scholarly journals Joining the Dots: Linking Disconnected Networks of Evidence Using Dose-Response Model-Based Network Meta-Analysis

2021 ◽  
Vol 41 (2) ◽  
pp. 194-208
Author(s):  
Hugo Pedder ◽  
Sofia Dias ◽  
Meg Bennetts ◽  
Martin Boucher ◽  
Nicky J. Welton
Keyword(s):  
Dose Response ◽  
Meta Analysis ◽  
Relative Effectiveness ◽  
Data Sets ◽  
Response Relationship ◽  
Phase Ii Trials ◽  
Dose Response Relationship ◽  
Data Set ◽  
Model Based ◽  
Multiple Doses

Background Network meta-analysis (NMA) synthesizes direct and indirect evidence on multiple treatments to estimate their relative effectiveness. However, comparisons between disconnected treatments are not possible without making strong assumptions. When studies including multiple doses of the same drug are available, model-based NMA (MBNMA) presents a novel solution to this problem by modeling a parametric dose-response relationship within an NMA framework. In this article, we illustrate several scenarios in which dose-response MBNMA can connect and strengthen evidence networks. Methods We created illustrative data sets by removing studies or treatments from an NMA of triptans for migraine relief. We fitted MBNMA models with different dose-response relationships. For connected networks, we compared MBNMA estimates with NMA estimates. For disconnected networks, we compared MBNMA estimates with NMA estimates from an “augmented” network connected by adding studies or treatments back into the data set. Results In connected networks, relative effect estimates from MBNMA were more precise than those from NMA models (ratio of posterior SDs NMA v. MBNMA: median = 1.13; range = 1.04–1.68). In disconnected networks, MBNMA provided estimates for all treatments where NMA could not and were consistent with NMA estimates from augmented networks for 15 of 18 data sets. In the remaining 3 of 18 data sets, a more complex dose-response relationship was required than could be fitted with the available evidence. Conclusions Where information on multiple doses is available, MBNMA can connect disconnected networks and increase precision while making less strong assumptions than alternative approaches. MBNMA relies on correct specification of the dose-response relationship, which requires sufficient data at different doses to allow reliable estimation. We recommend that systematic reviews for NMA search for and include evidence (including phase II trials) on multiple doses of agents where available.

Blood Pressure, Hypertension and The Risk of Aortic Dissection Incidence and Mortality: results from the Japan-Specific Health Checkups Study, the UK Biobank Study and a Meta-analysis of Cohort Studies

Circulation ◽  
2021 ◽  
Author(s):  
Makoto Hibino ◽  
Yoichiro Otaki ◽  
Elsa Kobeissi ◽  
Han Pan ◽  
Hiromi Hibino ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Aortic Dissection ◽  
Dose Response ◽  
Meta Analysis ◽  
Response Relationship ◽  
Uk Biobank ◽  
Dose Response Relationship ◽  
Fractional Polynomial ◽  
The Uk ◽  
Specific Health

Background: Hypertension or elevated blood pressure (BP) is an important risk factor for aortic dissection (AD); however, few prospective studies concerning this topic have been published. We investigated the association between hypertension/elevated BP and AD in two cohorts and conducted a meta-analysis of published prospective studies, including these two studies. Methods: We analyzed data from the Japan Specific Health Checkups (J-SHC) Study and UK Biobank, which prospectively followed 534,378 and 502,424 participants, respectively. Multivariable Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of hypertension/elevated BP with AD incidence in the UK Biobank and AD mortality in the J-SHC Study. In the meta-analysis, summary relative risks (RRs) were calculated using random effects models. A potential nonlinear dose-response relationship between BP and AD was tested using fractional polynomial models, and the best-fitting second-order fractional polynomial regression model was determined. Results: In the J-SHC Study and UK Biobank, there were 84 and 182 ADs during 4- and 9-year follow-up, and the adjusted HRs of AD were 3.57 (95% CI, 2.17-6.11) and 2.68 (95% CI: 1.78-4.04) in hypertensive individuals, 1.33 (95% CI: 1.05-1.68) and 1.27 (95% CI: 1.11-1.48) per 20-mmHg increase in systolic BP (SBP), and 1.67 (95% CI: 1.40-2.00) and 1.66 (95% CI: 1.46-1.89) per 10-mmHg increase in diastolic BP (DBP), respectively. In the meta-analysis, the summary RRs were 3.07 (95% CI 2.15-4.38, I2=76.7%, n=7 studies, 2,818 ADs, 4,563,501 participants) for hypertension and 1.39 (95% CI: 1.16-1.66, I2=47.7%, n=3) and 1.79 (95% CI: 1.51-2.12, I2=57.0%, n=3) per 20-mmHg increase in SBP and per 10-mmHg in DBP, respectively. The AD risk showed a strong, positive dose-response relationship with SBP and even more so with DBP. The risk of AD in the nonlinear dose-response analysis was significant at SBP >132 mmHg and DBP >75 mmHg. Conclusions: Hypertension and elevated SBP and DBP are associated with a high risk of AD. The risk of AD was positively dose-dependent, even within the normal BP range. These findings provide further evidence for the optimization of BP to prevent AD.

Abstract P209: Dose-Response Relationship Between Dietary Intake of Alpha-linolenic Acid and Risk of Coronary Heart Disease: A Meta-analysis of Prospective Studies

Circulation ◽  
2017 ◽  
Vol 135 (suppl_1) ◽  
Author(s):  
Jingkai Wei ◽  
Yuzhi Xi ◽  
Ruixue Hou ◽  
Alysse Kowalski ◽  
Hao Sun ◽  
...  
Keyword(s):  
Dose Response ◽  
Meta Analysis ◽  
Pooled Analysis ◽  
Controlled Trials ◽  
Response Relationship ◽  
Alpha Linolenic Acid ◽  
Dose Response Relationship ◽  
Randomized Controlled ◽  
Chd Risk ◽  
Reduced Risk

Introduction: Previous studies show that alpha-linolenic acid (ALA) is associated with reduced risk of coronary heart disease (CHD). However, it remains unclear whether and how dietary ALA doses are related to CHD. Hypothesis: We hypothesized that higher dietary ALA intake is associated with a greater reduction in risk of CHD. Methods: We searched PubMed, EMBASE, and Web of Science for prospective studies examining the association between dietary ALA intake and CHD risk. Dietary ALA intake was assigned or measured by self-report. Outcomes were reported as total and fatal CHD and/or myocardial infarction, which were obtained from blinded endpoint assessments or medical records. Two-stage fixed-effects dose-response meta-analyses were conducted to estimate the association between increasing ALA intake (relative to study-specific referents) and CHD. Results: Fifteen published articles were identified and included in the meta-analysis (13 cohort studies and 2 randomized controlled trials). The pooled analysis was based on 310,768 individuals with 12,049 events with a mean length of follow-up of 9.6 years. The analysis showed a J-shaped curve between ALA intake and relative risk of total CHD (Chi-square=21.08, p<0.001). ALA intake from 0.3-1.4g/day showed reduced risk of total CHD, while intake ≥2.5g/day was associated with increased risk of CHD, compared to people without ALA intake (Figure 1A). Approximately 1g/day of ALA intake was associated with the lowest risk of total CHD. ALA intake was linearly associated with fatal CHD - every 1g/day increase in ALA intake was associated with an 11% decrease in fatal CHD risk (95% CI: -0.16, -0.05) (Figure 1B). Conclusion: The J-shaped dose-response relationship based on our pooled analysis suggests that 1g/day of dietary ALA may be optimal for total CHD prevention. Though a higher dietary ALA intake was associated with reduced risk of fatal CHD, the excess total CHD risk at higher ALA intakes warrants further investigation, especially through randomized controlled trials.

scholarly journals Dose-Response Relationship Between Serum 2,3,7,8-Tetrachlorodibenzo-p-Dioxin and Diabetes Mellitus: A Meta-Analysis

2015 ◽  
Vol 181 (6) ◽  
pp. 374-384 ◽  
Author(s):  
Michael Goodman ◽  
K. M. Venkat Narayan ◽  
Dana Flanders ◽  
Ellen T. Chang ◽  
Hans-Olov Adami ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Dose Response ◽  
Meta Analysis ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Tetrachlorodibenzo P Dioxin

scholarly journals The association and dose–response relationship between dietary intake of α-linolenic acid and risk of CHD: a systematic review and meta-analysis of cohort studies

2018 ◽  
Vol 119 (1) ◽  
pp. 83-89 ◽  
Author(s):  
Jingkai Wei ◽  
Ruixue Hou ◽  
Yuzhi Xi ◽  
Alysse Kowalski ◽  
Tiansheng Wang ◽  
...  
Keyword(s):  
Cohort Studies ◽  
Linolenic Acid ◽  
Random Effects ◽  
Dose Response ◽  
Meta Analysis ◽  
Geographic Region ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Chd Risk ◽  
Reduced Risk

AbstractPrevious studies show inconsistent associations between α-linolenic acid (ALA) and risk of CHD. We aimed to examine an aggregate association between ALA intake and risk of CHD, and assess for any dose–response relationship. We searched the PubMed, EMBASE and Web of Science databases for prospective cohort studies examining associations between ALA intake and CHD, including composite CHD and fatal CHD. Data were pooled using random-effects meta-analysis models, comparing the highest category of ALA intake with the lowest across studies. Subgroup analysis was conducted based on study design, geographic region, age and sex. For dose–response analyses, we used two-stage random-effects dose–response models. In all, fourteen studies of thirteen cohorts were identified and included in the meta-analysis. The pooled results showed that higher ALA intake was associated with modest reduced risk of composite CHD (risk ratios (RR)=0·91; 95 % CI 0·85, 0·97) and fatal CHD (RR=0·85; 95 % CI 0·75, 0·96). The analysis showed a J-shaped relationship between ALA intake and relative risk of composite CHD (χ2=21·95, P<0·001). Compared with people without ALA intake, only people with ALA intake <1·4 g/d showed reduced risk of composite CHD. ALA intake was linearly associated with fatal CHD – every 1 g/d increase in ALA intake was associated with a 12 % decrease in fatal CHD risk (95 % CI −0·21, −0·04). Though a higher dietary ALA intake was associated with reduced risk of composite and fatal CHD, the excess composite CHD risk at higher ALA intakes warrants further investigation, especially through randomised controlled trials.

Shift work and ischaemic heart disease: meta-analysis and dose–response relationship

2019 ◽  
Vol 69 (3) ◽  
pp. 182-188 ◽  
Author(s):  
Man Cheng ◽  
Heng He ◽  
Dongming Wang ◽  
Luli Xu ◽  
Bin Wang ◽  
...  
Keyword(s):  
Heart Disease ◽  
Ischaemic Heart Disease ◽  
Shift Work ◽  
Dose Response ◽  
Meta Analysis ◽  
Response Relationship ◽  
Dose Response Relationship

scholarly journals Fruit and Vegetable Intake and the Risk of Chronic Obstructive Pulmonary Disease: A Dose-Response Meta-Analysis of Observational Studies

2020 ◽  
Vol 2020 ◽  
pp. 1-12
Author(s):  
Hongrui Zhai ◽  
Yu Wang ◽  
Wenjie Jiang
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Dose Response ◽  
Vegetable Intake ◽  
Meta Analysis ◽  
Fruit And Vegetable Intake ◽  
Chronic Obstructive ◽  
Response Relationship ◽  
Fruit And Vegetable ◽  
Dose Response Relationship ◽  
Obstructive Pulmonary Disease

Object. Results on the associations of fruit and vegetable intake with risk of chronic obstructive pulmonary disease (COPD) are still in conflict. Hence, we conducted a meta-analysis to quantitatively evaluate the association between fruit and vegetable intake and the risk of COPD. Methods. PubMed, Web of Science, and China National Knowledge Infrastructure (CNKI) were searched for relevant studies published up to September 2019. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated with the random effects model (REM). Dose-response relationship was assessed by the restricted cubic spline model. Results. There are 8 studies involving 5,787 COPD cases among 244,154 participants included in this meta-analysis. For the highest versus the lowest level, the pooled RR of COPD was 0.75 (95% CI, 0.68–0.84; I2 = 46.7%) for fruits plus vegetables, 0.72 (95% CI, 0.66–0.79; I2 = 1.3%) for fruits, and 0.76 (95% CI, 0.63–0.92; I2 = 62.7%) for vegetables. In subgroup analysis of fruit plus vegetable intake and COPD risk, the inverse association exists in all three study designs. A nonlinear dose-response relationship was found for COPD risk with fruit (Pnon−linearity<0.01). Conclusions. This meta-analysis indicates that fruit and vegetable intake might be related to a lower risk of COPD.

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