementia. Data sources searched included Medline, LILACS, Scopus, Web of Science and reference lists, up to September 2009. Cohort and case-control studies were included. Three independent reviewers selected the studies and extracted the data on to standardized forms. Nine cohort and two case-control studies were included. Quantitative data synthesis of the most precise estimates from each study was accomplished through random effects meta-analysis. Heterogeneity was quantified using the I2 statistic. The outcomes of the studies considered for meta-analysis were Alzheimers disease in four studies, dementia or cognitive impairment in two studies, and cognitive decline in three studies. The summary relative risk (RR) for the association between caffeine intake and different measures of cognitive impairment/decline was 0.84 [95% Confidence Interval (95% CI): 0.72-0.99; I2=42.6%]. When considering only the cohort studies, the summary RR was 0.93 (95% CI: 0.83-1.04, I2= 0.0%), and 0.77 (95% CI: 0.63-0.95, I2= 34.7%), if the most influential study was excluded. This systematic review and meta-analysis found a trend towards a protective effect of caffeine, but the large methodological heterogeneity across a still limited number of epidemiological studies precludes robust and definite statements on this topic. and definite statements on this topic.

Clinical comparability of the new antiepileptic drugs in refractory partial epilepsy : a systematic review and meta-analysis

Purpose:  Evaluate the clinical comparability of new antiepileptic drugs (AEDs) in partial refractory epilepsy.

Risk of pneumonia associated with use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers: systematic review and meta-analysis

Objective To systematically review longitudinal studies evaluating use of angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) and risk of pneumonia. Design Systematic review and meta-analysis. Data sources Medline through PubMed, Web of Science with conference proceedings (inception to June 2011), and US Food and Drug Administration website (June 2011). Systematic reviews and references of retrieved articles were also searched. Study selection Two reviewers independently selected randomised controlled trials and cohort and case-control studies evaluating the use of ACE inhibitors or ARBs and risk of pneumonia and retrieved characteristics of the studies and data estimates. Data synthesis The primary outcome was incidence of pneumonia and the secondary outcome was pneumonia related mortality. Subgroup analyses were carried according to baseline morbidities (stroke, heart failure, and chronic kidney disease) and patients’ characteristics (Asian and non-Asian). Pooled estimates of odds ratios and 95% confidence intervals were derived by random effects meta-analysis. Adjusted frequentist indirect comparisons between ACE inhibitors and ARBs were estimated and combined with direct evidence whenever available. Heterogeneity was assessed using the I2 test. Results 37 eligible studies were included. ACE inhibitors were associated with a significantly reduced risk of pneumonia compared with control treatment (19 studies: odds ratio 0.66, 95% confidence interval 0.55 to 0.80; I2=79%) and ARBs (combined direct and indirect odds ratio estimate 0.69, 0.56 to 0.85). In patients with stroke, the risk of pneumonia was also lower in those treated with ACE inhibitors compared with control treatment (odds ratio 0.46, 0.34 to 0.62) and ARBs (0.42, 0.22 to 0.80). ACE inhibitors were associated with a significantly reduced risk of pneumonia among Asian patients (0.43, 0.34 to 0.54) compared with non-Asian patients (0.82, 0.67 to 1.00; P<0.001). Compared with control treatments, both ACE inhibitors (seven studies: odds ratio 0.73, 0.58 to 0.92; I2=51%) and ARBs (one randomised controlled trial: 0.63, 0.40 to 1.00) were associated with a decrease in pneumonia related mortality, without differences between interventions. Conclusions The best evidence available points towards a putative protective role of ACE inhibitors but not ARBs in risk of pneumonia. Patient populations that may benefit most are those with previous stroke and Asian patients. ACE inhibitors were also associated with a decrease in pneumonia related mortality, but the data lacked strength.

Lower‐limb amputation following foot ulcers in patients with diabetes: classification systems, external validation and comparative analysis

This study aimed to validate and compare the existing systems developed to stratify subjects with diabetic foot ulcers by risk of consequent lower extremity amputation.

Custo‐efetividade dos novos anticoagulantes orais na fibrilhação auricular em Portugal

INTRODUCTION AND OBJECTIVES Recently, three novel non-vitamin K antagonist oral anticoagulants received approval for reimbursement in Portugal for patients with non-valvular atrial fibrillation (AF). It is therefore important to evaluate the relative cost-effectiveness of these new oral anticoagulants in Portuguese AF patients. METHODS A Markov model was used to analyze disease progression over a lifetime horizon. Relative efficacy data for stroke (ischemic and hemorrhagic), bleeding (intracranial, other major bleeding and clinically relevant non-major bleeding), myocardial infarction and treatment discontinuation were obtained by pairwise indirect comparisons between apixaban, dabigatran and rivaroxaban using warfarin as a common comparator. Data on resource use were obtained from the database of diagnosis-related groups and an expert panel. Model outputs included life years gained, quality-adjusted life years (QALYs), direct healthcare costs and incremental cost-effectiveness ratios (ICERs). RESULTS Apixaban provided the most life years gained and QALYs. The ICERs of apixaban compared to warfarin and dabigatran were €5529/QALY and €9163/QALY, respectively. Apixaban was dominant over rivaroxaban (greater health gains and lower costs). The results were robust over a wide range of inputs in sensitivity analyses. Apixaban had a 70% probability of being cost-effective (at a threshold of €20 000/QALY) compared to all the other therapeutic options. CONCLUSIONS Apixaban is a cost-effective alternative to warfarin and dabigatran and is dominant over rivaroxaban in AF patients from the perspective of the Portuguese national healthcare system. These conclusions are based on indirect comparisons, but despite this limitation, the information is useful for healthcare decision-makers.

Análise da revisão Cochrane : anti-fator de crescimento vascular endotelial na prevenção da hemorragia vítrea pós-operatória após vitrectomia por retinopatia diabética proliferativa : Cochrane Database Syst Rev. 2015;8:CD008214

Postoperative vitreous hemorrhage is a complication following vitrectomy for proliferative diabetic retinopathy, delaying visual recovery and making fundus examination and disease follow-up more difficult. Anti-vascular endothelial growth factor drugs such as bevacizumab, when injected in the vitreous cavity, reduce vascular proliferation and their use has been proposed to reduce the incidence of postoperative vitreous hemorrhage. The authors of this Cochrane systematic review evaluated all randomized controlled trials on the pre- or intraoperative use of anti-vascular endothelial growth factor to reduce postoperative vitreous hemorrhage occurrence after vitrectomy in patients with proliferative diabetic retinopathy. The results suggested that the use of intravitreal bevacizumab was effective in reducing early postoperative vitreous hemorrhage (i.e. at four weeks) occurrence, with a good safety profile. This work aims to summarize and discuss the findings and clinical implications of this Cochrane systematic review.

Cochrane Corner – administração de corticosteroides para miocardite de etiologia viral

The causes of myocarditis are diverse, but a viral etiology is the most common. In this systematic review by the Cochrane Collaboration, the authors assessed the efficacy of corticosteroid therapy in patients with viral myocarditis. Eight randomized controlled trials with 719 patients (two trials in pediatric populations) were included for analysis. Pooled results did not show significant differences in mortality with the use of corticosteroids. Patients on corticosteroid therapy had significantly higher post-treatment left ventricular ejection fraction values compared to control. These results are limited by the significant heterogeneity associated with clinical trials. The best available evidence does not support the routine use of corticosteroids in patients with viral myocarditis.

Impacto da frequência posológica na adesão terapêutica em doenças cardiovasculares crónicas : revisão sistemática e meta‐análise

INTRODUCTION AND OBJECTIVE Non-adherence to drug treatment is a major health problem. In Europe, it has been estimated that 9% of cardiovascular events can be attributed to non-adherence. The complexity of dosing regimens is one of the factors identified as contributing to non-adherence. In this systematic review we aimed to assess the impact of dosing frequency on adherence to drug treatment in patients with chronic cardiovascular disease. METHODS MEDLINE and the Cochrane Library (November 2013) were searched for randomized controlled trials (RCTs) comparing different dosing regimens (once-daily administration vs. two or more daily administrations) and assessing adherence to therapy in patients with chronic cardiovascular disease. Only trials with at least five months of follow-up were included. The results of the studies were pooled through a random effects meta-analysis. Relative risk (RR) and 95% confidence interval (CI) were derived. Statistical heterogeneity was calculated using the I(2) test. RESULTS Four RCTs (a total of 2557 patients) were included. Dosing regimens with once-daily administration were associated with a significant 56% reduction in risk of non-adherence to drug therapy (RR: 0.44; 95% CI: 0.35-0.54, I(2)=25%). CONCLUSIONS Few clinical trials have assessed the long-term impact of dosing frequency on medication adherence in chronic cardiovascular disease. The best available evidence suggests that taking medication once daily decreases the risk of non-adherence to treatment by approximately 50%. The impact on clinical outcomes remains to be established.

Análise da Revisão Cochrane: Pregabalina no Tratamento da Dor Crónica Moderada a Grave em Adultos com Fibromialgia. Cochrane Database Syst Rev. 2016;9:CD011790 e 2016;4:CD009002.

Fibromyalgia can be clinically defined by widespread pain lasting for longer than 3 months with tenderness on palpation in 11 or more of 18 specified tender points. Many people with fibromyalgia are significantly disabled, and experience moderate to severe pain for many years, for which conventional analgesics are usually not effective. For these patients treatment options generally include antidepressants like tricyclic agents, serotonin and noradrenaline reuptake inhibitors, or anticonvulsants like pregabalin or gabapentin. Pregabalin is a drug licensed for the treatment of fibromyalgia in the United States of America, with a mechanism of action similar to gabapentin. This mode of action confers antiepileptic, analgesic, and anxiolytic effects. This Cochrane systematic review included 8 randomized, placebo-controlled trials with low risk of bias, which studied the effect of a daily dose of pregabalin for the treatment of moderate to severe pain in adult patients suffering from fibromyalgia. Of the main results of this systematic review we highlight the major effect that a daily dose of 300 to 600 mg of pregabalin had in the reduction of pain intensity over a follow-up period of 12 to 26 weeks, with tolerable adverse effects, for a minority of people with moderate to severe pain due to fibromyalgia. This paper aims to summarize and discuss the main results and conclusions of this systematic review, as well as its implications for the daily clinical practice.