An informatics consult approach for generating clinical evidence for treatment decisions

Abstract Background An Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis. Methods We examined four sources of evidence for the effect of warfarin on stroke risk or all-cause mortality from: (1) randomised controlled trials (RCTs), (2) meta-analysis of prior observational studies, (3) trial emulation (using population electronic health records (N = 3,854,710) and (4) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems. Results We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71, CI 0.39–1.29). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61, CI 0.49–0.76) and ischaemic stroke (HR = 0.27, CI 0.08–0.91). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results. Conclusion We performed a proof-of-concept Informatics Consult for evidence generation, which may inform treatment decisions in situations where there is dearth of randomised trials. Patients are surprised to know that their clinicians are currently not able to learn in clinic from data on ‘patients like me’. We identify the key challenges in offering such an Informatics Consult as a service.

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An Informatics Consult approach for generating clinical evidence for treatment decisions

10.1101/2021.01.10.21249331 ◽

2021 ◽

Author(s):

Alvina G. Lai ◽

Wai Hoong Chang ◽

Constantinos A. Parisinos ◽

Michail Katsoulis ◽

Ruth M. Blackburn ◽

...

Keyword(s):

Observational Studies ◽

Large Scale ◽

Stroke Risk ◽

Meta Analysis ◽

Return Of Results ◽

Mendelian Randomisation ◽

Vitamin K1 ◽

Specific Patient ◽

All Cause Mortality ◽

Electronic Health

AbstractAn Informatics Consult has been proposed in which clinicians request novel evidence from large scale health data resources, tailored to the treatment of a specific patient, with return of results in clinical timescales. However, the availability of such consultations is lacking. We seek to provide an Informatics Consult for a situation where a treatment indication and contraindication coexist in the same patient, i.e., anti-coagulation use for stroke prevention in a patient with both atrial fibrillation (AF) and liver cirrhosis. We examined four sources of evidence for the effect of warfarin on stroke risk (efficacy) or all-cause mortality (safety) from: (i) randomised controlled trials (RCTs), (ii) meta- analysis of prior observational studies, (iii) trial emulation (using population electronic health records (N = 3,854,710) and (iv) genetic evidence (Mendelian randomisation). We developed prototype forms to request an Informatics Consult and return of results in electronic health record systems. We found 0 RCT reports and 0 trials recruiting for patients with AF and cirrhosis. We found broad concordance across the three new sources of evidence we generated. Meta-analysis of prior observational studies showed that warfarin use was associated with lower stroke risk (hazard ratio [HR] = 0.71). In a target trial emulation, warfarin was associated with lower all-cause mortality (HR = 0.61) and ischaemic stroke (HR = 0.27). Mendelian randomisation served as a drug target validation where we found that lower levels of vitamin K1 (warfarin is a vitamin K1 antagonist) are associated with lower stroke risk. A pilot survey with an independent sample of 34 clinicians revealed that 85% of clinicians found information on prognosis useful and that 79% thought that they should have access to the Informatics Consult as a service within their healthcare systems. We identified candidate steps for automation to scale evidence generation and to accelerate the return of results within clinical timescales.

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Approaches for combining primary care electronic health record data from multiple sources: a systematic review of observational studies

BMJ Open ◽

10.1136/bmjopen-2020-037405 ◽

2020 ◽

Vol 10 (10) ◽

pp. e037405

Author(s):

Daniel Dedman ◽

Melissa Cabecinha ◽

Rachael Williams ◽

Stephen J W Evans ◽

Krishnan Bhaskaran ◽

...

Keyword(s):

Systematic Review ◽

Primary Care ◽

Electronic Health Record ◽

Observational Studies ◽

Meta Analysis ◽

Data Sources ◽

Health Record ◽

Two Stage ◽

One Stage ◽

Electronic Health

ObjectiveTo identify observational studies which used data from more than one primary care electronic health record (EHR) database, and summarise key characteristics including: objective and rationale for using multiple data sources; methods used to manage, analyse and (where applicable) combine data; and approaches used to assess and report heterogeneity between data sources.DesignA systematic review of published studies.Data sourcesPubmed and Embase databases were searched using list of named primary care EHR databases; supplementary hand searches of reference list of studies were retained after initial screening.Study selectionObservational studies published between January 2000 and May 2018 were selected, which included at least two different primary care EHR databases.Results6054 studies were identified from database and hand searches, and 109 were included in the final review, the majority published between 2014 and 2018. Included studies used 38 different primary care EHR data sources. Forty-seven studies (44%) were descriptive or methodological. Of 62 analytical studies, 22 (36%) presented separate results from each database, with no attempt to combine them; 29 (48%) combined individual patient data in a one-stage meta-analysis and 21 (34%) combined estimates from each database using two-stage meta-analysis. Discussion and exploration of heterogeneity was inconsistent across studies.ConclusionsComparing patterns and trends in different populations, or in different primary care EHR databases from the same populations, is important and a common objective for multi-database studies. When combining results from several databases using meta-analysis, provision of separate results from each database is helpful for interpretation. We found that these were often missing, particularly for studies using one-stage approaches, which also often lacked details of any statistical adjustment for heterogeneity and/or clustering. For two-stage meta-analysis, a clear rationale should be provided for choice of fixed effect and/or random effects or other models.

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Prognostic Value of Serum Magnesium in Mortality Risk among Patients on Hemodialysis: A Meta-Analysis of Observational Studies

Kidney Diseases ◽

10.1159/000510513 ◽

2020 ◽

pp. 1-10

Author(s):

Hongwei Wu ◽

Qiang Li ◽

Lijing Fan ◽

Dewang Zeng ◽

Xianggeng Chi ◽

...

Keyword(s):

Mortality Risk ◽

Cardiovascular Mortality ◽

Observational Studies ◽

Prognostic Value ◽

Meta Analysis ◽

Serum Magnesium ◽

Cochrane Library ◽

Lower Serum ◽

All Cause Mortality ◽

End Stage

Background: Previous studies have reported that serum magnesium (Mg) deficiency is involved in the development of heart failure, particularly in patients with end-stage kidney disease. The association between serum Mg levels and mortality risk in patients receiving hemodialysis is controversial. We aimed to estimate the prognostic value of serum Mg concentration on all-cause mortality and cardiovascular mortality in patients receiving hemodialysis. Methods: We did a systematic literature search in PubMed, EMBASE, Cochrane Library, and Web of Science to identify eligible studies that reported the prognostic value of serum Mg levels in mortality risk among patients on hemodialysis. We performed a meta-analysis by pooling and analyzing hazard ratios (HRs) and 95% confidence intervals (CIs). Results: We identified 13 observational studies with an overall sample of 42,967 hemodialysis patients. Higher all-cause mortality (adjusted HR 1.58 [95% CI: 1.31–1.91]) and higher cardiovascular mortality (adjusted HR 3.08 [95% CI: 1.27–7.50]) were found in patients with lower serum Mg levels after multivariable adjustment. There was marked heterogeneity (I2 = 79.6%, p < 0.001) that was partly explained by differences in age stratification and study area. In addition, subgroup analysis showed that a serum Mg concentration of ≤1.1 mmol/L might be the vigilant cutoff value. Conclusion: A lower serum Mg level was associated with higher all-cause mortality and cardiovascular mortality in patients receiving hemodialysis.

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Preoperative statin therapy is associated with reduced 30-day postoperative all-cause mortality in patients undergoing coronary artery bypass surgery: A meta-analysis of large size observational studies

International Journal of Cardiology ◽

10.1016/j.ijcard.2014.11.216 ◽

2015 ◽

Vol 181 ◽

pp. 11-13 ◽

Cited By ~ 3

Author(s):

Jiayang Wang ◽

Chengxiong Gu ◽

Mingxin Gao ◽

Wenyuan Yu ◽

Yang Yu

Keyword(s):

Coronary Artery ◽

Statin Therapy ◽

Coronary Artery Bypass ◽

Observational Studies ◽

Coronary Artery Bypass Surgery ◽

Bypass Surgery ◽

Meta Analysis ◽

Artery Bypass ◽

Large Size ◽

All Cause Mortality

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Prognostic Impact of Metabolic Syndrome in Patients With Heart Failure: A Meta-Analysis of Observational Studies

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.704446 ◽

2021 ◽

Vol 8 ◽

Author(s):

Zhuo-Ming Huang ◽

Wen-Rong Chen ◽

Qi-Wen Su ◽

Zhuo-Wen Huang

Keyword(s):

Heart Failure ◽

Metabolic Syndrome ◽

Cardiovascular Mortality ◽

Cardiovascular Events ◽

Observational Studies ◽

Meta Analysis ◽

Prognostic Impact ◽

The Metabolic Syndrome ◽

All Cause Mortality ◽

The Impact

Background: The metabolic syndrome (MS) is significantly associated with the risk of incident heart failure (HF). However, there are still great controversies about the impact of MS on the prognosis in patients with established HF. This meta-analysis aimed to ascertain the effect of MS on the prognosis in patients with HF.Methods: We searched multiple electronic databases, including PubMed, Opengrey, EMBASE, and Cochran Library, for potential studies up to February 15, 2021. Observational studies that reported the impact of MS on the prognosis in patients with established HF were included for meta-analysis.Results: Ten studies comprising 18,590 patients with HF were included for meta-analysis. The median follow-up duration of the included studies was 2.4 years. Compared with HF patients without MS, the risk of all-cause mortality and cardiovascular mortality was not increased in HF with MS (HR = 1.04, 95% CI = 0.88–1.23 for all-cause mortality; HR = 1.66, 95% CI = 0.56–4.88 for cardiovascular mortality, respectively). However, there was a significant increase in composited cardiovascular events in the HF patients with MS compared with those without MS (HR = 1.73, 95% CI = 1.23–2.45).Conclusions: In patients with established HF, the presence of MS did not show an association on the risk of all-cause mortality or cardiovascular mortality, while it may increase the risk of composite cardiovascular events.

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Fish consumption and risk of all-cause and cardiovascular mortality: a dose–response meta-analysis of prospective observational studies

Public Health Nutrition ◽

10.1017/s1368980017003834 ◽

2018 ◽

Vol 21 (7) ◽

pp. 1297-1306 ◽

Cited By ~ 24

Author(s):

Ahmad Jayedi ◽

Sakineh Shab-Bidar ◽

Saragol Eimeri ◽

Kurosh Djafarian

Keyword(s):

Relative Risk ◽

Dose Response ◽

Fish Consumption ◽

Regional Differences ◽

Observational Studies ◽

Meta Analysis ◽

Asian Studies ◽

Linear Dose ◽

All Cause Mortality ◽

Cvd Mortality

AbstractObjectiveThere are some indications of regional differences in the association between fish consumption and clinical outcomes. We aimed to test the linear and potential non-linear dose–response relationships between fish consumption and risk of all-cause and cardiovascular (CVD) mortality, and possible confounding by region.DesignSystematic review and dose–response meta-analysis.SettingSystematic search using PubMed and Scopus, from inception up to September 2016.SubjectsProspective observational studies reporting the estimates of all-cause and CVD mortality in relation to three or more categories of fish intake were included. Random-effects dose–response meta-analysis was conducted.ResultsFourteen prospective cohort studies (ten publications) with 911 348 participants and 75 451 incident deaths were included. A 20 g/d increment in fish consumption was significantly and inversely associated with the risk of CVD mortality (relative risk=0·96; 95 % CI 0·94, 0·98; I2=0 %, n 8) and marginally and inversely associated with the risk of all-cause mortality (relative risk=0·98; 95 % CI 0·97, 1·00; I2=81·9 %, n 14). Subgroup analysis resulted in a significant association only in the subgroup of Asian studies, compared with Western studies, in both analyses. Analysis of Western studies suggested a nearly U-shaped association, with a nadir at fish consumption of ~20 g/d in analysis of both outcomes. Meanwhile, the associations appeared to be linear in Asian studies.ConclusionsThere was potential evidence of regional differences in the association between fish consumption and mortality. It may be helpful to examine the associations by considering types of fish consumed and methods of fish preparation.

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Brachial Pulse Pressure and Cardiovascular or All-Cause Mortality in the General Population: A Meta-Analysis of Prospective Observational Studies

Journal of Clinical Hypertension ◽

10.1111/jch.12375 ◽

2014 ◽

Vol 16 (9) ◽

pp. 678-685 ◽

Cited By ~ 32

Author(s):

Leilei Zhao ◽

Yijuan Song ◽

Pingshuan Dong ◽

Zhijuan Li ◽

Xuming Yang ◽

...

Keyword(s):

General Population ◽

Pulse Pressure ◽

Observational Studies ◽

Meta Analysis ◽

All Cause Mortality

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C-reactive protein for predicting all-cause mortality in patients with acute ischemic stroke: a meta-analysis

Bioscience Reports ◽

10.1042/bsr20181135 ◽

2019 ◽

Vol 39 (2) ◽

Cited By ~ 6

Author(s):

Bo Yu ◽

Ping Yang ◽

Xuebi Xu ◽

Lufei Shao

Keyword(s):

Ischemic Stroke ◽

Acute Ischemic Stroke ◽

Observational Studies ◽

Meta Analysis ◽

C Reactive Protein ◽

Stroke Patients ◽

Reactive Protein ◽

Increased Risk ◽

All Cause Mortality ◽

Unit Increase

Abstract Studies on the association of C-reactive protein (CRP) with all-cause mortality in acute ischemic stroke patients have yielded conflicting results. The objective of this meta-analysis was to evaluate the prognostic value of CRP elevation in predicting all-cause mortality amongst patients with acute ischemic stroke. We searched the original observational studies that evaluated the association of CRP elevation with all-cause mortality in patients with acute ischemic stroke using PubMed and Embase databases until 20 January 2018. Pooled multivariate-adjusted hazard ratio (HR) with 95% confidence intervals (CI) of all-cause mortality was obtained for the highest compared with the lowest CRP level or per unit increment CRP level. A total of 3604 patients with acute ischemic stroke from eight studies were identified. Acute ischemic stroke patients with the highest CRP level were independently associated with an increased risk of all-cause mortality (HR: 2.07; 95% CI: 1.60–2.68) compared with the lowest CRP category. The pooled HR of all-cause mortality was 2.40 (95% CI: 1.10–5.21) for per unit increase in log-transformed CRP. Elevated circulating CRP level is associated with the increased risk of all-cause mortality in acute ischemic stroke patients. This meta-analysis supports the routine use of CRP for the death risk stratification in such patients.

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Clinical Outcomes of Concomitant Use of Proton Pump Inhibitors and Dual Antiplatelet Therapy: A Systematic Review and Meta-Analysis

Frontiers in Pharmacology ◽

10.3389/fphar.2021.694698 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hongzhou Guo ◽

Zhishuai Ye ◽

Rongchong Huang

Keyword(s):

Antiplatelet Therapy ◽

Proton Pump Inhibitors ◽

Proton Pump ◽

Cardiovascular Events ◽

Observational Studies ◽

Dual Antiplatelet Therapy ◽

Meta Analysis ◽

Gi Bleeding ◽

Coronary Syndrome ◽

All Cause Mortality

Background: The safety and efficacy associated with the use of proton pump inhibitors (PPIs) by patients with coronary artery disease receiving dual antiplatelet therapy (DAPT) remain unclear.Methods: The evaluated outcomes included combined major adverse cardiovascular events (MACEs), myocardial infarction (MI), all-cause mortality, and gastrointestinal (GI) bleeding. A random effects meta-analysis, stratified by study design, was performed and heterogeneity was assessed using the I2 statistic.Results: In total, 6 randomized controlled trials (RCTs) (6930 patients) and 16 observational studies (183,546 patients) were included. Analysis of RCTs showed that there were no significant differences in the incidences of MACEs (risk ratio [RR] = 0.89 [95% confidence interval (CI) = 0.75–1.05]), MI (RR = 0.93 [95% CI = 0.76–1.15]), and all-cause mortality (RR = 0.79 [95% CI = 0.50–1.23]) in the PPI groups vs. the non-PPI groups. Pooled data from observational studies revealed an inconsistent association between the use of each PPI subtype and the increased risks of MACEs during clopidogrel treatment. There was no increased risk of MACEs or all-cause mortality associated with the use of PPIs (as a class) and other P2Y12 inhibitors. Both the RCTs and observational studies revealed that the use of PPIs significantly reduced the risks of GI bleeding.Conclusion: The use of PPIs was associated with a reduced risk of GI bleeding in patients treated with DAPT after percutaneous coronary intervention or acute coronary syndrome. There was no clear evidence of an association between the use of PPIs and adverse cardiovascular events.Clinical Trial Registration: identifier [CRD42020190315]

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Selenium and the risk of cardiovascular disease and all-cause mortality: a meta-analysis of prospective observational studies and randomized controlled trials

10.21203/rs.3.rs-358602/v1 ◽

2021 ◽

Author(s):

Hualei Sun ◽

Shao Rong Long ◽

Gaiyun Chen ◽

Yajuan Wang ◽

Rui Liang ◽

...

Keyword(s):

Cardiovascular Disease ◽

Randomized Controlled Trials ◽

Observational Studies ◽

Meta Analysis ◽

Controlled Trials ◽

Serum Selenium ◽

Inverse Association ◽

Significant Inverse Association ◽

Randomized Controlled ◽

All Cause Mortality

Abstract BackgroundThis meta-analysis of prospective observational studies and randomized controlled trials (RCTs) was carried out to explore the association between selenium and the risk of cardiovascular disease (CVD) and all-cause mortality.Methods and Study DesignWe searched the PubMed, EMBASE and Web of Science database for eligible studies which included the relationship between selenium and the outcomes of interest. 25 prospective observational studies and 9 RCTs were included in our meta-analysis.ResultsThe observational studies showed that there was a significant inverse association between serum selenium and the risk of CVD (RR: 0.78; 95% CI: 0.68–0.89), coronary heart disease (CHD) (RR: 0.75; 95% CI: 0.58–0.95) and all-cause mortality (RR: 0.77; 95% CI: 0.71–0.84). We also found a significant inverse association between selenium supplements and the risk of total CVD (RR: 0.78; 95% CI: 0.62–0.98) and all-cause mortality (RR: 0.81; 95% CI: 0.65-1.00) in RCTs studies.ConclusionsOur meta-analysis found a significant inverse association between selenium and CVD, CHD, and all-cause mortality in prospective observational studies and RCTs, which indicate the selenium has protective effect in cardiovascular disease and all-cause mortality.

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