scholarly journals The level of bilirubin and the risk of ischemic stroke: a systematic review and dose-response meta-analysis of real-world studies

2020 ◽  
Author(s):  
Xiao Wang ◽  
Yang Zhou ◽  
Xiaofei Ye ◽  
Fangchen Liu ◽  
Xi Zhu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Dose Response ◽  
Meta Analysis ◽  
Epidemiological Studies ◽  
Secondary Outcome ◽  
Serum Total Bilirubin ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Meta Analyses ◽  
The Relationship

Abstract Background: Bilirubin, a marker of hepatic and hematological diseases in clinical practice, is not only a waste end-product but also an antioxidant that may protect against diseases associated with oxidative stress. Numerous epidemiological studies have shown an inverse relationship between the serum total bilirubin (TBIL) level and the risk of ischemic stroke (IS). However, markedly elevated TBIL levels may exert neurotoxic effects. Based on this, we conducted a dose-response meta-analysis to quantify the relationship between blood TBIL and IS as well as between TBIL and all types of stroke (AS) in the physiological range of bilirubin.Methods: PubMed, Embase, Web of Science, and Cochrane Central databases were searched up to March 2019. Additional studies were identified by reviewing references and contacting authors. Categorical and dose-response meta-analyses were performed to quantify the relationship between TBIL and IS. The primary outcome was ischemic stroke, and the secondary outcome was all types of stroke.Results: Nine observational studies (seven publications) involving 110,032 participants and 3710 stroke cases were included for analysis. The average OR of IS for every 1 µmol/L increment in TBIL level was 0.978 (95% CI: 0.957–0.999). The summary OR of AS for every 1 µmol/L increment in TBIL level was 0.974 (95% CI: 0.956–0.992). Subgroup analysis based on gender showed a negative dose-response relationship between the circulating TBIL level and IS or AS in males, but not in females.Conclusions: The present study found a negative dose-response relationship between the circulating TBIL level and the risk of IS or AS within physiologic range of serum TBIL in males. Moderately elevated blood TBIL levels might be associated with a diminished prevalence of IS. Every 1 µmol/L increment in serum TBIL level was associated with a 2.2% decrease in the risk of IS and a 2.6% decrease in the risk of AS. However, due to the limitations in the number of included studies and their quality, large-scaled prospective cohort studies are needed to confirm the conclusion of the current analysis.Trial registration: This study was registered at PROSPERO (https://www.crd. york.ac.uk/PROSPERO/[CRD42017075988]).

scholarly journals The level of Bilirubin and the risk of ischemic stroke: a systematic review and dose-response meta-analysis of real-world studies

2019 ◽  
Author(s):  
Xiao Wang ◽  
Yang Zhou ◽  
Xiaofei Ye ◽  
Fangchen Liu ◽  
Xi Zhu ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Dose Response ◽  
Meta Analysis ◽  
Epidemiological Studies ◽  
Secondary Outcome ◽  
Serum Total Bilirubin ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Meta Analyses ◽  
The Relationship

Abstract Background: Bilirubin, a marker of hepatic and hematological diseases in clinical practice, is not only a waste end-product but also an antioxidant that may protect against diseases associated with oxidative stress. Numerous epidemiological studies have shown an inverse relationship between the serum total bilirubin (TB) level and the risk of ischemic stroke (IS). However, markedly elevated TB levels may exert neurotoxic effects. Based on this, we conducted a dose-response meta-analysis to quantify the relationship between blood TB and IS as well as between TB and all types of stroke (AS) in the physiological range of bilirubin.Methods: PubMed, Embase, Web of Science, and Cochrane Central databases were searched up to March 2019. Additional studies were identified by reviewing references and contacting authors. Categorical and dose-response meta-analyses were performed to quantify the relationship between TB and IS. The primary outcome was ischemic stroke, and the secondary outcome was all types of stroke.Results: Nine observational studies (seven publications) involving 110,032 participants and 3710 stroke cases were included for analysis. The average OR of IS for every 1 µmol/L increment in TB level was 0.978 (95%CI: 0.957–0.999). The summary OR of AS for every 1 µmol/L increment in TB level was 0.974 (95%CI: 0.956–0.992). Subgroup analysis based on gender showed a negative dose-response relationship between the circulating TB level and IS or AS in males, but not in females.Conclusions: The present study indicates a negative dose-response relationship between the circulating TB level and the risk of IS or AS within physiologic range of serum TB in males. Moderately elevated blood TB levels were associated with a diminished prevalence of IS. Every 1 µmol/L increment in serum TB level was associated with a 2.2% decrease in the risk of IS and a 2.6% decrease in the risk of AS. Large-scaled prospective studies are needed to confirm the conclusion of the current analysis.Trial registration: This study was registered at PROSPERO(https://www.crd. york.ac.uk/PROSPERO/[CRD42017075988]).

scholarly journals Alcohol consumption and incidence of prostate cancer among Chinese people: A systematic review and meta-analysis

2020 ◽  
Vol 8 (1) ◽  
pp. 12-28
Author(s):  
Jinhui Zhao ◽  
Di Gao ◽  
Yanhui Li ◽  
Tim Stockwell ◽  
Jun Ma
Keyword(s):  
Prostate Cancer ◽  
Alcohol Consumption ◽  
Dose Response ◽  
Alcohol Intake ◽  
Meta Analysis ◽  
Chinese Language ◽  
Response Relationship ◽  
Chinese People ◽  
Dose Response Relationship ◽  
Meta Analyses

Aims: Meta-analyses have suggested a dose-response relationship between level of alcohol use and risk of prostate cancer, but the populations in the included studies are predominantly Caucasian. Many Chinese language studies have not been included in published reviews and/or meta-analyses. The present meta–analysis accessed research reports in both English and Chinese language sources in order to investigate this relationship specifically among Chinese people. Methods: Searches in five large Chinese biomedical bibliographic databases were made for case–control and cohort studies of alcohol consumption and prostate cancer incidence and death (ICD–10: C61) up to May 2017. Studies were coded for design, outcome, drinker and non-drinkers, extent of control for confounding and other study characteristics. Mixed models were used to estimate relative risk (RR) of incidence or death from prostate cancer due to alcohol consumption with study level controls for designs, drinker bias and types of drinkers. Findings: A total of 415 studies were identified of which 25 (20 in Chinese from five Chinese databases and 5 in English from published meta-analyses) satisfied inclusion criteria providing 36 risk estimates of prostate cancer for drinkers versus non-drinkers. There was a total of 36 OR estimates; 27 using patients as controls and 9 using healthy people. Nine studies (14 OR estimates) specified reference abstainers as “never drank” or “no drinking”. Adjusted RR estimates indicated a significantly increased risk of prostate cancer among drinkers (RR=1.46, 95% CI: 1.40 – 1.52, t-test P<0.001) compared to non-drinkers. Dose-response relationships (t-test P<0.001) were evident in three studies that assessed level of alcohol intake. Conclusions: There is a significantly higher risk of prostate cancer incidence among Chinese drinkers than non-drinkers, with some evidence of a dose-response relationship. However, almost all the identified studies suffered from former and/or occasional drinker biases. Few studies had adequate measures of level of alcohol intake and further well-designed studies are required.

Dose-Response Relationship in Selective Serotonin and Norepinephrine Reuptake Inhibitors in the Treatment of Major Depressive Disorder: A Meta-Analysis and Network Meta-Analysis of Randomized Controlled Trials

2021 ◽  
pp. 1-10
Author(s):  
Lena Rink ◽  
Anne Adams ◽  
Cora Braun ◽  
Tom Bschor ◽  
Kathrin Kuhr ◽  
...  
Keyword(s):  
Major Depressive Disorder ◽  
Depressive Disorder ◽  
Dose Response ◽  
Meta Analysis ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Major Depressive ◽  
Meta Analyses ◽  
Higher Doses ◽  
Norepinephrine Reuptake

<b><i>Introduction:</i></b> Selective serotonin and norepinephrine reuptake inhibitors (SNRI) are among the most prescribed antidepressants, and dose escalation is a frequently applied strategy after non-response to an initially prescribed dose. <b><i>Objective:</i></b> This meta-analysis aimed to find evidence of a dose-response relationship or to the contrary in direct comparisons of different SNRI doses in patients with major depressive disorder. <b><i>Methods:</i></b> A systematic literature search for RCTs comparing at least two doses of SNRIs was carried out in CENTRAL, PubMed, PsycINFO, and EMBASE. Doses were classified as high, medium, and low according to manufacturers’ product monographs and analyses at the level of SNRIs as a group and for single substances, accompanied by sensitivity network meta-analyses (Prospero CRD42018081031). <b><i>Results:</i></b> From 2,070 studies screened, we included 26 studies with a total of 10,242 patients. Comparisons of medium versus low and high versus medium doses resulted in clinically and statistically non-significant standardized mean differences of –0.06 (–0.16 to 0.04) and –0.06 (–0.16 to 0.03) in favor of higher doses. In the analyses of single substances, no statistically significant results emerged, and many contrasts yielded very small effect sizes. Dropouts due to side effects tended to be more frequent with higher doses. Heterogeneity was low. Network meta-analyses of direct comparisons supported the findings, as did a risk of bias analysis. <b><i>Conclusion:</i></b> Based on the lack of positive evidence for a dose-response relationship in SNRIs as a group and in single SNRIs, we recommend prescribing medium doses. In case of insufficient response, we do not recommend increasing the dose of SNRIs.

scholarly journals Dietary magnesium and calcium intake and risk of depression in the general population: A meta-analysis

2016 ◽  
Vol 51 (3) ◽  
pp. 219-229 ◽  
Author(s):  
Bingrong Li ◽  
Jing Lv ◽  
Weijing Wang ◽  
Dongfeng Zhang
Keyword(s):  
Relative Risk ◽  
Confidence Interval ◽  
Dose Response ◽  
Meta Analysis ◽  
Epidemiological Studies ◽  
Response Analysis ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Relative Risks ◽  
Dietary Magnesium

Objective: Several epidemiological studies have evaluated the associations between dietary magnesium (Mg) and calcium (Ca) intake and the risk of depression. However, the results of these studies remain controversial. Thus, we performed a meta-analysis to explore these associations and to investigate the possible dose–response relationship between dietary Mg intake and risk of depression. Methods: MEDLINE, Web of Science, Embase, Cochrane CENTRAL, CINAHL database, Chinese National Knowledge Infrastructure, Wan fang databases and Databases of Chinese Scientific and Technical Periodicals were searched for eligible publications up to September 2016. Pooled relative risks with 95% confidence intervals were calculated using random-effects model. Publication bias was estimated using Egger’s test and the funnel plot. Dose–response relationship was assessed by restricted cubic spline functions. Results: A total of 17 epidemiological studies from 12 articles were included in the present meta-analysis. Among these studies, 11 studies evaluated the association between dietary Mg intake and risk of depression and 6 studies evaluated the association between dietary Ca intake and risk of depression. When comparing the highest with the lowest intake, the pooled relative risks of depression were 0.81 (95% confidence interval = [0.70, 0.92]) for Mg and 0.66 (95% confidence interval = [0.42, 1.02]) for Ca. Dietary Mg intake was significantly associated with a reduced risk of depression among studies conducted in Asia (relative risk  = 0.57; 95% confidence interval = [0.44, 0.74]) and in studies adjusting for energy intake (relative risk  = 0.73; 95% confidence interval = [0.58, 0.92]). For dose–response analysis, evidence of a nonlinear relationship was found between dietary Mg intake and risk of depression, and the largest risk reductions were observed for 320 mg/day. Conclusion: This meta-analysis indicated that moderate Mg intake may be inversely associated with the risk of depression, which still needs to be confirmed by larger prospective cohort studies.

scholarly journals Dose–Response Relationship between Physical Workload and Specific Shoulder Diseases—A Systematic Review with Meta-Analysis

2020 ◽  
Vol 17 (4) ◽  
pp. 1243
Author(s):  
Andreas Seidler ◽  
Karla Romero Starke ◽  
Alice Freiberg ◽  
Janice Hegewald ◽  
Albert Nienhaus ◽  
...  
Keyword(s):  
Systematic Review ◽  
Rotator Cuff ◽  
Dose Response ◽  
Meta Analysis ◽  
Epidemiological Studies ◽  
Physical Workload ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Doubling Dose ◽  
Risk Increase

Several epidemiological studies have found an association between shoulder-loaded work activities and specific shoulder diseases. No study has derived the dose-response relationship and resulting doubling dose, important for the recognition of occupational diseases. This systematic review is an update of the van der Molen et al. (2017) review. Based on its methodologies, we identified new studies published up to November 2018. The dose-response relationship between physical occupational demands (hands at/above shoulder level, repetitive movements, forceful work, hand-arm vibrations) and specific shoulder diseases (defined as ICD-10 M 75.1-5: rotator cuff syndrome, bicipital tendinitis, calcific tendinitis, impingement, and bursitis) was derived. No evidence for sex-specific differences in the dose-response relationship was found. If there were at least two studies with comparable exposures, a meta-analysis was carried out. The pooled analysis resulted in a 21% risk increase (95% CI 4–41%) per 1000 h of work with hands above shoulder level. A meta-analysis was not possible for other occupational burdens due to the low number of studies and differing exposure measurements; an estimate of the doubling dose was made based on the cohort study of Dalbøge et al. (2014). To conclude, the present systematic review with meta-analysis contributes to knowledge of the level of exposure at which specific shoulder diseases—particularly rotator cuff lesions—should be recognized as an occupational disease.

Underestimation of Dose - Response Relationship with Particular Reference to the Relationship between the Dietary Intake of Mercury and its Concentration in Blood

1988 ◽  
Vol 7 (2) ◽  
pp. 129-132 ◽  
Author(s):  
J.C. Sherlock ◽  
M.J. Quinn
Keyword(s):  
Linear Regression ◽  
Dietary Intake ◽  
Dose Response ◽  
Mercury Concentration ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Blood Mercury ◽  
Relationship Of ◽  
The Relationship ◽  
Blood Mercury Concentration

Wide discrepancies have been observed between controlled and uncontrolled intake studies of the relationship of blood mercury concentration to intake of mercury. The probable reason for the apparent discrepancies is that the within-subject variation of mercury intake in the uncontrolled studies was almost certainly considerably larger than the within-subject variation in blood mercury concentration; in these circumstances, the apparent slope obtained from a linear regression of blood mercury on intake will invariably be much smaller than the true slope. Studies of the exposure or intake of any substance should therefore include a consideration of the likely within-subject variation in the exposure or intake relative to that in the effect.

scholarly journals Association of psychiatric comorbidities with the risk of transport accidents in ADHD and MPH

2021 ◽  
Vol 30 ◽  
Author(s):  
Yi-Chun Liu ◽  
Vincent Chin-Hung Chen ◽  
Yao-Hsu Yang ◽  
Yi-Lung Chen ◽  
Michael Gossop
Keyword(s):  
Dose Response ◽  
Case Series ◽  
Autism Spectrum ◽  
Research Database ◽  
Accident Risk ◽  
Response Relationship ◽  
Dose Response Relationship ◽  
Series Analysis ◽  
The Relationship ◽  
Transport Accidents

Abstract Aims Although the relationship between attention-deficit/hyperactivity disorder (ADHD) and transport accidents has been shown, there is limited information on the relationship between medication and dose–response effects and transport accident risk. This study aims to determine whether young people with ADHD, including adolescents, are more prone to transport accidents than those without, and the extent to which methylphenidate (MPH) prescription in these patients reduces the risk. Methods We identified 114 486 patients diagnosed with ADHD from Taiwan's National Health Insurance Research Database from 1997 to 2013. Using a Cox regression model, we compared the risk of transport accidents between ADHD and non-ADHD groups and estimated the effect of MPH on accidents. Furthermore, we applied a self-control case-series analysis to compare the risk of accidents during the medication periods with the same patients' non-medication periods. Results Male ADHD patients had a higher risk of transport accidents than non-ADHD individuals (adjusted hazard ratio [aHR] = 1.24, [95% confidence interval (CI) 1.10–1.39]), especially for those comorbid with epilepsy, oppositional defiant disorder/conduct disorder (ODD/CD), and intellectual disabilities (ID). Female ADHD patients showed no relationship, except for comorbid with autism spectrum disorder (ASD) or ID. We found a reduced risk of transport accidents in patients with ADHD with MPH medication than those without MPH, with a plausible dose–response relationship (aHR of 0.23 to 0.07). A similar pattern was found in self-controlled case-series analysis. Conclusions Male patients with ADHD, especially those comorbid with epilepsy, ODD/CD, or ID, were at high risk of transport accidents. Female patients, when comorbid with ASD or ID, also exhibited a higher risk of accidents. MPH treatment lowered the accident risk with a dose–response relationship.

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.

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