The Triangulation WIthin a STudy (TWIST) framework for causal inference within pharmacogenetic research

by Jack Bowden, Luke Pilling, Deniz T ürkmen, Chia-Ling Kuo, David Melzer In this paper we review the methodological underpinnings of the general pharmacogenetic approach for uncovering genetically-driven treatment effect heterogeneity. This typically utilises only individuals who are treated and relies on fairly strong baseline assumptions to estimate what we term the ‘genetically moderated treatment effect’ (GMTE). When these assumptions are seriously violated, we show that a robust but less efficient estimate of the GMTE that incorporates information on the population of untreated individuals can instead be used. In cases of partial violation, we clarify wh en Mendelian randomization and a modified confounder adjustment method can also yield consistent estimates for the GMTE. A decision framework is then described to decide when a particular estimation strategy is most appropriate and how specific estimators can be combined to further improve efficienc y. Triangulation of evidence from different data sources, each with their inherent biases and limitations, is becoming a well established principle for strengthening causal analysis. We call our framework ‘Triangulation WIthin a STudy’ (TWIST)’ in order to emphasise that an analysis in this sp irit is also possible within a single data set, using causal estimates that are approximately uncorrelated, but reliant on different sets of assumptions. We illustrate these approaches by re-analysin...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research

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Background: The long-term effects of statin use on rehospitalization due to ischemic stroke (reHospIS) in hyperlipidemic patients are still unknown. Therefore, we aimed to assess the long-term risks of reHospIS for hyperlipidemic patients who were taking statins and nonstatin lipid-lowering medicines on a regular basis.Methods and Materials: The National Health Insurance Research Database in Taiwan was used to conduct a 6-year cohort study of patients>45 years old (n = 9,098) who were newly diagnosed with hyperlipidemia and hospitalized for the first or second time due to ischemic stroke (IS). The risk of reHospIS ...
Source: Frontiers in Pharmacology - Category: Drugs & Pharmacology Source Type: research
Older adults without heart disease shouldn’t take daily low-dose aspirin to prevent a first heart attack or stroke, an influential health guidelines group said in preliminary updated advice released Tuesday. Bleeding risks for adults in their 60s and up who haven’t had a heart attack or stroke outweigh any potential benefits from aspirin, the U.S. Preventive Services Task Force said in its draft guidance. For the first time, the panel said there may be a small benefit for adults in their 40s who have no bleeding risks. For those in their 50s, the panel softened advice and said evidence of benefit is less clear....
Source: TIME: Health - Category: Consumer Health News Authors: Tags: Uncategorized healthscienceclimate Research wire Source Type: news
This study uniquely compares the management and outcomes of MINOCA patients with a medically managed obstructive ACS (M-ACS) population. We retrospectively analysed registry data for consecutive patients admitted to the Gold Coast University Hospital with ACS requiring coronary angiography and identified patients with MINOCA and M-ACS. Baseline characteristics, pharmacological therapy and in-hospital outcomes were compared. In hospital outcomes were composite NACE, heart failure, stroke and major bleeding. Multivariate regression analysis was also performed to identify independent predictors of MINOCA. Multivariate regress...
Source: Heart and Vessels - Category: Cardiology Source Type: research
ConclusionBy analyzing EMR data representing routine practice in Korea, we found that patients with very high-risk ASCVD were at substantial risk of further cardiovascular events in 3  years. Given the observed risk of recurrent events with suboptimal lipid management by statin, additional treatment to control LDL-C might be necessary to reduce the burden of further cardiovascular events for very high-risk ASCVD patients.
Source: Cardiovascular Drugs and Therapy - Category: Cardiology Source Type: research
In conclusion, premature thymic involution and chronic inflammation greatly contribute to increased morbidity and mortality in CKD patients. Mechanisms are likely to be multiple and interlinked. Even when the quest to fountain of youth is a pipe dream, there are many scientific opportunities to prevent or to, at least in part, reverse CKD-related immune senescence. Further studies should precisely define most important pathways driving premature immune ageing in CKD patients and best therapeutic options to control them. Extending Life Without Extending Health: Vast Effort Directed to the Wrong Goals https://www...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
AbstractPurposeAdults with atherosclerotic cardiovascular disease (ASCVD) are recommended high-intensity statins, with those at very high risk for recurrent events recommended adding ezetimibe and/or a proprotein convertase subtilisin/kexin type 9 inhibitor if their low-density lipoprotein cholesterol (LDL-C) is ≥70 mg/dL. We estimated the number of recurrent ASCVD events potentially averted if all adults in the United States (US) ≥45 years of age with ASCVD achieved an LDL-C
Source: Cardiovascular Drugs and Therapy - Category: Cardiology Source Type: research
The aging of large blood vessels in the brain, and their resulting dysfunctions, are quite different from those of the small vessels, the microvasculature. Large vessels are predominantly affected by atherosclerosis, the buildup of fatty plaques that weaken and narrow blood vessels, leading to the catastrophic structural failure of a stroke. Small vessels, on the other hand, appear to be affected by a collection of mechanisms that cause functional deterioration, such as pathological amyloid deposition, with atherosclerosis as only one of that list of harmful processes. This is the point made in the open access paper here, ...
Source: Fight Aging! - Category: Research Authors: Tags: Daily News Source Type: blogs
ConclusionHigh intensity statin loading before primary PCI resulted in improved post-procedural TIMI flow, MBG, complete ST-segment resolution and ejection fraction as measured by M-mode but did not decrease incidence of in-hospital MACE.
Source: QJM - Category: Internal Medicine Source Type: research
The objective of this article is to review the current guidelines on stroke prevention measures after ICH as well as the new findings and controversies for future guidance.Recent FindingsIntensive blood pressure reduction might benefit ICH survivors significantly. Cholesterol levels and the risk of ICH have an inverse relationship, but statin therapy after ICH might be still beneficial. Anticoagulation in atrial fibrillation after ICH specifically with novel oral anticoagulants may be associated with better long-term outcomes. Left atrial appendage occlusion may be an alternative for stroke prevention in ICH survivors with...
Source: Current Cardiology Reports - Category: Cardiology Source Type: research
Expert Opin Investig Drugs. 2021 Sep 24. doi: 10.1080/13543784.2021.1985463. Online ahead of print.ABSTRACTINTRODUCTION: Recent years have witnessed unprecedented progress in stroke care, but unmet needs persist regarding the efficacy of acute treatment and secondary prevention. Novel approaches are being tested to enhance the efficacy of thrombolysis or provide neuroprotection in non-thrombolized patients.AREAS COVERED: The current review highlights pharmaceutical agents under evaluation in clinical trials concerning the acute, subacute, and chronic phase post-stroke. We examine the evidence in favor of tenecteplase as an...
Source: Expert Opinion on Investigational Drugs - Category: Drugs & Pharmacology Authors: Source Type: research
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