<!DOCTYPE article
PUBLIC "-//NLM//DTD JATS (Z39.96) Journal Archiving and Interchange DTD with MathML3 v1.3 20210610//EN" "JATS-archivearticle1-3-mathml3.dtd">
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" dtd-version="1.3" xml:lang="en" article-type="research-article"><?properties manuscript?><processing-meta base-tagset="archiving" mathml-version="3.0" table-model="xhtml" tagset-family="jats"><restricted-by>pmc</restricted-by></processing-meta><front><journal-meta><journal-id journal-id-type="nlm-journal-id">9421530</journal-id><journal-id journal-id-type="pubmed-jr-id">27360</journal-id><journal-id journal-id-type="nlm-ta">J Agromedicine</journal-id><journal-id journal-id-type="iso-abbrev">J Agromedicine</journal-id><journal-title-group><journal-title>Journal of agromedicine</journal-title></journal-title-group><issn pub-type="ppub">1059-924X</issn><issn pub-type="epub">1545-0813</issn></journal-meta><article-meta><article-id pub-id-type="pmid">37128886</article-id><article-id pub-id-type="pmc">10664175</article-id><article-id pub-id-type="doi">10.1080/1059924X.2023.2209091</article-id><article-id pub-id-type="manuscript">HHSPA1941846</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title-group><article-title>Dairy Farm Work and Protection from Gastrointestinal Illness</article-title></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0002-8733-8703</contrib-id><name><surname>VanWormer</surname><given-names>Jeffrey J.</given-names></name><xref rid="A1" ref-type="aff">a</xref></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid" authenticated="false">http://orcid.org/0000-0002-3419-6940</contrib-id><name><surname>Bendixsen</surname><given-names>Casper G.</given-names></name><xref rid="A2" ref-type="aff">b</xref></contrib><contrib contrib-type="author"><name><surname>Shukla</surname><given-names>Sanjay K.</given-names></name><xref rid="A3" ref-type="aff">c</xref></contrib></contrib-group><aff id="A1"><label>a</label>Center for Clinical Epidemiology &#x00026; Population Health, Marshfield Clinic Research Institute, Marshfield, WI, USA;</aff><aff id="A2"><label>b</label>National Farm Medicine Center, Marshfield Clinic Research Institute, Marshfield, WI, USA;</aff><aff id="A3"><label>c</label>Center for Precision Medicine Research, Marshfield Clinic Research Institute, Marshfield, WI, USA</aff><author-notes><corresp id="CR1"><label>&#x02709;</label><bold>CONTACT</bold> Jeffrey J. VanWormer <email>vanwormer.jeffrey@marshfieldresearch.org</email> Center for Clinical Epidemiology &#x00026; Population Health, Marshfield Clinic Research Institute, 1000 N Oak Ave, Marshfield, WI 54449, USA</corresp></author-notes><pub-date pub-type="nihms-submitted"><day>10</day><month>11</month><year>2023</year></pub-date><pub-date pub-type="ppub"><month>10</month><year>2023</year></pub-date><pub-date pub-type="epub"><day>02</day><month>5</month><year>2023</year></pub-date><pub-date pub-type="pmc-release"><day>22</day><month>11</month><year>2023</year></pub-date><volume>28</volume><issue>4</issue><fpage>640</fpage><lpage>646</lpage><abstract id="ABS1"><p id="P1">Gastrointestinal (GI) disorders are a major public health burden in the United States. Due to close contact with animals, farmers may be a high risk subgroup for acute GI infections, though some studies suggest farm work is actually protective against GI illness. The purpose of this study was to examine associations between dairy farm work and GI symptoms over 3 years. A prospective, matched cohort study was used that included 70 adult dairy farm workers and 74 matched (age, gender, ZIP code) non-farm participants from central Wisconsin. The outcome was mean GI symptom scores for abdominal pain, diarrhea, constipation, dyspepsia, nausea, and reflux, per the 23-item Gastrointestinal Symptoms Severity Index (GISSI). After adjustment for potential confounding variables, linear regression results indicated dairy farm workers had significantly lower GISSI scores for abdominal pain (mean&#x000b1;SE = 4.3 &#x000b1; 1.1 dairy vs. 7.6 &#x000b1; 1.1 non-farm, <italic toggle="yes">p</italic> = .047), diarrhea (3.2 &#x000b1; 1.0 dairy vs. 7.0 &#x000b1; 1.0 non-farm, <italic toggle="yes">p</italic> = .010), constipation (2.0 &#x000b1; 0.8 dairy vs. 6.6 &#x000b1; 0.8 non-farm, <italic toggle="yes">p</italic> &#x0003c; .001), and dyspepsia (2.0 &#x000b1; 0.6 dairy vs. 3.9 &#x000b1; 0.5 non-farm, <italic toggle="yes">p</italic> = .026). Working on a dairy farm was associated with significantly less frequent and severe GI illness symptoms in adults. Future research should identify underlying causal pathways, including possible farm animal exposures, that influence beneficial gut microbiota that could inform therapeutic remedies to help prevent clinical GI disorders.</p></abstract><kwd-group><kwd>Farm</kwd><kwd>adults</kwd><kwd>gastrointestinal</kwd><kwd>symptoms</kwd><kwd>cohort</kwd></kwd-group></article-meta></front><body><sec id="S1"><title>Introduction</title><p id="P2">With estimated costs exceeding 140 billion dollars annually, the burden of gastrointestinal (GI) disorders is considerable in the United States.<sup><xref rid="R1" ref-type="bibr">1</xref></sup> Affecting~60% of adults in any given week, GI illness symptoms are common.<sup><xref rid="R2" ref-type="bibr">2</xref></sup> White females, as well as younger and more educated individuals, are more likely to report GI symptoms.<sup><xref rid="R2" ref-type="bibr">2</xref></sup></p><p id="P3">Farmers are also considered to be at higher risk of some GI disorders. Prior studies have shown farm workers and residents of watersheds with high concentrations of farm animals are more susceptible to severe GI infections.<sup><xref rid="R3" ref-type="bibr">3</xref>&#x02013;<xref rid="R7" ref-type="bibr">7</xref></sup> For dairy farm workers, this is probably related to contact with animal excreta secondary to livestock management, manure handling, and related exposures to antimicrobial-resistant microorganisms.<sup><xref rid="R8" ref-type="bibr">8</xref></sup> These observations are not uniform, however, as a survey in Quebec found residents of the most intense farming regions had 30% lower odds of acute GI illness.<sup><xref rid="R9" ref-type="bibr">9</xref></sup> Few studies have examined associations between dairy farm work and general GI illness symptoms, which are precursors to clinical GI disorders.</p></sec><sec id="S2"><title>Methods</title><sec id="S3"><title>Design and setting</title><p id="P4">Utilizing a prospective matched cohort design, the Dairy Microbiome (DOME) study examined seasonal changes in nasal and gut microbiota exchange between dairy farm workers and cows. The source population included residents of the Marshfield Epidemiologic Study Area (MESA)<sup><xref rid="R10" ref-type="bibr">10</xref></sup> and adjacent ZIP codes. MESA is a population-based research resource that captures information from individuals who receive care from the Marshfield Clinic Health System (MCHS) and reside in the 14 ZIP codes surrounding Marshfield, Wisconsin (USA). Residents of MESA receive over 90% of their healthcare from MCHS providers.<sup><xref rid="R11" ref-type="bibr">11</xref></sup></p></sec><sec id="S4"><title>Participants</title><p id="P5">Two groups were enrolled, including dairy farm workers and a matched comparison group of non-farm individuals. All participants were age&#x02265;18 years. Dairy farm workers had&#x02265;4 hours per week of close contact with farm animals. For each dairy farm worker, an adult who was unexposed to farm environments, and matched on age (&#x000b1;2 years), gender, and residential ZIP code, was also enrolled. Procedures were approved by the MCHS Institutional Review Board and included written informed consent and HIPAA authorization.</p></sec><sec id="S5"><title>Recruitment</title><p id="P6">Recruitment was conducted over one year beginning in spring 2019. Dairy farm workers were recruited from dairy operations, as identified by the Wisconsin register of licensed dairy producers.<sup><xref rid="R12" ref-type="bibr">12</xref></sup> Dairy operation addresses were linked to MCHS patient records and dairy operation proprietors were invited to participate in DOME. An initial mailed outreach, along with several phone follow-ups, were made to describe the study and invite all farm workers at each dairy operation. After phone screening, an enrollment visit was setup for interested individuals. Dairy operations within MESA were invited first, followed by operations in ZIP codes adjacent to MESA. Once a dairy farm worker was enrolled, those unexposed to farm work were contacted similarly until an age/gender/ZIP matched individual was enrolled.</p></sec><sec id="S6"><title>Measures</title><p id="P7">The outcome was GI illness symptoms. Six GI component scores were calculated from the Gastrointestinal Symptoms Severity Index (GISSI),<sup><xref rid="R13" ref-type="bibr">13</xref></sup> which captures abdominal pain, diarrhea, constipation, dyspepsia, nausea, and reflux. The instrument has shown good test-retest reliability across component scores (range 0.70&#x02013;0.93), as well as discriminant validity via significant prediction of patients presenting with primary diagnoses of each condition represented by the component scores. GISSI items assess self-reported frequency, severity, and bothersomeness across 23 different symptoms over the prior 30 days. Symptom features are combined to create each component score, which is standardized to 0&#x02013;100 points (higher scores = more frequent/severe GI symptoms). The GISSI was administered quarterly and, to summarize the breadth and variability of GI symptoms, component scores were averaged across participants&#x02019; enrollment periods (up to 3 years).</p></sec><sec id="S7"><title>Covariates</title><p id="P8">Based on their potential to confound GI associations, several sociodemographic and clinical covariates were selected <italic toggle="yes">a priori</italic> from enrollment surveys and linked MCHS electronic health records. Covariates included age, gender, education, season of enrollment, smoking, body mass index (normal weight, overweight, obese),<sup><xref rid="R14" ref-type="bibr">14</xref></sup> and number of GISSI assessments available during the study.</p></sec><sec id="S8"><title>Analyses</title><p id="P9">Linear regression was used to compare GISSI component scores (separately) between groups. Univariate models were initially created, followed by multivariable models that included all covariates simultaneously. To assess potential confounding, differences were noted between the univariate vs. multivariable modeled estimates for dairy farm workers.</p></sec></sec><sec id="S9"><title>Results</title><p id="P10">The sample included 70 individuals in the dairy farm group and 74 in the matched, non-farm group (4 replacements in this group were retained in analyses). The two groups were similar on most baseline characteristics, but the non-farm group had a significantly greater percentage of individuals with a college degree, obesity, and were current smokers (<xref rid="T1" ref-type="table">Table 1</xref>). Overall, 77% of participants reported at least one GI symptom during their enrollment period, with diarrhea (46%) the most common, followed by constipation (40%), abdominal pain (40%), reflux (40%), dyspepsia (32%), and nausea (20%).</p><p id="P11">In univariate models, dairy farm workers had significantly lower GISSI scores for abdominal pain (mean&#x000b1;SE = 3.9 &#x000b1; 0.8 dairy vs. 7.9 &#x000b1; 1.2 non-farm, <italic toggle="yes">p</italic> = .007), diarrhea (3.1 &#x000b1; 0.6 dairy vs. 7.1 &#x000b1; 1.1 non-farm, <italic toggle="yes">p</italic> = .002), constipation (2.1 &#x000b1; 0.4 dairy vs. 6.5 &#x000b1; 1.0 non-farm, <italic toggle="yes">p</italic> &#x0003c; .001), and dyspepsia (1.8 &#x000b1; 0.4 dairy vs. 4.0 &#x000b1; 0.6 non-farm, <italic toggle="yes">p</italic> = .004). Nausea (2.1 &#x000b1; 0.4 dairy vs. 3.6 &#x000b1; 0.8 non-farm, <italic toggle="yes">p</italic> = .091) and reflux (3.3 &#x000b1; 0.6 dairy vs. 4.6 &#x000b1; 0.6 non-farm, <italic toggle="yes">p</italic> = .144), while trending lower in dairy farm workers, were not significantly different. In the covariate adjusted models summarized in <xref rid="T2" ref-type="table">Table 2</xref> and <xref rid="F1" ref-type="fig">Figure 1</xref>, the magnitude and significance of these associations were slightly attenuated, but remained similar. With the exceptions of smoking and gender in the dyspepsia and nausea models, no covariates were significant predictors of GISSI component scores, nor did they appreciably shift any univariate estimates of differences between groups (indicating no confounding).</p></sec><sec id="S10"><title>Discussion</title><p id="P12">As expected,<sup><xref rid="R2" ref-type="bibr">2</xref></sup> GI illness symptoms impacted most participants at some point during the 3-year DOME study. The overall burden of GI symptoms, however, was consistently lower in dairy farm workers. In particular, constipation and diarrhea scores were 2&#x02013;3 times greater in the non-farm group. This was intriguing given that prior research suggests farm workers, as well as those who live in watersheds with high concentrations of livestock, are more apt to develop severe GI infections.<sup><xref rid="R3" ref-type="bibr">3</xref>&#x02013;<xref rid="R7" ref-type="bibr">7</xref></sup></p><p id="P13">Dairy farm workers are in regular, close contact with cows (e.g., milking, cleaning animals and facilities) and handling of antimicrobial saturated manure (shedding up to 10<sup>7</sup>
<italic toggle="yes">Escherichia coli</italic> bacteria per gram<sup><xref rid="R15" ref-type="bibr">15</xref></sup> is an occupational hazard that can, for example, double the risk of <italic toggle="yes">Cryptosporidium</italic> infection, which can trigger life threatening diarrhea.<sup><xref rid="R16" ref-type="bibr">16</xref></sup> Our study findings, however, were actually more consistent with a survey by Febriani and colleagues,<sup><xref rid="R9" ref-type="bibr">9</xref></sup> who found residents of the most intense farming regions of Quebec reported persistent vomiting and diarrhea less often than residents of other watersheds. Discrepant findings in this body of literature are likely a function of methodological differences in GI distress measures and target samples/regions, including animal mixes and watersheds with varying diversity of bacterial and protozoal pathogens. It could be that farm workers are both more susceptible to acute GI infection resulting in hospitalization, yet experience sub-clinical GI symptoms less often.</p><p id="P14">Causal mechanisms for the GI illness symptom protection observed in dairy workers in DOME are unknown. The associations were robust in multivariable models that accounted for some typical GI risk factors such as age, gender, smoking, and obesity, but other potential confounding variables like antibiotic use were not measured. Superior diet quality in farm workers seems an unlikely explanation,<sup><xref rid="R17" ref-type="bibr">17</xref></sup> but greater abundance of beneficial microbes in dairy farmer workers&#x02019; GI tract could be a contributor.<sup><xref rid="R18" ref-type="bibr">18</xref></sup> As observed in farm children, regular exposure to animals primes immune-protective pathways that result in fewer cases of asthma and atopic diseases,<sup><xref rid="R19" ref-type="bibr">19</xref>,<xref rid="R20" ref-type="bibr">20</xref></sup> and per-haps prevention of other pro-inflammatory conditions.<sup><xref rid="R21" ref-type="bibr">21</xref></sup> Additionally, farm workers have greater microbial diversity in their nasal cavity, which is hypothesized to protect against staphylococcal infection.<sup><xref rid="R22" ref-type="bibr">22</xref></sup> As microbiomes and resistomes can readily shift for people exposed to farm environments (including non-farmers),<sup><xref rid="R23" ref-type="bibr">23</xref></sup> future analyses should consider bacterial enterotype comparisons between individuals with and without GI disorders to examine how protective gut microbiota may differ in dairy farm workers, analogous to studies by Costea and colleagues.<sup><xref rid="R24" ref-type="bibr">24</xref></sup></p><p id="P15">Strengths of this study included the prospective cohort design, matched analyses, and defined source population. The chief limitations were the small sample size and self-reported GI outcomes. This precluded examination of important subgroups and increased risks of recall and self presentation biases (e.g., farmer stoicism) of symptom severity. The degree to which increased GISSI scores translate into clinical GI disorders remains unknown, as less than 20% of adults seek medical care following GI symptom onset,<sup><xref rid="R25" ref-type="bibr">25</xref></sup> and some potential confounders (e.g., antibiotic use, dietary habits) were unavailable. In addition, the source population was racially homogenous and focused on dairy farming, thereby limiting generalizability to more diverse groups or other agricultural specialties. Future research should target broader populations, along with more robust control matching, assessments of nutrition and health attitudes, and detailed information on animal exposures.</p><p id="P16">Working on a dairy farm was associated with significantly less frequent/severe GI illness symptoms in adults. Causal factors underlying this observation remain unknown, but highlight the need for more research into potentially beneficial environmental exposures where interactions with farm animals (and associated microbiota) are routine. This could eventually guide therapeutic remedies to help prevent clinical GI disorders.</p></sec></body><back><ack id="S12"><title>Acknowledgments</title><p id="P18">The authors gratefully acknowledge the assistance of all DOME study staff.</p><sec id="S13"><title>Funding</title><p id="P19">This work was supported by the National Institute of Occupational Safety and Health (CDC) under Grant WU-19-126 (Shukla, S. PI).</p></sec></ack><fn-group><fn fn-type="COI-statement" id="FN1"><p id="P20">Disclosure statement</p><p id="P21">The authors have no relevant financial or non-financial competing interests to report.</p></fn></fn-group><sec sec-type="data-availability" id="S11"><title>Data availability statement</title><p id="P17">The data that support the study conclusions are unavailable for public access because informed consent to share said data (beyond the research team) was not obtained from study participants.</p></sec><ref-list><title>References</title><ref id="R1"><label>1.</label><mixed-citation publication-type="journal"><name><surname>Everhart</surname><given-names>JE</given-names></name>, <name><surname>Ruhl</surname><given-names>CE</given-names></name>. <article-title>Burden of digestive diseases in the United States part I: overall and upper gastrointestinal diseases</article-title>. <source>Gastroenterology</source>. <year>2009</year>;<volume>136</volume>(<issue>2</issue>):<fpage>376</fpage>&#x02013;<lpage>386</lpage>. doi:<pub-id pub-id-type="doi">10.1053/j.gastro.2008.12.015</pub-id>.<pub-id pub-id-type="pmid">19124023</pub-id></mixed-citation></ref><ref id="R2"><label>2.</label><mixed-citation publication-type="journal"><name><surname>Almario</surname><given-names>CV</given-names></name>, <name><surname>Ballal</surname><given-names>ML</given-names></name>, <name><surname>Chey</surname><given-names>WD</given-names></name>, <name><surname>Nordstrom</surname><given-names>C</given-names></name>, <name><surname>Khanna</surname><given-names>D</given-names></name>, <name><surname>Spiegel</surname><given-names>BMR</given-names></name>. <article-title>Burden of gastrointestinal symptoms in the United States: results of a nationally representative survey of over 71,000 Americans</article-title>. <source>Am J Gastroenterol</source>. <year>2018</year>;<volume>113</volume>:<fpage>1701</fpage>&#x02013;<lpage>1710</lpage>. doi:<pub-id pub-id-type="doi">10.1038/s41395-018-0256-8</pub-id>.<pub-id pub-id-type="pmid">30323268</pub-id></mixed-citation></ref><ref id="R3"><label>3.</label><mixed-citation publication-type="journal"><name><surname>Locking</surname><given-names>ME</given-names></name>, <name><surname>O&#x02019;Brien</surname><given-names>SJ</given-names></name>, <name><surname>Reilly</surname><given-names>WJ</given-names></name>, <etal/>
<article-title>Risk factors for sporadic cases of Escherichia coli O157 infection: the importance of contact with animal excreta</article-title>. <source>Epidemiol Infect</source>. <year>2001</year>;<volume>127</volume>:<fpage>215</fpage>&#x02013;<lpage>220</lpage>. doi:<pub-id pub-id-type="doi">10.1017/S0950268801006045</pub-id>.<pub-id pub-id-type="pmid">11693498</pub-id></mixed-citation></ref><ref id="R4"><label>4.</label><mixed-citation publication-type="journal"><name><surname>Potter</surname><given-names>RC</given-names></name>, <name><surname>Kaneene</surname><given-names>JB</given-names></name>, <name><surname>Gardiner</surname><given-names>J</given-names></name>. <article-title>A comparison of campylobacter jejuni enteritis incidence rates in high- and low-poultry-density counties: Michigan 1992&#x02013;1999</article-title>. <source>Vector Borne Zoonotic Dis</source>. <year>2002</year>;<volume>2</volume>(<issue>3</issue>):<fpage>137</fpage>&#x02013;<lpage>143</lpage>. doi:<pub-id pub-id-type="doi">10.1089/15303660260613701</pub-id>.<pub-id pub-id-type="pmid">12737543</pub-id></mixed-citation></ref><ref id="R5"><label>5.</label><mixed-citation publication-type="journal"><name><surname>Febriani</surname><given-names>Y</given-names></name>, <name><surname>Levallois</surname><given-names>P</given-names></name>, <name><surname>Lebel</surname><given-names>G</given-names></name>, <name><surname>Gingras</surname><given-names>S</given-names></name>. <article-title>Association between indicators of livestock farming intensity and hospitalization rate for acute gastroenteritis</article-title>. <source>Epidemiol Infect</source>. <year>2009</year>;<volume>137</volume>(<issue>8</issue>):<fpage>1073</fpage>&#x02013;<lpage>1085</lpage>. doi:<pub-id pub-id-type="doi">10.1017/S0950268808001647</pub-id>.<pub-id pub-id-type="pmid">19243650</pub-id></mixed-citation></ref><ref id="R6"><label>6.</label><mixed-citation publication-type="journal"><name><surname>Haus-Cheymol</surname><given-names>R</given-names></name>, <name><surname>Espie</surname><given-names>E</given-names></name>, <name><surname>Che</surname><given-names>D</given-names></name>, <name><surname>Vaillant</surname><given-names>V</given-names></name>, <name><surname>de Valk</surname><given-names>H</given-names></name>, <name><surname>Desenclos</surname><given-names>JC</given-names></name>. <article-title>Association between indicators of cattle density and incidence of paediatric haemolytic &#x02013; uraemic syndrome (HUS) in children under 15 years of age in France between 1996 and 2001: an ecological study</article-title>. <source>Epidemiol Infect</source>. <year>2006</year>;<volume>134</volume> (<issue>4</issue>):<fpage>712</fpage>&#x02013;<lpage>718</lpage>. doi:<pub-id pub-id-type="doi">10.1017/S095026880500542X</pub-id>.<pub-id pub-id-type="pmid">16371171</pub-id></mixed-citation></ref><ref id="R7"><label>7.</label><mixed-citation publication-type="journal"><name><surname>Valcour</surname><given-names>JE</given-names></name>. <article-title>Associations between indicators of live-stock farming intensity and incidence of human Shiga toxin-producing Escherichia coli infection</article-title>. <source>Emerg Infect Dis</source>. <year>2002</year>;<volume>8</volume>(<issue>3</issue>):<fpage>252</fpage>&#x02013;<lpage>257</lpage>. doi:<pub-id pub-id-type="doi">10.3201/eid0803.010159</pub-id>.<pub-id pub-id-type="pmid">11927021</pub-id></mixed-citation></ref><ref id="R8"><label>8.</label><mixed-citation publication-type="journal"><name><surname>Landers</surname><given-names>TF</given-names></name>, <name><surname>Cohen</surname><given-names>B</given-names></name>, <name><surname>Wittum</surname><given-names>TE</given-names></name>, <name><surname>Larson</surname><given-names>EL</given-names></name>. <article-title>A review of antibiotic use in food animals: perspective, policy, and potential</article-title>. <source>Public Health Rep</source>. <year>2012</year>;<volume>127</volume>(<issue>1</issue>):<fpage>4</fpage>&#x02013;<lpage>22</lpage>. doi:<pub-id pub-id-type="doi">10.1177/003335491212700103</pub-id>.<pub-id pub-id-type="pmid">22298919</pub-id></mixed-citation></ref><ref id="R9"><label>9.</label><mixed-citation publication-type="journal"><name><surname>Febriani</surname><given-names>Y</given-names></name>, <name><surname>Levallois</surname><given-names>P</given-names></name>, <name><surname>Gingras</surname><given-names>S</given-names></name>, <name><surname>Gosselin</surname><given-names>P</given-names></name>, <name><surname>Majowicz</surname><given-names>SE</given-names></name>, <name><surname>Fleury</surname><given-names>MD</given-names></name>. <article-title>The association between farming activities, precipitation, and the risk of acute gastrointestinal illness in rural municipalities of Quebec, Canada: a cross-sectional study</article-title>. <source>BMC Public Health</source>. <year>2010</year>;<volume>10</volume>(<issue>1</issue>):<fpage>48</fpage>. doi:<pub-id pub-id-type="doi">10.1186/1471-2458-10-48</pub-id>.<pub-id pub-id-type="pmid">20113516</pub-id></mixed-citation></ref><ref id="R10"><label>10.</label><mixed-citation publication-type="journal"><name><surname>DeStefano</surname><given-names>F</given-names></name>, <name><surname>Eaker</surname><given-names>ED</given-names></name>, <name><surname>Broste</surname><given-names>SK</given-names></name>, <etal/>
<article-title>Epidemiologic research in an integrated regional medical care system: the Marshfield epidemiologic study area</article-title>. <source>J Clin Epidemiol</source>. <year>1996</year>;<volume>49</volume>(<issue>6</issue>):<fpage>643</fpage>&#x02013;<lpage>652</lpage>. doi:<pub-id pub-id-type="doi">10.1016/0895-4356(96)00008-X</pub-id>.<pub-id pub-id-type="pmid">8656225</pub-id></mixed-citation></ref><ref id="R11"><label>11.</label><mixed-citation publication-type="journal"><name><surname>Kieke</surname><given-names>AL</given-names></name>, <name><surname>Kieke</surname><given-names>BA</given-names><suffix>Jr</suffix></name>, <name><surname>Kopitzke</surname><given-names>SL</given-names></name>, <etal/>
<article-title>Validation of health event capture in the Marshfield epidemiologic study area</article-title>. <source>Clin Med Res</source>. <year>2015</year>;<volume>13</volume>(<issue>3&#x02013;4</issue>):<fpage>103</fpage>&#x02013;<lpage>111</lpage>. doi:<pub-id pub-id-type="doi">10.3121/cmr.2014.1246</pub-id>.<pub-id pub-id-type="pmid">25487238</pub-id></mixed-citation></ref><ref id="R12"><label>12.</label><mixed-citation publication-type="webpage"><collab>Wisconsin department of agriculture, trade and consumer protection</collab>. <source>food, dairy, and retail food licenses</source>. <comment><ext-link xlink:href="https://datcp.wi.gov/Pages/Licenses_Permits/FoodLicenses.aspx" ext-link-type="uri">https://datcp.wi.gov/Pages/Licenses_Permits/FoodLicenses.aspx</ext-link>.</comment>
<comment>Accessed</comment>
<date-in-citation>August 31, 2022</date-in-citation>.</mixed-citation></ref><ref id="R13"><label>13.</label><mixed-citation publication-type="journal"><name><surname>Crowell</surname><given-names>MD</given-names></name>, <name><surname>Umar</surname><given-names>SB</given-names></name>, <name><surname>Lacy</surname><given-names>BE</given-names></name>, <name><surname>Jones</surname><given-names>MP</given-names></name>, <name><surname>DiBaise</surname><given-names>JK</given-names></name>, <name><surname>Talley</surname><given-names>NJ</given-names></name>. <article-title>multi-dimensional gastrointestinal symptom severity index: validation of a brief GI symptom assessment tool</article-title>. <source>Dig Dis Sci</source>. <year>2015</year>;<volume>60</volume>(<issue>8</issue>):<fpage>2270</fpage>&#x02013;<lpage>2279</lpage>. doi:<pub-id pub-id-type="doi">10.1007/s10620-015-3647-3</pub-id>.<pub-id pub-id-type="pmid">25842355</pub-id></mixed-citation></ref><ref id="R14"><label>14.</label><mixed-citation publication-type="webpage"><collab>U.S. Centers for Disease Control and Prevention</collab>. <source>About adult BMI</source>. <comment><ext-link xlink:href="https://www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/index.html" ext-link-type="uri">https://www.cdc.gov/healthyweight/assessing/bmi/adult_bmi/index.html</ext-link>.</comment>
<comment>Accessed</comment>
<date-in-citation>August 22, 2022</date-in-citation>.</mixed-citation></ref><ref id="R15"><label>15.</label><mixed-citation publication-type="journal"><name><surname>Munns</surname><given-names>KD</given-names></name>, <name><surname>Zaheer</surname><given-names>R</given-names></name>, <name><surname>Xu</surname><given-names>Y</given-names></name>, <etal/>
<article-title>comparative genomic analysis of Escherichia coli O157: h7 isolated from super-shedder and low-shedder cattle</article-title>. <source>PLoS One</source>. <year>2016</year>;<volume>11</volume>(<issue>3</issue>):<fpage>e0151673</fpage>. doi:<pub-id pub-id-type="doi">10.1371/journal.pone.0151673</pub-id>.<pub-id pub-id-type="pmid">27018858</pub-id></mixed-citation></ref><ref id="R16"><label>16.</label><mixed-citation publication-type="journal"><name><surname>Lengerich</surname><given-names>EJ</given-names></name>, <name><surname>Addiss</surname><given-names>DG</given-names></name>, <name><surname>Marx</surname><given-names>JJ</given-names></name>, <name><surname>Ungar</surname><given-names>BL</given-names></name>, <name><surname>Juranek</surname><given-names>DD</given-names></name>. <article-title>Increased exposure to cryptosporidia among dairy farmers in Wisconsin</article-title>. <source>J Infect Dis</source>. <year>1993</year>;<volume>167</volume>(<issue>5</issue>):<fpage>1252</fpage>&#x02013;<lpage>1255</lpage>. doi:<pub-id pub-id-type="doi">10.1093/infdis/167.5.1252</pub-id>.<pub-id pub-id-type="pmid">8486966</pub-id></mixed-citation></ref><ref id="R17"><label>17.</label><mixed-citation publication-type="journal"><name><surname>Lighthall</surname><given-names>D</given-names></name>
<article-title>The poor health of farm workers</article-title>. <source>West J Med</source>. <year>2001</year>;<volume>175</volume>(<issue>4</issue>):<fpage>223</fpage>&#x02013;<lpage>224</lpage>. doi:<pub-id pub-id-type="doi">10.1136/ewjm.175.4.223</pub-id>.<pub-id pub-id-type="pmid">11577037</pub-id></mixed-citation></ref><ref id="R18"><label>18.</label><mixed-citation publication-type="journal"><name><surname>Shin</surname><given-names>A</given-names></name>, <name><surname>Preidis</surname><given-names>GA</given-names></name>, <name><surname>Shulman</surname><given-names>R</given-names></name>, <name><surname>Kashyap</surname><given-names>PC</given-names></name>. <article-title>The gut microbiome in adult and pediatric functional gastro-intestinal disorders</article-title>. <source>Clin Gastroenterol Hepatol</source>. <year>2019</year>;<volume>17</volume>(<issue>2</issue>):<fpage>256</fpage>&#x02013;<lpage>274</lpage>. doi:<pub-id pub-id-type="doi">10.1016/j.cgh.2018.08.054</pub-id>.<pub-id pub-id-type="pmid">30153517</pub-id></mixed-citation></ref><ref id="R19"><label>19.</label><mixed-citation publication-type="journal"><name><surname>Steiman</surname><given-names>CA</given-names></name>, <name><surname>Evans</surname><given-names>MD</given-names></name>, <name><surname>Lee</surname><given-names>KE</given-names></name>, <etal/>
<article-title>Patterns of farm exposure are associated with reduced incidence of atopic dermatitis in early life</article-title>. <source>J Allergy Clin Immunol</source>. <year>2020</year>;<volume>146</volume>(<issue>6</issue>):<fpage>1379</fpage>&#x02013;<lpage>1386</lpage>. doi:<pub-id pub-id-type="doi">10.1016/j.jaci.2020.06.025</pub-id>.<pub-id pub-id-type="pmid">32650021</pub-id></mixed-citation></ref><ref id="R20"><label>20.</label><mixed-citation publication-type="journal"><name><surname>Illi</surname><given-names>S</given-names></name>, <name><surname>Depner</surname><given-names>M</given-names></name>, <name><surname>Genuneit</surname><given-names>J</given-names></name>, <etal/>
<article-title>Protection from childhood asthma and allergy in alpine farm environments&#x02014;the GABRIEL advanced studies</article-title>. <source>J Allergy Clin Immunol</source>. <year>2012</year>;<volume>129</volume>(<issue>6</issue>):<fpage>1470</fpage>&#x02013;<lpage>1477</lpage>. doi:<pub-id pub-id-type="doi">10.1016/j.jaci.2012.03.013</pub-id>.<pub-id pub-id-type="pmid">22534534</pub-id></mixed-citation></ref><ref id="R21"><label>21.</label><mixed-citation publication-type="journal"><name><surname>Rook</surname><given-names>GA</given-names></name>. <article-title>Regulation of the immune system by bio-diversity from the natural environment: an ecosystem service essential to health</article-title>. <source>Proc Natl Acad Sci U S A</source>. <year>2013</year>;<volume>110</volume>(<issue>46</issue>):<fpage>18360</fpage>&#x02013;<lpage>18367</lpage>. doi:<pub-id pub-id-type="doi">10.1073/pnas.1313731110</pub-id>.<pub-id pub-id-type="pmid">24154724</pub-id></mixed-citation></ref><ref id="R22"><label>22.</label><mixed-citation publication-type="journal"><name><surname>Shukla</surname><given-names>SK</given-names></name>, <name><surname>Ye</surname><given-names>Z</given-names></name>, <name><surname>Sandberg</surname><given-names>S</given-names></name>, <etal/>
<article-title>The nasal microbiota of dairy farmers is more complex than oral microbiota, reflects occupational exposure, and provides competition for staphylococci</article-title>. <source>PLoS One</source>. <year>2017</year>;<volume>12</volume>(<issue>8</issue>):<fpage>e0183898</fpage>. doi:<pub-id pub-id-type="doi">10.1371/journal.pone.0183898</pub-id>.<pub-id pub-id-type="pmid">28850578</pub-id></mixed-citation></ref><ref id="R23"><label>23.</label><mixed-citation publication-type="journal"><name><surname>Sun</surname><given-names>J</given-names></name>, <name><surname>Liao</surname><given-names>XP</given-names></name>, <name><surname>D&#x02019;Souza</surname><given-names>AW</given-names></name>, <etal/>
<article-title>Environmental remodeling of human gut microbiota and antibiotic resistome in livestock farms</article-title>. <source>Nat Commun</source>. <year>2020</year>;<volume>11</volume> (<issue>1</issue>):<fpage>1427</fpage>. doi:<pub-id pub-id-type="doi">10.1038/s41467-020-15222-y</pub-id>.<pub-id pub-id-type="pmid">32188862</pub-id></mixed-citation></ref><ref id="R24"><label>24.</label><mixed-citation publication-type="journal"><name><surname>Costea</surname><given-names>PI</given-names></name>, <name><surname>Hildebrand</surname><given-names>F</given-names></name>, <name><surname>Arumugam</surname><given-names>M</given-names></name>, <etal/>
<article-title>Enterotypes in the landscape of gut microbial community composition</article-title>. <source>Nat Microbiol</source>. <year>2017</year>;<volume>3</volume>(<issue>1</issue>):<fpage>8</fpage>&#x02013;<lpage>16</lpage>. doi:<pub-id pub-id-type="doi">10.1038/s41564-017-0072-8</pub-id>.<pub-id pub-id-type="pmid">29255284</pub-id></mixed-citation></ref><ref id="R25"><label>25.</label><mixed-citation publication-type="journal"><name><surname>Sandler</surname><given-names>RS</given-names></name>, <name><surname>Stewart</surname><given-names>WF</given-names></name>, <name><surname>Liberman</surname><given-names>JN</given-names></name>, <name><surname>Ricci</surname><given-names>JA</given-names></name>, <name><surname>Zorich</surname><given-names>NL</given-names></name>. <article-title>Abdominal pain, bloating, and diarrhea in the United States: prevalence and impact</article-title>. <source>Dig Dis Sci</source>. <year>2000</year>;<volume>45</volume>(<issue>6</issue>):<fpage>1166</fpage>&#x02013;<lpage>1171</lpage>. doi:<pub-id pub-id-type="doi">10.1023/A:1005554103531</pub-id>.<pub-id pub-id-type="pmid">10877233</pub-id></mixed-citation></ref></ref-list></back><floats-group><fig position="float" id="F1"><label>Figure 1.</label><caption><p id="P22">Multivariable model-based estimates of Gastrointestinal Symptoms Severity Index (GISSI) component scores between.</p></caption><graphic xlink:href="nihms-1941846-f0001" position="float"/></fig><table-wrap position="float" id="T1" orientation="landscape"><label>Table 1.</label><caption><p id="P23">Characteristics of adults who do vs. do not work on dairy farms in central Wisconsin.</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" valign="middle" span="1"/><col align="left" valign="middle" span="1"/><col align="left" valign="middle" span="1"/><col align="left" valign="middle" span="1"/></colgroup><thead><tr><th align="left" valign="bottom" rowspan="1" colspan="1"/><th align="center" valign="bottom" rowspan="1" colspan="1">Dairy farm worker <italic toggle="yes">n</italic> = 70</th><th align="center" valign="bottom" rowspan="1" colspan="1">Non-farm <italic toggle="yes">n</italic> = 74</th><th align="center" valign="bottom" rowspan="1" colspan="1">
<italic toggle="yes">P</italic>
</th></tr></thead><tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Age (y)</td><td align="center" valign="top" rowspan="1" colspan="1">42.3 &#x000b1; 14.2</td><td align="center" valign="top" rowspan="1" colspan="1">43.1 &#x000b1; 14.3</td><td align="center" valign="top" rowspan="1" colspan="1">0.735</td></tr><tr><td colspan="4" align="left" valign="top" rowspan="1">Gender</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Female</td><td align="center" valign="top" rowspan="1" colspan="1">22 (31%)</td><td align="center" valign="top" rowspan="1" colspan="1">22 (30%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Male</td><td align="center" valign="top" rowspan="1" colspan="1">48 (69%)</td><td align="center" valign="top" rowspan="1" colspan="1">52 (70%)</td><td align="center" valign="top" rowspan="1" colspan="1">0.825</td></tr><tr><td colspan="4" align="left" valign="top" rowspan="1">Race/Ethnicity</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;White, non-Hispanic</td><td align="center" valign="top" rowspan="1" colspan="1">67 (96%)</td><td align="center" valign="top" rowspan="1" colspan="1">73 (99%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Non-White or Hispanic</td><td align="center" valign="top" rowspan="1" colspan="1">3 (4%)</td><td align="center" valign="top" rowspan="1" colspan="1">1 (1%)</td><td align="center" valign="top" rowspan="1" colspan="1">0.284</td></tr><tr><td colspan="4" align="left" valign="top" rowspan="1">Education</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Less than high school</td><td align="center" valign="top" rowspan="1" colspan="1">10 (14%)</td><td align="center" valign="top" rowspan="1" colspan="1">2 (3%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;High school</td><td align="center" valign="top" rowspan="1" colspan="1">15 (21%)</td><td align="center" valign="top" rowspan="1" colspan="1">19 (26%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Associate degree or some college</td><td align="center" valign="top" rowspan="1" colspan="1">30 (43%)</td><td align="center" valign="top" rowspan="1" colspan="1">33 (46%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;College degree</td><td align="center" valign="top" rowspan="1" colspan="1">11 (16%)</td><td align="center" valign="top" rowspan="1" colspan="1">20 (27%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Unknown</td><td align="center" valign="top" rowspan="1" colspan="1">4 (6%)</td><td align="center" valign="top" rowspan="1" colspan="1">0 (6%)</td><td align="center" valign="top" rowspan="1" colspan="1">0.014</td></tr><tr><td colspan="4" align="left" valign="top" rowspan="1">Season of enrollment</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Spring</td><td align="center" valign="top" rowspan="1" colspan="1">18 (26%)</td><td align="center" valign="top" rowspan="1" colspan="1">21 (28%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Summer</td><td align="center" valign="top" rowspan="1" colspan="1">15 (24%)</td><td align="center" valign="top" rowspan="1" colspan="1">18 (24%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Fall</td><td align="center" valign="top" rowspan="1" colspan="1">17 (21%)</td><td align="center" valign="top" rowspan="1" colspan="1">18 (24%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Winter</td><td align="center" valign="top" rowspan="1" colspan="1">20 (29%)</td><td align="center" valign="top" rowspan="1" colspan="1">17 (23%)</td><td align="center" valign="top" rowspan="1" colspan="1">0.882</td></tr><tr><td colspan="4" align="left" valign="top" rowspan="1">Body mass index</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Obese</td><td align="center" valign="top" rowspan="1" colspan="1">23 (33%)</td><td align="center" valign="top" rowspan="1" colspan="1">36 (49%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Overweight</td><td align="center" valign="top" rowspan="1" colspan="1">25 (36%)</td><td align="center" valign="top" rowspan="1" colspan="1">23 (31%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Normal weight</td><td align="center" valign="top" rowspan="1" colspan="1">13 (19%)</td><td align="center" valign="top" rowspan="1" colspan="1">15 (20%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Unknown</td><td align="center" valign="top" rowspan="1" colspan="1">9 (13%)</td><td align="center" valign="top" rowspan="1" colspan="1">0 (0%)</td><td align="center" valign="top" rowspan="1" colspan="1">0.007</td></tr><tr><td colspan="4" align="left" valign="top" rowspan="1">Smoker</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Current</td><td align="center" valign="top" rowspan="1" colspan="1">5 (7%)</td><td align="center" valign="top" rowspan="1" colspan="1">12 (16%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Former</td><td align="center" valign="top" rowspan="1" colspan="1">3 (4%)</td><td align="center" valign="top" rowspan="1" colspan="1">15 (20%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Never</td><td align="center" valign="top" rowspan="1" colspan="1">51 (73%)</td><td align="center" valign="top" rowspan="1" colspan="1">44 (59%)</td><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Unknown</td><td align="center" valign="top" rowspan="1" colspan="1">11 (16%)</td><td align="center" valign="top" rowspan="1" colspan="1">3 (4%)</td><td align="center" valign="top" rowspan="1" colspan="1">0.001</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Number of GISSI&#x02019;s available (over 3 years)</td><td align="center" valign="top" rowspan="1" colspan="1">9.1 &#x000b1; 4.1</td><td align="center" valign="top" rowspan="1" colspan="1">8.6 &#x000b1; 3.4</td><td align="center" valign="top" rowspan="1" colspan="1">0.440</td></tr></tbody></table><table-wrap-foot><fn id="TFN1"><p id="P24">Values are reported as mean &#x000b1;SD or frequency (% of total). GISSI = Gastrointestinal Symptoms Severity Index.</p></fn></table-wrap-foot></table-wrap><table-wrap position="float" id="T2" orientation="landscape"><label>Table 2.</label><caption><p id="P25">Multivariable linear regression models of Gastrointestinal Symptoms Severity Index (GISSI) component scores between adults who do vs. do not work on dairy farms in central Wisconsin.</p></caption><table frame="hsides" rules="groups"><colgroup span="1"><col align="left" valign="middle" span="1"/><col align="left" valign="middle" span="1"/><col align="left" valign="middle" span="1"/><col align="left" valign="middle" span="1"/><col align="left" valign="middle" span="1"/><col align="left" valign="middle" span="1"/><col align="left" valign="middle" span="1"/></colgroup><thead><tr><th align="center" valign="middle" rowspan="1" colspan="1"/><th colspan="6" align="center" valign="middle" style="border-bottom: solid 1px" rowspan="1">GISSI scores (mean &#x000b1;SE points difference), p</th></tr><tr><th align="center" valign="middle" rowspan="1" colspan="1"/><th align="center" valign="middle" rowspan="1" colspan="1">Abdominal pain</th><th align="center" valign="middle" rowspan="1" colspan="1">Diarrhea</th><th align="center" valign="middle" rowspan="1" colspan="1">Constipation</th><th align="center" valign="middle" rowspan="1" colspan="1">Dyspepsia</th><th align="center" valign="middle" rowspan="1" colspan="1">Nausea</th><th align="center" valign="middle" rowspan="1" colspan="1">Reflux</th></tr></thead><tbody><tr><td align="left" valign="top" rowspan="1" colspan="1">Group</td><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Dairy farm vs. Non-farm</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;<bold>3.3 &#x000b1; 1.7, <italic toggle="yes">p</italic> = .047</bold></td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;<bold>3.8 &#x000b1; 1.4, <italic toggle="yes">p</italic> = .010</bold></td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;<bold>4.7 &#x000b1; 1.2, p &#x0003c; .001</bold></td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;<bold>1.9 &#x000b1; 0.8, <italic toggle="yes">p</italic> = .026</bold></td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;1.1 &#x000b1; 1.0, <italic toggle="yes">p</italic> = .278</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;1.0 &#x000b1; 1.0, <italic toggle="yes">p</italic> = .324</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Age (yrs)</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;0.1 &#x000b1;0.1, <italic toggle="yes">p</italic> = .360</td><td align="center" valign="top" rowspan="1" colspan="1">0.0 &#x000b1; 0.1, <italic toggle="yes">p</italic> = .509</td><td align="center" valign="top" rowspan="1" colspan="1">0.0 &#x000b1; 0.1, <italic toggle="yes">p</italic> = .369</td><td align="center" valign="top" rowspan="1" colspan="1">0.0 &#x000b1; 0.0, <italic toggle="yes">p</italic> = .814</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;0.1 &#x000b1;0.0, <italic toggle="yes">p</italic> = .190</td><td align="center" valign="top" rowspan="1" colspan="1">0.0 &#x000b1; 0.0, <italic toggle="yes">p</italic> = .834</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Gender</td><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Female vs. Male</td><td align="center" valign="top" rowspan="1" colspan="1">2.8 &#x000b1; 1.8, <italic toggle="yes">p</italic> = .115</td><td align="center" valign="top" rowspan="1" colspan="1">0.2 &#x000b1; 1.5, <italic toggle="yes">p</italic> = .874</td><td align="center" valign="top" rowspan="1" colspan="1">1.3 &#x000b1; 1.3, <italic toggle="yes">p</italic> = .333</td><td align="center" valign="top" rowspan="1" colspan="1">0.9 &#x000b1; 0.9, <italic toggle="yes">p</italic> = .327</td><td align="center" valign="top" rowspan="1" colspan="1">
<bold>2.9 &#x000b1; 1.0, <italic toggle="yes">p</italic> = .006</bold>
</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;0.3 &#x000b1; 1.0, <italic toggle="yes">p</italic> = .758</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Education</td><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Less than high school vs. College degree</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;2.6 &#x000b1; 3.6, <italic toggle="yes">p</italic> = .785</td><td align="center" valign="top" rowspan="1" colspan="1">1.2 &#x000b1; 3.1, <italic toggle="yes">p</italic> = .698</td><td align="center" valign="top" rowspan="1" colspan="1">2.1 &#x000b1; 2.7, <italic toggle="yes">p</italic> = .443</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;0.4 &#x000b1; 1.8, <italic toggle="yes">p</italic> = .828</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;2.6 &#x000b1; 2.1, <italic toggle="yes">p</italic> = .223</td><td align="center" valign="top" rowspan="1" colspan="1">0.3 &#x000b1; 2.1, <italic toggle="yes">p</italic> = .906</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;High school vs. College degree</td><td align="center" valign="top" rowspan="1" colspan="1">1.6 &#x000b1; 2.3, <italic toggle="yes">p</italic> = .492</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;1.0 &#x000b1; 2.0, <italic toggle="yes">p</italic> = .638</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;2.2 &#x000b1;1.7, <italic toggle="yes">p</italic> = .313</td><td align="center" valign="top" rowspan="1" colspan="1">1.0 &#x000b1; 1.1, <italic toggle="yes">p</italic> = .401</td><td align="center" valign="top" rowspan="1" colspan="1">0.3 &#x000b1; 1.4, <italic toggle="yes">p</italic> = .850</td><td align="center" valign="top" rowspan="1" colspan="1">1.2 &#x000b1; 1.4, <italic toggle="yes">p</italic> = .383</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Associates degree vs. College degree</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;0.5 &#x000b1; 2.1, <italic toggle="yes">p</italic> = .821</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;2.1 &#x000b1;1.8, <italic toggle="yes">p</italic> = .251</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;1.9 &#x000b1; 1.5, <italic toggle="yes">p</italic> = .208</td><td align="center" valign="top" rowspan="1" colspan="1">0.9 &#x000b1; 1.0, <italic toggle="yes">p</italic> = .363</td><td align="center" valign="top" rowspan="1" colspan="1">1.4 &#x000b1; 1.2, <italic toggle="yes">p</italic> = .236</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;0.1 &#x000b1; 1.2, <italic toggle="yes">p</italic> = .953</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Unknown vs. College degree</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;2.2 &#x000b1; 5.0, <italic toggle="yes">p</italic> = .663</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;4.0 &#x000b1; 4.3, <italic toggle="yes">p</italic> = .359</td><td align="center" valign="top" rowspan="1" colspan="1">0.5 &#x000b1; 3.7, <italic toggle="yes">p</italic> = .898</td><td align="center" valign="top" rowspan="1" colspan="1">0.6 &#x000b1; 2.5, <italic toggle="yes">p</italic> = .805</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;0.3 &#x000b1; 2.9, <italic toggle="yes">p</italic> = .917</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;2.0 &#x000b1; 2.6, <italic toggle="yes">p</italic> = .500</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Season of enrollment</td><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Spring vs. Fall</td><td align="center" valign="top" rowspan="1" colspan="1">2.2 &#x000b1; 3.3, <italic toggle="yes">p</italic> = .330</td><td align="center" valign="top" rowspan="1" colspan="1">1.6 &#x000b1; 2.0, <italic toggle="yes">p</italic> = .415</td><td align="center" valign="top" rowspan="1" colspan="1">1.5 &#x000b1; 1.7, <italic toggle="yes">p</italic> = .365</td><td align="center" valign="top" rowspan="1" colspan="1">2.0 &#x000b1; 1.1, <italic toggle="yes">p</italic> = .069</td><td align="center" valign="top" rowspan="1" colspan="1">2.0 &#x000b1; 1.3, <italic toggle="yes">p</italic> = .131</td><td align="center" valign="top" rowspan="1" colspan="1">1.5 &#x000b1; 1.3, <italic toggle="yes">p</italic> = .261</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Summer vs. Fall</td><td align="center" valign="top" rowspan="1" colspan="1">0.0 &#x000b1; 2.3, <italic toggle="yes">p</italic> = .996</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;1.1 &#x000b1; 2.0, <italic toggle="yes">p</italic> = .564</td><td align="center" valign="top" rowspan="1" colspan="1">1.4 &#x000b1; 1.7, <italic toggle="yes">p</italic> = .421</td><td align="center" valign="top" rowspan="1" colspan="1">0.2 &#x000b1; 1.1, <italic toggle="yes">p</italic> = .844</td><td align="center" valign="top" rowspan="1" colspan="1">1.3 &#x000b1; 1.3, <italic toggle="yes">p</italic> = .323</td><td align="center" valign="top" rowspan="1" colspan="1">1.6 &#x000b1; 1.3, <italic toggle="yes">p</italic> = .248</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Winter vs. Fall</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;2.2 &#x000b1; 2.4, <italic toggle="yes">p</italic> = .352</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;1.7 &#x000b1; 2.1, <italic toggle="yes">p</italic> = .412</td><td align="center" valign="top" rowspan="1" colspan="1">0.4 &#x000b1; 1.8, <italic toggle="yes">p</italic> = .840</td><td align="center" valign="top" rowspan="1" colspan="1">0.2 &#x000b1; 1.2, <italic toggle="yes">p</italic> = .886</td><td align="center" valign="top" rowspan="1" colspan="1">0.6 &#x000b1; 1.4, <italic toggle="yes">p</italic> = .682</td><td align="center" valign="top" rowspan="1" colspan="1">0.0 &#x000b1; 1.4, <italic toggle="yes">p</italic> = .978</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Body mass index (categories)</td><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Obese vs. Normal weight</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;0.3 &#x000b1; 2.2, <italic toggle="yes">p</italic> = .905</td><td align="center" valign="top" rowspan="1" colspan="1">2.6 &#x000b1; 1.9, <italic toggle="yes">p</italic> = .172</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;2.0 &#x000b1; 1.6, <italic toggle="yes">p</italic> = .223</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;1.0 &#x000b1; 1.1, <italic toggle="yes">p</italic> = .373</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;1.3 &#x000b1; 1.3, <italic toggle="yes">p</italic> = .299</td><td align="center" valign="top" rowspan="1" colspan="1">0.5 &#x000b1; 1.3, <italic toggle="yes">p</italic> = .687</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Overweight vs. Normal weight</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;0.4 &#x000b1; 2.3, <italic toggle="yes">p</italic> = .844</td><td align="center" valign="top" rowspan="1" colspan="1">3.4 &#x000b1; 2.0, <italic toggle="yes">p</italic> = .091</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;2.9 &#x000b1; 1.7, <italic toggle="yes">p</italic> = .091</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;1.2 &#x000b1; 1.1, <italic toggle="yes">p</italic> = .296</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;0.1 &#x000b1;1.3, <italic toggle="yes">p</italic> = .918</td><td align="center" valign="top" rowspan="1" colspan="1">1.7 &#x000b1; 1.3, <italic toggle="yes">p</italic> = .196</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Unknown vs. Normal weight</td><td align="center" valign="top" rowspan="1" colspan="1">0.7 &#x000b1; 4.8, <italic toggle="yes">p</italic> = .887</td><td align="center" valign="top" rowspan="1" colspan="1">2.7 &#x000b1; 4.1, <italic toggle="yes">p</italic> = .522</td><td align="center" valign="top" rowspan="1" colspan="1">0.6 &#x000b1; 3.6, <italic toggle="yes">p</italic> = .877</td><td align="center" valign="top" rowspan="1" colspan="1">0.7 &#x000b1; 2.4, <italic toggle="yes">p</italic> = .771</td><td align="center" valign="top" rowspan="1" colspan="1">4.4 &#x000b1; 2.8, <italic toggle="yes">p</italic> = .119</td><td align="center" valign="top" rowspan="1" colspan="1">1.7 &#x000b1; 2.8, <italic toggle="yes">p</italic> = .538</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Smoking</td><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/><td align="center" valign="top" rowspan="1" colspan="1"/></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Current vs. Never</td><td align="center" valign="top" rowspan="1" colspan="1">3.2 &#x000b1; 2.5, <italic toggle="yes">p</italic> = .193</td><td align="center" valign="top" rowspan="1" colspan="1">3.6 &#x000b1; 2.1, <italic toggle="yes">p</italic> = .099</td><td align="center" valign="top" rowspan="1" colspan="1">2.7 &#x000b1; 1.8, <italic toggle="yes">p</italic> = .152</td><td align="center" valign="top" rowspan="1" colspan="1">
<bold>3.9 &#x000b1; 1.2, <italic toggle="yes">p</italic> = .002</bold>
</td><td align="center" valign="top" rowspan="1" colspan="1">
<bold>3.7 &#x000b1; 1.4, <italic toggle="yes">p</italic> = .012</bold>
</td><td align="center" valign="top" rowspan="1" colspan="1">1.9 &#x000b1; 1.5, <italic toggle="yes">p</italic> = .201</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Former vs. Never</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;0.3 &#x000b1; 2.6, <italic toggle="yes">p</italic> = .910</td><td align="center" valign="top" rowspan="1" colspan="1">0.5 &#x000b1; 2.3, <italic toggle="yes">p</italic> = .811</td><td align="center" valign="top" rowspan="1" colspan="1">0.3 &#x000b1; 1.9, <italic toggle="yes">p</italic> = .869</td><td align="center" valign="top" rowspan="1" colspan="1">1.6 &#x000b1; 1.3, <italic toggle="yes">p</italic> = .211</td><td align="center" valign="top" rowspan="1" colspan="1">1.3 &#x000b1; 1.5, <italic toggle="yes">p</italic> = .398</td><td align="center" valign="top" rowspan="1" colspan="1">2.8 &#x000b1; 1.5, <italic toggle="yes">p</italic> = .074</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">&#x02003;Unknown vs. Never</td><td align="center" valign="top" rowspan="1" colspan="1">1.2 &#x000b1; 3.8, <italic toggle="yes">p</italic> = .761</td><td align="center" valign="top" rowspan="1" colspan="1">0.9 &#x000b1; 3.3, <italic toggle="yes">p</italic> = .782</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;0.9 &#x000b1; 2.9, <italic toggle="yes">p</italic> = .748</td><td align="center" valign="top" rowspan="1" colspan="1">1.9 &#x000b1; 1.9, <italic toggle="yes">p</italic> = .312</td><td align="center" valign="top" rowspan="1" colspan="1">
<bold>6.0 &#x000b1;2.2, <italic toggle="yes">p</italic> = .008</bold>
</td><td align="center" valign="top" rowspan="1" colspan="1">2.6 &#x000b1; 2.2, <italic toggle="yes">p</italic> = .243</td></tr><tr><td align="left" valign="top" rowspan="1" colspan="1">Number of GISSI&#x02019;s available (over 3 years)</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;0.2 &#x000b1; 0.2, <italic toggle="yes">p</italic> = .477</td><td align="center" valign="top" rowspan="1" colspan="1">0.0 &#x000b1; 0.2, <italic toggle="yes">p</italic> = .873</td><td align="center" valign="top" rowspan="1" colspan="1">0.2 &#x000b1; 0.2, <italic toggle="yes">p</italic> = .276</td><td align="center" valign="top" rowspan="1" colspan="1">0.0 &#x000b1; 0.1, <italic toggle="yes">p</italic> = .826</td><td align="center" valign="top" rowspan="1" colspan="1">0.1 &#x000b1;0.1, <italic toggle="yes">p</italic> = .591</td><td align="center" valign="top" rowspan="1" colspan="1">&#x02212;0.1 &#x000b1;0.1, <italic toggle="yes">p</italic> = .649</td></tr></tbody></table><table-wrap-foot><fn id="TFN2"><p id="P26">Bold values indicate a significant association with GISSI scores.</p></fn></table-wrap-foot></table-wrap></floats-group></article>