5-FU for genital warts in non-immunocompromised individuals

BackgroundGenital warts are common and usually are harmless but can be painful and psychologically burdensome. Several local treatments can be used, including topical 5-Fluorouracil (5-FU).ObjectivesTo determine the effectiveness and safety of 5-FU topical treatment for genital warts in nonimmunocompromised individuals.Search strategyDatabases searched were Cochrane Central Register of Controlled Trials (The Cochrane Library 2009 Issue 3), MEDLINE (1966 to August 2009), EMBASE (until August 2009), LILACS (1982 to August 2009). the search had no language or publication restrictions.Selection criteriaThe review included randomised controlled trials (RCTs) among women, men, or both sexes, aged 18 years and older, comparing: 5-FU versus placebo or no treatment; 5-FU in any dose versus other isolated treatment, topical or systemic; 5-FU in any dose associated with other treatment versus placebo; 5-FU in any dose associated with other treatment versus other isolated treatment, topical or systemic; 5-FU in any dose associated with other treatment versus other associated treatment, topical or systemic.Data collection and analysisTwo authors independently assessed trial quality and extracted data from the original publications.Main resultsSix trials involving 988 patients (645 women and 343 men) and reporting eight comparisons were found. Two studies reported withdrawals and dropouts, but none mentioned analysis by intention to treat (ITT). 5-FU presented better results for cure than placebo or no treatment (relative risk (RR) 0.39, 95% confidence interval (CI) 0.23 to 0.67), meta-cresol-sulfonic acid (MCSA) (RR 2.11, 95% CI 0.83 to 5.37), Podophylin 2%, 4% or 25% (RR 1.26, 95% CI 0.86 to 1.82). There were no statistical differences for treatment failure for 5-FU versus CO2 Laser (RR 0.69, 95% CI 0.43 to 1.11) versus 5-FU + INF alpha-2a (low dose) (RR 1.02, 95% CI 0.87 to 1.119). Worse results were found for 5-FU versus 5-FU + INF alpha-2a (high dose) (RR 10.78, 95% CI 1.50 to 77.36), and 5-FU + CO2 Laser INF alpha-2a (high dose) (RR 7.97, 95% CI 2.87 to 22.13).Authors' conclusionsThe reviewed trials were highly variable in methods and quality, and the evidence provided by these studies was weak. Cure rates with several treatments were variable, and although 5-FU presents therapeutic results that are inferior to those seen with 5-FU + Inf alpha-2a (high dose) and 5-FU + CO2 Laser + Inf alpha-2a (high dose), the treatment should not be abandoned. Topical treatment with 5-FU has a therapeutic effect; however, the benefits and risks have not been determined clearly and further studies are needed.Universidade Federal de São Paulo, Dept Med, Escola Paulista Med, São Paulo, BrazilUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, Escola Paulista Med, São Paulo, BrazilUniv Fed Rio Grande do Norte, Dept Med, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, Escola Paulista Med, São Paulo, BrazilUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, Escola Paulista Med, São Paulo, BrazilWeb of Scienc

Beta-blockers for preventing stroke recurrence

BackgroundStroke affects 15 million people per year worldwide. Despite recent developments in acute stroke treatment, prevention remains very important. Stroke has a high rate of recurrence; therefore secondary prevention is also important. Many clinical approaches to control risk factors have been proposed. One of these approaches is the prescription of beta-blockers that have effects beyond the reduction of blood pressure, which can reduce the recurrence of stroke.ObjectivesTo evaluate the efficacy of beta-blockers for preventing stroke recurrence and for reducing death and major vascular events in people with a previous stroke or transient ischaemic attack (TIA), and to determine their safety, particularly with regard to the development of diabetes mellitus.Search methodsWe searched the Cochrane Stroke Group Trials Register (May 2014), the Cochrane Central Register of Controlled Trials (CENTRAL) and the Cochrane Database of Systematic Reviews (CDSR) (The Cochrane Library 2014, Issue 5), the Database of Abstracts of Reviews of Effects (DARE) (May 2014), MEDLINE (1966 to May 2014), EMBASE (1980 to May 2014), and Latin American and Caribbean Health Sciences Literature (LILACS) (1982 to May 2014). We also searched ongoing trials registers and reference lists.Selection criteriaRandomised controlled trials (RCTs) that included participants with previous stroke or TIA due to arterial thrombosis or embolism. the intervention was any beta-blocker versus control, or beta-blocker plus other treatment versus other treatment.Data collection and analysisTwo review authors independently screened the trials identified, appraised quality, and extracted data.Main resultsWe included two RCTs involving 2193 participants in the review. Both studies randomised participants to either beta-blocker (atenolol 5 mg) or placebo and were of a high methodological quality. We noted no statistical differences among the groups in risks of fatal and non-fatal stroke (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.76 to 1.18). for other outcomes analysed (major vascular events, death from all causes, death from cardiovascular causes), we observed no significant differences between the groups. There were minor blood pressure reductions in the intervention group. Neither of the included studies reported the occurrence of diabetes among their outcomes or assessed quality of life. Adverse events were significantly more frequent in participants taking atenolol than in those given placebo, and were the most common reason given for discontinuing treatment (RR 1.85, 95% CI 1.45 to 2.35).Authors' conclusionsTo date, no available evidence supports the routine use of beta-blockers for secondary prevention after stroke or TIA. More studies with larger samples are needed.Brazilian Cochrane Centre, BrazilCoordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Comissao de Aperfeicoamento de Pessoal de Ensino SuperiorUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, BR-04038000 São Paulo, SP, BrazilSanta Casa Campo Mourao, Dept Med, São Paulo, BrazilCtr Estudos Saude Baseada Evidencias & Avaliacao, Brazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, BR-04038000 São Paulo, SP, BrazilUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, BR-04038000 São Paulo, SP, BrazilUniversidade Federal de São Paulo, BR-04038000 São Paulo, SP, BrazilWeb of Scienc

Prevention and treatment for mucositis in bone marrow grafted patients: a systematic review and meta-analysis

Universidade Federal de São Paulo, São Paulo, BrazilUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, EPM, São Paulo, BrazilUniversidade Federal de São Paulo, Brazilian Cochrane Ctr, São Paulo, BrazilWeb of Scienc

Occlusal splints for treating sleep bruxism (tooth grinding)

BackgroundSleep bruxism is an oral activity characterised by teeth grinding or clenching during sleep. Several treatments for sleep bruxism have been proposed such as pharmacological, psychological, and dental.ObjectivesTo evaluate the effectiveness of occlusal splints for the treatment of sleep bruxism with alternative interventions, placebo or no treatment.Search strategyWe searched the Cochrane Oral Health Group's Trials Register ( to May 2007); the Cochrane Central Register of Controlled Trials ( CENTRAL) ( the Cochrane Library 2007, Issue 1); MEDLINE ( 1966 to May 2007); EMBASE ( 1980 to May 2007); LILACS ( 1982 to May 2007); Biblioteca Brasileira de Odontologia ( 1982 to May 2007); Dissertation, Theses and Abstracts (1981 to May 2007); and handsearched abstracts of particular importance to this review. Additional reports were identified from the reference lists of retrieved reports and from article reviews about treating sleep bruxism. There were no language restrictions.Selection criteriaWe selected randomised or quasi-randomised controlled trials (RCTs), in which splint therapy was compared concurrently to no treatment, other occlusal appliances, or any other intervention in participants with sleep bruxism.Data collection and analysisData extraction was carried out independently and in duplicate. Validity assessment of the included trials was carried out at the same time as data extraction. Discrepancies were discussed and a third review author consulted. the author of the primary study was contacted when necessary.Main resultsThirty-two potentially relevant RCTs were identified. Twenty-four trials were excluded. Five RCTs were included. Occlusal splint was compared to: palatal splint, mandibular advancement device, transcutaneous electric nerve stimulation, and no treatment. There was just one common outcome ( arousal index) which was combined in a meta-analysis. No statistically significant differences between the occlusal splint and control groups were found in the meta-analyses.Authors'conclusionsThere is not sufficient evidence to state that the occlusal splint is effective for treating sleep bruxism. Indication of its use is questionable with regard to sleep outcomes, but it may be that there is some benefit with regard to tooth wear. This systematic review suggests the need for further investigation in more controlled RCTs that pay attention to method of allocation, outcome assessment, large sample size, and sufficient duration of follow up. the study design must be parallel, in order to eliminate the bias provided by studies of crossover type. A standardisation of the outcomes of the treatment of sleep bruxism should be established in the RCTs.Universidade Federal de São Paulo, Dept Med, BR-04039001 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Med, BR-04039001 São Paulo, BrazilWeb of Scienc

Depot versus daily administration of gonadotrophin-releasing hormone agonist protocols for pituitary down regulation in assisted reproduction cycles

BackgroundGonadotrophin-releasing hormone agonist (GnRHa) is commonly used to switch off (down regulate) the pituitary gland and thus suppress ovarian activity in women undergoing in vitro fertilisation (IVF). Other fertility drugs (gonadotrophins) are then used to stimulate ovulation in a controlled manner. Among the various types of pituitary down regulation protocols in use, the long protocol achieves the best clinical pregnancy rate. the long protocol requires GnRHa administration until suppression of ovarian activity occurs, within approximately 14 days. GnRHa can be used either as daily low-dose injections or through a single injection containing higher doses of the drug (depot). It is unclear which of these two forms of administration is best, and whether single depot administration may require higher doses of gonadotrophins.ObjectivesTo compare the effectiveness and safety of a single depot dose of GHRHa versus daily GnRHa doses in women undergoing IVF.Search methodsWe searched the following databases: Cochrane Menstrual Disorders and Subfertility Group Trials Register (searched July 2012), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), MEDLINE (1966 to July 2012), EMBASE (1980 to July 2012) and LILACS (1982 to July 2012). We also screened the reference lists of articles.Selection criteriaWe included RCTs comparing depot and daily administration of GnRHa for long protocols in IVF treatment cycles in couples with any cause of infertility, using various methods of ovarian stimulation. the primary review outcomes were live birth or ongoing pregnancy, clinical pregnancy and ovarian hyperstimulation syndrome (OHSS). Other outcomes included number of oocytes retrieved, miscarriage, multiple pregnancy, number of gonadotrophin (FSH) units used for ovarian stimulation, duration of gonadotrophin treatment, cost and patient convenience.Data collection and analysisTwo review authors independently selected studies, extracted data and assessed study quality. for dichotomous outcomes, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) per woman randomised. Where appropriate, we pooled studies.Main resultsSixteen studies were eligible for inclusion (n = 1811 participants), 12 (n = 1366 participants) of which were suitable for meta-analysis. No significant heterogeneity was detected.There were no significant differences between depot GnRHa and daily GnRHa in live birth/ongoing pregnancy rates (OR 0.95, 95% CI 0.70 to 1.31, seven studies, 873 women), but substantial differences could not be ruled out. Thus for a woman with a 24% chance of achieving a live birth or ongoing pregnancy using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 18% and 29%.There was no significant difference between the groups in clinical pregnancy rate (OR 0.96, 95% CI 0.75 to 1.23, 11 studies, 1259 women). for a woman with a 30% chance of achieving clinical pregnancy using daily GnRHa injections, the corresponding chance using GnRHa depot would be between 25% and 35%.There was no significant difference between the groups in the rate of severe OHSS (OR 0.84, 95% CI 0.29 to 2.42, five studies, 570 women), but substantial differences could not be ruled out. for a woman with a 3% chance of severe OHSS using daily GnRHa injections, the corresponding risk using GnRHa depot would be between 1% and 6%.Compared to women using daily GnRHa, those on depot administration required significantly more gonadotrophin units for ovarian stimulation (standardised mean difference (SMD) 0.26, 95% CI 0.08 to 0.43, 11 studies, 1143 women) and a significantly longer duration of gonadotrophin use (mean difference (MD) 0.65, 95% CI 0.46 to 0.84, 10 studies, 1033 women).Study quality was unclear due to poor reporting. Only four studies reported live births as an outcome and only five described adequate methods for concealment of allocation.Authors' conclusionsWe found no evidence of a significant difference between depot and daily GnRHa use for pituitary down regulation in IVF cycles using the long protocol, but substantial differences could not be ruled out. Since depot GnRHa requires more gonadotrophins and a longer duration of use, it may increase the overall costs of IVF treatment.Cochrane Menstrual Disorders and Subfertility Group, New ZealandBrazilian Cochrane Center, BrazilFertivitro Ctr Reprod Humana, Human Reprod Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilSanta Casa Campo Mourao, Dept Med, Campo Mourao, BrazilCtr Reprod Humana Fertivitro, IVF Lab, São Paulo, BrazilCtr Estudos Med Baseada Evidencias & Avaliacao Te, Brazilian Cochrane Ctr, São Paulo, BrazilUniversidade Federal de São Paulo, São Paulo, BrazilWeb of Scienc

iNOS-derived Nitric Oxide Modulates Infection-stimulated Bone Loss

Nitric oxide (NO) derived from inducible nitric oxide synthase (iNOS) plays an important role in host defense, as well as in inflammation-induced tissue lesions. Here we evaluated the role of NO in bone loss in bacterial infection-induced apical periodontitis by using iNOS-deficient mice (iNOS(-/-)). The iNOS(-/-) mice developed greater inflammatory cell recruitment and osteolytic lesions than WT mice. Moreover, tartrate-resistant acid-phosphatase-positive (TRAP(+)) osteoclasts were significantly more numerous in iNOS-/- mice. Furthermore, the increased bone resorption in iNOS(-/-) mice also correlated with the increased expression of receptor activator NF-kappaB (RANK), stromal-cell-derived factor-1 alpha (SDF-1 alpha/CXCL12), and reduced expression of osteoprotegerin (OPG). These results show that NO deficiency was associated with an imbalance of bone-resorption-modulating factors, leading to severe infection-stimulated bone loss.Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)undacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP), Brazi