Pooled Mean Change Research Articles

The physiological effects of concurrent strength and endurance training sequence: A systematic review and meta-analysis

ABSTRACTWe conducted a systematic literature review and meta-analysis to assess the chronic effects of the sequence of concurrent strength and endurance training on selected important physiological and performance parameters, namely lower body 1 repetition maximum (1RM) and maximal aerobic capacity (VO2max/peak). Based on predetermined eligibility criteria, chronic effect trials, comparing strength-endurance (SE) with endurance-strength (ES) training sequence in the same session were included. Data on effect sizes, sample size and SD as well other related study characteristics were extracted. The effect sizes were pooled using, Fixed or Random effect models as per level of heterogeneity between studies and a further sensitivity analyses was carried out using Inverse Variance Heterogeneity (IVHet) models to adjust for potential bias due to heterogeneity. Lower body 1RM was significantly higher when strength training preceded endurance with a pooled mean change of 3.96 kg (95%CI: 0.81 to 7.10 kg). However, the training sequence had no impact on aerobic capacity with a pooled mean difference of 0.39 ml.kg.min−1 (95%CI: −1.03 to 1.81 ml.kg.min−1). Sequencing strength training prior to endurance in concurrent training appears to be beneficial for lower body strength adaptations, while the improvement of aerobic capacity is not affected by training order.

Renal safety of catheter-based renal denervation: systematic review and meta-analysis.

Catheter-based renal denervation (RDN) is a possible treatment to lower blood pressure. The invasive nature of RDN and the use of contrast agents raise concerns about potential consequent kidney damage. Our objective was to determine the change in renal function after RDN by performing a systematic review on hypertensive patients treated with RDN. A systematic search was performed in the Embase and MEDLINE databases to identify studies reporting on the effects of catheter-based RDN on renal outcome. Studies published between January 2009 and May 2016, irrespective of study design, device used or indication for treatment were included. We performed random effects meta-analyses on the change in estimated glomerular filtration rate (eGFR), serum creatinine, serum cystatin C and albumin:creatinine ratio after RDN. We only extracted and meta-analysed data from patients treated with RDN. From 1034 citations, 52 studies (38 cohort studies, 4 non-randomized comparative studies and 10 randomized controlled trials) reporting on 56 RDN cohorts were included in meta-analyses and another 14 studies in a qualitative review. Of these 56 cohorts, 48 were specifically eligible for determining the change in eGFR after RDN, totaling 2381 patients. There was no statistically significant change in eGFR after a mean follow-up time of 9.1 ± 7.0 months [0.64 mL/min/1.73 m 2 (95% confidence interval -0.47 to 1.76), P = 0.26]. The pooled mean change in serum creatinine and the results of the qualitative review further supported these findings. Based on meta-analyses of 52 studies and a qualitative review of an additional 14 studies, reporting on 2898 patients in total, we conclude that renal function does not significantly change up to at least 9 months after RDN.

The association between consistent licorice ingestion, hypertension and hypokalaemia: a systematic review and meta-analysis.

There have been numerous case reports of severe adverse events including deaths following chronic licorice ingestion. The aim of the present study was to evaluate the effect of chronic ingestion of licorice on blood pressure, plasma potassium, plasma renin activity and plasma aldosterone. A search of MEDLINE, PubMed, EMBASE, CENTRAL, DARE, CINAHL and Current Contents Connect was performed from inception through to 26 April 2017. Trials that included a treatment group ingesting a product containing at least 100 mg of glycyrrhizic acid daily were selected. Pooled mean changes from baseline with 95% confidence intervals were calculated for diastolic blood pressure, systolic blood pressure, plasma potassium, plasma renin activity and plasma aldosterone using a random effects model. An assessment of dose-response was also undertaken. A total of 18 studies (n=337) were included in the meta-analysis. There was a statistically significant increase in mean systolic blood pressure (5.45 mm Hg, 95% CI 3.51-7.39) and diastolic blood pressure (3.19 mm Hg, 95% CI 0.10-6.29) after chronic ingestion of a product containing glycyrrhizic acid. Plasma potassium (-0.33 mmol l-1, 95% CI -0.42 to 0.23), plasma renin activity (-0.82 ngml-1 per hour, 95% CI -1.27 to -0.37) and plasma aldosterone (-173.24 pmol l-1, 95% CI -231.65 to -114.83) were all significantly decreased. A significant correlation was noted between daily dose of glycyrrhizic acid and systolic blood pressure (r2=0.55) and diastolic blood pressure (r2=0.65), but not for the other outcome measures. Hence, chronic licorice ingestion is associated with an increase in blood pressure and a drop in plasma potassium, even at modest doses. This is of particular relevance for individuals with existing cardiovascular disease.

Weight loss and carotid intima-media thickness-a meta-analysis.

Obesity is a risk factor for clinical cardiovascular disease, putatively via increased burden of atherosclerosis. It remains contentious as to whether weight loss in people with obesity is accompanied by a reduction in intima-media thickness, a noninvasive marker of subclinical atherosclerosis, consistent with a lowering of risk of cardiovascular events. A systematic literature search was performed to identify all surgical and nonsurgical weight loss interventions that reported intima-media thickness. A meta-analysis was undertaken to obtain pooled estimates for change in intima-media thickness. From the 3,197 articles screened, 9 studies were included in the meta-analysis, with a total of 393 participants who lost an average of 16 kg (95% CI 9.4-22.5) of body weight over an average follow-up of 20 months. The pooled mean change in carotid intima-media thickness was -0.03 mm (95% CI -0.05 to -0.01), which was similar between surgical and nonsurgical interventions. In people with obesity, weight loss was associated with a reduction in carotid intima-media thickness, consistent with a lowering in risk of cardiovascular events.

Tanezumab Reduces Pain in Women with Interstitial Cystitis/Bladder Pain Syndrome and Patients with Nonurological Associated Somatic Syndromes

We performed pooled analyses from 3 small, clinical trials of tanezumab in patients with urological chronic pelvic pain, including chronic prostatitis/chronic pelvic pain syndrome and interstitial cystitis/bladder pain syndrome, to identify patient subpopulations more likely to benefit from tanezumab treatment. Pooled analyses included data from 208 patients with interstitial cystitis/bladder pain syndrome or chronic prostatitis/chronic pelvic pain syndrome randomized to placebo (104, 65 [62.5%] female) or tanezumab (104, 63 [60.6%] female) who received 1 dose or more of study medication. Data on tanezumab were from study A4091010 (interstitial cystitis/bladder pain syndrome) on 200 μg/kg intravenous, study A4091019 (chronic prostatitis/chronic pelvic pain syndrome) on 20 mg intravenous and study A4091035 (interstitial cystitis/bladder pain syndrome) on 20 mg subcutaneous. Primary study end points were evaluated using analysis of covariance with gender, study and baseline pain as covariates. For pooled analyses least squares mean (SE) change from baseline in 24-hour pain intensity vs placebo was -0.60 (0.24, 90% CI -0.99, -0.20) overall and -0.99 (0.32, p=0.002) and -0.17 (0.36, p=0.650) for females and males, respectively. The improvement in pain intensity was significant (p=0.011) for patients with symptoms suggesting the concomitant presence of nonurological associated somatic syndromes but not for those with pelvic pain symptoms only (p=0.507). Women with interstitial cystitis/bladder pain syndrome and patients with symptoms suggesting the concomitant presence of nonurological associated somatic syndromes were more likely to experience significant pain reduction with tanezumab than with placebo therapy. In contrast, no difference was reported in response between tanezumab and placebo therapy for men with chronic prostatitis/chronic pelvic pain syndrome symptoms only.

Association of obesity and inflammatory marker levels on treatment outcome: results from a double-blind, randomized study of adjunctive L-methylfolate calcium in patients with MDD who are inadequate responders to SSRIs.

Adjunctive treatment with L-methylfolate calcium significantly improved treatment outcomes in patients with major depressive disorder (MDD) and an inadequate response to antidepressants. This post hoc exploratory analysis evaluated baseline concentrations of cytokines (interleukin [IL]-1α, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-13, and IL-17; tumor necrosis factor α [TNF-α]; and interferon γ [IFN-γ]), high-sensitivity C-reactive protein (hsCRP), insulin, adiponectin and leptin and body mass index (BMI [kg/m2]) on L-methylfolate calcium treatment response. Adults with DSM-IV MDD and an inadequate response to a selective serotonin reuptake inhibitor (SSRI) were eligible. Patients were randomized 3:3:2 according to the sequential parallel comparison design to placebo versus placebo, placebo versus L-methylfolate calcium (15 mg/d), or L-methylfolate calcium versus L-methylfolate calcium (15 mg/d) during two 30-day phases. The primary outcome was change on the 17-item Hamilton Depression Rating Scale (HDRS-17). Treatment effect with 95% CIs was estimated from baseline concentrations of individual biomarkers and combinations. Cytokines were measured by immunoassay; adiponectin, insulin, and leptin by radioimmunoassay; and hsCRP by a standard turbidimetric assay. The effects of baseline biomarker levels (above and below the median) on outcome were analyzed. The first participant was enrolled July 14, 2009, and the last participant completed April 28, 2011. Mean change on HDRS-17 from baseline was significantly improved with L-methylfolate calcium versus placebo (pooled treatment effect, -2.74; 95% CI, -4.99 to -0.48; P = .017) overall and for those with baseline BMI ≥ 30 (pooled treatment effect, -4.66; 95% CI, -7.22 to -1.98; P = .001) but not BMI < 30. Pooled mean changes in depression across treatment for baseline levels of individual markers above median were significant (L-methylfolate calcium vs placebo) for TNF-α, IL-8, hsCRP, and leptin (pooled treatment effects, -4.33 to -3.94 [P ≤ .02]) and for combinations of BMI ≥ 30 with elevated levels of TNF-α, IL-6, IL-8, hsCRP, and leptin (pooled treatment effects, -6.31 to -3.98 [P ≤ .05]). In this exploratory analysis, inflammatory and obesity-related factors were associated with greater symptom improvement with L-methylfolate calcium. Combinations of BMI ≥ 30 with elevated IL-6, IL-8, hsCRP, TNF-α, and leptin predicted improved response to L-methylfolate calcium in MDD patients with an inadequate antidepressant response. Further studies are necessary to confirm these findings. ClinicalTrials.gov identifier: NCT00955955.

Association between fine particulate matter exposure and subclinical atherosclerosis: A meta-analysis.

Epidemiological studies in humans that have evaluated the association between fine particulate matter (PM2.5) and atherosclerosis have yielded mixed results. In order to further investigate this relationship, we conducted a comprehensive search for studies published through May 2014 and performed a meta-analysis of all available observational studies that investigated the association between PM2.5 and three noninvasive measures of clinical and subclinical atherosclerosis: carotid intima media thickness, arterial calcification, and ankle-brachial index. Five reviewers selected studies based on predefined inclusion criteria. Pooled mean change estimates and 95% confidence intervals were calculated using random-effects models. Assessment of between-study heterogeneity was performed where the number of studies was adequate. Our pooled sample included 11,947 subjects for carotid intima media thickness estimates, 10,750 for arterial calcification estimates, and 6497 for ankle-brachial index estimates. Per 10 µg/m(3) increase in PM2.5 exposure, carotid intima media thickness increased by 22.52 µm but this did not reach statistical significance (p = 0.06). We did not find similar associations for arterial calcification (p = 0.44) or ankle-brachial index (p = 0.85). Our meta-analysis supports a relationship between PM2.5 and subclinical atherosclerosis measured by carotid intima media thickness. We did not find a similar relationship between PM2.5 and arterial calcification or ankle-brachial index, although the number of studies was small.

Rotigotine in the treatment of primary restless legs syndrome: A meta-analysis of randomized placebo-controlled trials.

The aim of this study was to summarize the efficacy and tolerability of rotigotine in the treatment of primary restless legs syndrome (RLS). PubMed, EMBASE, and Cochrane Central Register of Controlled Trials (CENTRAL) were searched for English-language randomized controlled trials (RCTs) that assessed the effectiveness of rotigotine for RLS. The pooled mean change from baseline in International RLS (IRLS) Study Group Rating Scalescore and relative risk (RR) of response based on the Clinical Global Impression-Improvement (CGI-I) scale score were applied to evaluate the outcomes. The pooled proportions of adverse events (AEs) were also estimated. Six RCTs were included. The meta-analysis showed a favorable effectiveness of rotigotine versus placebo on RLS [mean change on IRLS score: mean difference (MD)=-4.80; 95% confidence interval (CI): -5.90 to -3.70; P<0.00001 and RR of response on CGI-I was 2.19; 95% CI: 1.86 to 2.58, P<0.00001]. The most common AEs were application site reactions, nausea, headache and fatigue. In general, rotigotine was well-tolerated in patients with primary RLS. Based on the findings from the meta-analysis, rotigotine was more significantly efficacious in the treatment of RLS than placebo. Nevertheless, long-term studies and more evidence of comparisons of rotigotine with other dopamine agonists are needed.

Comparative Efficacy of Radiofrequency and Laser Ablation for the Treatment of Benign Thyroid Nodules: Systematic Review Including Traditional Pooling and Bayesian Network Meta-analysis

To compare the efficacy of radiofrequency ablation (RFA) and laser ablation (LA) for treatment of benign solid thyroid nodules, using a systematic review including traditional pooling and Bayesian network meta-analysis. A comprehensive literature search in PubMed-MEDLINE, EMBASE, and the Cochrane Library databases identified prospective studies evaluating the percentage mean change [absolute mean change (mL)] in nodule volume after RFA or LA. Studies from January 1, 2000, to November 1, 2013, were included. Review of 128 potential papers, including a full-text review of 33, identified 10 eligible papers covering a total of 184 patients for meta-analysis. The percentage mean change [absolute mean change] in nodule volume over a 6-month follow-up was compared between RFA and LA. Based on the traditional frequentist approach, the pooled percentage mean changes (95% confidence interval) of RFA and LA were 76.1% (70.1-82.1) and 49.9% (41.4-58.5), respectively, and the pooled absolute mean changes (95% confidence interval) of RFA and LA were 8.9 mL (6.6-11.2) and 5.2 mL (4.3-6.1), respectively. Based on the Bayesian network meta-analysis, RFA achieved a larger pooled percentage mean change (95% credible interval) and absolute mean change (95% credible interval) compared to LA [77.8% (67.7-88.0) vs 49.5% (26.7-72.4), and 9.2 mL (5.8-11.9) vs 5.3 mL (2.1-8.5), respectively]. The RFA group has the highest probability of having the most efficacious treatment (98.7%). There were no major complications after either RFA or LA. RFA appears to be superior to LA in reducing benign solid thyroid nodule volume, despite the smaller number of treatment sessions without major side effects.

Effect of niacin on lipids and glucose in patients with type 2 diabetes: A meta-analysis of randomized, controlled clinical trials

This study aims to conduct a meta-analysis to evaluate the effects of niacin on serum lipids and glucose in patients with type 2 diabetes mellitus (T2DM). A comprehensive literature search in Medline, Scopus, AMED, Cochrane and Clinical trial registry databases was performed to identify randomized controlled trials investigating the effect of niacin on serum HDL cholesterol (HDL-c), LDL cholesterol (LDL-c), triglycerides (TG) and fasting plasma glucose (FPG). Pooled effects were measured by weighted mean difference (WMD) using fixed-effects or random-effects models. Quality assessment, and subgroup, meta-regression and sensitivity analyses were conducted using standard methods. Inter-study heterogeneity was assessed and quantified. The estimated pooled mean changes (95% confidence interval) with niacin were 0.27 (95% CI: 0.24 to 0.30; P < 0.001) mmol/L for HDL-c, -0.250 (95% CI: -0.47 to -0.03; P < 0.05) mmol/L for LDL-c and -0.39 (95% CI: -0.43 to -0.34; P < 0.001) mmol/L for TG compared with controls. There was a significant heterogeneity for the impact of niacin on LDL-c and FPG. Subgroup analyses revealed a significant increase in FPG 0.085 (95% CI: 0.029 to 0.141; P < 0.05) mmol/L compared with controls in patients with long term treatment. Our analysis also showed the absence of publication bias and any dose-response relations between niacin and effect size. Analysis of the results showed that niacin alone or in combination significantly improved lipid abnormalities in patients with TDM, but requires monitoring of glucose in long term treatment.

Effect of adjunctive L-methylfolate 15 mg among inadequate responders to SSRIs in depressed patients who were stratified by biomarker levels and genotype: results from a randomized clinical trial.

Specific genetic or biological markers may predict inadequate response to therapy for major depressive disorder (MDD). The objective of the current post hoc analysis was to evaluate the effect of specific biological and genetic markers on the antidepressant efficacy of adjunctive L-methylfolate 15 mg versus placebo from a trial of inadequate responders to selective serotonin reuptake inhibitors (SSRIs). The double-blind, randomized, placebo-controlled trial used the sequential parallel comparison design. Outpatients with SSRI-resistant MDD (DSM-IV criteria) received L-methylfolate 15 mg/d for 60 days, placebo for 30 days followed by L-methylfolate 15 mg/d for 30 days, or placebo for 60 days. The effects of baseline levels of select biological and genetic markers individually and combined on treatment response to L-methylfolate versus placebo were evaluated; the primary response measure was the 28-Item Hamilton Depression Rating Scale (HDRS-28). The first patient was enrolled July 14, 2009, and the last patient completed April 28, 2011. Seventy-five patients were enrolled. Patients with specific biological (body mass index ≥ 30 kg/m², elevated plasma levels of high-sensitivity C-reactive protein or 4-hydroxy-2-nonenal, low S-adenosylmethionine/S-adenosylhomocysteine ratio) and genetic markers at baseline had significantly (P ≤ .05) greater pooled mean change from baseline on the HDRS-28 with L-methylfolate versus placebo. Pooled mean change from baseline on the Clinical Global Impressions-Severity of Illness scale was significantly (P < .05) greater with L-methylfolate versus placebo for most genetic markers. Most combinations of baseline biological and genetic markers predicted significantly (P ≤ .05) greater reductions in pooled mean change from baseline in HDRS-28 scores with L-methylfolate versus placebo. Biomarkers associated with inflammation or metabolism and genomic markers associated with L-methylfolate synthesis and metabolism may identify patients with SSRI-resistant depression who are responsive to adjunctive therapy with L-methylfolate 15 mg. Confirmatory studies are needed. ClinicalTrials.gov identifier: NCT00955955.

A systematic review and meta-analysis of randomized controlled trials investigating the effects of curcumin on blood lipid levels

Curcumin is a polyphenolic natural compound with diverse and attractive biological activities. There has been in-vitro, preclinical and clinical evidence on the cardioprotective and lipid-lowering effects of curcumin. The present review aimed to systematically review and meta-analyze current clinical evidence on the effects of curcumin supplementation on blood lipids. A comprehensive literature search in Medline, Scopus, AMED, Cochrane and clinical trial registry databases was performed to identify randomized controlled trials investigating the effect of curcumin on any component of serum lipid profile including total cholesterol, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides. Meta-analysis of eligible studies was conducted using a random-effects approach. Five studies comprising 10 treatment arms (n = 133 in the curcumin and 90 in the control group) fulfilled the inclusion criteria. Meta-analysis of findings did not indicate a significant effect of curcumin on any of the lipid parameters. The estimated pooled mean changes (95% confidence interval) following curcumin supplementation were 8.97 (95% CI: -4.56 to 22.51) mg/dL (for total cholesterol; p = 0.19); 16.15 (-4.43 to 36.74) mg/dL (for LDL-C; p = 0.12); -0.59 (-1.66 to 0.49) mg/dL (for HDL-C; p = 0.28) and -1.29 (-9.05 to 6.48) mg/dL (for triglycerides; p = 0.75). In the same manner, subgroup analysis of studies on patients at cardiovascular risk did not indicate any significant effect of curcumin on circulating lipid levels. There was a significant heterogeneity for the impact of curcumin on total cholesterol, LDL-C and triglycerides but not HDL-C. In light of the present meta-analysis, curcumin supplementation has apparently no effect on serum total cholesterol, LDL-C, triglycerides and HDL-C levels when considering heterogeneous populations. However, further randomized controlled trials with longer supplementation duration, and bioavailability-improved formulations of curcumin are warranted to be conducted in dyslipidemic subjects for a more robust assessment of the lipid-modulating properties of this phytochemical.

Vascular Endothelial Growth Factor Inhibitors for Treatment of Corneal Neovascularization

To evaluate the therapeutic effect of bevacizumab (Avastin) on corneal neovascularization (NV). Systematic review and meta-analysis of the literature was performed. Seven eligible clinical human studies and 18 eligible experimental animal studies examining the effectiveness of bevacizumab treatment on corneal NV were included in the meta-analysis. Pertinent publications were identified through a systematic search of PubMed. All references of relevant reviews and eligible articles were also screened, and data were extracted from each eligible study. The random-effects model (of DerSimonian and Laird) was used to combine the results from the selected studies. Heterogeneity was explored using available data. Publication bias was also assessed. A significant reduction of corneal neovascularized area was seen in clinical human studies, with a pooled reduction of 36% [95% confidence interval (CI), 18%-54%] overall, of 32% (95% CI, 10%-54%) for subconjunctival anti-vascular endothelial growth factor injections, and 48% (95% CI, 32%-65%) for topical treatment. Pooled mean change in best-corrected visual acuity showed an improvement in best-corrected visual acuity by 0.04. The summary standardized mean difference in animal studies indicated a statistically significant reduction in the area of corneal NV when treated with bevacizumab compared with the control group by -1.71 (95% CI, -2.12 to -1.30). The subtotal pooled standardized mean differences were -1.83 (95% CI, -2.38 to -1.28) for subconjunctival anti-vascular endothelial growth factor injections and -1.50 (95% CI, -1.88 to -1.12) for topical treatment. Our results suggest that both topical and subconjunctival bevacizumab achieve significant reduction in the area of corneal NV. This meta-analysis provides an evidential basis for the new therapeutic concept of treating corneal NV with antiangiogenic therapy.

462 – Quetiapine monotherapy in acute phase for major depressive disorder: a metaanalysis of randomized, placebo-controlled trials

Introduction The efficacy, acceptability and/or tolerability of available antidepressants are not yet satisfactory. Objectives This meta-analysis aimed to summarize the efficacy, acceptability and tolerability of quetiapine treatment for MDD. Method MEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Efficacy outcomes were pooled mean changed scores of the standard depressive rating scales. The overall discontinuation rate and discontinuation rate due to adverse events were considered as the measure of acceptability and tolerability, respectively. Results A total of 1497 participants in three published RCTs were included. The pooled mean changed score of the Montgomery-Asberg Depression Rating Scale and Hamilton Depression Rating Scale of the quetiapine-treated group were higher than those of the placebo-treated group with WMDs (95%CI) of 3.37 (-3.95, -2.79) and -2.46 (-3.47, -1.45), respectively. The overall response and remission rates were greater in the quetiapine-treated group with RRs (95%CIs) of 1.44 (1.26, 1.64) and 1.37 (1.12, 1.68), respectively. The pooled overall discontinuation rate was not different between groups with an RR (95%CI) of 1.16 (0.97, 1.39). The pooled discontinuation rate due to adverse event was greater in the quetiapine group with an RR (95%CI) of 2.90 (1.87, 4.48). The pooled mean change Pittsburgh Sleep Quality Index scores was also higher in the quetiapine-treated group [WMD (95%CI) of -1.21 (-1.81, -0.61)]. Conclusions Quetiapine XR is effective for the treatment of MDD. These patients may not accept and tolerate this agent well. Its advantage on sleep improvement may be of benefit for patients with MDD.

Quetiapine monotherapy in acute phase for major depressive disorder: a meta-analysis of randomized, placebo-controlled trials

BackgroundSchizophrenia and bipolar depression trials suggest that quetiapine may have an antidepressant effect.ObjectivesThis meta-analysis aimed to determine the efficacy, acceptability and tolerability of quetiapine treatment for major depressive disorder (MDD). Only the randomized controlled trials (RCTs) comparison between quetiapine and placebo were included. The authors searched such clinical trials carried out between 1991 and February 2012.Data sourcesMEDLINE, EMBASE, CINHL, PsycINFO and Cochrane Controlled Trials Register were searched in February 2012. Study populations comprised adults with MDD or major depression.Study eligible criteria, participants and interventionsEligible studies were randomized, placebo-controlled trials of quetiapine monotherapy carried out in adults with MDD and presenting endpoint outcomes relevant to: i) depression severity, ii) response rate, iii) overall discontinuation rate, or iv) discontinuation rate due to adverse events. No language restriction was applied.Study appraisal and synthesis methodsAll abstracts identified by the electronic searches were examined. The full reports of relevant studies were assessed, and the data of interest were extracted. Based on the Cochrane methods of bias assessment, risks of bias were determined. The studies with two risks or less were included. The efficacy outcomes were the mean change scores of depression rating scales, the overall response rate, and the overall remission rates. The overall discontinuation rate was considered as a measure of acceptability. The discontinuation rate due to adverse events was a measure of tolerability. Relative risks (RRs) and weighted mean differences (WMDs) with 95% confidence intervals (CIs) were computed by using a random effect model.ResultsA total of 1,497 participants in three RCTs were included. All trials examined the quetiapine extended-release (XR). The pooled mean change scores of the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Depression Rating Scale (HAM-D) of the quetiapine-treated group were higher than those of the placebo-treated group with the WMDs (95%CI) of -3.37 (-3.95, -2.79) and -2.46 (-3.47, -1.45), respectively. All studies defined the response and remission as ≥ 50% reduction of the MADRS total score and the MADRS total score of ≤8 at endpoint, respectively. The overall response and remission rates were significantly greater in the quetiapine-treated group with RRs (95%CIs) of 1.44 (1.26, 1.64) and 1.37 (1.12, 1.68), respectively. The pooled discontinuation rate was not significantly different between groups with an RR (95%CI) of 1.16 (0.97, 1.39). The pooled discontinuation rate due to adverse event was greater in the quetiapine group with an RR (95%CI) of 2.90 (1.87, 4.48). With respect to sleep time, the pooled mean change Pittsburgh Sleep Quality Index (PSQI) scores of the quetiapine-treated group was also significantly higher than that of the placebo-treated group [WMD (95%CI) of -1.21 (-1.81, -0.61)].LimitationsVariety of quetiapine XR doses and the small number of RCTs were key limitations of this meta-analysis.ConclusionsBased on the limited evidence obtained from three RCTs, quetiapine XR is effective for adult patients with MDD. The high dropout rate due to adverse events suggests that some MDD patients may not be able to tolerate quetiapine XR. Due to the balance of its efficacy benefit and risk of side effects, as the overall discontinuation rate shown, the acceptability of this agent is not more than placebo. These results should be viewed as the very preliminary one. Further studies in this area are warranted.Implication of key findingsQuetiapine may be an alternative antidepressant. However, both risk and benefit of this agent should be taken into account for an individual patient with MDD.

Efficacy of antidepressants: a re-analysis and re-interpretation of the Kirsch data

Recently there has been much debate on the true usefulness of antidepressant therapy especially after the publication of a meta-analysis by Kirsch et al. (PLoS Medicine 2008, 5, e45). The aim of the current paper was to recalculate and re-interpret the data of that study. Effect-size and mean-score changes were calculated for each agent separately as well as pooled effect sizes and mean changes on the basis of the data reported by Kirsch et al. The weighted mean improvement was (depending on the method of calculation) 10.04 or 10.16 points on the Hamilton Depression Rating Scale (HAMD) in the drug groups, instead of 9.60, and thus the correct drug-placebo difference is 2.18 or 2.68 instead of 1.80. Kirsch et al. failed to report that that the change in HAMD score was 3.15 or 3.47 points for venlafaxine and 3.12 or 3.22 for paroxetine, which are above the NICE threshold. Still the figures for fluoxetine and nefazodone are low. Thus it seems that the Kirsch et al.'s meta-analysis suffered from important flaws in the calculations; reporting of the results was selective and conclusions unjustified and overemphasized. Overall the results suggest that although a large percentage of the placebo response is due to expectancy this is not true for the active drug and effects are not additive. The drug effect is always present and is unrelated to depression severity, while this is not true for placebo.

Intravesical Oxybutynin for Children With Poorly Compliant Neurogenic Bladder: A Systematic Review

Children with neurogenic bladder and poor bladder compliance are usually treated with bladder catheterization and oral anticholinergic medication. They may become nonresponders to the drug or present with severe side effects. We evaluated the effectiveness and tolerability of intravesical oxybutynin in children with poorly compliant neurogenic bladder. We conducted a search of MEDLINE, EMBASE, CINAHL, SciELO, dissertations/theses in ProQuest, LILACS, the Cochrane Library, protocol registries and the gray literature. Two reviewers independently assessed study quality and extracted data. Eight studies (2 prospective, 6 retrospective) assessed the effectiveness and side effects of intravesical oxybutynin in children with neurogenic bladder. A total of 297 children started treatment, of whom 22% (66 patients) discontinued therapy, with 9% (28) quitting due to systemic side effects. Mean change in bladder compliance (primary outcome) was reported in only 2 studies (+7.4 and +7.5 ml/cm H(2)O). The pooled mean change in pressure at maximum bladder capacity was -16.4 cm H(2)O (95% CI -22.8 to -10.0). Incontinence improved significantly in most studies, with "dry and improved" rates ranging from 61% to 83%. The funnel plot of pressure at maximum bladder capacity suggested no publication bias. Adjunctive intravesical oxybutynin therapy increased mean maximum bladder capacity and decreased bladder pressure in children with neurogenic bladder. However, identified studies offered a low level of evidence, with most being poorly reported retrospective case series with potential biases. Although the incidence of side effects was lower with the intravesical route, side effects are still possible and should be discussed with patients and families. The evidence available is insufficient to recommend this therapy. Research of more sound study design such as a randomized controlled trial should be conducted to assess the efficacy and side effects of intravesical oxybutynin in children.

Ocular symptom reduction in patients with seasonal allergic rhinitis treated with the intranasal corticosteroid mometasone furoate

Allergic rhinitis (AR) is more appropriately termed allergic rhinoconjunctivitis owing to the equally bothersome nasal and ocular symptoms. Extensive evidence supports the ability of intranasal corticosteroids to reduce nasal symptoms of AR, although less evidence is available to define clearly their impact on allergic conjunctivitis. To determine the effect of the intranasal corticosteroid mometasone furoate nasal spray (NS) on the ocular symptoms of seasonal AR. This retrospective pooled analysis of 4 placebo-controlled clinical studies randomized patients 12 years and older with symptomatic seasonal AR to receive mometasone furoate NS, 200 microg once daily (n = 491), or placebo (n = 492). Ocular symptom (eye tearing [epiphora], itching [pruritus], and redness [erythema]) severity was rated by patients twice daily on a 4-point scale (0 = none to 3 = severe) in the morning and evening, with scores averaged to obtain a daily mean score. Efficacy variables were the pooled mean change from baseline in the averaged morning and evening total ocular symptom score (TOSS) and the individual ocular symptom scores. The change in mean TOSS from baseline to days 1 to 15 was -1.33 (-19.8%) with mometasone furoate NS and -0.93 (-5.6%) with placebo (P < .001). Improvements in individual symptoms were significantly better with mometasone furoate NS than with placebo on days 2 (tearing) and 4 (itching and redness). A slightly greater reduction in TOSS was seen with mometasone furoate NS treatment in the evening than in the morning. This detailed analysis of an intranasal corticosteroid on individual ocular symptoms supports the positive impact of mometasone furoate NS on ocular symptoms.

Exogenous pulmonary surfactant for the treatment of adult patients with acute respiratory distress syndrome: results of a meta-analysis

IntroductionThe purpose of this study was to perform a systematic review and meta-analysis of exogenous surfactant administration to assess whether this therapy may be useful in adult patients with acute respiratory distress syndrome.MethodsWe performed a computerized literature search from 1966 to December 2005 to identify randomized clinical trials. The primary outcome measure was mortality 28–30 days after randomization. Secondary outcome measures included a change in oxygenation (PaO2:FiO2 ratio), the number of ventilation-free days, and the mean duration of ventilation. Meta-analysis was performed using the inverse variance method.ResultsTwo hundred and fifty-one articles were identified. Five studies met our inclusion criteria. Treatment with pulmonary surfactant was not associated with reduced mortality compared with the control group (odds ratio 0.97; 95% confidence interval (CI) 0.73, 1.30). Subgroup analysis revealed no difference between surfactant containing surface protein or not – the pooled odds ratio for mortality was 0.87 (95% CI 0.48, 1.58) for trials using surface protein and the odds ratio was 1.08 (95% CI 0.72, 1.64) for trials without surface protein. The mean difference in change in the PaO2:FiO2 ratio was not significant (P = 0.11). There was a trend for improved oxygenation in the surfactant group (pooled mean change 13.18 mmHg, standard error 8.23 mmHg; 95% CI -2.95, 29.32). The number of ventilation-free days and the mean duration of ventilation could not undergo pooled analysis due to a lack of sufficient data.ConclusionExogenous surfactant may improve oxygenation but has not been shown to improve mortality. Currently, exogenous surfactant cannot be considered an effective adjunctive therapy in acute respiratory distress syndrome.

Tanzanian Forest Edge Microclimatic Gradients: Dynamic Patterns1

ABSTRACTAir temperature, vapor pressure deficit, and light intensity microclimatic gradients were examined along four forest edge and four paired forest interior transects in the East and West Usambara Mountains, Tanzania. Between 14 August 1995 and 11 August 1998, 287, 282, and 196 air temperature, vapor pressure deficit, and light intensity gradients, respectively, were measured along the four forest edge and four interior transects. The relationship between microclimate and distance from the forest edge was examined using piecewise linear regression. All microclimatic gradients were classified into one of nine shapes based on the sign and the size of the two estimated slopes. The relative frequency in the shapes of 65 percent of air temperature gradients, 52 percent of vapor pressure deficit gradients, and 62 percent of light intensity gradients along forest edge transects exceeded the relative frequency of these same shapes along forest interior transects, indicating that a majority of the forest edge microclimatic gradients measured were influenced by edge effects. Yet this result also indicated that approximately one‐third of all air temperature and light intensity gradients and nearly one‐half of all vapor pressure deficit gradients recorded during this study were affected by factors independent of edge effects per se, and that forest edge microclimatic gradients were temporally nonconstant. For air temperature and vapor pressure deficit gradients, low spatial but high temporal variation existed in estimated edge width and the relative change in microclimate between the forest edge and interior. For light intensity gradients, both high spatial and temporal variability characterized estimated edge width and relative change in microclimate between the forest edge and interior. The pooled mean edge width and relative change in microclimate between die forest edge and interior across the four forest edge transects for air temperature, vapor pressure deficit, and light intensity gradients were 94.1 m and 2.00°C, 82.6 m and 0.29 kPa, and 60.5 m and 10.6 joules/sec/m2, respectively. These results suggest that forest edge microclimatic gradients in general may be inherently dynamic and nonconstant.