Ximelagatran versus warfarin for prophylaxis of venous thromboembolism in major orthopedic surgery: systematic review of randomized controlled trials

INTRODUÇÃO: O ximelagatrano foi recentemente estudada para profilaxia do tromboembolismo venoso (TEV). OBJETIVO: Avaliar se o ximelagatrano comparado com a varfarina melhora a profilaxia do TEV em pacientes submetidos à cirurgia ortopédica do joelho. FONTE DE DADOS: Estudos randomizados identificados por pesquisa eletrônica na literatura médica, até 2006, cujos dados foram compilados no programa Review Manager, versão 4.2.5. RESULTADOS: Foram incluídos três estudos randomizados bem conduzidos envolvendo 4.914 participantes. Foram definidos dois sub-grupos com dosagens diferentes de ximelagatrano (24 mg and 36 mg, duas vezes ao dia). O tratamento com ximelagatrano mostrou freqüência significantemente menor de TEV que o tratamento com varfarina, mas somente na dosagem de 36-mg [risco relativo, RR 0.72 ([intervalo de confiança, IC, 95% 0.64, 0.81), p < 0.00001]. A freqüência de TEV no sub-grupo de 24-mg foi similar a da varfarina [RR 0.86 (IC 95% 0.73, 1.01), p = 0.06]. Para TEV maior, embolia pulmonar, sangramento e sangramento maior não houve diferença entre varfarina e a ximelagatrano. Ao final do tratamento, a elevação da alanino-aminotransferase (ALT) foi menos freqüente no sub-grupo de 24 mg de ximelagatrano que no grupo da varfarina [RR 0.33 (IC 95% 0.12, 0.91) p = 0.03], mas no período de acompanhamento essa elevação foi maior com 36 mg de ximelagatrano [RR 6.97 (IC 95% 1.26, 38.50) p = 0.03]. CONCLUSÃO: O ximelagatrano foi mais efetivo que a varfarina quando usado em dosagens maiores (36 mg, 2 vezes ao dia), mas às expensas de aumento de enzimas hepáticas no período de acompanhamento.

Cabergoline versus bromocriptine in the treatment of hyperprolactinemia: a systematic review of randomized controlled trials and meta-analysis

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effects of motor intervention in elderly patients with dementia: An analysis of randomized controlled trials

The objective of this study was to analyze randomized controlled trials published in the last decades involving motor intervention as a treatment for dementia, based on Physiotherapy Evidence Database (PEDro) criteria. A database search was performed using the following keywords: randomized controlled trial, dementia, physiotherapy, physical therapy, occupational therapy, physical education, motor approach, exercise, and physical activity. Ten trials were found: 4 related to physiotherapy, 3 to occupational therapy, 1 to physical education, and 2 to interdisciplinary motor intervention. The efficacy of motor intervention was confirmed in the following variables: psychosocial function, physical health and function, affective status, and caregiver's distress (P < .05). Results related to mobility were not significant (P > .05). Behavior, cognitive performance, activities of daily living, and risk of falls were not similar among the articles. From a total score of 10 points, with excellence characterized as the highest punctuation, the articles were classified between 3 and 7 by PEDro. Motor intervention was shown to be an alternative for minimizing physical and mental decline. PEDro has been confirmed as a very reliable tool to analyze studies and as an evaluation criteria, both qualitative and quantitative, allowing the establishment of motor intervention strategies for the treatment of patients with dementia. © 2007 Lippincott Williams & Wilkins, Inc.

Systematic review of randomized controlled trials of new anticoagulants for venous thromboembolism prophylaxis in major orthopedic surgeries, compared with enoxaparin

Background: In the past 10 years, new anticoagulants (NACs) have been studied for venous thromboembolism (VTE) prophylaxis. Objective: To evaluate the risk/benefit profile of NACs versus enoxaparin for VTE prophylaxis in major orthopedic surgery. Methods: A systematic review of double-blind randomized phase III studies was performed. The search strategy was run from 2000 to 2011 in the main medical electronic databases in any language. Independent extraction of articles was performed by 2 authors using predefined data fields, including study quality indicators. Results: Fifteen published clinical trials evaluating fondaparinux, rivaroxaban, dabigatran, and apixaban were included. Primary efficacy (any deep vein thrombosis [DVT], nonfatal pulmonary embolism, or all-cause mortality) favored fondaparinux (relative risk [RR] 0.50; 95% CI, 0.39, 0.63) and rivaroxaban (RR, 0.50; 95% CI, 0.34, 0.73) over enoxaparin, although significant heterogeneity was observed in both series. The primary efficacy of dabigatran at 220 mg, apixaban, and bemiparin were similar, with RRs of 1.02 (95% CI, 0.86, 1.20), 0.63 (95% CI, 0.39, 1.01), and 0.87 (95% CI, 0.65, 1.17), respectively. The primary efficacy of dabigatran at 150 mg (RR, 1.20; 95% CI, 1.03, 1.41), was inferior to enoxaparin. The incidence of proximal DVT favored apixaban (RR, 0.45; 95% CI, 0.27, 0.75) only. Rivaroxaban (RR, 0.45; 95% CI, 0.27, 0,77) and apixaban (RR, 0.38; 95% CI, 0.16, 0.90) produced significantly lower frequencies of symptomatic DVT. The incidence of major VTE favored rivaroxaban (RR, 0.44; 95% CI, 0.25, 0.81), only. Bleeding risk was similar for all NACs, except fondaparinux (RR, 1.27; 95% CI, 1.04, 1.55), which exhibited a significantly higher any-bleeding risk compared with enoxaparin, and apixaban (RR, 0.88; 95% CI, 0.79, 0.99), which was associated with a reduced risk of any bleeding. Alanine amino transferase was significantly lower with 220 mg of dabigatran, (RR, 0.67; 95% CI, 0.79, 0.99) than with enoxaparin. Conclusions: NACs can be considered alternatives to conventional thromboprophylaxis regimens in patients undergoing elective major orthopedic surgery, depending on clinical characteristics and cost-effectiveness. The knowledge of some differences concerning efficacy or safety profile, pointed out in this systematic review, along with the respective limitations, may be useful in clinical practice. © 2013 Elsevier Inc. All rights reserved.

A randomised controlled trial of periconal eye blockade with or without ultrasound guidance

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

IVF/ICSI outcomes after culture of human embryos at low oxygen tension: a meta-analysis

Background: Improved pregnancy, implantation, and birth rates have been reported after the use of reduced O2 concentration during embryo culture, mainly due to a reduction of the cumulative detrimental effects of reactive oxygen species. However, some studies have failed to report any positive effects. The objective of this meta-analysis was to evaluate the effect of a low-O2 environment on IVF/intracytoplasmic sperm injection (ICSI) outcomes.Methods: All available published and ongoing randomised trials that compared the effects of low (similar to 5%; OC similar to 5) and atmospheric (similar to 20%; OC similar to 20) oxygen concentrations on IVF/ICSI outcomes were included. Search strategies included online surveys of databases from 1980 to 2011. The outcomes measured were fertilisation rate, implantation rate and ongoing pregnancy rates. The fixed effects model was used to calculate the odds ratio.Results: Seven studies were included in this analysis. The pooled fertilisation rate did not differ significantly (P = 0.54) between the group of oocytes cultured at low O2 tension and the group at atmospheric O2 tension. Concerning all cycles, the implantation (P = 0.06) and ongoing pregnancy (P = 0.051) rates were not significantly different between the group receiving transferred sets containing only OC similar to 5 embryos and the group receiving transferred sets with only OC similar to 20 embryos. In a meta-analysis performed for only those trials in which embryos were transferred on day 2/3, implantation (P = 0.63) and ongoing pregnancy (P = 0.19) rates were not significantly different between the groups. In contrast, when a meta-analysis was performed using only trials in which embryos were transferred on days 5 and 6 (at the blastocyst stage), the group with transferred sets of only OC similar to 5 embryos showed a statistically significantly higher implantation rate (P = 0.006) than the group receiving transferred sets with only OC similar to 20 embryos, although the ongoing pregnancy (P = 0.19) rates were not significantly different between the groups.Conclusions: Despite some promising results, it seems too early to conclude that low O2 culture has an effect on IVF outcome. Additional randomised controlled trials are necessary before evidence-based recommendations can be provided. It should be emphasised that the present meta-analysis does not provide any evidence that low oxygen concentration is unnecessary.

Single crowns versus conventional fillings for the restoration of root filled teeth

BackgroundEndodontic treatment, involves removal of the dental pulp and its replacement by a root canal filling. Restoration of root filled teeth can be challenging due to structural differences between vital and non-vital root filled teeth. Direct restoration involves placement of a restorative material e.g. amalgam or composite directly into the tooth. Indirect restorations consist of cast metal or ceramic (porcelain) crowns. The choice of restoration depends on the amount of remaining tooth which may influence long term survival and cost. The comparative in service clinical performance of crowns or conventional fillings used to restore root filled teeth is unclear.ObjectivesTo assess the effects of restoration of endodontically treated teeth (with or without post and core) by crowns versus conventional filling materials.Search methodsWe searched the following databases: the Cochrane Oral Health Group's Trials Register, CENTRAL, MEDLINE via OVID, EMBASE via OVID, CINAHL via EBSCO, LILACS via BIREME and the reference lists of articles as well as ongoing trials registries. There were no restrictions regarding language or date of publication. Date of last search was 13 February 2012.Selection criteriaRandomised controlled trials (RCTs) or quasi-randomised controlled trials in participants with permanent teeth which have undergone endodontic treatment. Single full coverage crowns compared with any type of filling materials for direct restoration, as well as indirect partial restorations (e.g. inlays and onlays). Comparisons considered the type of post and core used (cast or prefabricated post), if any.Data collection and analysisTwo review authors independently assessed trial quality and extracted data.Main resultsOne trial judged to be at high risk of bias due to missing outcome data, was included. 117 participants with a root filled premolar tooth restored with a carbon fibre post, were randomised to either a full coverage metal-ceramic crown or direct adhesive composite restoration. At 3 years there was no reported difference between the non-catastrophic failure rates in both groups. Decementation of the post and marginal gap formation occurred in a small number of teeth.Authors' conclusionsThere is insufficient evidence to support or refute the effectiveness of conventional fillings over crowns for the restoration of root filled teeth. Until more evidence becomes available clinicians should continue to base decisions on how to restore root filled teeth on their own clinical experience, whilst taking into consideration the individual circumstances and preferences of their patients.

Enzyme replacement therapy for Anderson-Fabry disease.

Anderson-Fabry disease is an X-linked defect of glycosphingolipid metabolism. Progressive renal insufficiency is a major source of morbidity, additional complications result from cardio- and cerebro-vascular involvement. Survival is reduced among affected males and symptomatic female carriers. To evaluate the effectiveness and safety of enzyme replacement therapy compared to other interventions, placebo or no interventions, for treating Anderson-Fabry disease. We searched 'Clinical Trials' on The Cochrane Library, MEDLINE, EMBASE, LILACS and the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register (date of the most recent search: 11 September 2012). The original search was performed in September 2008.Date of the most recent search of the Cystic Fibrosis and Genetic Disorders Group's Inborn Errors of Metabolism Trials Register: 11 September 2012. Randomized controlled trials of agalsidase alfa or beta in participants diagnosed with Anderson-Fabry disease. Two authors selected relevant trials, assessed methodological quality and extracted data. Six trials comparing either agalsidase alfa or beta in 223 participants fulfilled the selection criteria.Both trials comparing agalsidase alfa to placebo reported on globotriaosylceramide concentration in plasma and tissue; aggregate results were non-significant. One trial reported pain scores, there was a statistically significant improvement for participants receiving treatment at up to three months, mean difference -2.10 (95% confidence interval (CI) -3.79 to -0.41); at up to five months, mean difference -1.90 (95% CI -3.65 to -0.15); and at up to six months, mean difference -2.00 (95% CI -3.66 to -0.34). There was a significant difference in pain-related quality of life at over five months and up to six months, mean difference -2.10 (95% CI -3.92 to -0.28) but not at other time-points. Neither trial reported deaths.One of the three trials comparing agalsidase beta to placebo reported on globotriaosylceramide concentration in plasma and tissue and showed significant improvement: kidney, mean difference -1.70 (95% CI -2.09 to -1.31); heart, mean difference -0.90 (95% CI -1.18 to -0.62); and composite results (renal, cardiac, and cerebrovascular complications and death), mean difference -4.80 (95% CI -5.45 to -4.15). There was no significant difference between groups for death; no trials reported on pain.Only one trial compared agalsidase alfa to agalsidase beta. There was no significant difference between the groups for any adverse events, risk ratio 0.36 (95% CI 0.08 to 1.59), or any serious adverse events; risk ratio 0.30; 95% CI 0.03 to 2.57). Six small, poor quality randomised controlled trials provide no robust evidence for use of either agalsidase alfa and beta to treat Anderson-Fabry disease.

Early light reduction for preventing retinopathy of prematurity in very low birth weight infants

BackgroundRetinopathy of prematurity (ROP) is a complex condition of the developing retinal blood vessels and is one of the leading causes of preventable childhood blindness. Several risk factors for ROP have been studied over the past 50 years. Among them, general immaturity (low birth weight and low gestational age) and prolonged oxygen therapy have been consistently related to disease onset. However, it is understood that the progression of the disease is multifactorial and may be associated with others risk factors, such as multiple gestation, apnoea, intracranial haemorrhage, anaemia, sepsis, prolonged mechanical ventilation, multiple transfusions and light exposure. Furthermore, the precise role of these individual factors in the development of the disease has not yet been well established.ObjectivesTo determine whether the reduction of early environmental light exposure reduces the incidence of retinopathy of prematurity (ROP) or poor ROP outcomes among very low birth weight infants.Search methodsWe searched the following databases: the Cochrane Neonatal Group Specialised Register, CENTRAL (The Cochrane Library), MEDLINE, EMBASE, CINAHL, HealthSTAR, Science Citation Index Database, CANCERLIT, the Oxford Database of Perinatal Trials and www.clinicaltrials.gov. We also searched previous reviews including cross-references, abstracts, conference and symposia proceedings, and contacted expert informants. This search was updated in October 2012.Selection criteriaRandomised or quasi-randomised controlled trials that reduced light exposure to premature infants within the first seven days following birth were considered for this review. We also considered cluster-randomised controlled trials.Data collection and analysisData on clinical outcomes including any acute ROP and poor ROP outcome were extracted by both review authors independently and consensus reached. We conducted data analysis according to the standards of the Cochrane Neonatal Review Group.Main resultsData from four randomised trials with a total of 897 participants failed to show any reduction in acute ROP or poor ROP outcome with the reduction of ambient light to premature infants' retinas. The overall methodological quality of the included studies was about evenly split between those in which the classification was unclear and those in which the studies were categorised as low risk of bias. There was no report on the secondary outcomes considered in this review: quality of life measures; and time of exposure to oxygen.Authors' conclusionsThe evidence shows that bright light is not the cause of retinopathy of prematurity and that the reduction of exposure of the retinas of premature infants to light has no effect on the incidence of the disease.

Antidepressants for anorexia nervosa

Background Anorexia Nervosa ( AN) is an illness characterised by extreme concern about body weight and shape, severe self-imposed weight loss, and endocrine dysfunction. In spite of its high mortality, morbidity and chronicity, there are few intervention studies on the subject.Objectives The aim of this review was to evaluate the efficacy and acceptability of antidepressant drugs in the treatment of acute AN.Search strategy The strategy comprised of database searches of the Cochrane Collaboration Depression, Anxiety and Neurosis Controlled Trials Register, MEDLINE (1966 to April 28th, 2005), EMBASE (1980 to week 36, 2004), PsycINFO (1969 to August week 5, 2004), handsearching the International Journal of Eating Disorders and searching the reference lists of all papers selected. Personal letters were sent to researchers in the field requesting information on unpublished or in-progress trials.Selection criteria All randomised controlled trials of antidepressant treatment for AN patients, as de fined by the Diagnostic and Statistical Manual, fourth edition (DSM-IV) or similar international criteria, were selected.Data collection and analysis Quality ratings were made giving consideration to the strong relationship between allocation concealment and potential for bias in the results; studies meeting criteria A and B were included. Trials were excluded if non-completion rates were above 50%. The standardised mean difference and relative risk were used for continuous data and dichotomous data comparisons, respectively. Whenever possible, analyses were performed according to intention- to-treat principles. Heterogeneity was tested with the I-squared statistic. Weight change was the primary outcome. Secondary outcomes were severity of eating disorder, depression and anxiety symptoms, and global clinical state. Acceptability of treatment was evaluated by considering non-completion rates.Main results Only seven studies were included. Major methodological limitations such as small trial size and large confidence intervals decreased the power of the studies to detect differences between treatments, and meta-analysis of data was not possible for the majority of outcomes. Four placebo-controlled trials did not find evidence that antidepressants improved weight gain, eating disorder or associated psychopathology. Isolated findings, favouring amineptine and nortriptyline, emerged from the antidepressant versus antidepressant comparisons, but cannot be conceived as evidence of efficacy of a specific drug or class of antidepressant in light of the findings from the placebo comparisons. Non-completion rates were similar between the compared groups.Authors' conclusions A lack of quality information precludes us from drawing de finite conclusions or recommendations on the use of antidepressants in acute AN. Future studies testing safer and more tolerable antidepressants in larger, well designed trials are needed to provide guidance for clinical practice.

Abatacept in children with juvenile idiopathic arthritis: a randomised, double-blind, placebo-controlled withdrawal trial

Background Some children with juvenile idiopathic arthritis either do not respond, or are intolerant to, treatment with disease-modifying antirheumatic drugs, including anti-tumour necrosis factor (TNF) drugs. We aimed to assess the safety and efficacy of abatacept, a selective T-cell costimulation modulator, in children with juvenile idiopathic arthritis who had failed previous treatments.Methods We did a double-blind, randomised controlled withdrawal trial between February, 2004, and June, 2006. We enrolled 190 patients aged 6-17 years, from 45 centres, who had a history of active juvenile idiopathic arthritis; at least five active joints; and an inadequate response to, or intolerance to, at least one disease-modifying antirheumatic drug. All 190 patients were given 10 mg/kg of abatacept intravenously in the open-label period of 4 months. of the 170 patients who completed this lead-in course, 47 did not respond to the treatment according to predefined American College of Rheumatology (ACR) paediatric criteria and were excluded. of the patients who did respond to abatacept, arthritis, and 62 were randomly assigned to receive placebo at the same dose and timing. The primary endpoint was time to flare of arthritis. Flare was defined as worsening of 30% or more in at least three of six core variables, with at least 30% improvement in no more than one variable. We analysed all patients who were treated as per protocol. This trial is registered, number NCT00095173.Findings Flares of arthritis occurred in 33 of 62 (53%) patients who were given placebo and 12 of 60 (20%) abatacept patients during the double-blind treatment (p=0.0003). Median time to flare of arthritis was 6 months for patients given placebo (insufficient events to calculate IQR); insufficient events had occurred in the abatacept group for median time to flare to be assessed (p=0.0002). The risk of flare in patients who contined abatacept was less than a third of that for controls during that double-blind period (hazard ratio 0.31, 95% CI 0.16-0.95). During the double-blind period, the frequency of adverse events did not differ in the two treatment groups, Adverse events were recorded in 37 abatacept recipients (62%) and 34 (55%) placebo recipients (p=0.47); only two serious adverse events were reported, bouth in controls (p=0.50).Interpretation Selective modulation of T-cell costimulation with abatacept is a rational alternative treatment for children with juvenile idiopathic arthritis.Funding Bristol-Myers Squibb.