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Increase in core body temperature of Alzheimer's disease patients as a possible indicator of chronic neuroinflammation: a meta-analysis.

BACKGROUND: Neuroinflammation contributes to the pathogenesis of Alzheimer's disease (AD). Increased pro-inflammatory cytokine levels have been reported in the brain and cerebro-spinal fluid of individuals affected by this neurodegenerative disorder. These same cytokines, including interleukin -1, interleukin-6 and tumor necrosis factor-alpha, are also believed to be involved in thermoregulation. Furthermore, their effects are thought to be mediated through the induction of cyclooxygenases resulting in increased production of inflammatory prostaglandins. Such increases have been observed in AD brains. We hypothesized that these increased levels of inflammatory mediators could lead to an increase in core body temperature in AD patients. OBJECTIVE: To determine whether clinical signs of AD are accompanied by an increase in core body temperature. METHODS: Analysis of the scientific literature identified six studies that used continuous rectal measurements of core body temperature in AD and control patients. Meta-analysis was performed on these published data. RESULTS: Meta-analysis showed that the mean core body temperature in AD patients was significantly increased by 0.10 degrees C when compared to healthy elderly subjects. The two-sided p value was 0.0355, and the 95% confidence interval was 0.0068-0.1950. The severity of AD pathology did not appear to contribute significantly (p = 0.235) to the heterogeneity in the core body temperature among different groups of AD patients. CONCLUSION: The significant increase in core body temperature in AD patients could be a direct consequence of local inflammatory reactions in the brain. Although the changes observed are probably too small to be of any diagnostic value, these observations lend further support to the neuroinflammatory hypothesis of AD pathology.

Alzheimer Disease↗

Review in depth and meta-analysis of controlled trials on colorectal cancer screening by faecal occult blood test.

BACKGROUND: Several randomized studies have shown that colorectal cancer (CRC) screening by faecal occult blood test (FOBT) reduces CRC mortality. These trials have different designs, especially concerning FOBT frequency and duration, as well as the length of follow-up after stopping FOBT campaigns. AIMS: To review the effectiveness of screening for CRC with FOBT, to consider the reduction in mortality during or after screening or to identify factors associated with a significant mortality reduction. METHODS: A systematic review of trials of FOBT screening with a meta-analysis of four controlled trials selected for their biennial and population-based design. The main outcome measurements were mortality relative risk (RR) and 95% confidence interval (CI) of biennial FOBT during short (10 years, i.e. five or six rounds) or long-term (six or more rounds) screening periods, as well as after stopping screening and follow-up during 5-7 years. The meta-analysis used the Mantel-Haenszel method with fixed effects when the heterogeneity test was not significant, and used 'intent to screen' results. RESULTS: Although the quality of the four trials was high, only three were randomized, and one used rehydrated biennial FOBT associated with a high colonoscopy rate (28%). A meta-analysis of mortality results showed that subjects allocated to screening had a reduction of CRC mortality during a 10-year period (RR 0.86; CI 0.79-0.94) although CRC mortality was not decreased during the 5-7 years after the 10-year (six rounds) screening period, nor in the last phase (8-16 years after the onset of screening) of a long-term (16 years or nine rounds) biennial screening. Whatever the design of the period of ongoing FOBT, CRC incidence neither decreased nor increased, although it was reduced for 5-7 years after the 10-year screening period. Neither the design nor the clinical or demographic parameters of these trials were independently associated with CRC mortality reduction. CONCLUSION: Biennial FOBT decreased CRC mortality by 14% when performed over 10 years, without evidence-based benefit on CRC mortality when performed over a longer period. No independent predictors of CRC mortality reduction have been identified in order to allow a CRC screening programme in any subgroups of subjects at risk.

Aged↗

Review of analytical methods for prospective cohort studies using time to event data: single studies and implications for meta-analysis.

Prospective cohort studies are extremely important in epidemiological research as they give direct information on the sequence of events, which can be used to demonstrate causality. They also have the advantage that many diseases can be studied simultaneously. However, they are usually very time consuming and expensive to run. In addition, practitioners of evidence-based medicine prefer to make decisions based on several studies rather than a single study, hence the need for meta-analysis. The use of meta-analyses in order to synthesize the evidence from randomized controlled trials is extremely popular in medicine and is also being utilized increasingly in epidemiology. The statistical methodology for meta-analyses of epidemiological studies is a long way behind in terms of the advances made in the methodology for randomized controlled trials. Numerous methodological issues, particularly in respect to dealing with biases inherent in these types of studies, have made the results of meta-analyses of epidemiological studies that use summary data open to criticism. This review mainly concentrates on analytical methods for prospective cohort studies that have survival outcomes. In addition, the implications for meta-analysis assuming that the analyst has access to individual participant data are also discussed. The approaches are described with respect to underlying theory and assumptions. It is hoped that this review will promote the use of these approaches in meta-analyses conducted in epidemiology as well as providing some directions for future research.

Cohort Studies↗

A meta-analysis of the published research on the affective, cognitive, and behavioral effects of corporal punishment.

The present study is a meta-analysis of the published research on the effects of corporal punishment on affective, cognitive, and behavioral outcomes. The authors included 70 studies published between 1961 and 2000 and involving 47,751 people. Most of the studies were published between 1990 and 2000 (i.e., 53 or 68%) and were conducted in the United States (65 or 83.3%). Each of the dependent variables was coded, and effect sizes (ds) were computed. Average unweighted and weighted ds for each of the outcome variables were .35 and .20 for affective outcomes, .33 and .06 for cognitive outcomes, and .25 and .21 for behavioral outcomes, respectively. The analyses suggested small negative behavioral and emotional effects of corporal punishment and almost no effect of such punishment on cognition. Analyses of several potentially moderating variables, such as gender or socioeconomic status, and the frequency or age of first experience of corporal punishment, the relationship of the person administering the discipline, and the technique of the discipline all had no affect on effect size outcome. There was insufficient data about a number of the moderator variables to conduct meaningful analyses. The results of the present meta-analysis suggest that exposure to corporal punishment does not substantially increase the risk to youth of developing affective, cognitive, or behavioral pathologies.

Affect↗

Efficacy of current approaches to non-invasive diagnosis of skin cancer and the potential impact of artificial intelligence: A systematic review and meta-analysis.

BACKGROUND: Skin cancer is one of the most prevalent malignancies worldwide, particularly within Caucasian populations. This systematic review and meta-analysis aimed to quantitatively review the current literature on non-invasive diagnosis of skin cancer and evaluate the current evidence to support the use of tools in addition to, or in replacement of clinician face-to-face assessment. METHODS: A literature search was conducted for publications in PubMed, Medline and Embase databases. Articles describing accuracy, sensitivity, specificity and outcomes of their mode of assessment were included. A total of 208 articles met the inclusion criteria. RESULTS AND CONCLUSION: This systematic review and meta-analysis showed that the diagnostic performance of artificial intelligence (AI) in the interpretation of dermatoscopic images was high for melanoma diagnosis, basal cell carcinoma or malignancy, in comparison to dermatoscopic assessment alone by clinicians and experts. Although AI interpretation of images demonstrated higher sensitivity for melanoma diagnosis in comparison to clinical assessment combined with dermatoscopic assessment, it is unclear if this is also the case for basal cell carcinoma and squamous cell carcinoma diagnosis. Reflectance confocal microscopy, a non-invasive high resolution imaging technique, is known to have a high sensitivity for diagnosing cutaneous malignancy, and this may have applications within secondary care. Therefore, AI could help reduce resource burden and aid in clinical assessment, particularly within primary care settings.

Humans↗

Effectiveness of smoking cessation therapies: a systematic review and meta-analysis.

BACKGROUND: Smoking remains the leading preventable cause of premature deaths. Several pharmacological interventions now exist to aid smokers in cessation. These include Nicotine Replacement Therapy [NRT], bupropion, and varenicline. We aimed to assess their relative efficacy in smoking cessation by conducting a systematic review and meta-analysis. METHODS: We searched 10 electronic medical databases (inception to Sept. 2006) and bibliographies of published reviews. We selected randomized controlled trials [RCTs] evaluating interventions for smoking cessation at 1 year, through chemical confirmation. Our primary endpoint was smoking cessation at 1 year. Secondary endpoints included short-term smoking cessation (approximately 3 months) and adverse events. We conducted random-effects meta-analysis and meta-regression. We compared treatment effects across interventions using head-to-head trials and when these did not exist, we calculated indirect comparisons. RESULTS: We identified 70 trials of NRT versus control at 1 year, Odds Ratio [OR] 1.71, 95% Confidence Interval [CI], 1.55-1.88, P =< 0.0001). This was consistent when examining all placebo-controlled trials (49 RCTs, OR 1.78, 95% CI, 1.60-1.99), NRT gum (OR 1.60, 95% CI, 1.37-1.86) or patch (OR 1.63, 95% CI, 1.41-1.89). NRT also reduced smoking at 3 months (OR 1.98, 95% CI, 1.77-2.21). Bupropion trials were superior to controls at 1 year (12 RCTs, OR1.56, 95% CI, 1.10-2.21, P = 0.01) and at 3 months (OR 2.13, 95% CI, 1.72-2.64). Two RCTs evaluated the superiority of bupropion versus NRT at 1 year (OR 1.14, 95% CI, 0.20-6.42). Varenicline was superior to placebo at 1 year (4 RCTs, OR 2.96, 95% CI, 2.12-4.12, P =< 0.0001) and also at approximately 3 months (OR 3.75, 95% CI, 2.65-5.30). Three RCTs evaluated the effectiveness of varenicline versus bupropion at 1 year (OR 1.58, 95% CI, 1.22-2.05) and at approximately 3 months (OR 1.61, 95% CI, 1.16-2.21). Using indirect comparisons, varenicline was superior to NRT when compared to placebo controls (OR 1.66, 95% CI 1.17-2.36, P = 0.004) or to all controls at 1 year (OR 1.73, 95% CI 1.22-2.45, P = 0.001). This was also the case for 3-month data. Adverse events were not systematically different across studies. CONCLUSION: NRT, bupropion and varenicline all provide therapeutic effects in assisting with smoking cessation. Direct and indirect comparisons identify a hierarchy of effectiveness.

Benzazepines↗

Simultaneous rhytidectomy and full-face carbon dioxide laser resurfacing: a case series and meta-analysis.

BACKGROUND: The combination of facial rhytidectomy and full-face carbon dioxide laser resurfacing would theoretically provide for superior aesthetic rejuvenation of the face, but some reports have advised against this combination (particularly using chemical peel). However, significant differences exist between previous studies of combination therapy. OBJECTIVE: To evaluate these differences and determine protocol for care and carbon dioxide laser settings for resurfacing when done in combination with full-face rhytidectomy. DESIGN: (1) A case series of 30 patients treated in a private practice over 26 months with simultaneous rhytidectomy and full-face laser resurfacing; (2) a meta-analysis of 3 and 1/2 years of literature reporting the same combination procedure (453 patients). Variables evaluated include rhytidectomy technique, laser type and settings, postoperative care, complications, and outcome analyses. OUTCOME MEASURES: Rate of postoperative complications, premorbidity, previous surgery, concurrent procedures, postoperative dressings, and follow-up status. SELECTION: Referred sample patients were determined by the single operating surgeon who performed all procedures. For literature meta-analysis, only peer-reviewed studies of simultaneous rhytidectomy and full-face laser resurfacing from January 1997 through May 2000 were included. RESULTS: Among the 30 patients treated over our 26-month case series accession period, there was no evidence of flap loss, skin slough, infection (viral or cellulitic), or hypopigmentation. Settings for laser resurfacing were determined. Of the 453 patients included in our meta-analysis, 1 (a smoker) sustained a 2-cm full-thickness flap necrosis, and 4 sustained varying degrees of skin slough in the postauricular area without full-thickness necrosis. The complication rate did not differ from that of rhytidectomy alone. CONCLUSION: Simultaneous rhytidectomy and full-face carbon dioxide laser resurfacing can safely provide a dual cosmetic benefit option for aesthetic rejuvenation of the face.

Adult↗

Antithrombin III in patients with severe sepsis. A randomized, placebo-controlled, double-blind multicenter trial plus a meta-analysis on all randomized, placebo-controlled, double-blind trials with antithrombin III in severe sepsis.

OBJECTIVES: To evaluate the safety and potential efficacy of antithrombin III (AT III) in reducing mortality in patients with severe sepsis. DESIGN: Prospective, randomized, placebo-controlled, double-blind, phase II, multicenter, multinational clinical trial. SETTING: Seven academic medical center intensive care units (ICU) in Belgium, Denmark, the Netherlands, Norway and Sweden. PATIENTS: 42 patients with severe sepsis who received standard supportive care and antimicrobial therapy, in addition to the administration of AT III or placebo. INTERVENTIONS: Patients received either an intravenous loading dose of 3000 IU AT III followed by a maintenance dose of 1500 IU every 12 h for 5 days or equivalent amounts of placebo. MEASUREMENTS AND RESULTS: All patients were evaluated for safety and for 30-day all-cause mortality. CONCLUSIONS: The administration of AT III was safe and well-tolerated. It was followed by a 39 % reduction in 30-day all-cause mortality (NS). The reduction in mortality was accompanied by a considerably shorter stay in the ICU. Patients treated with AT III exhibited a better performance in overall severity of illness and organ failure scores (Acute Physiology and Chronic Health Evaluation II, multiple organ failure, organ system failure), which was noticeable soon after initiation of treatment. Patients treated with AT III demonstrated a better resolution of pre-existing organ failures and a lower incidence of new organ failures during the observation period. A meta-analysis comprising this and two other double-blind, placebo-controlled trials with AT III with a total of 122 patients suffering from severe sepsis confirms the positive trend. The results of the meta-analysis demonstrate a 22.9 % reduction in 30-day all-cause mortality in patients treated with AT III. Although still too small to be confirmative, the meta-analysis clearly points to the fact that a sufficiently powered phase III trial is warranted to prove whether AT III has a beneficial role in the treatment of severe sepsis.

APACHE↗

Follicle-stimulating hormone versus human menopausal gonadotropin for in vitro fertilization cycles: a meta-analysis.

OBJECTIVE: To conduct a systematic overview of available data comparing FSH with hMG in IVF treatment cycles. DESIGN: A meta-analysis of randomized trials of FSH versus hMG use in ovarian stimulation protocols, with or without GnRH agonists, in IVF treatment cycles. Search strategies included on-line searching of the National Library of Medicine MEDLINE data base from 1975 to 1993 and hand searching of bibliographies of relevant publications and reviews and abstracts of scientific meetings. Common odds ratio (OR) and overall absolute treatment effect were calculated after demonstrating homogeneity of treatment effect across all trials. MAIN OUTCOME MEASURES: Clinical pregnancy rates per cycle start, per cycle reaching oocyte retrieval, and per cycle reaching ET. RESULTS: Eight trials met the inclusion criteria. The overall OR in favor of FSH for cycle start, oocyte retrieval, and ET were 1.71, 1.69 and 1.70, respectively, and represented an overall absolute treatment effect of 8.5%, 8.0% and 8.3%, respectively. CONCLUSIONS: This meta-analysis demonstrates that in IVF cycles the use of FSH is associated with a significantly higher clinical pregnancy rate than hMG.

Abortion, Spontaneous↗

Recurrence of hemolytic-uremic syndrome in renal transplant recipients: a meta-analysis.

BACKGROUND: Recurrence of hemolytic-uremic syndrome (HUS) in the allograft is associated with a very poor renal prognosis. Meta-analysis of previous trials may allow us to better estimate its real frequency, to identify risk factors for recurrence, and to predict the outcome of patients with definite recurrence. METHODS: An exhaustive search was conducted of HUS recurrence in renal transplantation from January 1977 to June 1997 using MEDLINE. RESULTS: Ten studies comprising 159 grafts in 127 patients were identified. The rate of recurrence was 27.8%. One-year graft survival was 76.6% in patients without recurrence and 33.3% in patients with recurrence (P<0.001). Older age at onset of HUS (16.96+/-7.6 years vs. 9.95+/-6.55 years; P<0.02), shorter mean interval between HUS and transplantation (2.51+/-2.7 years vs. 6.03+/-6.4 years; P<0.01), shorter mean interval between HUS and end-stage renal disease (0.79+/-0.39 years vs. 2.78+/-2.47 years; P<0.01), living-related donors, and the use of calcineurin inhibitors were associated with recurrence. CONCLUSION: Risk factors for HUS recurrence in renal transplantation could be identified through this meta-analysis.

Age Distribution↗

Antibiotics for the primary prevention of acute rheumatic fever: a meta-analysis.

BACKGROUND: Rheumatic fever continues to put a significant burden on the health of low socio-economic populations in low and middle-income countries despite the near disappearance of the disease in the developed world over the past century. Antibiotics have long been thought of as an effective method for preventing the onset of acute rheumatic fever following a Group-A streptococcal (GAS) throat infection; however, their use has not been widely adopted in developing countries for the treatment of sore throats. We have used the tools of systematic review and meta-analysis to quantify the effectiveness of antibiotic treatment for sore throat, with symptoms suggestive of group A streptococcal (GAS) infection, for the primary prevention of acute rheumatic fever. METHODS: Trials were identified through a systematic search of titles and abstracts found in the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 4, 2003), MEDLINE (1966-2003), EMBASE (1966-2003), and the reference lists of identified studies. The selection criteria included randomised or quasi-randomised controlled trials comparing the effectiveness of antibiotics versus no antibiotics for the prevention of rheumatic fever in patients presenting with a sore throat, with or without confirmation of GAS infection, and no history of rheumatic fever. RESULTS: Ten trials (n = 7665) were eligible for inclusion in this review. The methodological quality of the studies, in general, was poor. All of the included trials were conducted during the period of 1950 and 1961 and in 8 of the 10 trials the study population consisted of young adult males living on United States military bases. Fixed effects, meta-analysis revealed an overall protective effect for the use of antibiotics against acute rheumatic fever of 70% (RR = 0.32; 95% CI = 0.21-0.48). The absolute risk reduction was 1.67% with an NNT of 53. When meta-analysis was restricted to include only trials evaluating penicillin, a protective effect of 80% was found (Fixed effect RR = 0.20, 95% CI = 0.11-0.36) with an NNT of 60. The marginal cost of preventing one case of rheumatic fever by a single intramuscular injection of penicillin is approximately USD 46 in South Africa. CONCLUSION: Antibiotics appear to be effective in reducing the incidence of acute rheumatic fever following an episode of suspected GAS pharyngitis. This effect may be achieved at relatively low cost if a single intramuscular penicillin injection is administered.

Acute Disease↗

Risk factors for depression among elderly community subjects: a systematic review and meta-analysis.

OBJECTIVE: The goal of this study was to determine risk factors for depression among elderly community subjects. METHOD: MEDLINE and PsycINFO were searched for potentially relevant articles published from January 1966 to June 2001 and from January 1967 to June 2001, respectively. The bibliographies of relevant articles were searched for additional references. Twenty studies met the following six inclusion criteria: original research reported in an English or French publication, study group of community residents, age of subjects 50 years or more, prospective study design, examination of at least one risk factor, and use of an acceptable definition of depression. The validity of studies was assessed according to the four primary criteria for risk factor studies described by the Evidence-Based Medicine Working Group. Information about group size at baseline and follow-up, age, proportion of men, depression criteria, exclusion criteria at baseline, length of follow-up, number of incident cases of depression, and risk factors was abstracted from each report. RESULTS: Follow-up of the inception cohort was incomplete in most studies. In the qualitative meta-analysis, risk factors identified by both univariate and multivariate techniques in at least two studies each were disability, new medical illness, poor health status, prior depression, poor self-perceived health, and bereavement. In the quantitative meta-analysis, bereavement, sleep disturbance, disability, prior depression, and female gender were significant risk factors. CONCLUSIONS: Despite the methodologic limitations of the studies and this meta-analysis, bereavement, sleep disturbance, disability, prior depression, and female gender appear to be important risk factors for depression among elderly community subjects.

Age Factors↗

Role of the Fcgamma receptor IIa polymorphism in susceptibility to systemic lupus erythematosus and lupus nephritis: a meta-analysis.

OBJECTIVE: To assess the impact of the Fcgamma receptor type IIa (FcgammaRIIa)-R/H131 polymorphism on the risk for systemic lupus erythematosus (SLE) and development of lupus nephritis. METHODS: A meta-analysis was performed based on the Medline and Embase databases (last retrieval August 2001), assessment of bibliographies of pertinent articles, and additional data gathered after contact with primary investigators. RESULTS: A total of 25 comparisons from 17 studies involving R/H131 genotyping of 1,405 patients with lupus nephritis, 1,709 SLE patients without nephritis, and 2,580 non-SLE controls were included. No association between RR genotype and risk of lupus nephritis relative to both other genotypes (odds ratio [OR] 1.05, 95% confidence interval [95% CI] 0.88-1.27) was demonstrated in the total meta-analysis or in any racial subgroup. The RR genotype was more frequent in SLE patients as a whole (OR 1.30, 95% CI 1.10-1.52) and in SLE patients without nephritis (OR 1.27, 95% CI 1.04-1.55) compared with disease-free controls. A potential dose-response relation between the R131 allele and the risk of SLE was also identified, with an OR of 1.23 for RR versus RH (95% CI 1.03-1.46). The OR was 1.55 for RR versus HH (95% CI 1.21-1.98). There was no significant heterogeneity between racial subgroups. The population-attributable fractions of SLE cases due to the FcgammaRIIa-R131 allele were 13%, 40%, and 24% in subjects of European, African, and Asian descent, respectively. CONCLUSION: The FcgammaRIIa-R/H131 polymorphism represents a significant risk factor for SLE but has no clear effect on susceptibility for lupus nephritis.

Antigens, CD↗

A meta-analysis comparing buprenorphine to methadone for treatment of opiate dependence.

BACKGROUND: The unique pharmacological properties of buprenorphine may make it a useful maintenance therapy for opiate addiction. This meta-analysis considers the effectiveness of buprenorphine relative to methadone. METHODS: A systematic literature search identified five randomized clinical trials comparing buprenorphine to methadone. Data from these trials were obtained. Retention in treatment was analyzed with a Cox proportional hazards regression. Urinalyses for opiates were studied with analysis of variance and a common method of handling missing values. A meta-analysis was used to combine these results. RESULTS: Subjects who received 8-12 mg/day buprenorphine had 1.26 times the relative risk of discontinuing treatment (95% confidence interval 1.01-1.57) and 8.3% more positive urinalyses (95% confidence interval 2.7-14%) than subjects receiving 50-80 mg/day methadone. Buprenophrine was more effective than 20-35 mg/day methadone. There was substantial variation in outcomes in the different trials. CONCLUSIONS: The variation between trials may be due to differences in dose levels, patient exclusion criteria and provision of psychosocial treatment. The difference in the effectiveness of buprenorphine and methadone may be statistically significant, but the differences are small compared to the wide variance in outcomes achieved in different methadone treatment programs. Further research is needed to determine if buprenorphine treatment is more effective than methadone in particular settings or in particular subgroups of patients.

Analysis of Variance↗

Analysing the relationship between treatment effect and underlying risk in meta-analysis: comparison and development of approaches.

Three approaches for estimating the relationship between treatment effect and underlying risk in a meta-analysis of clinical trials have recently been published. The aim of each is to overcome the bias inherent in conventional regressions of treatment effect on control group risk, which arises from the measurement error in the observed control group risks in different trials. Here we describe these published approaches, and compare them with respect to their underlying models and methods of implementation. The underlying model for one of them is shown to be seriously flawed, while the other two are both statistically more appropriate than the conventional approaches, and differ from each other in only two assumptions. Both may be implemented using the Gibbs sampling algorithm in BUGS, and are exemplified here using a meta-analysis of mortality and bleeding data in trials of sclerotherapy for patients with cirrhosis. One approach is developed further; for the illustrative example considered, it is shown to be robust to different choices of prior distributions for the model parameters, and to the assumption of a linear relationship on a log-odds scale. It can also be used to estimate the level of underlying risk (and its standard error) at which the treatment effect crosses from benefit to harm, and other trial-level covariates may be included in the model as confounders. The BUGS code is provided in an Appendix, to enable applied researchers to perform the various analyses described.

Algorithms↗

Bayesian approaches to meta-analysis of ROC curves.

A comparative review of important classic and Bayesian approaches to fixed-effects and random-effects meta-analysis of binormal ROC curves and areas underneath them is presented. The ROC analyses results of seven evaluation studies concerning the dexamethasone suppression test provide the basis for a worked example. Particular attention is given to fully Bayesian inference, a novelty in the ROC context, based on Gibbs samples from posterior distributions of hierarchical model parameters and related quantities. Fully Bayesian meta-analysis may properly account for the uncertainty associated with the model parameters, possibly incorporating prior knowledge and beliefs, and allows clinically intuitive predictions of unobserved study effects via calculation of posterior predictive densities. The effects of various different prior specifications (six noninformative as well as one informative) on the posterior estimates are investigated (sensitivity-analysis). Recommendations and suggestions for further research are made. Computer code for the more advanced methods may either be downloaded via the Internet or be found elsewhere.

Bayes Theorem↗

The relationship between age and the prevalence of senile dementia: a meta-analysis of recent data.

A linear regression model derived from a meta-analysis of 13 epidemiological studies of senile dementia conducted since 1980, and employing internationally-known case-finding procedures, suggests a much lower general rate of dementia prevalence than has been previously estimated. An exponential increase with age is observed, with senile dementia prevalence diagnosed by Diagnostic and Statistical Manual (DSM-III) criteria doubling every 6 years and senile dementia of the Alzheimer's type (SDAT) every 4.2 years. Studies providing data for the oldest ages indicating a drop in the rate of increase after the age of 80 suggest that senile dementia may be age-related rather than ageing-related. Estimates derived from this model may provide a reasonably accurate means of estimating dementia prevalence in the general population. The limitations of this method for the purposes of prediction and studies of risk factors are discussed in relation to the hypothesized heterogeneity of senile dementia and possible cohort effects.

Age Factors↗

A meta-analysis of clinical trials of paclitaxel- and sirolimus-eluting stents in patients with obstructive coronary artery disease.

AIM: This meta-analysis was conducted to compare the effects of drug (paclitaxel and sirolimus)-eluting stents with bare metal stents on major adverse cardiac events, restenosis rates and late loss of arterial lumen diameter in patients with obstructive coronary artery disease. METHODS: Randomized, controlled clinical trials comparing sirolimus- and paclitaxel-eluting stents with bare metal stents were identified through electronic and manual search. Fixed effects method of Mantel-Haenszel and random effects method of DerSimonian and Laird were used for computing the pooled odds ratio (OR) and 95% confidence intervals (CI) for major adverse cardiac events and restenosis rates. Standardized mean difference with 95% CI was calculated for late-loss of arterial lumen diameter. RESULTS: A total of 13 studies were included in the meta-analysis. As compared with bare metal stents, the use of sirolimus- and paclitaxel-eluting stents significantly reduced the major adverse cardiac events (pooled OR 0.35; 95% CI 0.24-0.50), restenosis rates (pooled OR 0.27; 95% CI 0.15-0.47), and late loss of arterial lumen diameter (mean difference 0.57 mm, 95% CI 0.49-0.68). CONCLUSION: Paclitaxel- and sirolimus-eluting stents significantly reduced the incidence of major adverse cardiac events, restenosis rates, and late loss of arterial lumen diameter as compared with bare metal stents.

Cell Proliferation↗