Culprit or correlate? An application of the Bradford Hill criteria to Vitamin E acetate

2020 ◽  
Vol 94 (6) ◽  
pp. 2249-2254 ◽  
Author(s):  
Ryan Feldman ◽  
Jonathan Meiman ◽  
Matthew Stanton ◽  
David D. Gummin
Keyword(s):  
Vitamin E ◽  
Vitamin E Acetate ◽  
Bradford Hill ◽  
Bradford Hill Criteria ◽  
Hill Criteria

Ibuprofen and risk of hypoglycemia in diabetic and non-diabetic consumers: analysis of international pharmacovigilance data

2021 ◽  
Vol 9 (1) ◽  
pp. 5
Author(s):  
Mulugeta Russom ◽  
Filipos Yohannes ◽  
Abel Tekle ◽  
Ruth Ghirmay
Keyword(s):  
Individual Case ◽  
Causal Link ◽  
Epidemiological Evidence ◽  
Global Database ◽  
Bradford Hill ◽  
Bradford Hill Criteria ◽  
History Of ◽  
Hill Criteria ◽  
Time To Onset ◽  
Totality Of Evidence

Introduction: Ibuprofen was associated with hypoglycemia in a single published case report in a diabetic patient. Ibuprofen, however, has never been associated so far with hypoglycemia in previously healthy non-diabetic individuals and thus, it is not listed as adverse effect in its summary of product characteristics approved by major regulatory authorities. Objective: This study was conducted to assess the causal relationship between ibuprofen and hypoglycemia in diabetic and non-diabetic individuals. Materials and Methods: Analysis of the literature and the WHO global database of individual case safety reports, VigiBase, was made to explore evidence on the association of ibuprofen and hypoglycemia. The unpublished data and the currently availablepublished toxicological, biological, clinical and epidemiological evidence, if any, was systematically organized using Austin Bradford Hill criteria, causality assessment framework, to assess the causal link between ibuprofen and hypoglycemia. Results: In VigiBase, there were 125 cases of hypoglycemia associated with ibuprofen, reported from 19 countries. About 50% had history of diabetes. Ibuprofen was reported as sole suspect in 36.8% of the cases and the only drug administered in18.4%. Hypoglycemia resolved following discontinuation of ibuprofen in 21.6% and recurred in three patients with rechallenge. Outcome was fatal in 10.5%. Where ibuprofen was solely administered, median time-to-onset of hypoglycemia was one-day following administration of the drug. In an experimental study, a significant decrease in blood glucose level was observed at a higher dose of ibuprofen compared to a low-dose. Conclusion: Currently available totality of evidence reflects a possible causal association between ibuprofen and hypoglycemia that need to be substantiated with further studies.

Reviewing the role of human papillomavirus in oral cancer using the Bradford Hill criteria of causation

2019 ◽  
Vol 65 (6) ◽  
pp. 155-163 ◽  
Author(s):  
A. Thirumal Raj ◽  
Shankargouda Patil ◽  
Archana A. Gupta ◽  
Chandini Rajkumar ◽  
Kamran H. Awan
Keyword(s):  
Human Papillomavirus ◽  
Oral Cancer ◽  
Bradford Hill ◽  
Bradford Hill Criteria ◽  
Hill Criteria

scholarly journals Effectiveness of Take-Home Naloxone Programs in Athletic Training: An Evidence-to-Practice Review

2021 ◽  
Vol 4 (2) ◽  
pp. 26-32
Author(s):  
Michael J. Palm ◽  
Amanda N. Flanscha ◽  
Zachary K Winkelmann
Keyword(s):  
Crisis Management ◽  
Athletic Trainers ◽  
Public Health Intervention ◽  
Negative Consequences ◽  
Opioid Crisis ◽  
Bradford Hill ◽  
Bradford Hill Criteria ◽  
Hill Criteria ◽  
Practice Review ◽  
The Impact

The number of opioid overdoses (ODs) has risen in recent years and has become more complex due to the co-involvement of both prescription and illicit opioid drug use. Provisional programs for take-home naloxone (a medication designed to rapidly reverse opiate OD symptoms) kits have been distributed to combat this potentially fatal epidemic. Although there is strong evidence to support the efficacy of naloxone in the reversal of opiate OD, there is limited evidence to support the efficacy of take-home naloxone (THN) kits. The purpose of this evidence-to-practice review was to summarize a systematic review on the efficacy of THN programs. The authors aimed to include studies of THN programs that both trained opioid users in OD prevention and reported on OD outcomes. The Bradford Hill criteria (strength of association, temporality, consistency, specificity, dose-response relationship, biological plausibility, coherence, experimental evidence, and analogy) and five additional criteria (measure cost-effectiveness, absence of negative consequences, feasibility of implementation/expansion/ coverage, unanticipated benefits, and special populations) was used as dependent variables to determine the impact of public health intervention where randomized control trials (RCTs) are not ethically feasible or operationally practical. All 22 studies included provided empirical support using the Bradford Hill Criteria for community based THN programs. Despite being unable to deduce whether death would have occurred without the administration of THN, the studies combined accounted for an estimated 2316 successful opioid OD reversals. Thus, there is a strong association between THN administration and overdose survival. Additionally, there was a low rate of adverse events: withdrawal symptoms (2.8%), vomiting (2.2%), agitation (2.1%), seizures (0.1%). Consequently, we recommend that athletic trainers include opioid crisis management equipment and procedures in a site-specific policies manual. Clinical relevance is highly dependent on patient population and geographic location, considering 90% of reversed ODs were heroin induced. Application to individuals in organized sport is minimal, but nonetheless, individuals who are prescribed opioids for pain management should be candidates for THN programs. Athletic trainers and guardians of minors prescribed opioid medications should be educated on dispensing medication, best practices for opioid crisis management, and distribution of naloxone/THN.

Assessing causality in drug policy analyses: How useful are the Bradford Hill criteria in analysing take-home naloxone programs?

2017 ◽  
Vol 37 (4) ◽  
pp. 499-501 ◽  
Author(s):  
Anna Olsen ◽  
David McDonald ◽  
Simon Lenton ◽  
Paul M. Dietze
Keyword(s):  
Drug Policy ◽  
Bradford Hill ◽  
Bradford Hill Criteria ◽  
Hill Criteria

scholarly journals Is inflammation the cause of pre-eclampsia?

2011 ◽  
Vol 39 (6) ◽  
pp. 1619-1627 ◽  
Author(s):  
Wenda Ramma ◽  
Asif Ahmed
Keyword(s):  
Clinical Signs ◽  
Angiogenic Factors ◽  
Tyrosine Kinase Receptor ◽  
Bradford Hill ◽  
Disease Causation ◽  
Bradford Hill Criteria ◽  
Hill Criteria ◽  
High Doses ◽  
Pro Inflammatory Cytokines

It has been proposed that either excessive inflammation or an imbalance in angiogenic factors cause pre-eclampsia. In the present review, the arguments for and against the role of inflammation and/or angiogenic imbalance as the cause of pre-eclampsia are discussed on the basis of the Bradford–Hill criteria for disease causation. Although both angiogenic imbalance and systemic inflammation are implicated in pre-eclampsia, the absence of temporality of inflammatory markers with pre-eclampsia challenges the concept that excessive inflammation is the cause of pre-eclampsia. In contrast, the elevation of anti-angiogenic factors that precede the clinical signs of pre-eclampsia fulfils the criterion of temporality. The second most important criterion is the dose–response relationship. Although such a relationship has not been proven between pro-inflammatory cytokines and pre-eclampsia, high levels of anti-angiogenic factors have been shown to correlate with increased incidence and disease severity, hence satisfying this condition. Finally, as the removal of circulating sFlt-1 (soluble Fms-like tyrosine kinase receptor-1) from pre-eclamptic patients significantly improves the clinical outcome, it fulfils the Hill's experiment principle, which states that removal of the cause by an appropriate experimental regimen should ameliorate the condition. In contrast, treatment with high doses of corticosteroid fails to improve maternal outcome in pre-eclampsia, despite suppressing inflammation. Inflammation may enhance the pathology induced by the imbalance in the angiogenic factors, but does not by itself cause pre-eclampsia. Development of therapies based on the angiogenic and cytoprotective mechanisms seems more promising.

scholarly journals A Dormant Microbial Component in the Development of Pre-Eclampsia1

2016 ◽  
Author(s):  
Douglas B. Kell ◽  
Louise C. Kenny
Keyword(s):  
Oxidative Stress ◽  
Immune Response ◽  
Trophoblast Invasion ◽  
Microbial Infection ◽  
Considerable Evidence ◽  
Bradford Hill ◽  
Biological Insight ◽  
Bradford Hill Criteria ◽  
Hill Criteria ◽  
System Disorder

AbstractPre-eclampsia (PE) is a complex, multi-system disorder that remains a leading cause of morbidity and mortality in pregnancy. Four main classes of dysregulation accompany PE, and are widely considered to contribute to its severity. These are abnormal trophoblast invasion of the placenta, anti-angiogenic responses, oxidative stress, and inflammation. What is lacking, however, is an explanation of how these themselves are caused.We here develop the unifying idea, and the considerable evidence for it, that the originating cause of PE (and of the four classes of dysregulation) is in fact microbial infection, that most such microbes are dormant and hence resist detection by conventional (replication-dependent) microbiology, and that by occasional resuscitation and growth it is they that are responsible for all the observable sequelae, including the continuing, chronic inflammation. In particular, bacterial products such as lipopolysaccharide (LPS), also known as endotoxin, are well known as highly inflammagenic and stimulate an innate (and possibly trained) immune response that exacerbates the inflammation further. The known need of microbes for free iron can explain the iron dysregulation that accompanies PE. We describe the main routes of infection (gut, oral, urinary tract infection) and the regularly observed presence of microbes in placental and other tissues in PE. Every known proteomic biomarker of “pre-eclampsia” that we assessed has in fact also been shown to be raised in response to infection. An infectious component to PE fulfils the Bradford Hill criteria for ascribing a disease to an environmental cause, and suggests a number of treatments, some of which have in fact been shown to be successful.PE was classically referred to as endotoxaemia or toxaemia of pregnancy, and it is ironic that it seems that LPS and other microbial endotoxins really are involved. Overall, the recognition of an infectious component in the aetiology of PE mirrors that for ulcers and other diseases that were previously considered to lack one.Insight, innovation, integrationMany descriptors of pre-eclampsia are widely accepted (e.g. abnormal trophoblast invasion, oxidative stress, inflammation and altered immune response, and anti-angiogenic responses). However, without knowing what causes them, they do not explain the syndrome. The Biological Insight of this manuscript is that there is considerable evidence to the effect that each of these phenomena (hence PE) are caused by the resuscitation of dormant bacteria that shed (known and potent) inflammagens such as LPS, often as a consequence of iron availability. PE is thus seen as a milder form of sepsis. The Technological Innovations come from the use of molecular markers (of microbes and omics more generally, as well as novel markers of coagulopathies) to measure this. The Benefit of Integration comes from bringing together a huge number of disparate observations into a unifying theme.

scholarly journals Web of Causation between Dietary Patterns and Childhood Obesity: Applying Hill's Criteria

2018 ◽  
Vol 25 (4) ◽  
pp. 431-438
Author(s):  
Costela Lăcrimioara Șerban ◽  
Denis Mihai Șerban ◽  
Ștefania Ioana Butica ◽  
Diana Lungeanu
Keyword(s):  
Adipose Tissue ◽  
Childhood Obesity ◽  
Dietary Patterns ◽  
Dietary Pattern ◽  
Experimental Studies ◽  
Dietary Factors ◽  
Bradford Hill ◽  
Bradford Hill Criteria ◽  
Hill Criteria

Abstract Since their publication in 1965, the Bradford Hill criteria for causality have been largely used as a framework for causal inference in epidemiology. We aim at employing this classical approach to shed new light onto the web of causation of childhood obesity. Although the fundamental cause of obesity is the long-term imbalance between energetic need and intake, this medical condition is multifactorial in its origin, influenced by genetic, behavioral, socioeconomic, and environmental factors. This imbalance leads to accumulation of excessive adipose tissue. Observational studies tend to mostly quantify association between dietary factors and accumulation of adipose tissue. On the other hand, multivariate analysis proved some of these associations to be spurious, therefore prospective trials are needed to demonstrate causality. Short term experimental studies have been conducted to identify unique dietary pattern changes on specific outcomes, but long term, community-based studies would offer more comprehensive answers on dietary pattern effects. We conducted a literature review on PubMed, Scopus, Web of Science, and Google Scholar. From a total of 323 papers identified at first stage, we further discuss the applicability of Bradford Hill criteria for 31 articles, by examples of dietary patterns and accumulation of excess body fat as exposure-response associations. We also put forward and analyzed the evidence prospective studies would bring, as foundation for future interventions.

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