Doctor of Philosophy / Department of Hospitality Management / Kevin R. Roberts / In 2015, 902 foodborne illness outbreaks were reported to the Centers for Disease Control and Prevention, resulting in 15,202 illnesses, 950 hospitalizations, and 15 deaths. Previous literature from both survey and observational studies have reported low conformity with the U.S. Food and Drug Administration (FDA) Food Code guidelines. To effectively reduce foodborne illnesses, foodservice managers and food handlers must perform proper food safety behaviors. Therefore, the purpose of this project is to identify and explain the unobserved cognitive processes within food safety behavioral intention. An explanatory sequential mixed methods design was utilized. First, a systematic review and meta-analyses of the existing literature were conducted to quantify statistical power better and summarize the effect sizes with conflicting studies. Then, an in-depth qualitative study was conducted to help explain the statistical results. Using existing observed cognitive variables grounded by the Theory of Planned Behavior, the key idea is that the qualitative inquiry was built on the quantitative results. Thus, the syntheses of both studies help explained the unobserved heterogeneity information. Study 1 included a total of 1,550 studies for screening with 46 records meeting the inclusion criteria for analyses. The overall random effect size (r) was 0.282 (p < 0.001) providing collective evidence that the TPB constructs predict food safety behavioral intention. Subjective norms were noted as the most influencial variable to food safety behavioral intention. Studies with employee motivational constructs tend to show the most positive effect on food safety intention relationships. However, the Theory of Planned Behavior model only explained a combined 22% of total true effect variance. Thus, a considerable amount of the variance (78%) within food safety behavioral intention is still unexplained. Study 2 used an online questionnaire to measure individual-level norms. Open-ended questions (14) helped create qualitative narrative texts for analyses and establishing a demographic profile of the participants. A total of 104 responses from foodservice and restaurant employees were documented for coding. Most participants were female, with a mean age of 36 with an average of about 11 years of foodservice industry experiences. The results indicated that employees are usually not influenced of other managers or coworker’s approval or disapproval of their behavior. Rather, their behavior is guided by an innate motivation for moral consideration and ethical reasoning. The data further indicated that participants experience injunctive (subjective) norms, but more from a retrospective formation, rather than a forward-looking expectance regarding food safety practices. Intrinsic motivation should be an important antecedent to form normative beliefs of food safety-related behaviors. The findings of the study results challenge the previous understanding of path directions regarding normative pressure. Limitations and future studies related to maximize food safety behavioral intentions were discussed.

Objective: Diet lifestyle can influence the risk of endometriosis. Therefore, we conducted a systematicmeta-analysis to investigate the association between dairy products and the risk of endometriosis. Besides, we performed a dose-responsemeta-analysis to evaluate the amount of dairy intake affecting the risk of endometriosis. Methods: Relevant studies were searched from Pubmed, Embase databases, Cochrane Library, and Web of Science from the inception to November 6th, 2020. Also, the dose-response meta-analysis was conducted. All the pooled results were performed by risk ratios (RRs). Results: Finally, seven high-quality studies were included in the present meta-analysis. Total dairy intake was inversely associated with the risk of endometriosis, and the risk of endometriosis tended to decrease with a decrease in the risk of endometriosis when dairy products intake was over 21 servings/week (RR 0.87, 95% CI 0.76–1.00; pnon−linearity = 0.04). Similarly, people who consumed more than 18 servings of high-fat dairy products per week had a reduced risk of endometriosis (RR 0.86, 95% CI 0.76–0.96). When stratified-analyses were conducted based on specific dairy product categories, it indicated that people with high cheese intake might have a reduced risk of endometriosis (RR 0.86, 95%CI 0.74–1.00). Other specific dairy products such as whole milk (RR 0.90, 95% CI 0.72–1.12), reduced-fat/skim milk (RR 0.83, 95% CI 0.50–1.73), ice cream (RR 0.83, 95% CI 0.50–1.73), and yogurt (RR 0.83, 95% CI 0.62–1.11) have not shown significant evidence of an association with the risk of endometriosis. However, there is a higher risk of endometriosis in the females with high butter intake compared to females with low butter intake (1.27, 95% CI 1.03–1.55). Conclusions: Overall, dairy products intake was associated with a reduction in endometriosis, with significant effects when the average daily intake 3 servings. When analyzed according to the specific type of dairy product, it was shown that females with higher high-fat dairy and cheese intake might have a reduced risk of endometriosis. However, high butter intake might be associated to the increased risk of endometriosis. More future studies are needed to validate and add to this finding.

Background Social anxiety disorder (SAD) and posttraumatic stress disorder (PTSD) are prevalent, disabling and highly comorbid disorders. SAD is the most prevalent of the anxiety disorders, and PTSD is the central disorder in the DSM-5 section on trauma- and stressor-related disorders. Given the growing need to consider the totality of evidence for pharmacological treatment for SAD, the publication of systematic reviews and of novel meta-analytic approaches have become of interest for the use of medication in their treatment and decision making. This dissertation has three objectives 1) To update Cochrane reviews of pharmacotherapy for SAD and PTSD, 2) To conduct a qualitative systematic review of network meta-analyses for pharmacological treatment of common mental disorders, 3) To conduct network meta-analyses for SAD and for PTSD and to compare findings to standard pairwise meta-analytic methods. Methods To obtain eligible trials to answer each aim, trials were identified through a systematic search of a variety of electronic databases: the Cochrane Common Mental Disorders Controlled Trials Register (CCMDCTR-Studies and CCMDCTR-References), MEDLINE, EMBASE, PsycINFO, Google Scholar, Scopus, PubMed Central, the International Clinical Trials Registry Platform (ICTRP) (apps.who.int/trialsearch), clinicaltrials.gov, the National PTSD Center Pilots database and the metaRegister module [mRCT] of the Controlled Trials database, specific to each aim. RCTs of pharmacological treatments comparing active drug versus active drug or active drug versus placebo for SAD and PTSD were considered for inclusion in the respective chapters, and in answering the aims, with the inclusion of add on trials in the SAD and PTSD NMA reviews. Adult participants (18-65 years) diagnosed with SAD and PTSD according to the Diagnostic Statistical Manual for Mental Disorders (DSM, all versions) were included in the individual reviews (i.e. for chapter two, three, five and six). In chapter three adolescents and adults with common mental disorders (depression, GAD, PD, OCD, PTSD, SAD and specific phobia) diagnosed according to the DSM or the International Classification of Diseases ((ICD- 10) were included. The primary and secondary outcomes across aims and reviews include clinical response rates (i.e. the Clinical Global Impressions Improvement scale (CGI-I) or similar) and acceptability (i.e. dropouts due to side effects); and the investigation of symptom severity for SAD with the Liebowitz Social Anxiety Scale (LSAS) and PTSD with the Clinician Administered PTSD Scale (CAPS). In addition, the proportion of dropouts due to any cause were also assessed. The quality of each trial was assessed according to the Cochrane Risk of Bias Tool. GRADE was also used to grade the quality of evidence for the Cochrane reviews and NMAs and the International Society for Pharmacoeconomics and Outcomes Research checklist of good research practices for indirect treatment-comparison in assessing studies for aim two. For aim one, the extracted data for the SAD and PTSD Cochrane reviews was exported into RevMan 5.3.5. Software, which was used to conduct a meta-analysis for SAD and PTSD separately. Pre-planned subgroup and sensitivity analyses were conducted for each review, as well as the generation of funnel plots to assess publication bias with the Eggers' regression test using the R statistical computing platform for the SAD review. In answering aim three, standard pairwise meta-analyses were performed using a random effects model and Frequentist method in RStudio version 3.5 for the SAD NMA review, and Bayesian method using Markov chain Monte Carlo methods in WinBUGS version 1.4.3 for the PTSD NMA. The P-score, an analogue to the surface under the cumulative ranking curves (SUCRA), was used to rank the treatments on a continuous scale for all pairwise comparisons for the SAD NMA, and for the PTSD review, ranking probabilities using the surface under the cumulative ranking curve (SUCRA) and mean ranks were assessed. Results For aim one, the evidence for the standard pairwise Cochrane reviews of SAD and PTSD were most convincing for the treatment efficacy of SSRIs (number of studies (k) = 24, risk ratio (RR) 1.65; 95% confidence interval (CI) 1.48 to 1.85, N = 4984 and k = 8, RR 1.61; 95% CI 1.41 to 1.84, N = 1078, respectively), and was based on very low quality evidence. Evidence of a benefit for the SSRIs was also observed for the reduction of social anxiety symptoms on the LSAS (k = 14, mean difference (MD) −10.14 points, 95% CI −14.05 to −6.22, N = 1990) and posttraumatic symptoms on the CAPS (k = 14, MD −4.69 points, 95% CI −7.18 to −2.20, N = 2709). Other medications such as SSRIs, the serotonin–norepinephrine reuptake inhibitor (SNRI) venlafaxine, monoamine oxidase inhibitors (MAOIs), reversible monoamine oxidase inhibitors (RIMAs), benzodiazepines, the antipsychotic olanzapine, and the noradrenergic and specific serotonergic antidepressant (NaSSA) atomoxetine were also effective in reducing SAD symptoms, with evidence of a treatment response for anticonvulsants with gamma-amino butyric acid (GABA) analogues, the MAOIs, the RIMAs and the benzodiazepines. For the treatment of PTSD, the alpha-blocker prazosin and antipsychotics reduced symptom severity, and the alpha-blocker prazosin and the tricyclic antidepressant amitriptyline improved number of responders. Overall, SSRIs were less well tolerated than placebo in both reviews (SAD Review: k = 5131, RR 2.59; 95% CI 1.97 to 3.39, N = 5131; PTSD Review: (k = 15, RR 1.41; 95% CI 1.07 to 1.87, N = 2493), but there were low absolute rates of withdrawal compared to placebo (16% and 14%, respectively). There were no significant differences in dropouts due to any cause in both reviews for the SSRI intervention arms (SAD Review: k = 26, RR 1.01; 95% CI 0.90 to 1.14, N = 5208; ; PTSD Review: k = 21, RR 1.13; 95% CI 0.93 to 1.38, N = 3206). Twenty NMAs (i.e. investigating depressive disorder, GAD, SAD, PTSD and OCD) were found in answering aim three, and antidepressants were found to be the most efficacious and tolerable agents for these disorders based on rankings (45% of NMAs) or statistical significance (55% of NMAs). The quality of the reporting of each NMA was high. Seventy percent of the NMAs included a network diagram and 75% of the included NMAs assessed consistency, made use of a random effects model, provided information on the model used to fit the data and adjusted for covariates. The review also revealed that few NMAs reported rankings of treatments. The SAD and PTSD NMA provided similar findings to the Cochrane reviews, discussed in aim one. For aim three (the SAD NMA), the SSRI paroxetine was significantly more effective than placebo in reducing the number of responders (odds ratio (OR) 2.64; CI 1.97 to 3.54) and anxiety symptoms (mean difference (MD) -15.89; CI -29.94 to -1.84) yet performed worse in comparison to placebo for dropouts due to adverse events. Most of the medications (i.e.12 out of 19 comparisons) reported a decrease in dropout rates relative to placebo, but no statistically significant difference was found. There was also evidence that venlafaxine is efficacious in treating SAD symptoms. According to the rankings of individual treatments olanzapine performed better than the rest of the treatments in terms of treatment efficacy and buspirone for dropouts due to any cause. Bromazepam performed well in treating the number of responders due to adverse events. Similarly, for the PTSD NMA, paroxetine was also effective in the treatment of PTSD symptoms (MD -15.89; CI -29.94 to -1.84). Evidence was also observed for phenelzine, desipramine and risperidone for the treatment of PTSD symptoms. Mirtazapine yielded a relatively high rank for efficacy, but the respective value for acceptability was not among the best treatments. Most evidence from both NMAs was associated with low to very low-quality evidence. Conclusion Different meta-analytic approaches are useful in presenting, synthesising, and reporting data. The evidence discussed here suggest that SSRIs are effective in the treatment and reduction of SAD and PTSD symptoms, even though the tolerability of SSRIs was lower than placebo for each disorder. It is noteworthy that similar estimates were found across the different approaches to synthesising data and across the different patient groups (i.e. SAD and PTSD). In addition, the NMAs found in this dissertation show high quality of reporting and that study limitations do not impact on the network estimate. The quality of reporting of individual RCTs included across the review however remain low, and so additional research is needed in this area.

Central giant cell granuloma (CGCG) is an uncommon pathology of the maxillary bones, which has diverse clinical behavior. It can be treated either by surgical removal or by conservative methods such as systemic daily application of calcitonin and intralesional injections of corticosteroids. Recurrence of lesions seems to vary according to its clinical behavior, location and treatment modality. The aim of this study was to evaluate the recurrence rate of the CGCG of the jaws and its associated factors through a systematic review and meta-analyses. An electronic search in PubMed and Scopus databases was conducted in order to identify observational studies, published in English, that reported the recurrence rate of CGCG of the jaws regardless of treatment modality. In addition, a hand search of cross-references was also carried out identify additional studies. We excluded studies that did not report the main outcome of interest, with less than five cases and studies not available for full text review. Twenty-one studies, published between 1973 and 2011 met eligibility criteria and were included in this review. We observed a global recurrence rate of 13.4% (8.4%-19.1%, 95% CI). Surgical curettage showed the higher recurrence rate (15.8%, 10.7 – 21.7 95%CI), followed by calcitonin administration (9.7%, 0.0 – 31.8 95% CI) and surgical resection (0.16%, 0.0 – 0.07 95%CI). Lesion location was not associated with a higher risk of recurrence (RR = 1.7, 0.97 – 2.9, 95% CI). The results of this systematic review showed a high risk of lesion recurrence of aggressive CGCG treated with surgical curettage. / A lesão central de células gigantes (LCCG) é uma patologia incomum dos maxilares que apresenta comportamento clínico bastante variável. As modalidades terapêuticas para esta lesão variam desde tratamentos conservadores, com o uso de calcitonina e corticosteróides, a abordagens cirúrgicas mais radicais. As taxas de recidiva parecem variar de acordo com o comportamento clínico das lesões, tratamento indicado e localização. O objetivo deste trabalho foi, através de uma revisão sistemática com metanálise, avaliar as taxas de recidiva da LCCG dos maxilares e seus fatores associados. A revisão sistemática da literatura foi conduzida utilizando-se de busca eletrônica pelas bases de dados PubMed e Scopus. A lista de referências de todos os estudos elegíveis foi manualmente analisada para identificar estudos adicionais a serem incluídos. Foram incluídos estudos observacionais, publicados em língua inglesa, que relataram a taxa de recidiva da LCCG dos maxilares independente do tipo de tratamento realizado. Foram excluídos os estudos com menos de 5 casos, aqueles em que o desfecho de interesse não foi relatado e os artigos não disponíveis para leitura na íntegra. A heterogeneidade estatística entre os estudos foi analisada através do teste Q de Cochran e do índice I2 de Higgins e Thompson. As taxas de recidiva foram calculadas através de um modelo de efeitos randômicos após transformação do tipo Freeman-Tukey. O risco relativo para recidiva de acordo com comportamento clínico e localização das lesões foi calculado pelo método de Mantel-Haenszel. Foram incluídos 21 estudos observacionais, publicados entre 1973 e 2011. Foi observada uma taxa global de recidiva de 13.4% (IC 95% 8.4-19.1). Os pacientes tratados através de curetagem, ressecção cirúrgica e calcitonina tiveram taxas de recidiva de 15.8% (IC 95% 10.7-21.7), 0.16% (IC 95% 0.0-0.07) e 9.7% (0.0-31.8%), respectivamente. As lesões de comportamento agressivo tiveram um risco relativo para recidiva de 3.1 (IC 95% 1.7-5.7). Não foi observado aumento do risco em relação à localização da lesão (RR = 1.7; IC 95% 0.97-2.9). Desta forma, os resultados desta meta-análise indicam um risco elevado de recidiva em LCCG de comportamento agressivo e tratadas através de curetagem.

Ensuring the objectivity of systematic reviews and meta-analyses (SRMA) begins with comprehensive searches into diverse resources mining primary studies. Guidelines for systematic reviews recommend authors to routinely search of trial registries to identify unpublished studies. In this dissertation, I investigated the utilization of ClinicalTrials.gov (CTG), the world’s largest clinical trial registry that contains data from clinical trials of products that are subject to United States Food and Drug Administration (FDA) regulation, as an information resource in SRMAs. First, I examined the use of various information resources including CTG in SRMAs published from 2005-2016, and identified the factors associated with their use. Thereafter, to determine the accuracy of trial safety data reported at CTG, I compared the data at CTG with that in corresponding journal articles and FDA drug reviews. I found that trial safety data at both CTG and articles differed frequently from FDA drug reviews, but the differences were modest in magnitude. Finally, I repeated published meta-analysis (conducted using data from primary study articles) with data at CTG to find that most meta-analysis results were reproduced using CTG data. Taken together, this work suggests that CTG should not only be searched more often to find primary research for systematic reviews, but that data at CTG can also be used to conduct quantitative data synthesis.

<b>Background:</b> Comparative assessments of the vascular and upper gastrointestinal risks of different regimens of non-steroidal anti-inflammatory drugs (NSAIDs) are required. <b>Methods:</b> Meta-analyses were conducted, using individual participant data where possible, of placebo-controlled trials of a selective cyclo-oxygenase [COX]-2 inhibitor ('coxib') or traditional NSAID, or randomised trials of a coxib versus traditional NSAIDs. A prespecified subdivision of traditional NSAID regimens of those with antiplatelet activity (mainly naproxen) and those without (mainly diclofenac) was made. Primary outcomes were major vascular events (MVEs; nonfatal myocardial infarction, nonfatal stroke or vascular death) and upper gastrointestinal complications (UGICs; perforation, obstruction or bleed). <b>Findings:</b> Searches identified 788 trials: 200 comparisons of a coxib vs placebo (88,604 participants, mean follow-up 0.60 years), 206 comparisons of a traditional NSAID vs placebo (43,482 participants, 0.46 years) and 149 comparisons of a coxib vs traditional NSAID (137,466 participants, mean follow-up 0.95 years). Compared to placebo, allocation to a coxib increased the risk of MVEs (rate ratio 1.38, 95&percnt; CI 1.14-1.66), vascular mortality (1.58, 1.11-2.24) and UGICs (1.81, 1.17-2.81). Overall, in the population studied, coxibs were associated with three additional major vascular events (one fatal) and two (rarely fatal) upper gastrointestinal complications per 1000 person-years exposure. There was no evidence of heterogeneity by duration of follow-up, coxib type, dose (other than for celecoxib), or patient characteristics, for the primary outcomes. The risk of MVEs for traditional NSAIDs without antiplatelet activity (mostly diclofenac 75mg bd or ibuprofen 800mg tds) were comparable to coxibs (1.40, 1.15-1.72); but the risk of UGICs (1.98, 1.39-2.84) was significantly greater. For traditional NSAIDs with antiplatelet activity (mostly naproxen 500mg bd) there were no significant excess of MVEs (0.84, 0.66-1.08), but UGICs were substantially increased (4.06, 2.85-5.78). Both coxibs and traditional NSAIDs increased risk of hospitalisation for heart failure by about two-fold. <b>Interpretation:</b> The vascular and upper gastrointestinal risks of coxibs and high-dose tNSAID regimens can be predicted, allowing the choice of analgesia to be tailored for particular patients.

Les changements climatiques constituent l’un des enjeux les plus importants en santé publique du XXIème siècle. En effet, une hausse des températures provoquera une hausse de la mortalité attribuable à la chaleur. En outre, certaines populations et territoires sont particulièrement vulnérables aux effets de la chaleur. Il est donc nécessaire de les identifier clairement ainsi que les impacts futurs pour orienter avec équité les politiques publiques aujourd’hui et à l’avenir. L’objectif de cette thèse est de documenter les facteurs de vulnérabilité à la chaleur dans le présent et les éléments permettant leur prise en compte pour l’avenir dans le contexte des changements climatiques. Quatre étapes ont été menées pour répondre à cet objectif : a) Mener une revue systématique et une méta-Analyse des facteurs de vulnérabilité face aux risques de mortalité en lien avec la chaleur ; b) Analyser si l’exposition chronique à la pollution atmosphérique modifie la relation entre la chaleur et la mortalité dans un contexte urbain (Paris) et explorer la double interaction avec la défaveur sociale ; c) Développer une méthode de quantification des impacts liés à la chaleur en lien avec les changements climatiques en intégrant une grande diversité de simulations climatiques ; d) Estimer les inégalités d’années de vies perdues attribuables à la chaleur et leurs projections futures dans deux contextes distincts (Montréal et Paris) et comparer ces inégalités. Cette thèse a permis de mettre en évidence sur la base de la littérature épidémiologique les groupes de population qui sont les plus vulnérables face aux effets de la chaleur et de montrer qu’il y a plusieurs divergences par rapport aux recommandations émises par les institutions de santé publique vis-À-Vis de l’identification de populations vulnérables. Cette thèse a permis également d’identifier l’exposition chronique à la pollution atmosphérique comme nouveau facteur de vulnérabilité à la chaleur et que cette vulnérabilité était encore plus prononcée lorsqu’il s’agissait de populations défavorisées socialement. Puis, une méthode permettant de quantifier l’impact des changements climatiques sur les décès attribuables à la chaleur et ses sources d’incertitudes a été développée, et a permis de mettre en évidence que la probabilité que les changements climatiques conduisent à une augmentation de la mortalité en lien avec la chaleur est très forte. Cette méthode a ensuite été utilisée pour estimer que l’augmentation de la température conduira à une augmentation des inégalités sociales d’années de vie perdues à la fois à Montréal et à Paris, l’effet des changements climatiques sur l’accroissement de ces inégalités étant plus fort à Montréal qu’à Paris. Cette thèse, en se basant sur diverses méthodes épidémiologiques, a permis dans l’ensemble de clarifier quelles populations étaient particulièrement à risque face aux effets de la chaleur et de questionner les recommandations émises par les organismes tels que l’OMS. Elle a également permis de montrer l’effet des changements climatiques sur l’évolution de vulnérabilités face à la chaleur pour inciter dès aujourd’hui la mise en place de politiques publiques équitables et limiter l’impact des changements climatiques sur l’accroissement des inégalités de santé. / Climate change is one of the biggest public health threats in the 21th century. An increase in temperatures will lead to an increase in mortality attributable to temperature. In addition, some populations and territories are particularly vulnerable to the impact of increases in heat. It is thus necessary to identify these populations and territories as well as examine future heat-Related health impacts in order to recommend equity-Oriented policies today and in the future. The general objective of this thesis is to document current and future heat-Related vulnerability factors in the context of climate change. In order to address this general objective, the thesis involved four components: a) to conduct a systematic review and a meta-Analysis to assess the heterogeneity in the heat-Mortality associations with respect to individual and contextual population characteristics; b) to identify whether and how the magnitude of mean temperature effects on all-Cause mortality were modified by chronic air pollution exposure, social deprivation, and a combination of these two dimensions; c) to develop a method to quantify the climate change impacts on heat-Related mortality using climate modeling; d) to assess historical and future social disparities in years of life lost caused by ambient temperature in Montreal and Paris, and compare these estimates as well as the impact of climate change on social disparities between the two cities. This thesis highlights which populations are more vulnerable to heat and shows that several differences exist with regard to guidelines from international public health institutions for the identification of vulnerable populations. This thesis also identified chronic air pollution exposure as a new vulnerability factor in heat-Related mortality and that it has a double interaction with social deprivation. Furthermore, in this thesis a novel method to quantify future heat-Related mortality was developed which emphasized the strong evidence of an increase in heat-Related mortality under climate change. This method was then applied to estimate the increase in daily years of life lost social disparities in both Montreal and Paris under climate change which showed that this increase would be greater in Montreal compared to Paris in the future. Thus, this thesis which used a variety of epidemiologic methods has clarified which populations are particularly vulnerable to heat impacts and challenges guidelines for the identification of vulnerable populations from international public health institutions. It has also highlighted the climate change impacts on health inequalities and aims to reorient equity-Focused policies.

No description available.

Statistical heterogeneity refers to differences among results of studies combined in a meta-analysis beyond that expected by chance. On the one hand, excessive heterogeneity can diminish power to discover genetic signals; on the other, moderate heterogeneity can reveal important biological differences among studies. Given its double-edged nature, this thesis dissects heterogeneity in genetic association meta-analyses from three vantage points. First, a novel multi-variant statistic, M is proposed to detect genome-wide (systematic) heterogeneity patterns in genetic association meta-analyses. This was motivated by the limited availability of appropriate methodology to measure the impact of heterogeneity across genetic signals, since traditional metrics (Q, I² and T²) measure heterogeneity at individual variants. Second, given that meta-analyses comprising small numbers of studies typically report imprecise summary effect estimates; GWAS-derived empirical heterogeneity priors are used to improve precision in estimation of average genetic effects and heterogeneity in smaller meta-analyses (e.g. ≤ 10 studies). Third, a critical evaluation of the Han-Eskin random-effects model shows how it can identify small effect heterogeneous loci overlooked by traditional fixed and random-effects methods. This work draws attention to the existence of genome-wide heterogeneity patterns, to reveal systematic differences among the ascertainment criteria of participating studies in a meta-analysis of coronary disease (CAD) risk. Furthermore, simulation studies with the Han-Eskin random-effects model revealed inflated genetic signals at small effect loci when heterogeneity levels were high. However, it did reveal an additional CAD risk variant overlooked by traditional meta-analysis methods. We therefore recommend a holistic approach to exploring heterogeneity in meta-analyses which assesses heterogeneity of genetic effects both at individual variants with traditional statistics and across multiple genetic signals with the M statistic. Furthermore, it is critically important to review forest plots for small effect loci identified using the Han-Eskin random-effects model amidst moderate-to-high heterogeneity (I² ≥ 40%).