Moving from two- to multi-way interactions among binary risk factors on the additive scale

AbstractBackgroundEBV infection is thought to play a central role in the development of Multiple Sclerosis (MS). If causal, it represents a target for interventions to reduce MS risk.ObjectiveTo examine the evidence for interaction between EBV and other risk factors, and explore mechanisms via which EBV infection may influence MS risk.MethodsPubmed was searched using the terms “multiple sclerosis” AND “Epstein Barr virus”, “multiple sclerosis” AND EBV, “clinically isolated syndrome” AND “Epstein Barr virus” and “clinically isolated syndrome” AND EBV. All abstracts were reviewed for possible inclusion.Results262 full-text papers were reviewed. There was evidence of interaction on the additive scale between anti-EBV antibody titre and HLA genotype (AP 0.48, p<1×10−4; RERI 3.84, p<5×10−3; S 1.68, p=0.06). Previous IM was associated with increased OR of MS in HLA-DRB1*1501 positive but not HLA-DRB1*1501 negative persons. Smoking was associated with a greater risk of MS in those with high anti-EBV antibodies (OR 2.76) but not low anti-EBV antibodies (OR 1.16). No interaction between EBV and risk factors was found on a multiplicative scale.ConclusionsEBV appears to interact with at least some established MS risk factors. The mechanism via which EBV influences MS risk remains unknown.

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Systematic review and meta-analysis of the association between Epstein–Barr virus, multiple sclerosis and other risk factors

Multiple Sclerosis Journal ◽

10.1177/1352458520907901 ◽

2020 ◽

Vol 26 (11) ◽

pp. 1281-1297 ◽

Cited By ~ 4

Author(s):

Benjamin M Jacobs ◽

Gavin Giovannoni ◽

Jack Cuzick ◽

Ruth Dobson

Keyword(s):

Risk Factors ◽

Multiple Sclerosis ◽

Epstein Barr Virus ◽

Meta Analysis ◽

Clinically Isolated Syndrome ◽

Barr Virus ◽

Ebv Infection ◽

Epstein Barr ◽

Hla Genotype ◽

Additive Scale

Background: Epstein–Barr virus (EBV) infection is thought to play a central role in the development of multiple sclerosis (MS). If causal, it represents a target for interventions to reduce MS risk. Objective: To examine the evidence for interaction between EBV and other risk factors, and explore mechanisms via which EBV infection may influence MS risk. Methods: Pubmed was searched using the terms ‘multiple sclerosis’ AND ‘Epstein Barr virus’, ‘multiple sclerosis’ AND EBV, ‘clinically isolated syndrome’ AND ‘Epstein Barr virus’ and ‘clinically isolated syndrome’ AND EBV. All abstracts were reviewed for possible inclusion. Results: A total of 262 full-text papers were reviewed. There was evidence of interaction on the additive scale between anti-EBV antibody titre and HLA genotype (attributable proportion due to interaction (AP) = 0.48, p < 1 × 10−4). Previous infectious mononucleosis (IM) was associated with increased odds ratio (OR) of MS in HLA-DRB1*1501 positive but not HLA-DRB1*1501 negative persons. Smoking was associated with a greater risk of MS in those with high anti-EBV antibodies (OR = 2.76) but not low anti-EBV antibodies (OR = 1.16). No interaction between EBV and risk factors was found on a multiplicative scale. Conclusion: EBV appears to interact with at least some established MS risk factors. The mechanism via which EBV influences MS risk remains unknown.

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Population attributable fractions and joint effects of key risk factors for multiple sclerosis

Multiple Sclerosis Journal ◽

10.1177/1352458515594040 ◽

2015 ◽

Vol 22 (4) ◽

pp. 461-469 ◽

Cited By ~ 37

Author(s):

IAF van der Mei ◽

RM Lucas ◽

BV Taylor ◽

PC Valery ◽

T Dwyer ◽

...

Keyword(s):

Risk Factors ◽

Multiple Sclerosis ◽

Sun Exposure ◽

Population Based ◽

Population Attributable Fractions ◽

Attributable Fractions ◽

History Of ◽

Cns Demyelination ◽

Control Study ◽

Additive Scale

Aim: We examined the combined effect of having multiple key risk factors and the interactions between the key risk factors of multiple sclerosis (MS). Methods: We performed an incident case-control study including cases with a first clinical diagnosis of central nervous system demyelination (FCD) and population-based controls. Results: Compared to those without any risk factors, those with one, two, three, and four or five risk factors had increased odds of being an FCD case of 2.12 (95% confidence interval (CI), 1.11–4.03), 4.31 (95% CI, 2.24–8.31), 7.96 (95% CI, 3.84–16.49), and 21.24 (95% CI, 5.48–82.40), respectively. Only HLA-DR15 and history of infectious mononucleosis interacted significantly on the additive scale (Synergy index, 3.78; p = 0.03). The five key risk factors jointly accounted for 63.8% (95% CI, 43.9–91.4) of FCD onset. High anti-EBNA IgG was another important contributor. Conclusions: A high proportion of FCD onset can be explained by the currently known risk factors, with HLA-DR15, ever smoking and low cumulative sun exposure explaining most. We identified a significant interaction between HLA-DR15 and history of IM in predicting an FCD of CNS demyelination, which together with previous observations suggests that this is a true interaction.

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Elevated level of circulatory sTLT1 induces inflammation through SYK/MEK/ERK signalling in coronary artery disease

Clinical Science ◽

10.1042/cs20190999 ◽

2019 ◽

Vol 133 (22) ◽

pp. 2283-2299

Author(s):

Apabrita Ayan Das ◽

Devasmita Chakravarty ◽

Debmalya Bhunia ◽

Surajit Ghosh ◽

Prakash C. Mandal ◽

...

Keyword(s):

Risk Factors ◽

Coronary Artery Disease ◽

Coronary Artery ◽

Chronic Inflammation ◽

Ex Vivo ◽

Human Subjects ◽

Critical Role ◽

Atherosclerotic Cardiovascular Disease ◽

Tnf Α ◽

Artery Disease

Abstract The role of inflammation in all phases of atherosclerotic process is well established and soluble TREM-like transcript 1 (sTLT1) is reported to be associated with chronic inflammation. Yet, no information is available about the involvement of sTLT1 in atherosclerotic cardiovascular disease. Present study was undertaken to determine the pathophysiological significance of sTLT1 in atherosclerosis by employing an observational study on human subjects (n=117) followed by experiments in human macrophages and atherosclerotic apolipoprotein E (apoE)−/− mice. Plasma level of sTLT1 was found to be significantly (P<0.05) higher in clinical (2342 ± 184 pg/ml) and subclinical cases (1773 ± 118 pg/ml) than healthy controls (461 ± 57 pg/ml). Moreover, statistical analyses further indicated that sTLT1 was not only associated with common risk factors for Coronary Artery Disease (CAD) in both clinical and subclinical groups but also strongly correlated with disease severity. Ex vivo studies on macrophages showed that sTLT1 interacts with Fcɣ receptor I (FcɣRI) to activate spleen tyrosine kinase (SYK)-mediated downstream MAP kinase signalling cascade to activate nuclear factor-κ B (NF-kB). Activation of NF-kB induces secretion of tumour necrosis factor-α (TNF-α) from macrophage cells that plays pivotal role in governing the persistence of chronic inflammation. Atherosclerotic apoE−/− mice also showed high levels of sTLT1 and TNF-α in nearly occluded aortic stage indicating the contribution of sTLT1 in inflammation. Our results clearly demonstrate that sTLT1 is clinically related to the risk factors of CAD. We also showed that binding of sTLT1 with macrophage membrane receptor, FcɣR1 initiates inflammatory signals in macrophages suggesting its critical role in thrombus development and atherosclerosis.

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Hearing Loss Risk Factors and Strategies in Rural Areas

Perspectives on Aural Rehabilitation and Its Instrumentation ◽

10.1044/arii12.1.17 ◽

2004 ◽

Vol 12 (1) ◽

pp. 17-20

Author(s):

Gregory A. Flamme

Keyword(s):

Risk Factors ◽

Hearing Loss ◽

Rural Areas

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The Preschool Stuttering Screen for Health Care Professionals

Perspectives on Fluency and Fluency Disorders ◽

10.1044/ffd21.2.59 ◽

2011 ◽

Vol 21 (2) ◽

pp. 59-62

Author(s):

Joseph Donaher ◽

Christina Deery ◽

Sarah Vogel

Keyword(s):

Risk Factors ◽

Health Care ◽

Differential Diagnosis ◽

Preschool Children ◽

Health Care Professionals ◽

Healthcare Professionals ◽

Evidence Based ◽

Developmental Profile

Healthcare professionals require a thorough understanding of stuttering since they frequently play an important role in the identification and differential diagnosis of stuttering for preschool children. This paper introduces The Preschool Stuttering Screen for Healthcare Professionals (PSSHP) which highlights risk factors identified in the literature as being associated with persistent stuttering. By integrating the results of the checklist with a child’s developmental profile, healthcare professionals can make better-informed, evidence-based decisions for their patients.

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Clinical Response to Questions Regarding Outcomes and Therapy Efficacy

Perspectives on Fluency and Fluency Disorders ◽

10.1044/ffd20.3.76 ◽

2010 ◽

Vol 20 (3) ◽

pp. 76-83 ◽

Cited By ~ 1

Author(s):

Joseph Donaher ◽

Tom Gurrister ◽

Irving Wollman ◽

Tim Mackesey ◽

Michelle L. Burnett

Keyword(s):

Risk Factors ◽

Clinical Response ◽

Speech Language Pathologists ◽

Specific Therapy ◽

Therapy Efficacy ◽

Therapy Program ◽

Adults Who Stutter ◽

Cure Rates

Parents of children who stutter and adults who stutter frequently ask speech-language pathologists to predict whether or not therapy will work. Even though research has explored risk-factors related to persistent stuttering, there remains no way to determine how an individual will react to a specific therapy program. This paper presents various clinicians’answers to the question, “What do you tell parents or adults who stutter when they ask about cure rates, outcomes, and therapy efficacy?”

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