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1.
Background
Folic acid is widely used to lower homocysteine concentrations and prevent adverse cardiovascular outcomes. However, the effect of folic acid on cardiovascular events is not clear at the present time. We carried out a comprehensive systematic review and meta-analysis to assess the effects of folic acid supplementation on cardiovascular outcomes.Methodology and Principal Findings
We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings for relevant literature. We included randomized placebo-controlled trials that reported on the effects of folic acid on cardiovascular events compared to placebo. Of 1594 identified studies, we included 16 trials reporting data on 44841 patients. These studies reported 8238 major cardiovascular events, 2001 strokes, 2917 myocardial infarctions, and 6314 deaths. Folic acid supplementation as compared to placebo had no effect on major cardiovascular events (RR, 0.98; 95% CI, 0.93–1.04), stroke (RR, 0.89; 95% CI,0.78–1.01), myocardial infarction (RR, 1.00; 95% CI, 0.93–1.07), or deaths from any cause (RR, 1.00;95% CI, 0.96–1.05). Moreover, folic acid as compared to placebo also had no effect on the following secondary outcomes: risk of revascularization (RR, 1.05; 95%CI, 0.95–1.16), acute coronary syndrome (RR, 1.06; 95%CI, 0.97–1.15), cancer (RR, 1.08; 95%CI, 0.98–1.21), vascular death (RR, 0.94; 95%CI,0.88–1.02), or non-vascular death (RR, 1.06; 95%CI, 0.97–1.15).Conclusion/Significance
Folic acid supplementation does not effect on the incidence of major cardiovascular events, stroke, myocardial infarction or all cause mortality. 相似文献2.
Purpose
Epidemiologic studies exploring causal associations between serum lipids and breast cancer risk have reported contradictory results. We conducted a meta-analysis of prospective cohort studies to evaluate these associations.Methods
Relevant studies were identified by searching PubMed and EMBASE through April 2015. We included prospective cohort studies that reported relative risk (RR) estimates with 95% confidence intervals (CIs) for the associations of specific lipid components (i.e., total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides [TG]) with breast cancer risk. Either a fixed- or a random-effects model was used to calculate pooled RRs.Results
Fifteen prospective cohort studies involving 1,189,635 participants and 23,369 breast cancer cases were included in the meta-analysis. The pooled RRs of breast cancer for the highest versus lowest categories were 0.96 (95% CI: 0.86–1.07) for TC, 0.92 (95% CI: 0.73–1.16) for HDL-C, 0.90 (95% CI: 0.77–1.06) for LDL-C, and 0.93 (95% CI: 0.86–1.00) for TG. Notably, for HDL-C, a significant reduction of breast cancer risk was observed among postmenopausal women (RR = 0.77, 95% CI: 0.64–0.93) but not among premenopausal women. Similar trends of the associations were observed in the dose-response analysis.Conclusions
Our findings suggest that serum levels of TG but not TC and LDL-C may be inversely associated with breast cancer risk. Serum HDL-C may also protect against breast carcinogenesis among postmenopausal women. 相似文献3.
Ruzagira E Wandiembe S Abaasa A Bwanika AN Bahemuka U Amornkul P Price MA Grosskurth H Kamali A 《PloS one》2011,6(8):e24037
Objectives
To determine the incidence of and risk factors for HIV acquisition in a cohort of HIV-uninfected partners from HIV discordant couples in Masaka, Uganda, and to establish its suitability for HIV vaccine trials.Methods
HIV-uninfected adults living in HIV discordant couple relationships were enrolled and followed for 2 years. Interviews, medical investigations, HIV counseling and testing, syphilis and urine pregnancy (women) tests were performed at quarterly visits. Sexual risk behaviour data were collected every 6 months.Results
495 participants were enrolled, of whom 34 seroconverted during 786.6 person-years of observation (PYO). The overall HIV incidence rate [95% confidence interval (CI)] was 4.3 [3.1–6]; and 4.3 [2.8–6.4] and 4.4 [2.5–8] per 100 PYO in men and women respectively. Independent baseline predictors for HIV acquisition were young age [18–24 (aRR = 4.1, 95% CI 1.6–10.8) and 25–34 (aRR = 2.7, 95% CI 1.2–5.8) years]; alcohol use (aRR = 2.6, 95% CI 1.1–6); and reported genital discharge (aRR = 3.4, 95% CI 1.6–7.2) in the past year. Condom use frequency in the year preceding enrolment was predictive of a reduced risk of HIV acquisition [sometimes (aRR = 0.4, 95% CI 0.2–0.8); always (aRR = 0.1, 95% CI 0.02–0.9)]. In the follow-up risk analysis, young age [18–24 (aRR = 6.2, 95% CI 2.2–17.3) and 25-34 (aRR = 2.3, 95% CI 1.1–5.0) years], reported genital discharge (aRR = 2.5, 95% CI 1.1–5.5), serological syphilis (aRR 3.2, 95% CI 1.3–7.7) and the partner being ART naïve (aRR = 4.8, 95% CI 1.4–16.0) were independently associated with HIV acquisition. There were no seroconversions among participants who reported consistent condom use during the study.Conclusions
The study has identified important risk factors for HIV acquisition among HIV discordant couples. HIV-uninfected partners in discordant couples may be a suitable population for HIV vaccine efficacy trials. However, recent confirmation that ART reduces heterosexual HIV transmission may make it unfeasible to conduct HIV prevention trials in this population. 相似文献4.
Background
Recruitment of participants into randomised controlled trials (RCTs) is critical for successful trial conduct. Although there have been two previous systematic reviews on related topics, the results (which identified specific interventions) were inconclusive and not generalizable. The aim of our study was to evaluate the relative effectiveness of recruitment strategies for participation in RCTs.Methods and Findings
A systematic review, using the PRISMA guideline for reporting of systematic reviews, that compared methods of recruiting individual study participants into an actual or mock RCT were included. We searched MEDLINE, Embase, The Cochrane Library, and reference lists of relevant studies. From over 16,000 titles or abstracts reviewed, 396 papers were retrieved and 37 studies were included, in which 18,812 of at least 59,354 people approached agreed to participate in a clinical RCT. Recruitment strategies were broadly divided into four groups: novel trial designs (eight studies), recruiter differences (eight studies), incentives (two studies), and provision of trial information (19 studies). Strategies that increased people''s awareness of the health problem being studied (e.g., an interactive computer program [relative risk (RR) 1.48, 95% confidence interval (CI) 1.00–2.18], attendance at an education session [RR 1.14, 95% CI 1.01–1.28], addition of a health questionnaire [RR 1.37, 95% CI 1.14–1.66]), or a video about the health condition (RR 1.75, 95% CI 1.11–2.74), and also monetary incentives (RR1.39, 95% CI 1.13–1.64 to RR 1.53, 95% CI 1.28–1.84) improved recruitment. Increasing patients'' understanding of the trial process, recruiter differences, and various methods of randomisation and consent design did not show a difference in recruitment. Consent rates were also higher for nonblinded trial design, but differential loss to follow up between groups may jeopardise the study findings. The study''s main limitation was the necessity of modifying the search strategy with subsequent search updates because of changes in MEDLINE definitions. The abstracts of previous versions of this systematic review were published in 2002 and 2007.Conclusion
Recruitment strategies that focus on increasing potential participants'' awareness of the health problem being studied, its potential impact on their health, and their engagement in the learning process appeared to increase recruitment to clinical studies. Further trials of recruitment strategies that target engaging participants to increase their awareness of the health problems being studied and the potential impact on their health may confirm this hypothesis. Please see later in the article for the Editors'' Summary 相似文献5.
Background
Recent clinical trials and observational studies have reported increased coronary events associated with non steroidal anti-inflammatory drugs (NSAIDs). There appeared to be a disproportionate increase in non-fatal versus fatal events, however, numbers of fatal events in individual studies were too small, and event rates too low, to be meaningful.Objectives
We undertook a pooled analysis to investigate the effect of NSAIDs on myocardial infarction (MI) risk with the specific aim to differentiate non-fatal from fatal events.Methods
We searched Pubmed (January, 1990 to March, 2010) for observational studies and randomised controlled trials that assessed the effect of NSAIDs (traditional or selective COX-2 inhibitors [coxibs]) on MI incidence separately for fatal and non-fatal events. Summary estimates of relative risk (RR) for non-fatal and fatal MIs were calculated with a random effects model.Results
NSAID therapy carried a RR of 1.30 (95% CI, 1.20–1.41) for non-fatal MI with no effect on fatal MI (RR 1.02, 95% CI, 0.89–1.17) in six observational studies. Overall, the risk increase for non-fatal MI was 25% higher (95% CI, 11%–42%) than for fatal MI. The two studies that included only individuals with prior cardiovascular disease presented risk estimates for non-fatal MI on average 58% greater (95% CI, 26%–98%) than those for fatal MI. In nine randomised controlled trials, all investigating coxibs, the pooled RR estimate for non-fatal MI was 1.61 (95% CI, 1.04–2.50) and 0.86 (95% CI 0.51–1.47) for fatal MIs.Conclusions
NSAID use increases the risk of non-fatal MI with no substantial effect on fatal events. Such differential effects, with potentially distinct underlying pathology may provide insights into NSAID-induced coronary pathology. We studied the association between the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and the risk of myocardial infarction (MI), separating non-fatal from fatal events, summarizing the evidence from both observational studies and randomised controlled trials. An increased risk of non-fatal MI was clearly found in both types of studies while use of NSAID did not confer an increased risk of fatal MI. Our findings provide support for the concept that thrombi generated under NSAID treatment could be different from spontaneous thrombi. 相似文献6.
Efficacy of short-term high-dose statin in preventing contrast-induced nephropathy: a meta-analysis of seven randomized controlled trials 总被引：1，自引：0，他引：1
Background
A few studies focused on statin therapy as specific prophylactic measures of contrast-induced nephropathy have been published with conflicting results. In this meta-analysis of randomized controlled trials, we aimed to assess the effectiveness of shor-term high-dose statin treatment for the prevention of CIN and clinical outcomes and re-evaluate of the potential benefits of statin therapy.Methods
We searched PubMed, OVID, EMBASE, Web of science and the Cochrane Central Register of Controlled Trials databases for randomized controlled trials comparing short-term high-dose statin treatment versus low-dose statin treatment or placebo for preventing CIN. Our outcome measures were the risk of CIN within 2–5 days after contrast administration and need for dialysis.Results
Seven randomized controlled trials with a total of 1,399 patients were identified and analyzed. The overall results based on fixed-effect model showed that the use of short-term high-dose statin treatment was associated with a significant reduction in risk of CIN (RR = 0.51, 95% CI 0.34–0.76, p = 0.001; I2 = 0%). The incidence of acute renal failure requiring dialysis was not significant different after the use of statin (RR = 0.33, 95% CI 0.05–2.10, p = 0.24; I2 = 0%). The use of statin was not associated with a significant decrease in the plasma C-reactive protein level (SMD −0.64, 95% CI: −1.57 to 0.29, P = 0.18, I2 = 97%).Conclusions
Although this meta-analysis supports the use of statin to reduce the incidence of CIN, it must be considered in the context of variable patient demographics. Only a limited recommendation can be made in favour of the use of statin based on current data. Considering the limitations of included studies, a large, well designed trial that incorporates the evaluation of clinically relevant outcomes in participants with different underlying risks of CIN is required to more adequately assess the role for statin in CIN prevention. 相似文献7.
Background
It has been controversial whether abciximab offered additional benefits for diabetic patients who underwent percutaneous coronary intervention (PCI) with thienopyridines loading.Methods
MEDLINE, EMBASE, the Cochrane library clinical trials registry, ISI Science Citation Index, ISI Web of Knowledge and China National Knowledge Infrastructure (CNKI) were searched, supplemented with manual-screening for relevant publications. Quantitative meta-analyses were performed to assess differences between abciximab groups and controls with respect to post-PCI risk of major cardiac events (MACEs), angiographic restenosis and bleeding complications.Results
9 trials were identified, involving 2,607 diabetic patients receiving PCI for coronary artery diseases. Among those patients who underwent elective PCI or primary PCI, pooling results showed that abciximab did not significantly reduce risks of MACEs (for elective-PCI patients: RR1-month: 0.93, 95% CI: 0.60–1.44; RR1-year: 0.95, 95% CI: 0.81–1.11; for primary-PCI patients: RR1-month: 1.05, 95% CI: 0.70–1.57; RR1-year: 0.98, 95% CI: 0.80–1.21), nor all-cause mortality, re-infarction and angiographic restenosis in either group. The only beneficial effect by abciximab appeared to be a decrease 1-year TLR (target lesion revascularization) risk in elective-PCI patients (RR1-year: 0.83, 95% CI: 0.70–0.99). Moreover, occurrence of minor bleeding complications increased in elective-PCI patients treated with abciximab (RR: 2.94, 95% CI: 1.68–5.13, P<0.001), whereas major bleedings rate was similar (RR: 0.83, 95% CI: 0.27–2.57).Conclusions
Concomitant dosing of abciximab and thienopyridines provides no additional benefit among diabetic patients who underwent PCI; this conclusion, though, needs further confirmation in larger studies. 相似文献8.
Background
Alcohol consumption is increasing worldwide and is associated with numerous cancers. This systematic review examined the role of alcohol in the incidence of cancer in the Chinese population.Methods
Medline/PubMed, EMBASE, CNKI and VIP were searched to identify relevant studies. Cohort and case-control studies on the effect of alcohol use on cancers in Chinese were included. Study quality was evaluated using the Newcastle-Ottawa Scale. Data were independently abstracted by two reviewers. Odds ratios (OR) or relative risks (RR) were pooled using RevMan 5.0. Heterogeneity was evaluated using the Q test and I-squared statistic. P<.01 was considered statistically significant.Results
Pooled results from cohort studies indicated that alcohol consumption was not associated with gastric cancer, esophageal cancers (EC) or lung cancer. Meta-analysis of case-control studies showed that alcohol consumption was a significant risk factor for five cancers; the pooled ORs were 1.79 (99% CI, 1.47–2.17) EC, 1.40 (99% CI, 1.19–1.64) gastric cancer, 1.56 (99% CI, 1.16–2.09) hepatocellular carcinoma, 1.21 (99% CI, 1.00–1.46) nasopharyngeal cancer and 1.71 (99% CI, 1.20–2.44) oral cancer. Pooled ORs of the case-control studies showed that alcohol consumption was protective for female breast cancer and gallbladder cancer: OR 0.76 (99% CI, 0.60–0.97) and 0.70 (99% CI, 0.49–1.00) respectively. There was no significant correlation between alcohol consumption and lung cancer, colorectal cancer, pancreatic cancer, cancer of the ampulla of Vater, prostate cancer or extrahepatic cholangiocarcinoma. Combined results of case-control and cohort studies showed that alcohol consumption was associated with 1.78- and 1.40-fold higher risks of EC and gastric cancer but was not significantly associated with lung cancer.Conclusions
Health programs focused on limiting alcohol intake may be important for cancer control in China. Further studies are needed to examine the interaction between alcohol consumption and other risk factors for cancers in Chinese and other populations. 相似文献9.
Kazem Rahimi Neeraj Bhala Pieter Kamphuisen Jonathan Emberson Sara Biere-Rafi Vera Krane Michele Robertson John Wikstrand John McMurray 《PLoS medicine》2012,9(9)
Background
It has been suggested that statins substantially reduce the risk of venous thromboembolic events. We sought to test this hypothesis by performing a meta-analysis of both published and unpublished results from randomised trials of statins.Methods and Findings
We searched MEDLINE, EMBASE, and Cochrane CENTRAL up to March 2012 for randomised controlled trials comparing statin with no statin, or comparing high dose versus standard dose statin, with 100 or more randomised participants and at least 6 months'' follow-up. Investigators were contacted for unpublished information about venous thromboembolic events during follow-up. Twenty-two trials of statin versus control (105,759 participants) and seven trials of an intensive versus a standard dose statin regimen (40,594 participants) were included. In trials of statin versus control, allocation to statin therapy did not significantly reduce the risk of venous thromboembolic events (465 [0.9%] statin versus 521 [1.0%] control, odds ratio [OR] = 0.89, 95% CI 0.78–1.01, p = 0.08) with no evidence of heterogeneity between effects on deep vein thrombosis (266 versus 311, OR 0.85, 95% CI 0.72–1.01) and effects on pulmonary embolism (205 versus 222, OR 0.92, 95% CI 0.76–1.12). Exclusion of the trial result that provided the motivation for our meta-analysis (JUPITER) had little impact on the findings for venous thromboembolic events (431 [0.9%] versus 461 [1.0%], OR = 0.93 [95% CI 0.82–1.07], p = 0.32 among the other 21 trials). There was no evidence that higher dose statin therapy reduced the risk of venous thromboembolic events compared with standard dose statin therapy (198 [1.0%] versus 202 [1.0%], OR = 0.98, 95% CI 0.80–1.20, p = 0.87). Risk of bias overall was small but a certain degree of effect underestimation due to random error cannot be ruled out. Please see later in the article for the Editors'' Summary.Conclusions
The findings from this meta-analysis do not support the previous suggestion of a large protective effect of statins (or higher dose statins) on venous thromboembolic events. However, a more moderate reduction in risk up to about one-fifth cannot be ruled out. 相似文献10.
Background
The impact of pre-existing diabetes mellitus (DM) on hepatocellular carcinoma (HCC) occurrence and prognosis is complex and unclear. The aim of this meta-analysis is to evaluate the association between pre-existing diabetes mellitus and hepatocellular carcinoma occurrence and prognosis.Methods
We searched PubMed, Embase and the Cochrane Library from their inception to January, 2011 for prospective epidemiological studies assessing the effect of pre-existing diabetes mellitus on hepatocellular carcinoma occurrence, mortality outcomes, cancer recurrence, and treatment-related complications. Study-specific risk estimates were combined by using fixed effect or random effect models.Results
The database search generated a total of 28 prospective studies that met the inclusion criteria. Among these studies, 14 reported the risk of HCC incidence and 6 studies reported risk of HCC specific mortality. Six studies provided a total of 8 results for all-cause mortality in HCC patients. Four studies documented HCC recurrence risks and 2 studies reported risks for hepatic decomposition occurrence in HCC patients. Meta-analysis indicated that pre-existing diabetes mellitus (DM) was significantly associated with increased risk of HCC incidence [meta-relative risk (RR) = 1.87, 95% confidence interval (CI): 1.15–2.27] and HCC-specific mortality (meta-RR = 1.88, 95%CI: 1.39–2.55) compared with their non-DM counterparts. HCC patients with pre-existing DM had a 38% increased (95% CI: 1.13–1.48) risk of death from all-causes and 91% increased (95%CI: 1.41–2.57) risk of hepatic decomposition occurrence compared to those without DM. In DM patients, the meta-RR for HCC recurrence-free survival was 1.93(95%CI: 1.12–3.33) compared with non-diabetic patients.Conclusion
The findings from the current meta-analysis suggest that DM may be both associated with elevated risks of both HCC incidence and mortality. Furthermore, HCC patients with pre-existing diabetes have a poorer prognosis relative to their non-diabetic counterparts. 相似文献11.
Objective
To describe the likely extent of confounding in evaluating the risks of cardiovascular (CV) events and mortality in patients using diabetes medication.Methods
The General Practice Research Database was used to identify inception cohorts of insulin and different oral antidiabetics. An analysis of bias and incidence of mortality, acute coronary syndrome, stroke and heart failure were analysed in GPRD, Hospital Episode Statistics and death certificates.Results
206,940 patients were identified. The bias analysis showed that past thiazolidinedione users had a lower mortality risk compared to past metformin users. There were no differences between past users of rosiglitazone and pioglitazone (adjusted RR of 1.04; 95% CI 0.93–1.18). Current rosiglitazone users had an increased risk of death (adjusted RR 1.20; 95% CI 1.08–1.34) and of hospitalisation for heart failure (adjusted RR of 1.73; 95% CI 1.19–2.51) compared to current pioglitazone users. Risk of mortality was increased two-fold shortly after starting rosiglitazone. Excess risk of death over 3 years with rosiglitazone was 0.3 per 100 in those aged 50–64 years, 2.0 aged 65–74, 3.0 aged 75–84, and 7.0 aged 85+. The cause of death with rosiglitazone was more likely to be due to a disease of the circulatory system.Conclusions
Higher risks for death (overall and due to cardiovascular disease) and heart failure were found for rosiglitazone compared to pioglitazone. These excess risks were largest in patients aged 65 years or older. The European regulatory decision to suspend rosiglitazone is supported by this study. 相似文献12.
Burns KE Adhikari NK Slutsky AS Guyatt GH Villar J Zhang H Zhou Q Cook DJ Stewart TE Meade MO 《PloS one》2011,6(1):e14623
Background
Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are life threatening clinical conditions seen in critically ill patients with diverse underlying illnesses. Lung injury may be perpetuated by ventilation strategies that do not limit lung volumes and airway pressures. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing pressure and volume-limited (PVL) ventilation strategies with more traditional mechanical ventilation in adults with ALI and ARDS.Methods and Findings
We searched Medline, EMBASE, HEALTHSTAR and CENTRAL, related articles on PubMed™, conference proceedings and bibliographies of identified articles for randomized trials comparing PVL ventilation with traditional approaches to ventilation in critically ill adults with ALI and ARDS. Two reviewers independently selected trials, assessed trial quality, and abstracted data. We identified ten trials (n = 1,749) meeting study inclusion criteria. Tidal volumes achieved in control groups were at the lower end of the traditional range of 10–15 mL/kg. We found a clinically important but borderline statistically significant reduction in hospital mortality with PVL [relative risk (RR) 0.84; 95% CI 0.70, 1.00; p = 0.05]. This reduction in risk was attenuated (RR 0.90; 95% CI 0.74, 1.09, p = 0.27) in a sensitivity analysis which excluded 2 trials that combined PVL with open-lung strategies and stopped early for benefit. We found no effect of PVL on barotrauma; however, use of paralytic agents increased significantly with PVL (RR 1.37; 95% CI, 1.04, 1.82; p = 0.03).Conclusions
This systematic review suggests that PVL strategies for mechanical ventilation in ALI and ARDS reduce mortality and are associated with increased use of paralytic agents. 相似文献13.
Yang JJ Cho LY Ko KP Shin A Ma SH Choi BY Han DS Song KS Kim YS Lee JY Han BG Chang SH Shin HR Kang D Yoo KY Park SK 《PloS one》2012,7(2):e31020
Objectives
To evaluate whether genes that encode CagA-interacting molecules (SRC, PTPN11, CRK, CRKL, CSK, c-MET and GRB2) are associated with gastric cancer risk and whether an interaction between these genes and phytoestrogens modify gastric cancer risk.Methods
In the discovery phase, 137 candidate SNPs in seven genes were analyzed in 76 incident gastric cancer cases and 322 matched controls from the Korean Multi-Center Cancer Cohort. Five significant SNPs in three genes (SRC, c-MET and CRK) were re-evaluated in 386 cases and 348 controls in the extension phase. Odds ratios (ORs) for gastric cancer risk were estimated adjusted for age, smoking, H. pylori seropositivity and CagA strain positivity. Summarized ORs in the total study population (462 cases and 670 controls) were presented using pooled- and meta-analysis. Plasma concentrations of phytoestrogens (genistein, daidzein, equol and enterolactone) were measured using the time-resolved fluoroimmunoassay.Results
SRC rs6122566, rs6124914, c-MET rs41739, and CRK rs7208768 showed significant genetic effects for gastric cancer in both the pooled and meta-analysis without heterogeneity (pooled OR = 3.96 [95% CI 2.05–7.65], 1.24 [95% CI = 1.01–1.53], 1.19 [95% CI = 1.01–1.41], and 1.37 [95% CI = 1.15–1.62], respectively; meta OR = 4.59 [95% CI 2.74–7.70], 1.36 [95% CI = 1.09–1.70], 1.20 [95% CI = 1.00–1.44], and 1.32 [95% CI = 1.10–1.57], respectively). Risk allele of CRK rs7208768 had a significantly increased risk for gastric cancer at low phytoestrogen levels (p interaction<0.05).Conclusions
Our findings suggest that SRC, c-MET and CRK play a key role in gastric carcinogenesis by modulating CagA signal transductions and interaction between CRK gene and phytoestrogens modify gastric cancer risk. 相似文献14.
Background
QuantiFERON-TB Gold In Tube (QFT-GIT) is a tool for detecting M. tuberculosis infection. However, interpretation and utility of serial QFT-GIT testing of pediatric tuberculosis (TB) contacts is not well understood. We compared TB prevalence between baseline and 6 months follow-up using QFT-GIT and tuberculin skin testing (TST) in children who were household contacts of adults with pulmonary TB in South Africa, and explored factors associated with QFT-GIT conversions and reversions.Method
Prospective study with six month longitudinal follow-up.Results
Among 270 enrolled pediatric contacts, 196 (73%) underwent 6-month follow-up testing. The 6-month prevalence estimate of MTB infection in pediatric contacts increased significantly from a baseline of 29% (79/270, 95%CI [24–35]) to 38% (103/270, 95% CI [32–44], p<0.001) using QFT-GIT; prevalence increased from a baseline of 28% (71/254, 95%CI [23–34]) to 33% (88/263, 95%CI [21–32], p = 0.002) using TST. Prevalence estimates were influenced by thresholds for positivity for TST, but not for QFT-GIT. Among 134 children with a negative or indeterminate baseline QFT-GIT, 24 (18%) converted to positive at follow-up; conversion rates did not differ significantly when using more stringent thresholds to define QFT-GIT conversion. Older age >10 years (AOR 8.9 95%CI [1.1–72]) and baseline TST positivity ≥5 mm (AOR 5.2 95%CI [1.2–23]) were associated with QFT-GIT conversion. Among 62 children with a positive baseline QFT-GIT, 9 (15%) reverted to negative; female gender (AOR 18.5 95%CI [1.1–321]; p = 0.04] was associated with reversion, while children with baseline positive TST were less likely to have QFT-GIT reversion (AOR 0.01 95%CI [0.001–0.24]).Conclusion
Among pediatric contacts of adult household TB cases in South Africa, prevalence estimates of TB infection increased significantly from baseline to 6 months. Conversions and reversions occurred among pediatric TB contacts using QFT-GIT, but QFT-GIT conversion rates were less influenced by thresholds used for conversions than were TST conversion rates. 相似文献15.
Background
We sought to determine if a common polymorphism can influence vulnerability to LDL cholesterol, and thereby influence the clinical benefit derived from therapies that reduce LDL cholesterol.Methods
We conducted a meta-analysis of the association between a common Trp719Arg polymorphism in the kinesin-like protein 6 (KIF6) gene and the risk of cardiovascular disease (CVD), and a meta-regression analysis to measure the effect modification of this polymorphism on the association between LDL cholesterol and the risk of CVD. We used this measure of genetic effect modification to predict the expected difference in clinical benefit among KIF6 719Arg allele carriers and non-carriers in response to therapies that reduce LDL cholesterol. We then conducted a meta-analysis of statin trials to compare the expected difference in clinical benefit with the observed difference during treatment with a statin.Results
In a meta-analysis involving 144,931 participants, the KIF6 719Arg allele was not associated with the relative risk (RR) of CVD (RR: 1.02, 95%CI: 0.98–1.07, p = 0.288). Meta-regression analysis involving 88,535 participants, however, showed that the 719Arg allele appears to influence the effect of LDL cholesterol on the risk of CVD. KIF6 carriers experienced a 13% greater reduction in the risk of CVD per mmol/L decrease in LDL cholesterol than non-carriers. We interpreted this difference as the expected difference in clinical benefit among KIF6 carriers and non-carriers in response to therapies that lower LDL cholesterol. The difference in clinical benefit predicted by the increased vulnerability to LDL cholesterol among KIF6 carriers (ratio of RR: 0.87, 95%CI: 0.80–0.94, p = 0.001) agreed very closely with the observed difference among 50,060 KIF6 carriers and non-carriers enrolled in 8 randomized trials of statin therapy (ratio of RR: 0.87, 95%CI: 0.77–0.99, p = 0.038).Conclusion
The KIF6 719Arg allele increases vulnerability to LDL cholesterol and thereby influences the expected clinical benefit of therapies that reduce LDL cholesterol. 相似文献16.
Silva Idos S De Stavola B McCormack V;Collaborative Group on Pre-Natal Risk Factors Subsequent Risk of Breast Cancer 《PLoS medicine》2008,5(9):e193
Background
Birth size, perhaps a proxy for prenatal environment, might be a correlate of subsequent breast cancer risk, but findings from epidemiological studies have been inconsistent. We re-analysed individual participant data from published and unpublished studies to obtain more precise estimates of the magnitude and shape of the birth size–breast cancer association.Methods and Findings
Studies were identified through computer-assisted and manual searches, and personal communication with investigators. Individual participant data from 32 studies, comprising 22,058 breast cancer cases, were obtained. Random effect models were used, if appropriate, to combine study-specific estimates of effect. Birth weight was positively associated with breast cancer risk in studies based on birth records (pooled relative risk [RR] per one standard deviation [SD] [= 0.5 kg] increment in birth weight: 1.06; 95% confidence interval [CI] 1.02–1.09) and parental recall when the participants were children (1.02; 95% CI 0.99–1.05), but not in those based on adult self-reports, or maternal recall during the woman''s adulthood (0.98; 95% CI 0.95–1.01) (p for heterogeneity between data sources = 0.003). Relative to women who weighed 3.000–3.499 kg, the risk was 0.96 (CI 0.80–1.16) in those who weighed < 2.500 kg, and 1.12 (95% CI 1.00–1.25) in those who weighed ≥ 4.000 kg (p for linear trend = 0.001) in birth record data. Birth length and head circumference from birth records were also positively associated with breast cancer risk (pooled RR per one SD increment: 1.06 [95% CI 1.03–1.10] and 1.09 [95% CI 1.03–1.15], respectively). Simultaneous adjustment for these three birth size variables showed that length was the strongest independent predictor of risk. The birth size effects did not appear to be confounded or mediated by established breast cancer risk factors and were not modified by age or menopausal status. The cumulative incidence of breast cancer per 100 women by age 80 y in the study populations was estimated to be 10.0, 10.0, 10.4, and 11.5 in those who were, respectively, in the bottom, second, third, and top fourths of the birth length distribution.Conclusions
This pooled analysis of individual participant data is consistent with birth size, and in particular birth length, being an independent correlate of breast cancer risk in adulthood. 相似文献17.
Background
Vandetanib is a multikinase inhibitor that is under assessment for the treatment of various cancers. QTc interval prolongation is one of the major adverse effects of this drug, but the reported incidence varies substantially among clinical trials. We performed a systematic review and meta-analysis to obtain a better understanding in the risk of QTc interval prolongation among cancer patients administered vandetanib.Methodology and Principal Findings
Eligible studies were phase II and III prospective clinical trials that involved cancer patients who were prescribed vandetanib 300 mg/d and that included data on QTc interval prolongation. The overall incidence and risk of QTc interval prolongation were calculated using random-effects or fixed-effects models, depending on the heterogeneity of the included studies. Nine trials with 2,188 patients were included for the meta-analysis. The overall incidence of all-grade and high-grade QTc interval prolongation was 16.4% (95% CI, 8.1–30.4%) and 3.7% (8.1–30.4%), respectively, among non-thyroid cancer patients, and 18.0% (10.7–28.6%) and 12.0% (4.5–28.0%), respectively, among thyroid cancer patients. Patients with thyroid cancer who had longer treatment duration also had a higher incidence of high-grade events, with a relative risk of 3.24 (1.57–6.71), than patients who had non-thyroid cancer. Vandetanib was associated with a significantly increased risk of all-grade QTc interval prolongation with overall Peto odds ratios of 7.26 (4.36–12.09) and 5.70 (3.09–10.53) among patients with non-thyroid cancer and thyroid cancer, respectively, compared to the controls.Conclusions/Significance
Treatment with vandetanib is associated with a significant increase in the overall incidence and risk of QTc interval prolongation. Different cancer types and treatment durations may affect the risk of developing high-grade QTc interval prolongation. 相似文献18.
Background
Several studies have reported a reduction in acute coronary events (ACEs) in the general population after the enforcement of smoking regulations, although there is uncertainty concerning the magnitude of the effect of such interventions. We conducted a country-wide evaluation of the health effects of the introduction of a smoking ban in public places, using data on hospital admissions for ACEs from the Italian population after the implementation of a national smoking regulation in January 2005.Methods and Findings
Rates of admission for ACEs in the 20 Italian regions from January 2002 to November 2006 were analysed using mixed-effect regression models that allowed for long-term trends and seasonality. Standard methods for interrupted time-series were adopted to assess the immediate and gradual effects of the smoking ban. Effect modification by age was investigated, with the assumption that exposure to passive smoking in public places would be greater among young people. In total, 936,519 hospital admissions for ACEs occurred in the Italian population during the study period. A 4% reduction in hospital admissions for ACEs among persons aged less than 70 years was evident after the introduction of the ban (Rate Ratio [RR], 0.96; 95% Confidence Interval [CI], 0.95–0.98). No effect was found among persons aged at least 70 years (RR 1.00; 95% CI 0.99–1.02). Effect modification by age was further suggested by analyses using narrower age categories.Conclusions
Smoke-free policies can constitute a simple and inexpensive intervention for the prevention of cardiovascular diseases and thus should be included in prevention programmes. 相似文献19.
Background
The mortality rate from unnatural deaths for South Africa is nearly double the world average. Reliable data are limited by inaccurate and incomplete ascertainment of specific causes of unnatural death. This study describes trends in causes of unnatural death between 1992 and 2008 in a cohort of South African miners.Methodology/Principal Findings
The study used routinely-collected retrospective data with cause of death determined from multiple sources including the mine''s human resources database, medical records, death registration, and autopsy. Cause-specific mortality rates and Poisson regression coefficients were calculated by calendar year and age group. The cohort included 40,043 men. One quarter of all 2937 deaths were from unnatural causes (n = 805). Causes of unnatural deaths were road traffic accidents 38% (109/100,000 py), homicides 30% (88/100,000 py), occupational injuries 17% (50/100,000 py), suicides 8% (24/100,000 py), and other accidents 6% (19/100,000 py). Rates of unnatural deaths declined by 2% (95%CI -4%,-1%) per year over the study period, driven by declining rates of road traffic and other accidents. The rate of occupational injury mortality did not change significantly over time (-2% per year, 95%CI -5%,+2%). Unnatural deaths were less frequent in this cohort of workers than in the South African population (IRR 0.89, 95%CI 0.82–0.95), particularly homicides (IRR 0.48, 95%CI 0.42–0.55).Conclusions/Significance
Unnatural deaths were a common cause of preventable and premature death in this cohort of miners. While unnatural death rates declined between 1992 and 2008, occupational fatalities remained at a high level. Evidence-based prevention strategies to address these avoidable deaths are urgently needed. 相似文献20.