Weighted Mean Difference Method Research Articles

Impact of statin therapy on coronary plaque burden and composition assessed by coronary computed tomographic angiography: a systematic review and meta-analysis.

To clarify the potential role of coronary computed tomographic angiography (CCTA) in assessing the remodelling impact of statin therapy on plaque burden and compositions. A systematic literature review and meta-analysis were conducted to examine the effect of statin therapy on different plaque volumes assessed by serial CCTA. Twelve studies were included with a mean (±standard deviation) follow-up period of 14.5 ± 9.5 months. Data on plaque volume were pooled using weighted mean difference method. Available data on a total of 199 intensive statin therapy receivers, 404 moderate statin therapy receivers and 189 controls (mean age = 62 ± 5 years, male gender = 78%) were meta-analysed. Intensive statin therapy reduced total plaque volume (TPV) by -20.87 [95% confidence interval (CI) -31.17, -10.56; P < 0.001] mm3, while moderate statin therapy reduced it by -1.67 (95% CI -9.99, 6.65; P = 0.69) mm3. In contrast TPV increased significantly in controls by 14.96 (95% CI 5.28, 24.64; P = 0.002) mm3. Percents of mean volume regression were -3.6% and -0.7% in intensive and moderate statin receivers, respectively, vs. +5.8% progression in controls. Statin therapy decreased non-calcified plaque volume by -7.62 (95% CI -17.38, 2.13; P = 0.124) mm3 and low attenuation plaque volume by -5.84 (95% CI -8.02, -3.66; P < 0.001) mm3. In statin therapy receivers, calcified plaque volume increased by 11.83 (95% CI 3.37, 20.29; P = 0.006) mm3 and calcium signal intensity increased by 21.99 (95% CI 9.2, 34.8; P < 0.001) Hounsfield units. Initial studies demonstrated CCTA's possible role in evaluating the effect of statin therapy on plaque volume and composition. Further studies are warranted to delineate the mechanisms behind plaque changes.

A systematic review and meta-analysis of plasma amyloid 1-42 and tau as biomarkers for Alzheimer's disease.

Objective:Amyloid 1-42 (Aβ42) and tau in cerebrospinal fluid are currently used as markers for diagnosis of Alzheimer’s disease. Conflicting reports exist regarding their plasma levels in Alzheimer’s disease patients. A meta-analysis was performed to statistically validate the use of plasma Aβ42 and tau as biomarkers for Alzheimer’s disease.Methods:Different databases were searched using the search key: (amyloid OR amyloid1-42 OR Aβ42) AND (tau OR total tau) AND plasma AND (alzheimer’s OR alzheimer’s disease), and for databases not accepting boolean search, records were retrieved using the search key: plasma + amyloid + tau + alzheimer’s. A total of 1880 articles for Aβ42 and 1508 articles for tau were shortlisted. The abstracts were screened, and 69 articles reporting plasma Aβ42 levels and 6 articles reporting plasma tau were identified. After exclusion, 25 studies reporting plasma Aβ42 and 6 studies reporting total tau were analysed in Review Manager version 5.2 using weighted mean difference method, and the bias between studies was assessed using the funnel plot.Results:Plasma Aβ42 and tau did not vary significantly between Alzheimer’s disease patients and controls. The funnel plot showed that there was no bias between studies for Aβ42, while possible bias existed for tau due to availability of limited studies.Conclusion:This analysis pinpoints that plasma Aβ42 and tau could not serve as reliable markers independently for diagnosis of Alzheimer’s disease and a cohort study with age, sex and apolipoprotein E correction is warranted for their possible use as Alzheimer’s disease markers.

Diagnostic Accuracy and Radiation Dose of CT Coronary Angiography in Atrial Fibrillation: Systematic Review and Meta-Analysis

To determine by means of a systematic review and meta-analysis the diagnostic accuracy, associated radiation dose, and technical challenges of computed tomographic (CT) coronary angiography in patients with atrial fibrillation. A systematic literature search was performed to compare CT angiography with conventional coronary angiography in patients with atrial fibrillation and to compare CT angiography in patients with atrial fibrillation with that in patients with sinus rhythm. The search yielded seven eligible studies (247 patients) in which CT angiography was compared with conventional coronary angiography. Six additional studies were found for the assessment of CT angiography in patients with atrial fibrillation (n = 158) and those with sinus rhythm (n = 416). Extracted data were analyzed for diagnostic accuracy parameters. Mean effective radiation doses in patients with atrial fibrillation were compared with those in patients with sinus rhythm by using the weighted mean difference method. The Quality Assessment of Diagnostic Accuracy Studies tool was used to assess the quality of the selected studies. At per-patient analysis of the diagnostic accuracy of CT angiography versus conventional coronary angiography, the sensitivity, specificity, positive predictive value, and negative predictive value were 94% (95% confidence interval [CI]: 85%, 98%), 91% (95% CI: 85%, 94%), 79% (95% CI: 66%, 85%), and 97.5% (95% CI: 94%, 99%), respectively. Comparison of patients with atrial fibrillation and those with sinus rhythm showed no difference in heart rate (P = .16) or number of nondiagnostic segments (P = .10). Patients with atrial fibrillation were older than those with sinus rhythm (mean age ± standard deviation, 68 years ± 10 vs 61 years ± 12, respectively; P = .001). The effective radiation dose was significantly higher in patients with atrial fibrillation than in those with sinus rhythm, with a mean difference of 4.03 mSv (95% CI: 0.97, 7.1; P = .01). CT angiography has high diagnostic accuracy in patients with atrial fibrillation but is associated with significantly higher effective radiation dose than that in patients with sinus rhythm. The older age of patients with atrial fibrillation, however, may make the risk of developing cancer less of a concern.

Influence of Lipid Profiles on the Risk of Hemorrhagic Transformation after Ischemic Stroke: Systematic Review

Background: It has been suggested that low cholesterol levels might be associated with an increased risk of hemorrhagic transformation (HT) in patients with acute cerebral ischemia. We systematically reviewed the literature to determine the influence of lipid profiles on the HT risk. Methods: We searched PubMed from 1966 and EMBASE from 1980 for studies that investigated the association between lipid profiles and HT. We performed a meta-analysis (weighted mean difference method) for the comparison between presence and absence of HT (all or symptomatic) for total, low-density-lipoprotein (LDL) and high-density-lipoprotein (HDL) cholesterol, and triglycerides. Results: Eight studies investigating 1,763 patients were eligible, but none was designed specifically to address this question. All studies recruited acute stroke patients selected on the presumed cause of cerebral ischemia or treatment received. The meta-analysis showed that: (i) patients with all HT had lower LDL cholesterol levels (p = 0.008) but no difference in HDL cholesterol levels (p = 0.066), total cholesterol (p = 0.129) and triglycerides (p = 0.900); (ii) patients with symptomatic HT had lower total cholesterol levels (p = 0.035) but did not differ in LDL (p = 0.056) and HDL cholesterol (p = 0.138) and triglyceride (p = 0.851) levels. Conclusion: HT is associated with baseline total and LDL cholesterol levels, but the mechanism of this association needs to be explored to identify preventive strategies.

Efficacy of intensive versus nonintensive physiotherapy in children with cerebral palsy: a meta-analysis

A commonly used treatment for cerebral palsy in children is so-called 'conventional therapy', which includes physiotherapy or the neurodevelopmental approach. Although more intensive rehabilitative treatment is thought to be more effective than less intensive interventions, this assumption has not been proven. In this study we compared the efficacy of intensive versus nonintensive rehabilitative treatment in children with cerebral palsy. A meta-analysis of the studies published between January 1996 and July 2007 was performed. infants/children/adolescents (1-18 years old); randomized controlled trials using, as outcome measure, the Gross Motor Function Measure score. studies that included therapies not generally used in 'so-called' conventional treatment (i.e. constraint, taping). Treatment effects were combined using the weighted mean difference method. Fixed and random effect meta-analyses were carried out and results were compared. Heterogeneity was also assessed. Funnel plots were examined and the presence of small-study effects was tested. Intensive therapy tended to have a greater effect than nonintensive therapy (1.32; 95% confidence interval: 0.55-2.10). The effect of intensive treatment tended to be apparently stronger for children 2 years of age. Our meta-analysis shows that, in children with cerebral palsy, intensive conventional therapy may improve the functional motor outcome, but the effect size seems to be modest.

DNA adducts and cancer risk in prospective studies: a pooled analysis and a meta-analysis

Bulky DNA adducts are biomarkers of exposure to aromatic compounds and of the ability of the individual to metabolically activate carcinogens and to repair DNA damage. Their ability to predict cancer onset is uncertain. We have performed a pooled analysis of three prospective studies on cancer risk in which bulky DNA adducts have been measured in blood samples collected from healthy subjects (N = 1947; average follow-up 51-137 months). In addition, we have performed a meta-analysis by identifying all articles on the same subject published up to the end of 2006, including case-control studies. In the pooled analysis, a weakly statistically significant increase in the risk of lung cancer was apparent (14% per unit standard deviation change in adduct levels, 95% confidence interval 1-28%; using the weighted mean difference method, 0.15 SD, units higher adducts in cases than in controls). The association was evident only in current smokers and was absent in former smokers. Also the meta-analysis, which included both lung and bladder cancers, showed a statistically significant association in current smokers, whereas the results in never smokers were equivocal; in former smokers, no association was detected. The results of our pooled and meta-analyses suggest that bulky DNA adducts are associated with lung cancer arising in current smokers after a follow-up of several years.

High-intensity resistance training and postmenopausal bone loss: a meta-analysis

Conflicting evidence exists regarding the optimum exercise for postmenopausal bone loss. A systematic review and meta-analysis was undertaken to evaluate the effects of randomised controlled trials (RCTs) of progressive, high-intensity resistance training on bone mineral density (BMD) amongst postmenopausal women. Structured electronic searching of multiple databases and hand-searching of key journals and reference lists was undertaken to locate relevant studies up to December 2004. Study quality and possible publication bias were assessed using recognised methods. Primary outcomes were absolute changes in BMD at the lumbar spine (LS), femoral neck (FN) and total hip (TH). A priori defined subgroup analyses included concurrent hormonal or antiresorptive therapy or calcium supplementation during the intervention. The weighted mean difference method (WMD) was used for combining study group estimates. Random or fixed effect models were applied according to study heterogeneity observed from the I (2) statistic. At the LS, 14 RCT study groups were homogenous (I (2)=25.2%) in demonstrating a significant increase (P=0.006) in BMD of 0.006 g/cm(2) (fixed effect; 95% CI 0.002-0.011) following high-intensity resistance training. In contrast, marked heterogeneity (I (2)=88.2%) was apparent within 11 RCT study groups evaluating FN. For this comparison, a random effects model showed a positive change in FN BMD of 0.010 g/cm(2) (95% CI -0.002 to 0.021; P = 0.11). Subgroup analyses showed more anatomical variability of BMD responses to resistance training according to participants' hormone therapy use. Treatment effects for study groups increasing all participants' calcium intake showed significant positive BMD changes at TH (P=0.007). Methodological quality of all included studies was low, and a reporting bias towards studies with positive BMD outcomes was evident. These findings are relevant to the nonpharmacological treatment of postmenopausal bone loss.

Progressive High-Intensity Resistance Training and Bone Mineral Density Changes Among Premenopausal Women

Regular weight-bearing physical activity has been widely recommended for adult women and may be beneficial in preserving bone mineral density (BMD). However, there is conflicting evidence regarding the effects of resistance training on BMD in premenopausal women. Novel systematic review and meta-analysis evidence is presented on the effects of progressive high-intensity resistance training on BMD in premenopausal women. Structured computer searches of MEDLINE, EMBASE, PubMed, Web of Science, SportDiscus and Evidence Based Medicine Reviews Multifile were undertaken along with hand-searching of key journals and reference lists to locate relevant studies published up to September 2004. Criteria for included studies were published controlled studies and randomised controlled trials (RCTs) evaluating the effects of progressive, high-intensity resistance training studies on BMD in premenopausal women. Two authors reached consensus on all included and excluded studies. Study outcomes for analysis were radiographic BMD assessment from first follow-up at lumbar spine and femoral neck. Primary outcomes for analysis were absolute changes in BMD g/cm(2) at lumbar spine and femoral neck. Relative changes (percentage change) in BMD at lumbar spine were also assessed. Data were extracted from studies including study design, participant characteristics and treatment mode, intensity and duration, using electronic data extraction forms. Where necessary, relevant information was obtained by contacting study authors. Methodological quality of studies was assessed using a well recognised three-question instrument designed to assess bias. Informal assessment for small sample study effects and potential bias was undertaken through visual inspection of funnel plots. The weighted mean difference method (inverse of the variances) was used for combining study group estimates. Quantification of the effect of heterogeneity among study outcomes was assessed using the I(2) statistic. Random effects and fixed-effect models were applied according to observed study heterogeneity. Comparisons resulting in I(2) > 50.0% were considered heterogeneous. Where heterogeneity was observed, a random effects model was applied. Pooled estimates of effect were calculated using the Cochrane Collaboration's Review Manager (RevMan) 4.2.1 software.High-intensity progressive resistance training was shown to be efficacious in increasing absolute BMD at the lumbar spine (p < 0.00001) but not the femoral neck (p = 0.78) in premenopausal women. The weighted mean difference (WMD) using a fixed-effect model for six controlled trials investigating the lumbar spine BMD change was 0.014 g/cm(2) (95% CI 0.009, 0.019; p < 0.00001). The relative BMD change for this site was 0.98% (WMD [random effects], 95% CI 0.49, 3.91%; p = 0.04). In contrast, studies evaluating femoral neck BMD changes showed no significant BMD change (WMD [fixed effect], 0.001 g/cm(2) 95% CI -0.006, 0.008; p = 0.78). Funnel plot inspection of lumbar spine effects indicated that smaller studies demonstrated larger treatment effects. An asymmetry towards studies with positive BMD outcomes was also noted. The methodological quality score of all included studies was low and no study presented a valid intention-to-treat accounting for participant drop-out (attrition). As such, the modest overall treatment effects for resistance training on BMD among premenopausal women observed in this review may be biased and should be interpreted with caution. It is concluded that further RCTs of resistance training of sufficiently long duration and providing optimum type, intensity and volume of loading, with intention-to-treat analysis are now required.

Efficacy of cholinesterase inhibitors in the treatment of neuropsychiatric symptoms and functional impairment in Alzheimer disease: a meta-analysis.

Cholinesterase inhibitors are the primary treatment for the cognitive symptoms of Alzheimer disease (AD). Cholinergic dysfunction is also associated with neuropsychiatric and functional deficits, but results from randomized controlled trials of cholinesterase inhibitors are conflicting. To conduct a systematic review and meta-analysis to quantify the efficacy of cholinesterase inhibitors for neuropsychiatric and functional outcomes in patients with mild to moderate AD. We performed a literature search of trials using MEDLINE (January 1966-December 2001), Dissertations Abstracts On-line, PSYCHINFO, BIOSIS, PubMed, and the Cochrane Controlled Trials Register. We retrieved English- and non-English-language articles for review and collected references from bibliographies of reviews, original research articles, and other articles of interest. We searched for both published and unpublished trials, contacting researchers and pharmaceutical companies. We included 29 parallel-group or crossover randomized, double-blind, placebo-controlled trials of outpatients who were diagnosed as having mild to moderate probable AD and were treated for at least 1 month with a cholinesterase inhibitor. Sixteen trials included neuropsychiatric and 18 included functional measures. Two investigators (N.H.T. and J.H.) independently extracted study methods, sources of bias, and outcomes. Neuropsychiatric outcomes were measured with the Neuropsychiatric Inventory (NPI, 0-120 points) and the Alzheimer Disease Assessment Scale, noncognitive (ADAS-noncog, 0-50 points) and were analyzed with the weighted mean difference method. Functional outcomes were measured with several activities of daily living (ADL) and instrumental activities of daily living (IADL) scales and analyzed with the standardized mean difference method. For neuropsychiatric outcomes, 10 trials included the ADAS-noncog and 6 included the NPI. Compared with placebo, patients randomized to cholinesterase inhibitors improved 1.72 points on the NPI (95% confidence interval [CI], 0.87-2.57 points), and 0.03 points on the ADAS-noncog (95% CI, 0.00-0.05 points). For functional outcomes, 14 trials used ADL and 13 trials used IADL scales. Compared with placebo, patients randomized to cholinesterase inhibitors improved 0.1 SDs on ADL scales (95% CI, 0.00-0.19 SDs), and 0.09 SDs on IADL scales (95% CI, 0.01 to 0.17 SDs). There was no difference in efficacy among various cholinesterase inhibitors. These results indicate that cholinesterase inhibitors have a modest beneficial impact on neuropsychiatric and functional outcomes for patients with AD. Future research should focus on how such improvements translate into long-term outcomes such as patient quality of life, institutionalization, and caregiver burden.