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Jean-yves Reginster - One of the best experts on this subject based on the ideXlab platform.
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Vitamin D Analogs Versus Native Vitamin D in Preventing Bone Loss and Osteoporosis-Related Fractures: A Comparative Meta-analysis
Calcified Tissue International, 2005Co-Authors: Florent Richy, Erich Schacht, Olivier Bruyère, Olivier Ethgen, M. Gourlay, Jean-yves ReginsterAbstract:It has been suggested that early postmenopausal women and patients treated with steroids should receive preventive therapy (calcium, vitamin D, vitamin D analogs, estrogens, or bisphosphonates) to preserve their bone mineral density (BMD) and to avoid fragility fractures. We designed the present study to compare the effects of native vitamin D to its hydroxylated analogs alfacalcidol 1-α(OH)D and calcitriol 1,25(OH)_2D. All randomized, controlled, double-blinded trials comparing oral native vitamin D and its analogs, alfacalcidol or calcitriol, to Placebo or head-to-head trials in primary or corticosteroids-induced osteoporosis were included in the meta-analysis. Sources included the Cochrane Controlled Trials Register, EMBASE, MEDLINE, and a hand search of abstracts and references lists. The study period January 1985 to January 2003. Data were abstracted by two investigators, and methodological quality was assessed in a similar manner. Heterogeneity was extensively investigated. Results were expressed as effect-size (ES) for bone loss and as rate difference (RD) for fracture while allocated to active treatment or control. Publication bias was investigated. Fourteen Studies of native vitamin D, nine of alfacalcidol, and ten of calcitriol fit the inclusion criteria. The two vitamin D analogs appeared to exert a higher preventive effect on bone loss and fracture rates in patients not exposed to glucocorticoids. With respect to BMD, vitamin D analogs versus Placebo Studies had an ES of 0.36 ( P < 0.0001), whereas native vitamin D versus Placebo had an ES of 0.17 ( P = 0.0005), the interclass difference being highly significant (ANOVA-1, P < 0.05). When restricted to the lumbar spine, this intertreatment difference remained significant: ES = 0.43 ( P = 0.0002) for vitamin D analogs and ES = 0.21 ( P = 0.001) for native vitamin D (analysis of variance [ANOVA-1], P = 0.047). There were no significant differences regarding their efficacies on other measurement sites (ANOVA-1, P = 0.36). When comparing the adjusted global relative risks for fracture when allocated to vitamin D analogs or native vitamin D, alfacalcidol and calcitriol provided a more marked preventive efficacy against fractures: RD = 10% (95% Confidence interval [CI-2] to 17) compared to RD = 2% (95% CI, 1 to 2), respectively. The analysis of the spinal and nonspinal showed that fracture rates differed between the two classes, thereby confirming the benefits of vitamin D analogs, with significant 13.4% (95% CI 7.7 to 19.8) and. 6% (95% CI 1 to 12) lower fracture rates for vitamin D analogs, respectively. In patients receiving corticosteroid therapy, both treatments provided similar global ESs for BMD: ES = 0.38 for vitamin D analogs and ES = 0.41 for native vitamin D (ANOVA-1, P = 0.88). When restriced to spinal BMD, D analogs provided significant effects, whereas native vitamin D did not: ES = 0.43 ( P < 0.0001) and ES = 0.33 ( P = 0.21), respectively. The intertreatment difference was nonsignificant (ANOVA-1, P = 0.52). Neither D analogs for native vitamin D significantly prevented fractures in this subcategory of patients: RD = 2.6 (95%CI, −9.5 to 4.3) and RD = 6.4 (95%CI, −2.3 to 10), respectively. In head-to-head Studies comparing D analogs and native vitamin D in patients receiving corticosteroids, significant effects favoring D analogs were found for femoral neck BMD: ES = 0.31 at P = 0.02 and spinal fractures: RD = 15% (95%CI, 6.5 to 25). Publication bias was not significant. Our analysis demonstrates a superiority of the D analogs atfacalcidol and calcitriol in preventing bone loss and spinal fractures in primary osteoporosis, including postmenopausal women. In corticosteroid-induced osteoporosis, the efficacy of D analogs differed depending on the comparative approach: indirect comparisons led to nonsignificant differences, whereas direct comparison did provide significant differences. In this setting, D analogs seem to prevent spinal fractures to a greater extent than do native vitamin D, but this assumption should be confirmed on a comprehensive basis in multiarm Studies including an inactive comparator.
Florent Richy - One of the best experts on this subject based on the ideXlab platform.
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Vitamin D Analogs Versus Native Vitamin D in Preventing Bone Loss and Osteoporosis-Related Fractures: A Comparative Meta-analysis
Calcified Tissue International, 2005Co-Authors: Florent Richy, Erich Schacht, Olivier Bruyère, Olivier Ethgen, M. Gourlay, Jean-yves ReginsterAbstract:It has been suggested that early postmenopausal women and patients treated with steroids should receive preventive therapy (calcium, vitamin D, vitamin D analogs, estrogens, or bisphosphonates) to preserve their bone mineral density (BMD) and to avoid fragility fractures. We designed the present study to compare the effects of native vitamin D to its hydroxylated analogs alfacalcidol 1-α(OH)D and calcitriol 1,25(OH)_2D. All randomized, controlled, double-blinded trials comparing oral native vitamin D and its analogs, alfacalcidol or calcitriol, to Placebo or head-to-head trials in primary or corticosteroids-induced osteoporosis were included in the meta-analysis. Sources included the Cochrane Controlled Trials Register, EMBASE, MEDLINE, and a hand search of abstracts and references lists. The study period January 1985 to January 2003. Data were abstracted by two investigators, and methodological quality was assessed in a similar manner. Heterogeneity was extensively investigated. Results were expressed as effect-size (ES) for bone loss and as rate difference (RD) for fracture while allocated to active treatment or control. Publication bias was investigated. Fourteen Studies of native vitamin D, nine of alfacalcidol, and ten of calcitriol fit the inclusion criteria. The two vitamin D analogs appeared to exert a higher preventive effect on bone loss and fracture rates in patients not exposed to glucocorticoids. With respect to BMD, vitamin D analogs versus Placebo Studies had an ES of 0.36 ( P < 0.0001), whereas native vitamin D versus Placebo had an ES of 0.17 ( P = 0.0005), the interclass difference being highly significant (ANOVA-1, P < 0.05). When restricted to the lumbar spine, this intertreatment difference remained significant: ES = 0.43 ( P = 0.0002) for vitamin D analogs and ES = 0.21 ( P = 0.001) for native vitamin D (analysis of variance [ANOVA-1], P = 0.047). There were no significant differences regarding their efficacies on other measurement sites (ANOVA-1, P = 0.36). When comparing the adjusted global relative risks for fracture when allocated to vitamin D analogs or native vitamin D, alfacalcidol and calcitriol provided a more marked preventive efficacy against fractures: RD = 10% (95% Confidence interval [CI-2] to 17) compared to RD = 2% (95% CI, 1 to 2), respectively. The analysis of the spinal and nonspinal showed that fracture rates differed between the two classes, thereby confirming the benefits of vitamin D analogs, with significant 13.4% (95% CI 7.7 to 19.8) and. 6% (95% CI 1 to 12) lower fracture rates for vitamin D analogs, respectively. In patients receiving corticosteroid therapy, both treatments provided similar global ESs for BMD: ES = 0.38 for vitamin D analogs and ES = 0.41 for native vitamin D (ANOVA-1, P = 0.88). When restriced to spinal BMD, D analogs provided significant effects, whereas native vitamin D did not: ES = 0.43 ( P < 0.0001) and ES = 0.33 ( P = 0.21), respectively. The intertreatment difference was nonsignificant (ANOVA-1, P = 0.52). Neither D analogs for native vitamin D significantly prevented fractures in this subcategory of patients: RD = 2.6 (95%CI, −9.5 to 4.3) and RD = 6.4 (95%CI, −2.3 to 10), respectively. In head-to-head Studies comparing D analogs and native vitamin D in patients receiving corticosteroids, significant effects favoring D analogs were found for femoral neck BMD: ES = 0.31 at P = 0.02 and spinal fractures: RD = 15% (95%CI, 6.5 to 25). Publication bias was not significant. Our analysis demonstrates a superiority of the D analogs atfacalcidol and calcitriol in preventing bone loss and spinal fractures in primary osteoporosis, including postmenopausal women. In corticosteroid-induced osteoporosis, the efficacy of D analogs differed depending on the comparative approach: indirect comparisons led to nonsignificant differences, whereas direct comparison did provide significant differences. In this setting, D analogs seem to prevent spinal fractures to a greater extent than do native vitamin D, but this assumption should be confirmed on a comprehensive basis in multiarm Studies including an inactive comparator.
Richard L Page - One of the best experts on this subject based on the ideXlab platform.
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fish oil and post operative atrial fibrillation a meta analysis of randomized controlled trials
Journal of the American College of Cardiology, 2013Co-Authors: Dariush Mozaffarian, Jason H Y Wu, Marcia C De Oliveira Otto, Chriag M Sandesara, Robert G Metcalf, Roberto Latini, Peter Libby, Federico Lombardi, Patrick T Ogara, Richard L PageAbstract:Post-operative atrial fibrillation (PoAF) is among the most common complications of cardiac surgery and substantially increases morbidity and health care costs. Despite decades of surgical, anesthetic, and medical advances, rates of PoAF remain largely unchanged. Experiments and animal models suggest that peri-operative fish oil (omega-3 fatty acids) may reduce PoAF.(1) We recently reported in a large, multinational randomized trial that peri-operative fish oil did not reduce PoAF.(2) Yet, several other trials have evaluated this question, with mixed results. Most of these trials were small, and some were open label, i.e. neither double-blind nor Placebo-controlled. To compile all peer-reviewed evidence and evaluate reasons for potential heterogeneity, we conducted a meta-analysis, following PRISMA guidelines, of randomized trials of fish oil for preventing PoAF. We searched MEDLINE from earliest available indexing through Oct 2012, without language restrictions. Search terms were ("fatty acids, omega-3"[MeSH] or "eicosapentaenoic acid"[MeSH/tiab] or "docosahexaenoic acids"[MeSH/tiab] or "fish oils"[MeSH] or "omega-3"[tiab] or "n-3"[tiab] or "long chain n-3"[tiab] or "fish oil"[tiab]) and ("atrial fibrillation"[MeSH/tiab]) and (“clinical trial”[MeSH/tiab] or “cardiac surgical procedures”[MeSH/tiab]). Additional Studies were identified through hand-searching citation lists and directly contacting experts. Studies were included if they were randomized trials of oral or intravenous fish oil administration that evaluated PoAF following cardiac surgery; trials with additional concomitant interventions, observational Studies, and duplicate publications were excluded. Inclusion/exclusion decisions and data extraction were performed in duplicate by two investigators. Findings were pooled using inverse-variance weighted meta-analysis.(3) Fixedeffects models were prespecified based on large differences in sample sizes and results across Studies, for which random-effects models could dramatically overweight small, imprecise Studies. Prespecified potential sources of heterogeneity included Placebo-control (yes/no) and type of surgery (valve surgery, yes/no). Of 83 identified abstracts, 8 full-text articles were retrieved for review. Eight randomized trials met inclusion criteria, including 2,687 subjects and 859 PoAF events (Figure). Heterogeneity was evident (I2=52%, Q-statistic=14.5, P-heterogeneity=0.04), principally owing to extreme results of two small, open-label (no Placebo) Studies. Presence or absence of Placebo-control significantly modified the effect of fish oil on PoAF (P-interaction=0.028): benefits were seen in open-label, but not Placebo-controlled, trials. Also, a preponderance of small trials with risk estimates below the pooled estimate suggested potential publication bias toward small positive trials. Little heterogeneity was evident among Placebo-controlled trials (I2=16%, Q-statistic=5.9, P-heterogeneity=0.31), which both individually and together demonstrated no significant effect (pooled OR=0.92, 95%CI=0.78–1.10). In sensitivity analyses, we removed each trial individually from the pooled meta-analysis. Finding were similar; for example, removing the large OPERA trial, the pooled OR in the remaining Placebo-controlled trials was 0.86 (95%CI=0.65–1.15; I2=28%, Q-statistic=5.6). We note that only two open-label trials were identified, so generalizability of these findings to other research questions should not be assumed. Yet, the variation in findings of small and especially open-label Studies highlights the importance of large, adequately powered, Placebo-controlled trials as well as appropriately performed meta-analyses such as the present report. Figure Randomized Controlled Trials of Peri-Operative Fish Oil Supplementation to Prevent Post-Operative Atrial Fibrillation In the large OPERA trial, subgroup analyses suggested a potential benefit of fish oil treatment in patients undergoing valve surgery (P-interaction=0.06).(2) We pooled these results with four other Placebo-controlled trials that provided data stratified by type of cardiac surgery. In sum, data were available on 856 patients who underwent valve surgery and experienced 336 PoAF events, and 1,249 patients not undergoing valve surgery who experienced 358 PoAF events. Pooling all data, effects of fish oil on PoAF did not significantly differ according to valve surgery (P-interaction=0.94): the OR was 0.91 (95%CI=0.76–1.09) in patients undergoing valve surgery and 1.00 (95%CI=0.78–1.28) in patients not undergoing valve surgery. Dosing and duration of fish oil treatment were generally similar among trials, limiting ability to explore heterogeneity by these factors. We evaluated pooled evidence for safety including numbers of patients with major bleeding, total mortality, and other reported serious adverse events. Fish oil was associated with less bleeding (N=165 events, data reported in 5 trials: OR=0.76, 95%CI=0.60–0.96; I2=34.1, Q-statistic= 6.1, P-heterogeneity=0.19), a nonsignificant trend toward lower mortality (N=32 events, data reported in 6 trials: OR=0.68, 95%CI=0.32–1.41; I2=0%, Q-statistic=1.98, P-heterogeneity= 0.58), and no difference in other reported serious adverse events (N=528 events, data reported in 6 trials: OR=1.0, 95%CI=0.81–1.25; I2=0%, Q-statistic=4.7, P-heterogeneity= 0.45) The unexpectedly lower bleeding risk could be due to chance. Conversely, this observation could plausibly relate to lower cardiopulmonary bypass-induced activation and loss of platelets and clotting factors;(4) further investigation of potential mechanisms is required. At the least, the observed lower bleeding risk counters concerns that anti-platelet effects of fish oil might increase blood loss during cardiac surgery. Overall, the findings indicate that peri-operative fish oil use was well-tolerated and safe, suggesting little need for its discontinuation in patients who are taking fish oil prior to cardiac surgery. In sum, our meta-analysis provides convincing evidence that short-term fish oil use does not appreciably reduce PoAF, and indicates that heterogeneity in prior findings results from extreme results of small, open-label trials as well as potential publication bias. In addition, we found little evidence for differing efficacy according to type of cardiac surgery. There is also little evidence that intermediate-term (<1 year) fish oil use reduces recurrent arrhythmias in patients with established AF.(5) Fish oil may still prove useful in other clinical contexts, such as long-term use (years) for preventing the initial onset of AF among ambulatory elderly adults with hypertension or other risk factors. Such primary, rather than secondary, prevention approaches must be tested in large, appropriately powered, Placebo-controlled clinical trials.
Suvitesh Luthra - One of the best experts on this subject based on the ideXlab platform.
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Systematic Review of Randomized Controlled Trials of Endothelin Receptor Antagonists for Pulmonary Arterial Hypertension
Lung, 2016Co-Authors: Michael Kuntz, Miguel M. Leiva-juarez, Suvitesh LuthraAbstract:Background There are currently three Food and Drug Administration approved endothelin receptor antagonists (ERAs): bosentan, ambrisentan, and macitentan. There is a growing body of evidence that demonstrates the beneficial effects of ERAs in patients with pulmonary arterial hypertension (PAH). Objectives To compare the available evidence from randomized clinical trials for specific outcomes of different endothelin antagonists for the treatment of PAH. Methods A multi-database search of randomized controlled trials up to March 15, 2016 was conducted for those that would measure functional parameters of patients with PAH treated with ERA monotherapy versus Placebo. Studies that analyzed 6-min walking distance, pulmonary vascular resistance, pulmonary arterial pressure, or WHO functional status were incorporated for analysis. A total of 15 trials and 2 subanalyses were compiled and quality and abovementioned outcomes were compared among Studies. Results A constant decrease in pulmonary vascular resistance and pulmonary arterial pressure was globally reported among the different Studies, resulting in increased 6-min walking distance and functional status compared to Placebo. Conclusions Although this evidence clearly shows the benefit of ERAs, Studies, which compare ERAs against one another and with other therapies for progressive PAH, have been lacking. Larger and longer Studies are necessary to define the role of ERAs as standalone agents and in combination therapies.
Renate Drechsle - One of the best experts on this subject based on the ideXlab platform.
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are treatment effects of neurofeedback training in children with adhd related to the successful regulation of brain activity a review on the learning of regulation of brain activity and a contribution to the discussion on specificity
Frontiers in Human Neuroscience, 2015Co-Authors: Agnieszka Zubere, Daniel Andeis, Renate DrechsleAbstract:While issues of efficacy and specificity are crucial for the future of neurofeedback training, there may be alternative designs and control analyses to circumvent the methodological and ethical problems associated with double-blind Placebo Studies. Surprisingly, most NF Studies do not report the most immediate result of their NF training, i.e., whether or not children with ADHD gain control over their brain activity during the training sessions. For the investigation of specificity, however, it seems essential to analyze the learning and adaptation processes that take place in the course of the training and to relate improvements in self-regulated brain activity across training sessions to behavioral, neuropsychological and electrophysiological outcomes. To this aim, a review of Studies on neurofeedback training with ADHD patients which include the analysis of learning across training sessions or relate training performance to outcome is presented. Methods on how to evaluate and quantify learning of EEG regulation over time are discussed. “Non-learning” has been reported in a small number of ADHD-Studies, but has not been a focus of general methodological discussion so far. For this reason, selected results from the brain-computer interface (BCI) research on the so-called “brain-computer illiteracy”, the inability to gain control over one’s brain activity, are also included. It is concluded that in the discussion on specificity, more attention should be devoted to the analysis of EEG regulation performance in the course of the training and its impact on clinical outcome. It is necessary to improve the knowledge on characteristic cross-session and within-session learning trajectories in ADHD and to provide the best conditions for learning.