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Guideline statements may be supported by evidence obtained from various study designs, but randomized trials are usually considered most important for making recommendations about therapeutic and preventive interventions. This study evaluated the extent to which randomized trials are cited in guidelines published in major journals. The references of 191 guidelines of therapeutic and/or preventive interventions published in Annals of Internal Medicine, BMJ, JAMA, Lancet, NEJM and Pediatrics in 1979, 1984, 1989, 1994, and 1999, were analyzed. The percentage of guidelines not citing any randomized controlled trials (RCTs) decreased gradually from 95% in 1979 to 53% in 1999. Among 4,853 references of the guidelines, there were 393 RCTs (8.1% of total), 19 systematic reviews (0.4%), and 23 meta-analyses of RCTs (0.5%). Among 19 guidelines published in 1999 or 1994 with <2 RCTs cited, in eight cases additional pertinent RCTs were identified that had not been cited by the guideline. There is a clear increase in the use of randomized evidence by guidelines over time. However, several guidelines in major journals still cite few or no RCTs.

Objectives: We conducted a systematic review and network meta-analysis of randomized controlled trials (RCTs) including the comparison of non-vitamin K antagonist oral anticoagulants (NOACs) with warfarin for patients with atrial fibrillation (AF).Design: Network meta-analysis. Two authors independently extracted data. All authors evaluated overall confidence in the evidence.Results: Eighteen RCTs included in our review, a total of 78,796 patients with AF, with sample sizes from 90 to 21,105 patients. Apixaban 5 mg (OR: 0.79, 95% CI: 0.66 to 0.95), dabigatran 110 mg (0.91, 0.74-1.12), dabigatran 150 mg (0.66, 0.53-0.82), edoxaban 60 mg (0.87, 0.74-1.02), and rivaroxaban 20 mg (0.88, 0.74-1.03) reduced the risk of stroke or systemic embolism compared with warfarin. Dabigatran 150 mg had the highest P-score for reducing stroke or systemic embolic events. The risk of haemorhagic stroke and all-cause mortality was lower with all NOACs than with warfarin. Apixaban 5 mg (0.69, 0.60-0.80), dabigatran 110 mg (0.80, 0.69-0.93), dabigatran 150 mg (0.93, 0.80-1.08), edoxaban 30 mg (0.46, 0.40-0.54), and edoxaban 60 mg (0.78, 0.69-0.90) reduced the risk of major bleeding compared with warfarin. Edoxaban 30 mg had the highest P-score for reducing major bleeding. The plots of P-scores rank showed that apixaban offered the most favorable balance of efficacy and safety.Conclusions: This study adds an attempt for treatment ranking of both efficacy and safety outcomes. Future trials comparing directly NOACs are needed in order to provide conclusive proofs for these results and not only circumstantial evidence offered by a network meta-analysis. [ABSTRACT FROM AUTHOR]

Linezolid is an oxazolidinone antibacterial agent, with activity against Gram-positive bacteria. This study aimed to evaluate the efficacy and safety of linezolid in children with infections caused by Gram-positive pathogens. A systematic search was conducted by two independent reviewers to identify published studies up to September 2013. The accumulated relevant literature was subsequently systematically reviewed, and a meta-analysis was conducted. Eligible studies were randomized controlled trials assessing the clinical efficacy and safety of linezolid in children versus other antimicrobial agents for infections caused by Gram-positive bacteria. The primary outcome was treatment success in patients who received at least one dose of study drug, had clinical evidence of disease, and had complete follow-up. Meta-analysis was conducted with random effects models because of heterogeneity across the trials. Two randomized controlled trials (RCTs), involving 815 patients, were included. Linezolid was slightly more effective than control antibiotic agents, but the difference was not statistically significant [odds ratio (OR) = 1.39, 95 % confidence interval (CI) 0.98-1.98]. Treatment with linezolid was not associated with more adverse effects in general (OR = 0.61, 95 % CI 0.25-1.48). Eradication efficiency did not differ between linezolid and control regimens, but the sample size for these comparisons was small. Conclusion: The use of linezolid cannot be steadily supported from the results of the current meta-analysis. It appears to be slightly more effective than control antibiotic agents, but the difference was not significant, and the serious limitations present in this study restrict its use. Further studies providing evidence for clinical and microbiological efficacy of linezolid will support its use. [ABSTRACT FROM AUTHOR]

Aim To compare 24 h intraocular pressure (IOP) control obtained with preservative free (PF) tafluprost 0.0015% versus branded preservative containing latanoprost 0.005% administered as first choice monotherapy in patients with primary open angle glaucoma (POAG) or ocular hypertension (OHT). Methods This prospective, observer-masked, crossover study included consecutive newly diagnosed patients with POAG or OHT, and baseline IOP between 24 and 33 mm Hg. Qualifying patients underwent baseline untreated 24 h IOP monitoring in habitual positions, with Goldmann tonometry at times 10:00, 14:00, 18:00 and 22:00, and Perkins supine tonometry at times 02:00 and 06:00. They were then randomised to either latanoprost or tafluprost, administered in the evening, for 3 months and then switched to the opposite therapy for another 3 months. 24 h monitoring was repeated at the end of each treatment period. Results 38 patients completed the study. Mean untreated 24 h IOP (24.9 mm Hg) was significantly reduced with both prostaglandins (p<0.001). Tafluprost demonstrated similar mean 24 h efficacy compared with latanoprost (17.8 vs 17.7 mm Hg; p=0.417). Latanoprost demonstrated significantly better 24 h trough IOP (15.9 vs 16.3 mm Hg; p=0.041) whereas tafluprost provided significantly lower 24 h IOP fluctuation (3.2 vs 3.8 mm Hg; p=0.008). No significant difference existed between the two prostaglandins for any adverse event. Conclusions PF tafluprost achieved similar 24 h IOP reduction to branded latanoprost. The current study highlights the importance of complete assessment of efficacy over 24 h. [ABSTRACT FROM AUTHOR]

Background: To determine the adjunctive 24-h efficacy obtained with brinzolamide/timolol, or brimonidine/timolol fixed combinations (FCs) in open-angle glaucoma patients insufficiently controlled on travoprost monotherapy. Methods: Prospective, observer-masked, active controlled, crossover, comparison. Qualified primary open-angle or exfoliative glaucoma patients with a baseline intraocular pressure (IOP) >18 mm Hg at 10:00 on travoprost monotherapy were randomized for 3 months to either brinzolamide/timolol, or brimonidine/timolol FC therapy adjunct to travoprost. Patients were then crossed-over to the opposite therapy for another 3 months. At baseline and at the end of each treatment period, the patients underwent 24-h IOP monitoring. Results: Fifty patients completed the study. The mean 24-h baseline IOP on travoprost monotherapy was 20.1 mm Hg [95% confidence interval (CI): 19.6, 20.7 mm Hg]. Both adjunctive FC therapies significantly reduced the IOP at each time point and for the mean 24-h IOP ( P<0.001) compared with travoprost monotherapy. Brinzolamide/timolol FC provided a significantly lower mean 24-h IOP (17.2 mm Hg, 95% CI: 16.4, 17.9 mm Hg) than brimonidine/timolol FC (18.0 mm Hg, 95% CI: 17.3, 18.8 mm Hg) ( P<0.001). For all the 3 timepoints between 18:00 and 02:00, the brinzolamide/timolol FC provided a significantly lower IOP than the brimonidine/timolol FC ( P≤0.036). For the other 3 timepoints, no significant differences were detected. Conclusions: This study demonstrated that both FCs provide statistically and clinically significant incremental 24-h IOP lowering to travoprost monotherapy. The brinzolamide/timolol FC however achieves a better mean 24-h IOP control owing to the greater efficacy in late afternoon and during the night. [ABSTRACT FROM AUTHOR]

Background The aim of our study was to assess the extent of late presentation for HIV care in Northern Greece during the period 2000 to 2010 and to explore correlations aiming to provide guidance for future interventions. Methods HIV-positive patients with no prior history of HIV care at presentation and with a CD4 T cell count within three months from the first confirmatory Western blot result were eligible for this study. Late presentation and advanced HIV disease were defined in concordance with the recommendations of the European Late Presenter Consensus working group. Time trends in presentation status and risk factors linked to late presentation and advanced HIV disease were identified in multivariable logistic regression models. Additional analyses after multiple imputation of missing values were performed to assess the robustness of our findings. Results The status at presentation was evaluated for 631 eligible HIV-positive individuals. Overall, 52.5% (95% CI: 48.6% to 56.4%) of patients presented late for HIV care and 31.2% (95% CI: 27.6% to 34.8%) presented with advanced HIV disease. Time trends were consistent with an improvement in the presentation status of our study population ( p<0.001). Risk factors associated with late presentation in multivariable logistic regression were intravenous drug use, heterosexual HIV transmission, immigrant status and age at diagnosis. Conclusions Despite the trend for improvement, a significant proportion of newly diagnosed HIV-positive patients present late for care. Targeted interventions with focus on social groups such as the elderly, persons who inject drugs, immigrants and individuals at risk for heterosexual HIV transmission are mandated. [ABSTRACT FROM AUTHOR]

Reports on a study to compare results of randomized and nonrandomized studies that evaluated medical interventions and to examine characteristics that may explain discrepancies between the studies. Context; Objectives; Data sources; Study selection; Data extraction; Data Synthesis; Conclusions.

Background: Guidelines published in major medical journals are very influential in determining clinical practice. It would be essential to evaluate whether conflicts of interests are disclosed in these publications. We evaluated the reporting of conflicts of interest and the factors that may affect such disclosure in a sample of 191 guidelines on therapeutic and/or preventive measures published in 6 major clinical journals (Annals of Internal Medicine, BMJ, JAMA, Lancet, New England Journal of Medicine, Pediatrics) in 1979, 1984, 1989, 1994 and 1999.Results: Only 7 guidelines (3.7%) mentioned conflicts of interest and all were published in 1999 (17.5% (7/40) of guidelines published in 1999 alone). Reporting of conflicts of interest differed significantly by journal (p=0.026), availability of disclosure policy by the journal (p=0.043), source of funding (p < 0.001) and number of authors (p=0.004). In the entire database of 191 guidelines, a mere 18 authors disclosed a total of 24 potential conflicts of interest and most pertained to minor issues.Conclusions: Despite some recent improvement, reporting of conflicts of interest in clinical guidelines published in influential journals is largely neglected. [ABSTRACT FROM AUTHOR]