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  <front>
    <journal-meta>
      <journal-id journal-id-type="nlm-ta">Arq Bras Cardiol</journal-id>
      <journal-id journal-id-type="publisher-id">abc</journal-id>
      <journal-title-group>
        <journal-title>Arquivos Brasileiros de Cardiologia</journal-title>
        <abbrev-journal-title abbrev-type="publisher">Arq. Bras. Cardiol.</abbrev-journal-title>
      </journal-title-group>
      <issn pub-type="ppub">0066-782X</issn>
      <issn pub-type="epub">1678-4170</issn>
      <publisher>
        <publisher-name>Sociedade Brasileira de Cardiologia - SBC</publisher-name>
      </publisher>
    </journal-meta>
    <article-meta>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v3">yvX6pGqfNYNdNTG9ZvwGZgR</article-id>
      <article-id pub-id-type="publisher-id" specific-use="scielo-v2">S0066-782X2019000600749</article-id>
      <article-id pub-id-type="publisher-id" specific-use="previous-pid">S0066-782X2019005006101</article-id>
      <article-id pub-id-type="doi">10.5935/abc.20190049</article-id>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Original Article</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>The Relationship between Lifestyle and Costs Related to Medicine Use in Adults</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1576-8090</contrib-id>
          <name>
            <surname>Fernandes</surname>
            <given-names>Romulo Araujo</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
          <xref ref-type="corresp" rid="c1"/>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-2646-1350</contrib-id>
          <name>
            <surname>Mantovani</surname>
            <given-names>Alessandra Madia</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-4273-9375</contrib-id>
          <name>
            <surname>Codogno</surname>
            <given-names>Jamile Sanches</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2803-1058</contrib-id>
          <name>
            <surname>Turi-Lynch</surname>
            <given-names>Bruna Camilo</given-names>
          </name>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-1009-8553</contrib-id>
          <name>
            <surname>Pokhrel</surname>
            <given-names>Subhash</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-3615-344X</contrib-id>
          <name>
            <surname>Anokye</surname>
            <given-names>Nana</given-names>
          </name>
          <xref ref-type="aff" rid="aff3">3</xref>
        </contrib>
      </contrib-group>
      <aff id="aff1">
        <label>1</label>
        <institution content-type="orgname">Universidade Estadual Paulista</institution>
        <institution content-type="orgdiv1">Instituto de Bioci&#234;ncias</institution>
        <institution content-type="orgdiv2">Programa de P&#243;s-Gradua&#231;&#227;o em Ci&#234;ncias da Motricidade</institution>
        <addr-line>
          <city>Rio Claro</city>
          <state>SP</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Programa de P&#243;s-Gradua&#231;&#227;o em Ci&#234;ncias da Motricidade - Instituto de Bioci&#234;ncias - Universidade Estadual Paulista (UNESP), Rio Claro, SP - Brazil</institution>
      </aff>
      <aff id="aff2">
        <label>2</label>
        <institution content-type="orgname">Universidade Estadual Paulista</institution>
        <institution content-type="orgdiv1">Faculdade de Ci&#234;ncias e Tecnologia</institution>
        <institution content-type="orgdiv2">Departmento de Educa&#231;&#227;o F&#237;sica</institution>
        <addr-line>
          <city>Presidente Prudente</city>
          <state>SP</state>
        </addr-line>
        <country country="BR">Brazil</country>
        <institution content-type="original">Departmento de Educa&#231;&#227;o F&#237;sica - Faculdade de Ci&#234;ncias e Tecnologia - Universidade Estadual Paulista (UNESP), Presidente Prudente, SP - Brazil</institution>
      </aff>
      <aff id="aff3">
        <label>3</label>
        <institution content-type="orgname">Brunel University</institution>
        <institution content-type="orgdiv1">Institute of Environment - Health and Societies</institution>
        <addr-line>
          <city>Uxbridge</city>
          <state>London</state>
        </addr-line>
        <country country="GB">United Kingdom</country>
        <institution content-type="original">Institute of Environment - Health and Societies - Brunel University - Uxbridge, London - United Kingdom</institution>
      </aff>
      <author-notes>
        <corresp id="c1"><bold>Mailing Address: R&#244;mulo Ara&#250;jo Fernandes,</bold> Roberto Simonsen Avenue, 305. Centro Educacional. Postal Code 19060-900. Presidente Prudente, SP - Brazil. Email: <email>romulo_ef@yahoo.com.br</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Author contributions</bold>
          </p>
          <p>Conception and design of the research: Fernandes RA; Acquisition of data and Analysis and interpretation of the data: Mantovani AM; Statistical analysis: Mantovani AM, Anokye N; Writing of the manuscript: Codogno JS, Turi-Lynch BC, Anokye N; Critical revision of the manuscript for intellectual content: Codogno JS, Turi-Lynch BC, Pokhrel S.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potential Conflict of Interest</bold>
          </p>
          <p>No potential conflict of interest relevant to this article was reported.</p>
        </fn>
      </author-notes>
      <pub-date pub-type="epub">
        <day>14</day>
        <month>03</month>
        <year>2019</year>
      </pub-date>
      <pub-date pub-type="collection">
        <month>06</month>
        <year>2019</year>
      </pub-date>
      <volume>112</volume>
      <issue>6</issue>
      <fpage>749</fpage>
      <lpage>755</lpage>
      <history>
        <date date-type="received">
          <day>25</day>
          <month>05</month>
          <year>2018</year>
        </date>
        <date date-type="rev-recd">
          <day>18</day>
          <month>09</month>
          <year>2018</year>
        </date>
        <date date-type="accepted">
          <day>19</day>
          <month>09</month>
          <year>2018</year>
        </date>
      </history>
      <permissions>
        <license license-type="open-access" xlink:href="https://creativecommons.org/licenses/by/4.0/" xml:lang="en">
          <license-p>This is an Open Access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited</license-p>
        </license>
      </permissions>
      <abstract>
        <title>Abstract</title>
        <sec>
          <title>Background:</title>
          <p>The unhealthy lifestyle is growing and this can have repercussions on health status demanding actions on the occurrence of diseases and leads to increased expenses.</p>
        </sec>
        <sec>
          <title>Objective:</title>
          <p>To examine the interrelationship between the costs of medicine use and lifestyle behaviors.</p>
        </sec>
        <sec>
          <title>Methods:</title>
          <p>A cohort study with 118 participants, age around 51.7 &#177; 7.1 years old. It was collected personal and anthropometric data and information about medicine of continuous use to calculate the costs. Lifestyle variables included habitual physical activity (PA) assessed by pedometer, sedentary behavior by Baecke questionnaire, sleep quality by mini sleep questionnaire and self-report of smoke and alcohol consumption. Statistical analyses were performed by BioEstat (version 5.2) and the significance level set at p-value &lt; 0.05.</p>
        </sec>
        <sec>
          <title>Results:</title>
          <p>In 12 months, 62 subjects bought 172 medicines, representing an overall cost of US$ 3,087.01. Expenditures with drugs were negatively related to PA (r = -0.194, p-value = 0.035 and r = -0.281, p-value = 0.002), but positively related with sleep quality (r = 0.299, p-value=0.001 and r = 0.315, p-value = 0.001) and age (r = 0.274, p-value = 0.003). Four multivariate models were executed considering lifestyle behaviors in different moments of cohort and medicine costs, and all these models identify important relationship between lifestyle behaviors with expenditures with drugs.</p>
        </sec>
        <sec>
          <title>Conclusion:</title>
          <p>Worse sleep quality seems to increase the costs related to medicine use in adults, while obesity and ageing play a relevant role in this phenomenon and alcohol consumption seems a variable with relevant economic impact.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="en">
        <title>Keywords:</title>
        <kwd>Quality of Life</kwd>
        <kwd>Sedentary Lifestyle</kwd>
        <kwd>Obesity</kwd>
        <kwd>Sports Medicine</kwd>
        <kwd>Longevity</kwd>
        <kwd>Health Behavior, Exerc&#237;se</kwd>
      </kwd-group>
      <funding-group>
        <award-group>
          <funding-source>FAPESP</funding-source>
          <award-id>2017/50026-7</award-id>
          <award-id>2015/20460-1</award-id>
        </award-group>
      </funding-group>
    </article-meta>
  </front>
  <body>
    <sec sec-type="intro">
      <title>Introduction</title>
      <p>Over the last decades, the occurrence of obesity and chronic diseases has increased dramatically among adults worldwide.<xref ref-type="bibr" rid="B1">1</xref> On the other hand, advances in medical sciences, development of new generation of medicines/therapies, have significantly improved quality of life and longevity.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref>
			</p>
      <p>In developing countries, the use of any medicine is reported by 60% of the adult population, while the use of three or more medicines in the last two weeks is reported by about 18% of the population.<xref ref-type="bibr" rid="B4">4</xref> A similar pattern is observed in Central Eastern Europe where more than 20% of adults (18 years plus) report three or more medicine use.<xref ref-type="bibr" rid="B5">5</xref> Narayan et al.<xref ref-type="bibr" rid="B3">3</xref> found that in a period of nine years (from 2005 to 2013) the use of drugs for prevention purposes (aspirin, clopidogrel, statins and bisphosphonates) increased significantly among New Zealand adults aged 65 years or more (about 19.5%, 2.9%, 7% and 2.3%, respectively).</p>
      <p>The dramatic rise in the prevalence of obesity and its associations with the development of metabolic and cardiovascular diseases would explain, at least in part, this increase trend.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref> In fact, wide access to medicines by population signifies an improvement in the prevention/treatment of diseases.<xref ref-type="bibr" rid="B2">2</xref> However, the potential adverse drug reactions generated by the use of unprescribed medicines constitute a global public health concern related to high healthcare costs.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B8">8</xref>
			</p>
      <p>The economic burden related to medicine use involves not only health care costs resulting from inappropriate medication but also the purchase of prescribed and unprescribed medicines (public and out of pocket expenses).<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B9">9</xref> For example, in a period of five years from 2000 to 2004, the Brazilian Ministry of Health expended US$ 916 million in programs to provide high-cost drugs to population.<xref ref-type="bibr" rid="B10">10</xref> Despite the increasing economic burden related to medicines use, little is known about its underlying determinants. We need to know these determinants in order to identify target areas for policy making on managing health budgets, particularly in health systems in developing settings.</p>
      <p>Unhealthy lifestyle behaviors (alcohol consumption, smoking, poor sleep habits and sedentary behaviors [SB]) have been shown to play an important role in the development of many diseases,<xref ref-type="bibr" rid="B11">11</xref> but their direct relationship with the costs related to medicines use is unclear. For example, the occurrence of sleep disorders is highly prevalent in adults,<xref ref-type="bibr" rid="B12">12</xref> but its economic burden is unknown.<xref ref-type="bibr" rid="B13">13</xref> A longitudinal study carried out with 11,698 American employees identified that how worse were the sleep disorder reported the health care costs to increase in average US$ 725.15.<xref ref-type="bibr" rid="B13">13</xref> Similarly, in a 12-months study carried out in Taiwan, adults with positive diagnosis to obstructive sleep apnea were 66% more expensive (in terms of physician diagnoses, medications, treatments, surgeries, laboratory tests and diagnostic imaging) than those adults without the same diagnosis (US$ 1,734.10 versus US$ 1,041.30, respectively).<xref ref-type="bibr" rid="B14">14</xref> Conversely, improved levels of physical activity (PA) could reduce costs related to medicine use in adults,<xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref> but its role in the potential relationship between unhealthy lifestyle behaviors and costs of medicine use has not been studied to date.</p>
      <p>In this study, we examine the interrelationship between costs of medicine use and lifestyle behaviors (both healthy and unhealthy).</p>
    </sec>
    <sec sec-type="methods">
      <title>Methods</title>
      <sec>
        <title>Sample</title>
        <p>The data comes from a cohort study carried out in the city of Presidente Prudente which presents human development index 0.806,<xref ref-type="bibr" rid="B17">17</xref> placed on western Sao Paulo State (which is the state of the most industrialized Brazilian federation) from February/June 2014 (baseline) to May/December 2015 (follow-up). Sample size estimation was based on an equation for the correlation coefficient. Due to the absence of specific data about the relationship between lifestyle behaviors and health care costs in Brazil,<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref> we have adopted a correlation coefficient of 0.30 between PA and health care costs,<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref> z = 1.96 and power of 80% (adopting the above-mentioned parameters, the minimum sample size required for this study was 86 participants). The inclusion criteria for participants were: 40-65 years old, no diagnosis of previous cardiovascular complications (e.g. stroke, heart attack), no diabetes complications (amputation or visual problems), no regular medication use, and no physical disability.</p>
        <p>Invitation to participate in the study was conducted using advertisements (ie posters) in the Sao Paulo State University in Presidente Prudente and gyms/fitness centers across the city. Interested participants contacted the research staff, who then checked the profile of the participants against the inclusion criteria (participants who met all the inclusion criteria signed a written consent form). One hundred ninety-eight adults contacted the research staff and were considered eligible and undertook baseline assessment. The analysis herein covered 118 subjects (44 men and 74 women) assessed at both baseline and follow-up (12 months later). The excluded people were due to (a) dropouts (n = 62) and (b) provision of less than seven days of pedometer use at baseline (n = 18).</p>
        <p>All procedures (questionnaires, pedometers and body composition assessment) were performed by trained staff of researchers (Professors, MSc and PhD students) following the protocols of the Laboratory of Investigation in Exercise (LIVE), Brazil.<xref ref-type="bibr" rid="B19">19</xref> The Ethics committee of the Sao Paulo State University (UNESP), campus of Presidente Prudente, approved the study.</p>
      </sec>
      <sec>
        <title>Costs of medicines use</title>
        <p>At baseline, the participants were given a questionnaire (in diary form) for medicine use and instructions (further clarification offered face to face by research staff) on how to fulfil the questionnaire. The participants reported the following data: (a) number and type of all medicines (prescribed and unprescribed); (b) how they obtained the medicines - through the Brazilian National Health System [BNHS] or out of pocket expenditure. The diary was filled for each of the 12 months of the cohort study. At the end of the follow-up period, the research staff collected back the completed diaries (<xref ref-type="table" rid="t1">Table 1</xref>). To calculate the cost of medicines, we used national prices presented by BNHS (for medicines delivered by the BNHS) and market prices from drug stores in the study area (medicines obtained via personal expenses). Costs were computed in Brazilian currency (Real$) and converted to US dollar (US$) using the cambial information provided by the Central Bank of Brazil.</p>
        <table-wrap id="t1">
          <label>Table 1</label>
          <caption>
            <title>Most frequently bought medicines according to anatomical therapeutic chemical code</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="33%"/>
              <col width="33%"/>
              <col width="33%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left">Anatomical Therapeutic Chemical Code</th>
                <th align="center">Types of medicine</th>
                <th align="center">Number of medicines bought </th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Digestive tract and metabolism</td>
                <td align="center">18</td>
                <td align="center">33</td>
              </tr>
              <tr>
                <td align="left">Blood and Blood-forming organs</td>
                <td align="center">2</td>
                <td align="center">2</td>
              </tr>
              <tr>
                <td align="left">Cardiovascular system</td>
                <td align="center">31</td>
                <td align="center">42</td>
              </tr>
              <tr>
                <td align="left">Dermatological</td>
                <td align="center">1</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Genito-urinary system and sex hormones</td>
                <td align="center">9</td>
                <td align="center">25</td>
              </tr>
              <tr>
                <td align="left">Hormones, except sexual and insulin</td>
                <td align="center">10</td>
                <td align="center">10</td>
              </tr>
              <tr>
                <td align="left">Systemic anti-infective agents</td>
                <td align="center">1</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Anti-neoplastics and immune modulators</td>
                <td align="center">1</td>
                <td align="center">2</td>
              </tr>
              <tr>
                <td align="left">Muscle-skeletal system</td>
                <td align="center">7</td>
                <td align="center">9</td>
              </tr>
              <tr>
                <td align="left">Nervous system</td>
                <td align="center">28</td>
                <td align="center">38</td>
              </tr>
              <tr>
                <td align="left">Antiparasitics</td>
                <td align="center">1</td>
                <td align="center">2</td>
              </tr>
              <tr>
                <td align="left">Respiratory system</td>
                <td align="center">3</td>
                <td align="center">3</td>
              </tr>
              <tr>
                <td align="left">Sensory organs</td>
                <td align="center">1</td>
                <td align="center">1</td>
              </tr>
              <tr>
                <td align="left">Other</td>
                <td align="center">1</td>
                <td align="center">3</td>
              </tr>
              <tr>
                <td align="left">Overall</td>
                <td align="center">114</td>
                <td align="center">172</td>
              </tr>
            </tbody>
          </table>
        </table-wrap>
      </sec>
      <sec>
        <title>Lifestyle behavioral variables</title>
        <p>PA was measured using both objective and subjective measures at baseline and follow-up. Objective measure of PA was collected using pedometers (Yamax digiwalker, SW200 model, Japan), and specified in terms of step count. At both assessments periods (baseline and follow-up), pedometers were worn by participants for seven consecutive days. The pedometers were fixed laterally at the hip and were taken off only during periods of sleep and water-based activities. Participants logged (at the end of each day) the total step count. In the present study, PA denoted the number of days (out of 14 days assessed) that &#8805;7,500 steps were achieved. In line with Tudor-Locke et al.,<xref ref-type="bibr" rid="B20">20</xref> participants who reached &#8805;7,500 steps/day were classified as &#8220;sufficiently active&#8221;. The subjective measure of PA was collected using Baecke&#8217;s questionnaire.<xref ref-type="bibr" rid="B21">21</xref> The questionnaire is composed of 16 questions about three PA domains (occupational, sports participation and leisure-time PA).</p>
        <p>Data on SB at work (both baseline and follow up) were captured using the following question: &#8220;At work I sit&#8221;&#8230;; potential responses were: never [score attributed = 1], seldom [score attributed = 2], sometimes [score attributed = 3], often [score attributed = 4] and very often [score attributed = 5]).</p>
        <p>Quality of sleep was assessed at baseline and follow up using the Mini-Sleep Questionnaire,<xref ref-type="bibr" rid="B22">22</xref> which includes 10 questions, each one with seven possible answers (ranging from never to always). The sum of these 10 answers generates a numerical score ranging from 10 to 70 points (higher scores indicate worse sleep quality).</p>
        <p>Participants also self-reported at baseline and follow-up smoking status (yes or no current smoker) and weekly alcohol consumption (number of days per week with alcohol consumption).</p>
      </sec>
      <sec>
        <title>Covariates</title>
        <p>Covariates were data collected via questionnaire (sex [male or female], date of birth [chronological age estimated using the difference between birthday and date of assessment] and formal schooling [in years]). Clinical data also were evaluated (body fatness [dual-energy X-ray absorptiometry], systolic and diastolic blood pressure respectively). Researchers performed the clinical measures in university facilities with controlled temperature and followed standardized procedures.</p>
      </sec>
      <sec>
        <title>Statistical analyses</title>
        <p>Descriptive statistics were undertaken using mean, 95% confidence intervals (95%CI) and proportions as appropriate. Due to non-parametric distribution (attested by Kolmogorov-Smirnov test), the costs of medicine use were converted into base-10 logarithms.</p>
        <p>Both the Pearson correlation and linear regression were conducted to assess the relationship between the costs of medicines and the independent variables. In the former approach, Pearson correlation (expressed as standardized coefficients [&#8220;<italic>r</italic>&#8221; values]) analyzed the relationship of the costs of medicine use with lifestyle behaviors (sleep quality, PA, SB at work, smoking and alcohol consumption) and covariates (sex, age, schooling, blood pressure and body fatness) separately. In the latter, linear regression models (expressed as unstandardized coefficients [&#946; values]) were fitted to examine the relationship between the costs of medicine use and lifestyle behaviors controlling for all covariates. For each approach, four models were fitted based on different specifications of lifestyle behaviors ([A] only baseline values, [B] only follow-up values, [C] difference between follow-up and baseline and [D] sum of baseline and follow-up), to explore the differential relationship these specifications may present. Diagnosis of multicollinearity and homoscedasticity were assessed and the linear regression models were considered adequately fit.</p>
        <p>All analyzes were performed using BioEstat (version 5.2) and the significance level was set at p-value &lt; 0.05.</p>
      </sec>
    </sec>
    <sec sec-type="results">
      <title>Results</title>
      <p>At baseline, the mean age of the sample was 51.7 &#177; 7.1 years, ranging from 40 to 68 years (<xref ref-type="table" rid="t2">Table 2</xref>). Alcohol was consumed on average 2.1 days per week, while 5.1% of the sample were smokers. Expenses on medicine use were reported by 52.5% of the sample. During 12-months of follow-up, 62 subjects bought 172 medicines (<xref ref-type="table" rid="t2">Table 2</xref>), representing an overall cost of US$ 3,087.01 for the entire sample. There was no missing data.</p>
      <table-wrap id="t2">
        <label>Table 2</label>
        <caption>
          <title>Summarized characteristics of the sample (n = 118)</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="33%"/>
            <col width="33%"/>
            <col width="33%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left" rowspan="2">Variables</th>
              <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">Descriptive Statistic</th>
            </tr>
            <tr>
              <th align="center">Mean (95%CI)</th>
              <th align="center">Median (IR)</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">Age (years)<sub>baseline</sub></td>
              <td align="center">51.7 (50.4 to 53.1)</td>
              <td align="center">51.1 (10.1)</td>
            </tr>
            <tr>
              <td align="left">Body weight (kg)<sub>baseline</sub></td>
              <td align="center">74.6 (71.7 to 77.4)</td>
              <td align="center">72.6 (16.6)</td>
            </tr>
            <tr>
              <td align="left">Height (m)<sub>baseline</sub></td>
              <td align="center">1.65 (1.63 to 1.67)</td>
              <td align="center">1.65 (0.15)</td>
            </tr>
            <tr>
              <td align="left">BMI (Kg/m<sup>2</sup>)<sub>baseline</sub></td>
              <td align="center">26.92 (26.3 to 27.5)</td>
              <td align="center">26.41 (5.98)</td>
            </tr>
            <tr>
              <td align="left">Costs with medicine (US$) <sub>follow-up</sub></td>
              <td align="center">26.16 (17.7 to 34.62)</td>
              <td align="center">1.19 (42.91)</td>
            </tr>
            <tr>
              <td align="left">Alcohol consumption (days) <sub>baseline</sub></td>
              <td align="center">2.1 (1.9 to 2.3)</td>
              <td align="center">2 (2)</td>
            </tr>
            <tr>
              <td align="left">Alcohol consumption (days) <sub>follow-up</sub></td>
              <td align="center">1.9 (1.7 to 2.2)</td>
              <td align="center">1 (2)</td>
            </tr>
            <tr>
              <td align="left">Sleep quality (MSQ score) <sub>baseline</sub></td>
              <td align="center">26.6 (24.7 to 28.4)</td>
              <td align="center">25 (13)</td>
            </tr>
            <tr>
              <td align="left">Sleep quality (MSQ score) <sub>follow-up</sub></td>
              <td align="center">26.8 (24.8 to 28.7)</td>
              <td align="center">26 (15)</td>
            </tr>
            <tr>
              <td align="left">PA (&#8805;7,500 steps/day) <sub>baseline</sub></td>
              <td align="center">2.3 (1.8 to 2.7)</td>
              <td align="center">1 (5)</td>
            </tr>
            <tr>
              <td align="left">PA (&#8805;7,500 steps/day) <sub>follow-up</sub></td>
              <td align="center">1.9 (1.5 to 2.3)</td>
              <td align="center">1 (4)</td>
            </tr>
            <tr>
              <td align="left">SB at work (score) <sub>baseline</sub></td>
              <td align="center">3.2 (2.9 to 3.4)</td>
              <td align="center">3 (2)</td>
            </tr>
            <tr>
              <td align="left">SB at work (score) <sub>follow-up</sub></td>
              <td align="center">3.1 (2.9 to 3.3)</td>
              <td align="center">3 (2)</td>
            </tr>
            <tr>
              <td align="left">Smoking (yes [%]) <sub>baseline</sub></td>
              <td align="center">5.1% (1.1% to 9.1%)</td>
              <td align="center">---</td>
            </tr>
            <tr>
              <td align="left">Smoking (yes [%]) <sub>follow-up</sub></td>
              <td align="center">5.9% (1.6% to 10.1%)</td>
              <td align="center">---</td>
            </tr>
            <tr>
              <td align="left">Medicine use (yes [%]) <sub>follow-up</sub></td>
              <td align="center">52.5 (43.5% to 61.5%)</td>
              <td align="center">---</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN1">
            <p>95% CI: 95% confidence interval; IR: interquartile range; BMI: body mass index; MSQ: mini-sleep questionnaire; PA: physical activity; SB: sedentary behavior.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>PA decreased significantly from baseline to follow-up (p-value = 0.024), while the score for SB at work (p-value = 0.396), sleep quality (p-value = 0.951) and alcohol consumption (p-value = 0.100) remained stable between baseline and follow-up.</p>
      <p>In the bivariate analysis, costs of medicine use were negatively related to PA <sub>baseline</sub> (r = -0.194; p-value = 0.035), PA <sub>follow-up</sub> (r = -0.281; p-value = 0.002), but positively related with sleep quality <sub>baseline</sub> (r = 0.299; p-value= 0.001) and sleep quality <sub>follow-up</sub> (r = 0.315; p-value = 0.001), and age <sub>baseline</sub> (r = 0.274; p-value = 0.003). Gender, education, SB at work, alcohol consumption and smoking were not significantly related with costs of medicine use. There was no interrelationships among the lifestyle behaviors.</p>
      <p>In the multivariate model considering lifestyle behaviors at baseline (Model-A), sleep quality and body fatness were positively related to higher 12-months medicine costs, while alcohol consumption was negatively related to it. Model-A explained 19.1% of all variance in the outcome (<xref ref-type="table" rid="t3">Table 3</xref>). In the multivariate model considering lifestyle behaviors at follow-up (Model-B), only sleep quality was positively related to higher 12-months medical costs. Model-B explained 21.9% of all variance in the medicine costs.</p>
      <table-wrap id="t3">
        <label>Table 3</label>
        <caption>
          <title>Linear regression describing the relationship between 12-months medicine costs (dependent variable) and lifestyle behaviors (n= 118)</title>
        </caption>
        <table frame="hsides" rules="groups">
          <colgroup>
            <col width="20%"/>
            <col width="20%"/>
            <col width="20%"/>
            <col width="20%"/>
            <col width="20%"/>
          </colgroup>
          <thead>
            <tr>
              <th align="left" rowspan="3">Independent variables</th>
              <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Model - A</th>
              <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Model - B</th>
              <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Model - C</th>
              <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Model - D</th>
            </tr>
            <tr>
              <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Baseline</th>
              <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Follow-up</th>
              <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Follow-up minus Baseline</th>
              <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Baseline plus Follow-up</th>
            </tr>
            <tr>
              <th align="center">&#946; (&#946;<sub>95%CI</sub>)</th>
              <th align="center">&#946; (&#946;<sub>95%CI</sub>)</th>
              <th align="center">&#946; (&#946;<sub>95%CI</sub>)</th>
              <th align="center">&#946; (&#946;<sub>95%CI</sub>)</th>
            </tr>
          </thead>
          <tbody>
            <tr>
              <td align="left">PA (steps)</td>
              <td align="center">-0.011 (-0.078 to 0.056)</td>
              <td align="center">-0.048 (-0.122 to 0.027)</td>
              <td align="center">-0.18 (-0.092 to 0.056)</td>
              <td align="center">-0.017 (-0.058 to 0.025)</td>
            </tr>
            <tr>
              <td align="left">Sleep quality (MSQ score)</td>
              <td align="center">0.018 (0.001 to 0.034)</td>
              <td align="center">0.018 (0.002 to 0.033)</td>
              <td align="center">0.004 (-0.017 to 0.026)</td>
              <td align="center">0.011 (0.002 to 0.019)</td>
            </tr>
            <tr>
              <td align="left">Alcohol consumption (days)</td>
              <td align="center">-0.137 (-0.272 to -0.002)</td>
              <td align="center">-0.111 (-0.241 to 0.019)</td>
              <td align="center">0.034 (-0.140 to 0.208)</td>
              <td align="center">-0.073 (-0.145 to -0.001)</td>
            </tr>
            <tr>
              <td align="left">Smoking (yes)</td>
              <td align="center">0.157 (-0.514 to 0.828)</td>
              <td align="center">0.424 (-0.224 to 1.072)</td>
              <td align="center">0.819 (-0.376 to 2.014)</td>
              <td align="center">0.170 (-0.172 to 0.513)</td>
            </tr>
            <tr>
              <td align="left">SB at work (frequency)</td>
              <td align="center">0.021 (-0.114 to 0.157)</td>
              <td align="center">0.017 (-0.123 to 0.157)</td>
              <td align="center">0.023 (-0.154 to 0.201)</td>
              <td align="center">0.006 (-0.070 to 0.082)</td>
            </tr>
            <tr>
              <td align="left">Sex (female)<xref ref-type="table-fn" rid="TFN2">*</xref>
							</td>
              <td align="center">-0.447 (-0.900 to 0.007)</td>
              <td align="center">-0.341 (-0.780 to 0.098)</td>
              <td align="center">-0.302 (-0.731 to 0.126)</td>
              <td align="center">-0.421 (-0.872 to 0.029)</td>
            </tr>
            <tr>
              <td align="left">Age (years)<xref ref-type="table-fn" rid="TFN2">*</xref>
							</td>
              <td align="center">0.021 (-0.004 to 0.047)</td>
              <td align="center">0.020 (-0.004 to 0.044)</td>
              <td align="center">0.029 (0.003 to 0.056)</td>
              <td align="center">0.019 (-0.005 to 0.044)</td>
            </tr>
            <tr>
              <td align="left">Body fatness (%)<xref ref-type="table-fn" rid="TFN2">*</xref>
							</td>
              <td align="center">0.023 (0.003 to 0.043)</td>
              <td align="center">0.019 (-0.002 to 0.039)</td>
              <td align="center">0.027 (0.007 to 0.048)</td>
              <td align="center">0.020 (-0.001 to 0.040)</td>
            </tr>
            <tr>
              <td align="left">SBP (mmHg)<xref ref-type="table-fn" rid="TFN2">*</xref>
							</td>
              <td align="center">-0.005 (-0.028 to 0.019)</td>
              <td align="center">-0.005 (-0.028 to 0.017)</td>
              <td align="center">-0.004 (-0.028 to 0.020)</td>
              <td align="center">-0.005 (-0.028 to 0.018)</td>
            </tr>
            <tr>
              <td align="left">DBP (mmHg)<xref ref-type="table-fn" rid="TFN2">*</xref>
							</td>
              <td align="center">0.017 (-0.010 to 0.044)</td>
              <td align="center">0.021 (-0.005 to 0.047)</td>
              <td align="center">0.014 (-0.014 to 0.043)</td>
              <td align="center">0.020 (-0.007 to 0.046)</td>
            </tr>
            <tr>
              <td align="left">Schooling (years)<xref ref-type="table-fn" rid="TFN2">*</xref>
							</td>
              <td align="center">0.084 (-0.024 to 0.193)</td>
              <td align="center">0.091 (-0.020 to 0.202)</td>
              <td align="center">0.080 (-0.026 to 0.187)</td>
              <td align="center">0.092 (-0.019 to 0.202)</td>
            </tr>
            <tr>
              <td align="left">Linear regression parameters</td>
              <td align="center">
							</td>
              <td align="center">
							</td>
              <td align="center">
							</td>
              <td align="center">
							</td>
            </tr>
            <tr>
              <td align="left">R</td>
              <td align="center">0.527</td>
              <td align="center">0.549</td>
              <td align="center">0.473</td>
              <td align="center">0.548</td>
            </tr>
            <tr>
              <td align="left">r <sup>2</sup></td>
              <td align="center">0.278</td>
              <td align="center">0.301</td>
              <td align="center">0.224</td>
              <td align="center">0.300</td>
            </tr>
            <tr>
              <td align="left">r <sup>2</sup><sub>adjusted</sub></td>
              <td align="center">0.191</td>
              <td align="center">0.219</td>
              <td align="center">0.131</td>
              <td align="center">0.217</td>
            </tr>
          </tbody>
        </table>
        <table-wrap-foot>
          <fn id="TFN2">
            <label>*</label>
            <p>only baseline values were used; Model-A: lifestyle behaviors inserted as baseline values; Model-B: lifestyle behaviors inserted as follow-up values; Model-C: lifestyle behaviors inserted as follow-up minus baseline values; Model-D: lifestyle behaviors inserted as baseline plus follow-up values; 95%CI: 95% confidence interval; PA: physical activity; MSQ: mini-sleep questionnaire; SB: sedentary behavior; SBP: systolic blood pressure; DBP: diastolic blood pressure.</p>
          </fn>
        </table-wrap-foot>
      </table-wrap>
      <p>In the multivariate model considering changes over time in lifestyle behaviors (Model-C), age and body fatness were positively related to higher 12-months medicine costs. Model-C explained 13.1% of all variance in the medicine costs. In Model-D (sum of baseline and follow-up values), sleep quality had a positive relationship with medicine use (<xref ref-type="table" rid="t3">Table 3</xref>). On the other hand, alcohol consumption was negatively related to costs of medicine use. Model-D explained 21.7% of all variance in the medicine costs.</p>
    </sec>
    <sec sec-type="discussion">
      <title>Discussion</title>
      <p>This study shows that lifestyle behaviors particularly worse sleep quality leads to higher costs related to medicine use. Body fatness was also found to be an important predictor - positive effect on costs. In overall, 52.5% of adults reported any medicine use during the cohort period, while 20.5% (n = 24) of these same adults reported the use of three or more medicines. These rates are similar to Brazilian (18%) and European (20%) surveys, in which population-based samplings were carried out.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref>
			</p>
      <p>Another similarity with previous studies observed in our findings is that drugs for the treatment of cardiovascular diseases were the most reported by the participants. A study carried out in New Zealand examining the trends of medicine use in adults aged &#8805; 65 years from 2005 to 2013 identified that the use of drugs to prevent cardiovascular events (aspirin and statins) increased significantly.<xref ref-type="bibr" rid="B3">3</xref> The dynamics observed for medicines to the treatment of cardiovascular diseases seems affected by aging as well (in our study, a relevant covariate in the multivariate models). Previous data have identified that consumption of aspirin and dipyridamole increased in older adults at a higher rate than observed in younger ones.<xref ref-type="bibr" rid="B3">3</xref>
			</p>
      <p>The increased amount paid by older adults can be supported by the natural effects that ageing exert over organs of the human body and their functions,<xref ref-type="bibr" rid="B23">23</xref> but also boosted by the reduced PA observed in older groups.<xref ref-type="bibr" rid="B24">24</xref> In the analyzed sample, although the effect of age on costs with medicine use was not mediated by PA, they were related with other in crude analyzes, denoting the relevance of actions targeting the improvement of PA practice mainly in population groups composed of older adults.<xref ref-type="bibr" rid="B23">23</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref>
			</p>
      <p>In this sample, the higher cost with medicines in adults with sleep disorders can represent not only the treatment of the sleep disorders itself, but also the use of medicines to relief its symptoms and hence to maintain the daily activities, such as work.<xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B25">25</xref>
			</p>
      <p>The findings related to alcohol consumptions were surprising because usually the higher alcohol consumption is linked to higher health care costs,<xref ref-type="bibr" rid="B26">26</xref><sup>,</sup><xref ref-type="bibr" rid="B27">27</xref> and not the opposite as observed in our study. In fact, the linkage between alcohol consumption and health care costs can be direct (e.g. diseases directly linked to alcohol consumption) and indirect (e.g. traffic car accident), but it is important to take into account that some kinds of alcoholic drinks have healthy characteristics, such as anti-inflammatory properties observed in the red wine.<xref ref-type="bibr" rid="B28">28</xref> Therefore, the explanation for our interesting finding could be due to both the type and amount of alcohol consumed. However, our study looked at only the number of days per week with alcohol consumption, and not amount and type of alcohol consumed, which characterizes a limitation in our study.</p>
      <p>Other limitations of the study are worth mentioning. The first limitation of the study is the small sample size. The current study has statistical power of 80% to detect coefficient of correlation of 0.256 or higher, while the relationship between some behaviors and costs with medicine are around r = 0.110.<xref ref-type="bibr" rid="B16">16</xref> Even considering the fact that the inclusion of covariates increases the power of multivariate models,<xref ref-type="bibr" rid="B29">29</xref> the reduced sample size may have been responsible for the absence of significant relationship between PA and costs with medicine. Another limitation related to objective measures of PA is the logging of data by the participants because every day they had to note the number of steps displayed in the pedometer. Although this method is widely used,<xref ref-type="bibr" rid="B19">19</xref> it could have led to misreporting. As above mentioned, the absence of measures of amount and kind of alcoholic drinks and sedentary behavior (by screen time on TV or computer) constitute limitations as well. Further studies could explore the impact of these.</p>
    </sec>
    <sec sec-type="conclusions">
      <title>Conclusions</title>
      <p>Worse sleep quality seems to increase the costs related to medicine use in adults, while obesity and ageing play a relevant role in this phenomenon. Moreover, alcohol consumption seems a variable with relevant economic impact, but further studies are necessary to identify clearly the direction of its relationship with medicine costs.</p>
    </sec>
  </body>
  <back>
    <fn-group>
      <fn fn-type="financial-disclosure">
        <p>
          <bold>Sources of Funding</bold>
        </p>
        <p>There were no external funding sources for this study.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Study Association</bold>
        </p>
        <p>This article is part of the thesis of Doctoral submitted by Alessandra Madia Mantovani, from Universidade Estadual Paulista.</p>
      </fn>
      <fn fn-type="other">
        <p>
          <bold>Ethics approval and consent to participate</bold>
        </p>
        <p>This study was approved by the Ethics Committee of the Faculdade de Ci&#234;ncias e Tecnologia da Universidade Estadual Paulista under the protocol number 349.306/2013.</p>
      </fn>
    </fn-group>
    <ack>
      <title>Acknowledgment</title>
      <p>To the Funda&#231;&#227;o de Amparo a Pesquisa do Estado de S&#227;o Paulo (FAPESP) (process number: 2017/50026-7 and 2015/20460-1) and to the Coordena&#231;&#227;o de Aperfei&#231;oamento de Pessoal de N&#237;vel Superior (CAPES).</p>
    </ack>
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  <sub-article article-type="translation" id="s1" xml:lang="pt">
    <front-stub>
      <article-categories>
        <subj-group subj-group-type="heading">
          <subject>Artigo Original</subject>
        </subj-group>
      </article-categories>
      <title-group>
        <article-title>Rela&#231;&#227;o entre Estilo de Vida e Custos Relacionados ao Uso de Medicamentos em Adultos</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-1576-8090</contrib-id>
          <name>
            <surname>Fernandes</surname>
            <given-names>Romulo Araujo</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">1</xref>
          <xref ref-type="aff" rid="aff5">2</xref>
          <xref ref-type="corresp" rid="c2"/>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-2646-1350</contrib-id>
          <name>
            <surname>Mantovani</surname>
            <given-names>Alessandra Madia</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-4273-9375</contrib-id>
          <name>
            <surname>Codogno</surname>
            <given-names>Jamile Sanches</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">1</xref>
          <xref ref-type="aff" rid="aff5">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-2803-1058</contrib-id>
          <name>
            <surname>Turi-Lynch</surname>
            <given-names>Bruna Camilo</given-names>
          </name>
          <xref ref-type="aff" rid="aff4">1</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0002-1009-8553</contrib-id>
          <name>
            <surname>Pokhrel</surname>
            <given-names>Subhash</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">3</xref>
        </contrib>
        <contrib contrib-type="author">
          <contrib-id contrib-id-type="orcid">0000-0003-3615-344X</contrib-id>
          <name>
            <surname>Anokye</surname>
            <given-names>Nana</given-names>
          </name>
          <xref ref-type="aff" rid="aff6">3</xref>
        </contrib>
      </contrib-group>
      <aff id="aff4">
        <label>1</label>
        <institution content-type="original">Programa de P&#243;s-Gradua&#231;&#227;o em Ci&#234;ncias da Motricidade - Instituto de Bioci&#234;ncias - Universidade Estadual Paulista (UNESP), Rio Claro, SP - Brasil</institution>
      </aff>
      <aff id="aff5">
        <label>2</label>
        <institution content-type="original">Departmento de Educa&#231;&#227;o F&#237;sica - Faculdade de Ci&#234;ncias e Tecnologia - Universidade Estadual Paulista (UNESP), Presidente Prudente, SP - Brasil</institution>
      </aff>
      <aff id="aff6">
        <label>3</label>
        <institution content-type="original">Institute of Environment - Health and Societies - Brunel University - Uxbridge, London - United Kingdom</institution>
      </aff>
      <author-notes>
        <corresp id="c2"><bold>Correspond&#234;ncia: R&#244;mulo Ara&#250;jo Fernandes,</bold> Roberto Simonsen Avenue, 305. Centro Educacional. CEP 19060-900. Presidente Prudente, SP - Brasil. Email: <email>romulo_ef@yahoo.com.br</email>
				</corresp>
        <fn fn-type="con">
          <p>
            <bold>Contribui&#231;&#227;o dos autores</bold>
          </p>
          <p>Concep&#231;&#227;o e desenho da pesquisa: Fernandes RA; Obten&#231;&#227;o de dados e An&#225;lise e interpreta&#231;&#227;o dos dados: Mantovani AM; An&#225;lise estat&#237;stica: Mantovani AM, Anokye N; Reda&#231;&#227;o do manuscrito: Codogno JS, Turi-Lynch BC, Anokye N; Revis&#227;o cr&#237;tica do manuscrito quanto ao conte&#250;do intelectual importante: Codogno JS, Turi-Lynch BC, Pokhrel S.</p>
        </fn>
        <fn fn-type="conflict">
          <p>
            <bold>Potencial conflito de interesses</bold>
          </p>
          <p>Declaro n&#227;o haver conflito de interesses pertinentes.</p>
        </fn>
      </author-notes>
      <abstract>
        <title>Resumo</title>
        <sec>
          <title>Fundamento:</title>
          <p>O estilo de vida pouco saud&#225;vel est&#225; se expandindo e isso pode ter repercuss&#245;es no estado de sa&#250;de, exigindo a&#231;&#245;es contra a ocorr&#234;ncia de doen&#231;as e levando ao aumento de gastos.</p>
        </sec>
        <sec>
          <title>Objetivo:</title>
          <p>Examinar a interrela&#231;&#227;o entre os custos do uso de medicamentos e comportamentos de estilo de vida.</p>
        </sec>
        <sec>
          <title>M&#233;todos:</title>
          <p>Estudo de coorte com 118 participantes com idade de 51,7 &#177; 7,1 anos. Foram coletados dados pessoais e antropom&#233;tricos e informa&#231;&#245;es sobre medicamentos de uso cont&#237;nuo para calcular os custos. As vari&#225;veis de estilo de vida inclu&#237;ram: atividade f&#237;sica (AF) habitual, avaliada por ped&#244;metro; comportamento sedent&#225;rio, pelo question&#225;rio de Baecke; qualidade do sono, atrav&#233;s do Mini Question&#225;rio do Sono, e autorrelato de tabagismo e consumo de &#225;lcool. As an&#225;lises estat&#237;sticas foram realizadas no programa BioEstat (vers&#227;o 5.2), e o n&#237;vel de signific&#226;ncia estabelecido como p &lt; 0,05.</p>
        </sec>
        <sec>
          <title>Resultados:</title>
          <p>Em 12 meses, 62 indiv&#237;duos compraram 172 medicamentos, representando um custo total de US$ 3.087,01. Gastos com medicamentos foram negativamente relacionados &#224; AF (r = -0,194, p-valor = 0,035 e r = -0,281, p-valor = 0,002), mas relacionaram-se positivamente com a qualidade do sono (r = 0,299, p-valor=0,001 e r=0,315, p-valor = 0,001) e idade (r = 0,274, p-valor = 0,003). Quatro modelos multivariados foram executados, considerando os comportamentos de estilo de vida em diferentes momentos da coorte e custos dos medicamentos, e todos esses modelos identificam rela&#231;&#245;es importantes entre comportamentos de estilo de vida e gastos com medicamentos.</p>
        </sec>
        <sec>
          <title>Conclus&#227;o:</title>
          <p>A pior qualidade do sono parece aumentar os custos relacionados ao uso de medicamentos em adultos, enquanto a obesidade e o envelhecimento desempenham um papel relevante nesse fen&#244;meno, e o consumo de &#225;lcool parece ser uma vari&#225;vel com impacto econ&#244;mico significativo.</p>
        </sec>
      </abstract>
      <kwd-group xml:lang="pt">
        <title>Palavras-chave:</title>
        <kwd>Qualidade de Vida</kwd>
        <kwd>Estilo de Vida Sedent&#225;rio</kwd>
        <kwd>Obesidade</kwd>
        <kwd>Medicina Esportiva</kwd>
        <kwd>Longevidade</kwd>
        <kwd>Comportamento Relacionado &#224; Sa&#250;de</kwd>
        <kwd>Exerc&#237;cio</kwd>
      </kwd-group>
      <funding-group>
        <award-group>
          <funding-source>FAPESP</funding-source>
          <award-id>2017/50026-7</award-id>
          <award-id>2015/20460-1</award-id>
        </award-group>
      </funding-group>
    </front-stub>
    <body>
      <sec sec-type="intro">
        <title>Introdu&#231;&#227;o</title>
        <p>Nas &#250;ltimas d&#233;cadas, a ocorr&#234;ncia de obesidade e doen&#231;as cr&#244;nicas aumentou dramaticamente nos adultos em todo o mundo.<xref ref-type="bibr" rid="B1">1</xref> Por outro lado, os avan&#231;os nas ci&#234;ncias m&#233;dicas, o desenvolvimento de novas gera&#231;&#245;es de medicamentos/terapias, melhoraram significativamente a qualidade de vida e a longevidade.<xref ref-type="bibr" rid="B2">2</xref><sup>,</sup><xref ref-type="bibr" rid="B3">3</xref>
				</p>
        <p>Nos pa&#237;ses em desenvolvimento, o uso de qualquer medicamento &#233; relatado por 60% da popula&#231;&#227;o adulta, enquanto o uso de tr&#234;s ou mais medicamentos nas duas semanas anteriores &#233; relatado por cerca de 18% da popula&#231;&#227;o.<xref ref-type="bibr" rid="B4">4</xref> Um padr&#227;o similar &#233; observado na Europa Centro-Oriental, onde mais de 20% dos adultos (18 anos ou mais) relatam o uso de tr&#234;s ou mais medicamentos.<xref ref-type="bibr" rid="B5">5</xref> Narayan et al.,<xref ref-type="bibr" rid="B3">3</xref> descobriram que em um per&#237;odo de nove anos (de 2005 a 2013), o uso de medicamentos para fins de preven&#231;&#227;o (aspirina, clopidogrel, estatinas e bisfosfonatos) aumentaram significativamente entre os adultos da Nova Zel&#226;ndia com 65 anos ou mais (cerca de 19,5%, 2,9%, 7% e 2,3%, respectivamente).</p>
        <p>O aumento dram&#225;tico na preval&#234;ncia da obesidade e suas associa&#231;&#245;es com o desenvolvimento de doen&#231;as metab&#243;licas e cardiovasculares explicariam, pelo menos em parte, essa tend&#234;ncia de aumento.<xref ref-type="bibr" rid="B1">1</xref><sup>,</sup><xref ref-type="bibr" rid="B6">6</xref> Na realidade, o amplo acesso a medicamentos pela popula&#231;&#227;o significa uma melhoria na preven&#231;&#227;o/tratamento de doen&#231;as.<xref ref-type="bibr" rid="B2">2</xref> Entretanto, as potenciais rea&#231;&#245;es adversas a medicamentos geradas pelo uso de medicamentos n&#227;o prescritos constituem uma preocupa&#231;&#227;o global de sa&#250;de p&#250;blica, relacionada aos altos custos da sa&#250;de.<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B8">8</xref>
				</p>
        <p>A carga econ&#244;mica relacionado ao uso de medicamentos envolve n&#227;o apenas os custos dos tratamentos de sa&#250;de resultantes do uso inadequado de medicamentos, mas tamb&#233;m a compra de medicamentos prescritos e n&#227;o prescritos (despesas p&#250;blicas e pessoais).<xref ref-type="bibr" rid="B7">7</xref><sup>,</sup><xref ref-type="bibr" rid="B9">9</xref> Por exemplo, em um per&#237;odo de cinco anos, de 2000 a 2004, o Minist&#233;rio da Sa&#250;de do Brasil gastou o equivalente a US$ 916 milh&#245;es em programas para fornecer medicamentos de alto custo &#224; popula&#231;&#227;o.<xref ref-type="bibr" rid="B10">10</xref> Apesar do crescente gasto relacionado ao uso de medicamentos, pouco se sabe sobre seus determinantes subjacentes. Precisamos conhecer esses determinantes para identificar &#225;reas-alvo para a formula&#231;&#227;o de pol&#237;ticas de gerenciamento dos or&#231;amentos da sa&#250;de, particularmente em sistemas de sa&#250;de de locais em desenvolvimento.</p>
        <p>Comportamentos de estilo de vida n&#227;o saud&#225;veis (consumo de &#225;lcool, tabagismo, maus h&#225;bitos de sono e comportamentos sedent&#225;rios [CS]) demonstraram ter um papel importante no desenvolvimento de muitas doen&#231;as,<xref ref-type="bibr" rid="B11">11</xref> mas a sua rela&#231;&#227;o direta com os custos relacionados ao uso de medicamentos n&#227;o est&#225; clara. Por exemplo, a ocorr&#234;ncia de dist&#250;rbios do sono &#233; altamente prevalente em adultos,<xref ref-type="bibr" rid="B12">12</xref> mas sua carga econ&#244;mica &#233; desconhecida.<xref ref-type="bibr" rid="B13">13</xref> Um estudo longitudinal realizado com 11.698 empregados americanos identificou que, quanto pior o dist&#250;rbio do sono, os custos da assist&#234;ncia m&#233;dica aumentavam em m&#233;dia US$ 725.15.<xref ref-type="bibr" rid="B13">13</xref> De maneira similar, em um estudo de 12 meses realizado em Taiwan, adultos com o diagn&#243;stico positivo de apneia obstrutiva do sono apresentaram um custo 66% maior (em termos de diagn&#243;sticos, medicamentos, tratamentos, cirurgias, exames laboratoriais e diagn&#243;stico por imagem) do que os adultos sem o mesmo diagn&#243;stico (US$ 1,734.10 versus US$ 1,041.30, respectivamente).<xref ref-type="bibr" rid="B14">14</xref> Em contrapartida, uma melhora nos n&#237;veis de atividade f&#237;sica (AF) poderia reduzir os custos relacionados ao uso de medicamentos em adultos,<xref ref-type="bibr" rid="B15">15</xref><sup>,</sup><xref ref-type="bibr" rid="B16">16</xref> embora o seu papel na potencial rela&#231;&#227;o entre comportamentos de vida pouco saud&#225;veis e custos do uso de medicamentos ainda n&#227;o foi tenha sido estudado at&#233; o momento.</p>
        <p>Neste estudo, examinamos a interrela&#231;&#227;o entre os custos do uso de medicamentos e os comportamentos de estilo de vida (saud&#225;veis e n&#227;o-saud&#225;veis).</p>
      </sec>
      <sec sec-type="methods">
        <title>M&#233;todos</title>
        <sec>
          <title>Amostra</title>
          <p>Os dados s&#227;o provenientes de um estudo de coorte realizado na cidade de Presidente Prudente, com &#237;ndice de desenvolvimento humano 0,806,<xref ref-type="bibr" rid="B17">17</xref> situada no oeste de S&#227;o Paulo (que &#233; o estado da federa&#231;&#227;o brasileira mais industrializado), no per&#237;odo de fevereiro/junho de 2014 (linha de base) a maio/dezembro de 2015 (seguimento). A estimativa do tamanho da amostra foi baseada em uma equa&#231;&#227;o para o coeficiente de correla&#231;&#227;o. Devido &#224; aus&#234;ncia de dados espec&#237;ficos sobre a rela&#231;&#227;o entre comportamentos de estilo de vida e custos com a sa&#250;de no Brasil,<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref> adotamos um coeficiente de correla&#231;&#227;o de 0,30 entre AF e custos com a sa&#250;de,<xref ref-type="bibr" rid="B16">16</xref><sup>,</sup><xref ref-type="bibr" rid="B18">18</xref> z = 1,96 e poder de 80% (adotando os par&#226;metros acima mencionados, o tamanho m&#237;nimo da amostra necess&#225;rio para este estudo foi de 86 participantes). Os crit&#233;rios de inclus&#227;o para os participantes foram: ter entre 40 e 65 anos de idade, sem diagn&#243;stico de complica&#231;&#245;es cardiovasculares anteriores (por exemplo, acidente vascular cerebral, ataque card&#237;aco), sem complica&#231;&#245;es decorrentes da diabetes (amputa&#231;&#227;o ou problemas visuais), sem uso regular de medicamentos e sem incapacidade f&#237;sica.</p>
          <p>O convite para participar do estudo foi feito atrav&#233;s de an&#250;ncios (cartazes) na Universidade Estadual de S&#227;o Paulo, em Presidente Prudente, e gin&#225;sios/academias em toda a cidade. Os participantes interessados entraram em contato com a equipe de pesquisa, que verificou o perfil dos participantes em rela&#231;&#227;o aos crit&#233;rios de inclus&#227;o (os participantes que preencheram todos os crit&#233;rios de inclus&#227;o assinaram um termo de consentimento por escrito). Cento e noventa e oito adultos entraram em contato com a equipe de pesquisa e foram considerados eleg&#237;veis, sendo ent&#227;o submetidos a uma avalia&#231;&#227;o inicial. A an&#225;lise deste estudo abrangeu 118 indiv&#237;duos (44 homens e 74 mulheres) avaliados tanto no linha de base como no seguimento (12 meses depois). Participantes foram exclu&#237;dos devido a: (a) desist&#234;ncias (n = 62) e (b) disponibilidade de menos de sete dias para o uso de ped&#244;metro no in&#237;cio do estudo (n = 18).</p>
          <p>Todos os procedimentos (question&#225;rios, ped&#244;metros e avalia&#231;&#227;o da composi&#231;&#227;o corporal) foram realizados por equipe treinada de pesquisadores (docentes, mestrandos e doutorandos) segundo os protocolos do Laborat&#243;rio de Investiga&#231;&#227;o em Exerc&#237;cio (LIVE), Brasil.<xref ref-type="bibr" rid="B19">19</xref> O comit&#234; de &#233;tica da Universidade Estadual de S&#227;o Paulo (UNESP), campus de Presidente Prudente, aprovou o estudo.</p>
        </sec>
        <sec>
          <title>Custos do uso de medicamentos</title>
          <p>No in&#237;cio do estudo, os participantes receberam um question&#225;rio (em forma de di&#225;rio) para anotar o uso de medicamentos e contendo instru&#231;&#245;es (e esclarecimentos adicionais oferecidos pessoalmente pela equipe de pesquisa) sobre como preencher o question&#225;rio. Os participantes relataram os seguintes dados: (a) n&#250;mero e tipo de todos os medicamentos (prescritos e n&#227;o prescritos); (b) como conseguiram os medicamentos - atrav&#233;s do Sistema &#218;nico de Sa&#250;de (SUS) ou despesa pessoal. O di&#225;rio foi preenchido para cada um dos 12 meses do estudo de coorte. Ao final do per&#237;odo de seguimento, a equipe de pesquisa recolheu os di&#225;rios preenchidos (<xref ref-type="table" rid="t4">Tabela 1</xref>). Para calcular o custo dos medicamentos, foram utilizados os pre&#231;os nacionais indicados pelo SUS (para medicamentos entregues pelo SUS) e os pre&#231;os de mercado das farm&#225;cias na &#225;rea de estudo (medicamentos obtidos por meio de despesas pessoais). Os custos foram calculados em moeda brasileira (Real - R$) e convertidos para d&#243;lar norte-americano (US$) utilizando as informa&#231;&#245;es de c&#226;mbio fornecidas pelo Banco Central do Brasil.</p>
          <table-wrap id="t4">
            <label>Tabela 1</label>
            <caption>
              <title>Medicamentos mais frequentemente comprados de acordo com a classifica&#231;&#227;o Anat&#244;mica Terap&#234;utica Qu&#237;mica</title>
            </caption>
            <table frame="hsides" rules="groups">
              <colgroup>
                <col width="33%"/>
                <col width="33%"/>
                <col width="33%"/>
              </colgroup>
              <thead>
                <tr>
                  <th align="left">Classifica&#231;&#227;o Anat&#244;mica Terap&#234;utica Qu&#237;mica</th>
                  <th align="center">Tipos de medicamento</th>
                  <th align="center">N&#250;mero de medicamentos comprados</th>
                </tr>
              </thead>
              <tbody>
                <tr>
                  <td align="left">Trato digestivo e metabolismo</td>
                  <td align="center">18</td>
                  <td align="center">33</td>
                </tr>
                <tr>
                  <td align="left">Sangue e &#243;rg&#227;os formadores de sangue</td>
                  <td align="center">2</td>
                  <td align="center">2</td>
                </tr>
                <tr>
                  <td align="left">Sistema cardiovascular</td>
                  <td align="center">31</td>
                  <td align="center">42</td>
                </tr>
                <tr>
                  <td align="left">Dermatol&#243;gico</td>
                  <td align="center">1</td>
                  <td align="center">1</td>
                </tr>
                <tr>
                  <td align="left">Sistema genito-urin&#225;rio e horm&#244;nios sexuais</td>
                  <td align="center">9</td>
                  <td align="center">25</td>
                </tr>
                <tr>
                  <td align="left">Horm&#244;nios, exceto sexuais e insulina</td>
                  <td align="center">10</td>
                  <td align="center">10</td>
                </tr>
                <tr>
                  <td align="left">Agentes anti-infecciosos sist&#234;micos</td>
                  <td align="center">1</td>
                  <td align="center">1</td>
                </tr>
                <tr>
                  <td align="left">Antineopl&#225;sicos e moduladores imunol&#243;gicos</td>
                  <td align="center">1</td>
                  <td align="center">2</td>
                </tr>
                <tr>
                  <td align="left">Sistema musculoesquel&#233;tico</td>
                  <td align="center">7</td>
                  <td align="center">9</td>
                </tr>
                <tr>
                  <td align="left">Sistema nervoso</td>
                  <td align="center">28</td>
                  <td align="center">38</td>
                </tr>
                <tr>
                  <td align="left">Antiparasit&#225;rios</td>
                  <td align="center">1</td>
                  <td align="center">2</td>
                </tr>
                <tr>
                  <td align="left">Sistema respirat&#243;rio</td>
                  <td align="center">3</td>
                  <td align="center">3</td>
                </tr>
                <tr>
                  <td align="left">&#211;rg&#227;os sensoriais</td>
                  <td align="center">1</td>
                  <td align="center">1</td>
                </tr>
                <tr>
                  <td align="left">Outros</td>
                  <td align="center">1</td>
                  <td align="center">3</td>
                </tr>
                <tr>
                  <td align="left">Geral</td>
                  <td align="center">114</td>
                  <td align="center">172</td>
                </tr>
              </tbody>
            </table>
          </table-wrap>
        </sec>
        <sec>
          <title>Vari&#225;veis comportamentais do estilo de vida</title>
          <p>A AF foi medida utilizando-se medidas objetivas e subjetivas no in&#237;cio do estudo e no seguimento. A medida objetiva da AF foi coletada utilizando ped&#244;metros (Yamax digiwalker, modelo SW200, Jap&#227;o) e especificada em termos de contagem de passos. Em ambos os per&#237;odos de avalia&#231;&#227;o (basal e seguimento), os ped&#244;metros foram utilizados pelos participantes por sete dias consecutivos. Os ped&#244;metros foram fixados lateralmente no quadril e retirados somente durante os per&#237;odos de sono e atividades aqu&#225;ticas. Os participantes registraram (ao final de cada dia) a contagem total de passos. No presente estudo, a AF representou o n&#250;mero de dias (dos 14 dias avaliados) em que foi alcan&#231;ada uma quantidade de passos &#8805;7,500. De acordo com Tudor-Locke et al.,<xref ref-type="bibr" rid="B20">20</xref> participantes que alcan&#231;aram &#8805; 7.500 passos/dia foram classificados como &#8220;suficientemente ativos&#8221;. A medida subjetiva da AF foi coletada por meio do question&#225;rio de Baecke.<xref ref-type="bibr" rid="B21">21</xref> O question&#225;rio &#233; composto por 16 quest&#245;es sobre tr&#234;s dom&#237;nios da AF (ocupacional, atividades esportivas e AF de lazer).</p>
          <p>Os dados sobre CS no trabalho (basais e de seguimento) foram obtidos utilizando-se a seguinte pergunta: &#8220;No trabalho, eu sento&#8221;&#8230;; as respostas poss&#237;veis eram: nunca [pontua&#231;&#227;o atribu&#237;da = 1], raramente [pontua&#231;&#227;o atribu&#237;da = 2], algumas vezes [pontua&#231;&#227;o atribu&#237;da = 3], frequentemente [pontua&#231;&#227;o atribu&#237;da = 4] e muito frequentemente [pontua&#231;&#227;o atribu&#237;da = 5]).</p>
          <p>A qualidade do sono foi avaliada na linha de base e no seguimento utilizando-se o Mini Question&#225;rio do Sono,<xref ref-type="bibr" rid="B22">22</xref> que inclui 10 quest&#245;es, cada uma com sete respostas poss&#237;veis (variando de nunca a sempre). A soma dessas 10 respostas gera um escore num&#233;rico que varia de 10 a 70 pontos (escores mais altos indicam pior qualidade do sono).</p>
          <p>Os participantes tamb&#233;m auto-relataram o tabagismo (fumante atual ou n&#227;o) e o consumo de &#225;lcool semanal (n&#250;mero de dias por semana com consumo de &#225;lcool) no in&#237;cio do estudo e no seguimento.</p>
        </sec>
        <sec>
          <title>Covari&#225;veis</title>
          <p>As covari&#225;veis consistiram em dados coletados atrav&#233;s de question&#225;rio (sexo [masculino ou feminino], data de nascimento [idade cronol&#243;gica estimada pela diferen&#231;a entre a data de nascimento e a data da avalia&#231;&#227;o] e escolaridade formal [em anos]). Dados cl&#237;nicos tamb&#233;m foram avaliados (gordura corporal [absorciometria radiol&#243;gica de dupla energia], press&#227;o arterial sist&#243;lica e diast&#243;lica). Os pesquisadores realizaram as medidas cl&#237;nicas em instala&#231;&#245;es universit&#225;rias com temperatura controlada e de acordo com procedimentos padronizados.</p>
        </sec>
        <sec>
          <title>An&#225;lise estat&#237;stica</title>
          <p>A estat&#237;stica descritiva foi realizada utilizando m&#233;dia, intervalos de confian&#231;a de 95% (IC 95%) e propor&#231;&#245;es, conforme apropriado. Devido &#224; distribui&#231;&#227;o n&#227;o param&#233;trica (demonstrada pelo teste de Kolmogorov-Smirnov), os custos de uso de medicamentos foram convertidos em logaritmos de base 10.</p>
          <p>Tanto a correla&#231;&#227;o de Pearson quanto a regress&#227;o linear foram realizadas para avaliar a rela&#231;&#227;o entre os custos dos medicamentos e as vari&#225;veis independentes. Na primeira abordagem, a correla&#231;&#227;o de Pearson (expressa como coeficientes padronizados [valores de &#8220;<italic>r</italic>&#8221;]) analisou separadamente a rela&#231;&#227;o dos custos de uso de medicamentos com comportamentos de estilo de vida (qualidade do sono, AF, CS no trabalho, tabagismo e consumo de &#225;lcool) e covari&#225;veis (sexo, idade, escolaridade, press&#227;o arterial e gordura corporal). Para as covari&#225;veis, modelos de regress&#227;o linear (expressos como coeficientes n&#227;o padronizados [valores de &#946;]) foram ajustados para avaliar a rela&#231;&#227;o entre os custos do uso de medicamentos e o comportamentos de estilo de vida, controlando todas as covari&#225;veis. Para cada abordagem, quatro modelos foram ajustados com base em diferentes especifica&#231;&#245;es de comportamentos de estilo de vida ([A] apenas valores basais, [B] apenas valores de seguimento, [C] diferen&#231;a entre seguimento e valores basais e [D] soma dos valores basais e de seguimento) para explorar a rela&#231;&#227;o diferencial que essas especifica&#231;&#245;es podem apresentar. Os diagn&#243;sticos de multicolinearidade e homocedasticidade foram avaliados e os modelos de regress&#227;o linear foram considerados adequados.</p>
          <p>Todas as an&#225;lises foram realizadas utilizando-se o <italic>software</italic> BioEstat (vers&#227;o 5.2) e o n&#237;vel de signific&#226;ncia foi estabelecido em p &lt; 0,05.</p>
        </sec>
      </sec>
      <sec sec-type="results">
        <title>Resultados</title>
        <p>Na linha de base, a m&#233;dia de idade da amostra foi de 51,7 &#177; 7,1 anos, variando de 40 a 68 anos (<xref ref-type="table" rid="t5">Tabela 2</xref>). O &#225;lcool foi consumido em m&#233;dia 2,1 dias por semana, enquanto 5,1% da amostra eram fumantes. As despesas com uso de medicamentos foram relatadas por 52,5% da amostra. Durante 12 meses de seguimento, 62 indiv&#237;duos compraram 172 medicamentos (<xref ref-type="table" rid="t5">Tabela 2</xref>), representando um custo total de US$ 3.087,01 para toda a amostra. N&#227;o havia dados faltantes.</p>
        <table-wrap id="t5">
          <label>Tabela 2</label>
          <caption>
            <title>Caracter&#237;sticas resumidas da amostra (n = 118)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="33%"/>
              <col width="33%"/>
              <col width="33%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" rowspan="2">Vari&#225;veis</th>
                <th align="center" colspan="2" style="border-bottom-width:thin;border-bottom-style:solid">Estat&#237;stica descritiva</th>
              </tr>
              <tr>
                <th align="center">M&#233;dia (IC95%)</th>
                <th align="center">Mediana (IIQ)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">Idade (anos)<sub>basal</sub></td>
                <td align="center">51,7 (50,4 to 53,1)</td>
                <td align="center">51.1 (10.1)</td>
              </tr>
              <tr>
                <td align="left">Peso corporal (kg)<sub>basal</sub></td>
                <td align="center">74,6 (71,7 to 77,4)</td>
                <td align="center">72.6 (16.6)</td>
              </tr>
              <tr>
                <td align="left">Altura (m)<sub>basal</sub></td>
                <td align="center">1,65 (1,63 to 1,67)</td>
                <td align="center">1.65 (0.15)</td>
              </tr>
              <tr>
                <td align="left">IMC (Kg/m<sup>2</sup>)<sub>basal</sub></td>
                <td align="center">26,92 (26,3 to 27,5)</td>
                <td align="center">26.41 (5.98)</td>
              </tr>
              <tr>
                <td align="left">Custos com medicamentos (US$) <sub>seguimento</sub></td>
                <td align="center">26,16 (17,7 to 34,62)</td>
                <td align="center">1.19 (42.91)</td>
              </tr>
              <tr>
                <td align="left">Consumo de &#225;lcool (dias)<sub>basal</sub></td>
                <td align="center">2,1 (1,9 to 2,3)</td>
                <td align="center">2 (2)</td>
              </tr>
              <tr>
                <td align="left">Consumo de &#225;lcool (dias)<sub>seguimento</sub></td>
                <td align="center">1,9 (1,7 to 2,2)</td>
                <td align="center">1 (2)</td>
              </tr>
              <tr>
                <td align="left">Qualidade do sono (escore MQS)<sub>basal</sub></td>
                <td align="center">26,6 (24,7 to 28,4)</td>
                <td align="center">25 (13)</td>
              </tr>
              <tr>
                <td align="left">Qualidade do sono (escore MQS)<sub>seguimento</sub></td>
                <td align="center">26,8 (24,8 to 28,7)</td>
                <td align="center">26 (15)</td>
              </tr>
              <tr>
                <td align="left">AF (&#8805;7,500 passos/dia)<sub>basal</sub></td>
                <td align="center">2,3 (1,8 to 2,7)</td>
                <td align="center">1 (5)</td>
              </tr>
              <tr>
                <td align="left">AF (&#8805;7,500 passos/dia)<sub>seguimento</sub></td>
                <td align="center">1,9 (1,5 to 2,3)</td>
                <td align="center">1 (4)</td>
              </tr>
              <tr>
                <td align="left">CS no trabalho (escore)<sub>basal</sub></td>
                <td align="center">3,2 (2,9 to 3,4)</td>
                <td align="center">3 (2)</td>
              </tr>
              <tr>
                <td align="left">CS no trabalho (escore)<sub>seguimento</sub></td>
                <td align="center">3,1 (2,9 to 3,3)</td>
                <td align="center">3 (2)</td>
              </tr>
              <tr>
                <td align="left">Tabagismo (sim [%])<sub>basal</sub></td>
                <td align="center">5,1% (1,1% to 9,1%)</td>
                <td align="center">---</td>
              </tr>
              <tr>
                <td align="left">Tabagismos (sim [%])<sub>seguimento</sub></td>
                <td align="center">5,9% (1,6% to 10,1%)</td>
                <td align="center">---</td>
              </tr>
              <tr>
                <td align="left">Uso de medicamentos (sim [%])<sub>seguimento</sub></td>
                <td align="center">52,5 (43,5% to 61,5%)</td>
                <td align="center">---</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN3">
              <p>IC95%: intervalo de confian&#231;a de 95%; IIQ: intervalo interquartil; IMC: &#237;ndice de massa corporal; MQS: mini question&#225;rio do sono; AF: atividade f&#237;sica; CS: comportamento sedent&#225;rio</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>A AF diminuiu significativamente desde a linha de base at&#233; o seguimento (p-valor = 0,024), enquanto a pontua&#231;&#227;o para CS no trabalho (p-valor = 0,396), qualidade do sono (p-valor = 0,951) e consumo de &#225;lcool (p-valor = 0,100) manteve-se est&#225;vel da linha de base at&#233; o seguimento.</p>
        <p>Na an&#225;lise bivariada, os custos do uso de medicamentos foram negativamente relacionados com a AF<sub>basal</sub> (r = -0,194; p-valor = 0,035), AF<sub>seguimento</sub> (r = -0,281; p-valor = 0,002), mas positivamente relacionados com o qualidade do sono<sub>basal</sub> (r = 0,299; p-valor = 0,001) e qualidade do sono<sub>seguimento</sub> (r = 0,315; p-valor = 0,001) e idade<sub>basal</sub> (r = 0,274; p-valor = 0,003). Sexo, educa&#231;&#227;o, CS no trabalho, consumo de &#225;lcool e tabagismo n&#227;o foram significativamente relacionados com os custos do uso de medicamentos. N&#227;o houve interrela&#231;&#245;es entre os comportamentos de estilo de vida.</p>
        <p>No modelo multivariado, considerando-se os comportamentos de estilo de vida na linha basal (Modelo A), a qualidade do sono e a gordura corporal foram positivamente relacionadas com maiores custos do uso de medicamentos em 12 meses, enquanto o consumo de &#225;lcool foi negativamente relacionado. O Modelo A explicou 19,1% de toda a vari&#226;ncia no desfecho (<xref ref-type="table" rid="t6">Tabela 3</xref>). No modelo multivariado, considerando-se os comportamentos de estilo de vida no seguimento (Modelo B), apenas a qualidade do sono foi positivamente relacionada com maiores custos de uso de medicamentos em 12 meses. O Modelo B explicou 21,9% de toda a vari&#226;ncia nos custos relacionados ao uso de medicamentos.</p>
        <table-wrap id="t6">
          <label>Tabela 3</label>
          <caption>
            <title>Regress&#227;o linear descrevendo a rela&#231;&#227;o entre os custos dos medicamentos em 12 meses (vari&#225;vel dependente) e os comportamentos de estilo de vida (n = 118)</title>
          </caption>
          <table frame="hsides" rules="groups">
            <colgroup>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
              <col width="20%"/>
            </colgroup>
            <thead>
              <tr>
                <th align="left" rowspan="3">Vari&#225;veis independentes</th>
                <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Modelo - A</th>
                <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Modelo - B</th>
                <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Modelo - C</th>
                <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Modelo - D</th>
              </tr>
              <tr>
                <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Basal</th>
                <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Basal</th>
                <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Seguimento menos Basal</th>
                <th align="center" style="border-bottom-width:thin;border-bottom-style:solid">Basal mais Seguimento</th>
              </tr>
              <tr>
                <th align="center">&#946; (&#946;<sub>IC95%</sub>)</th>
                <th align="center">&#946; (&#946;<sub>IC95%</sub>)</th>
                <th align="center">&#946; (&#946;<sub>IC95%</sub>)</th>
                <th align="center">&#946; (&#946;<sub>IC95%</sub>)</th>
              </tr>
            </thead>
            <tbody>
              <tr>
                <td align="left">AF (passos)</td>
                <td align="center">-0,011 (-0,078 a 0,056)</td>
                <td align="center">-0,048 (-0,122 a 0,027)</td>
                <td align="center">-0,18 (-0,092 a 0,056)</td>
                <td align="center">-0,017 (-0,058 a 0,025)</td>
              </tr>
              <tr>
                <td align="left">Qualidade do sono (escore MQS)</td>
                <td align="center">0,018 (0,001 a 0,034)</td>
                <td align="center">0,018 (0,002 a 0,033)</td>
                <td align="center">0,004 (-0,017 a 0,026)</td>
                <td align="center">0,011 (0,002 a 0,019)</td>
              </tr>
              <tr>
                <td align="left">Consumo de &#225;lcool (dias)</td>
                <td align="center">-0,137 (-0,272 a -0,002)</td>
                <td align="center">-0,111 (-0,241 a 0,019)</td>
                <td align="center">0,034 (-0,140 a 0,208)</td>
                <td align="center">-0,073 (-0,145 a -0,001)</td>
              </tr>
              <tr>
                <td align="left">Tabagismo (sim)</td>
                <td align="center">0,157 (-0,514 a 0,828)</td>
                <td align="center">0,424 (-0,224 a 1,072)</td>
                <td align="center">0,819 (-0,376 a 2,014)</td>
                <td align="center">0,170 (-0,172 a 0,513)</td>
              </tr>
              <tr>
                <td align="left">CS no trabalho (frequ&#234;ncia)</td>
                <td align="center">0,021 (-0,114 a 0,157)</td>
                <td align="center">0,017 (-0,123 a 0,157)</td>
                <td align="center">0,023 (-0,154 a 0,201)</td>
                <td align="center">0,006 (-0,070 a 0,082)</td>
              </tr>
              <tr>
                <td align="left">Sexo (feminino)<xref ref-type="table-fn" rid="TFN4">*</xref>
								</td>
                <td align="center">-0,447 (-0,900 a 0,007)</td>
                <td align="center">-0,341 (-0,780 a 0,098)</td>
                <td align="center">-0,302 (-0,731 a 0,126)</td>
                <td align="center">-0,421 (-0,872 a 0,029)</td>
              </tr>
              <tr>
                <td align="left">Idade (anos)<xref ref-type="table-fn" rid="TFN4">*</xref>
								</td>
                <td align="center">0,021 (-0,004 a 0,047)</td>
                <td align="center">0,020 (-0,004 a 0,044)</td>
                <td align="center">0,029 (0,003 a 0,056)</td>
                <td align="center">0,019 (-0,005 a 0,044)</td>
              </tr>
              <tr>
                <td align="left">Gordura corporal (%)<xref ref-type="table-fn" rid="TFN4">*</xref>
								</td>
                <td align="center">0,023 (0,003 a 0,043)</td>
                <td align="center">0,019 (-0,002 a 0,039)</td>
                <td align="center">0,027 (0,007 a 0,048)</td>
                <td align="center">0,020 (-0,001 a 0,040)</td>
              </tr>
              <tr>
                <td align="left">PAS (mmHg)<xref ref-type="table-fn" rid="TFN4">*</xref>
								</td>
                <td align="center">-0,005 (-0,028 a 0,019)</td>
                <td align="center">-0,005 (-0,028 a 0,017)</td>
                <td align="center">-0,004 (-0,028 a 0,020)</td>
                <td align="center">-0,005 (-0,028 a 0,018)</td>
              </tr>
              <tr>
                <td align="left">PAD (mmHg)<xref ref-type="table-fn" rid="TFN4">*</xref>
								</td>
                <td align="center">0,017 (-0,010 a 0,044)</td>
                <td align="center">0,021 (-0,005 a 0,047)</td>
                <td align="center">0,014 (-0,014 a 0,043)</td>
                <td align="center">0,020 (-0,007 a 0,046)</td>
              </tr>
              <tr>
                <td align="left">Escolaridade (anos)<xref ref-type="table-fn" rid="TFN4">*</xref>
								</td>
                <td align="center">0,084 (-0,024 a 0,193)</td>
                <td align="center">0,091 (-0,020 a 0,202)</td>
                <td align="center">0,080 (-0,026 a 0,187)</td>
                <td align="center">0,092 (-0,019 a 0,202)</td>
              </tr>
              <tr>
                <td align="left">
                  <bold>Par&#226;metros de regress&#227;o linear</bold>
                </td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
                <td align="center">
								</td>
              </tr>
              <tr>
                <td align="left">R</td>
                <td align="center">0,527</td>
                <td align="center">0,549</td>
                <td align="center">0,473</td>
                <td align="center">0,548</td>
              </tr>
              <tr>
                <td align="left">r <sup>2</sup></td>
                <td align="center">0,278</td>
                <td align="center">0,301</td>
                <td align="center">0,224</td>
                <td align="center">0,300</td>
              </tr>
              <tr>
                <td align="left">r <sup>2</sup><sub>ajustado</sub></td>
                <td align="center">0,191</td>
                <td align="center">0,219</td>
                <td align="center">0,131</td>
                <td align="center">0,217</td>
              </tr>
            </tbody>
          </table>
          <table-wrap-foot>
            <fn id="TFN4">
              <label>*</label>
              <p>apenas valores basais foram utilizados; Modelo A: comportamentos de estilo de vida inseridos como valores basais; Modelo B: comportamentos de estilo de vida inseridos como valores de seguimento; Modelo-C: comportamentos de estilo de vida inseridos como seguimento menos os valores basais; Modelo-D: comportamentos de estilo de vida inseridos como valores basais mais os valores de seguimento; IC95%: intervalo de confian&#231;a de 95%; AF: atividade f&#237;sica; MQS: Mini Question&#225;rio do Sono; CS: comportamento sedent&#225;rio; PAS: press&#227;o arterial sist&#243;lica; PAD: press&#227;o arterial diast&#243;lica.</p>
            </fn>
          </table-wrap-foot>
        </table-wrap>
        <p>No modelo multivariado, considerando-se as mudan&#231;as ao longo do tempo nos comportamentos relacionados ao estilo de vida (Modelo C), a idade e a gordura corporal foram positivamente relacionadas a maiores gastos com medicamentos em 12 meses. O Modelo C explicou 13,1% de toda a vari&#226;ncia nos gastos com medicamentos. No Modelo D (somat&#243;ria dos valores basais e de seguimento), a qualidade do sono apresentou uma rela&#231;&#227;o positiva com o uso de medicamentos (<xref ref-type="table" rid="t6">Tabela 3</xref>). Por outro lado, o consumo de &#225;lcool foi negativamente relacionado aos custos de uso de medicamentos. O Modelo D explicou 21,7% de toda a vari&#226;ncia nos gastos com medicamentos.</p>
      </sec>
      <sec sec-type="discussion">
        <title>Discuss&#227;o</title>
        <p>Este estudo mostra que comportamentos de estilo de vida, particularmente uma pior qualidade do sono, levam a custos mais altos relacionados ao uso de medicamentos. A gordura corporal tamb&#233;m mostrou ser um importante preditor - efeito positivo nos custos. No total, 52,5% dos adultos relataram o uso de algum medicamento durante o per&#237;odo de coorte, enquanto 20,5% (n=24) desses mesmos adultos relataram o uso de tr&#234;s ou mais medicamentos. Essas taxas s&#227;o semelhantes &#224;s de pesquisas brasileiras (18%) e europeias (20%), nas quais foram realizadas amostragens de base populacional.<xref ref-type="bibr" rid="B4">4</xref><sup>,</sup><xref ref-type="bibr" rid="B5">5</xref>
				</p>
        <p>Outra semelhan&#231;a com estudos anteriores, observada em nossos achados, &#233; que os medicamentos para o tratamento de doen&#231;as cardiovasculares foram os mais relatados pelos participantes. Um estudo realizado na Nova Zel&#226;ndia, examinando as tend&#234;ncias de uso de medicamentos em adultos com idade maior ou igual a 65 anos, no per&#237;odo de 2005 a 2013, identificou que o uso de medicamentos para prevenir eventos cardiovasculares (aspirina e estatinas) havia aumentado significativamente.<xref ref-type="bibr" rid="B3">3</xref> A din&#226;mica observada para medicamentos utilizados no tratamento de doen&#231;as cardiovasculares tamb&#233;m parece ser afetada pelo envelhecimento (em nosso estudo, uma covari&#225;vel relevante nos modelos multivariados). Dados anteriores identificaram que o consumo de aspirina e dipiridamol aumentou em idosos a uma taxa mais alta do que a observada em jovens.<xref ref-type="bibr" rid="B3">3</xref>
				</p>
        <p>O aumento dos gastos pelos idosos pode ser explicado pelos efeitos naturais que o envelhecimento exerce sobre os &#243;rg&#227;os do corpo humano e suas fun&#231;&#245;es,<xref ref-type="bibr" rid="B23">23</xref> mas tamb&#233;m &#233; impulsionado pela redu&#231;&#227;o da AF observada na popula&#231;&#227;o mais idosa.<xref ref-type="bibr" rid="B24">24</xref> Na amostra analisada, embora o efeito da idade nos gastos com medicamentos n&#227;o tenha sido mediada pela AF, eles foram relacionados com outros efeitos na an&#225;lise bruta, denotando a relev&#226;ncia de a&#231;&#245;es voltadas para a melhoria da pr&#225;tica de AF, principalmente em grupos populacionais compostos por idosos.<xref ref-type="bibr" rid="B23">23</xref><sup>,</sup><xref ref-type="bibr" rid="B24">24</xref>
				</p>
        <p>Nesta amostra, o maior custo com medicamentos em adultos com dist&#250;rbios do sono pode indicar n&#227;o apenas o tratamento dos pr&#243;prios dist&#250;rbios do sono, mas tamb&#233;m o uso de medicamentos para aliviar seus sintomas e, consequentemente, manter as atividades di&#225;rias, como o trabalho.<xref ref-type="bibr" rid="B13">13</xref><sup>,</sup><xref ref-type="bibr" rid="B25">25</xref>
				</p>
        <p>Os achados relacionados ao consumo de bebidas alco&#243;licas foram surpreendentes, pois, geralmente, um maior consumo de &#225;lcool est&#225; vinculado a maiores gastos com a sa&#250;de,<xref ref-type="bibr" rid="B26">26</xref><sup>,</sup><xref ref-type="bibr" rid="B27">27</xref> e n&#227;o o contr&#225;rio, como observado em nosso estudo. De fato, a liga&#231;&#227;o entre o consumo de &#225;lcool e os custos com a sa&#250;de pode ser direta (por exemplo, com doen&#231;as relacionadas diretamente ao consumo de &#225;lcool) e indireta (por exemplo, acidentes de tr&#226;nsito), mas &#233; importante considerar que alguns tipos de bebidas alco&#243;licas t&#234;m caracter&#237;sticas positivas na sa&#250;de - como as propriedades anti-inflamat&#243;rias observadas no vinho tinto.<xref ref-type="bibr" rid="B28">28</xref> Portanto, a explica&#231;&#227;o para o nosso surpreendente achado pode estar relacionado tanto ao tipo quanto &#224; quantidade de &#225;lcool consumido. No entanto, nosso estudo analisou apenas o n&#250;mero de dias por semana com consumo de &#225;lcool, e n&#227;o a quantidade e o tipo de bebida alc&#243;olica consumida, o que caracteriza uma limita&#231;&#227;o em nosso estudo.</p>
        <p>Outras limita&#231;&#245;es do estudo s&#227;o dignas de men&#231;&#227;o. A primeira limita&#231;&#227;o do estudo &#233; o pequeno tamanho da amostra. O presente estudo possui poder estat&#237;stico de 80% para detectar um coeficiente de correla&#231;&#227;o de 0,256 ou superior, enquanto a rela&#231;&#227;o entre alguns comportamentos e gastos com medicamentos est&#227;o em torno de r = 0,110.<xref ref-type="bibr" rid="B16">16</xref> Mesmo considerando o fato de que a inclus&#227;o de covari&#225;veis aumenta o poder de modelos multivariados,<xref ref-type="bibr" rid="B29">29</xref> o tamanho reduzido da amostra pode ter sido respons&#225;vel pela aus&#234;ncia de rela&#231;&#227;o significativa entre a AF e os custos de uso de medicamentos. Outra limita&#231;&#227;o relacionada &#224;s medidas objetivas da AF &#233; o registro de dados pelos participantes, pois todos os dias eles tinham que anotar o n&#250;mero de passos exibidos no ped&#244;metro. Embora este m&#233;todo seja amplamente utilizado,<xref ref-type="bibr" rid="B19">19</xref> ele pode levar a erros de registro. Como mencionado acima, a aus&#234;ncia de medi&#231;&#245;es relacionadas &#224; quantidade e ao tipo de bebidas alco&#243;licas e ao comportamento sedent&#225;rio (pelo tempo de tela na TV ou computador) tamb&#233;m constituem limita&#231;&#245;es. Novos estudos poderiam explorar o impacto dessas medi&#231;&#245;es.</p>
      </sec>
      <sec sec-type="conclusions">
        <title>Conclus&#245;es</title>
        <p>A pior qualidade do sono parece aumentar os custos relacionados ao uso de medicamentos em adultos, enquanto a obesidade e o envelhecimento desempenham um papel relevante nesse fen&#244;meno. Al&#233;m disso, o consumo de &#225;lcool parece ser uma vari&#225;vel com impacto econ&#244;mico relevante, mas estudos adicionais s&#227;o necess&#225;rios para identificar claramente a dire&#231;&#227;o dessa rela&#231;&#227;o com os gastos com medicamentos.</p>
      </sec>
    </body>
    <back>
      <fn-group>
        <fn fn-type="financial-disclosure">
          <p>
            <bold>Fontes de financiamento</bold>
          </p>
          <p>O presente estudo n&#227;o teve fontes de financiamento externas.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Vincula&#231;&#227;o acad&#234;mica</bold>
          </p>
          <p>Este artigo &#233; parte de tese de Doutorado de Alessandra Madia Mantovani pela Universidade Estadual Paulista.</p>
        </fn>
        <fn fn-type="other">
          <p>
            <bold>Aprova&#231;&#227;o &#233;tica e consentimento informado</bold>
          </p>
          <p>Este estudo foi aprovado pelo Comit&#234; de &#201;tica da Faculdade de Ci&#234;ncias e Tecnologia da Universidade Estadual Paulista sob o n&#250;mero de protocolo 349.306/2013. Todos os procedimentos envolvidos nesse estudo est&#227;o de acordo com a Declara&#231;&#227;o de Helsinki de 1975, atualizada em 2013. O consentimento informado foi obtido de todos os participantes inclu&#237;dos no estudo.</p>
        </fn>
      </fn-group>
      <ack>
        <title>Agradecimento</title>
        <p>&#192; Funda&#231;&#227;o de Amparo a Pesquisa do Estado de S&#227;o Paulo (FAPESP) (processos n&#250;mero: 2017/50026-7 e 2015/20460-1) e &#224; Coordena&#231;&#227;o de Aperfei&#231;oamento de Pessoal de N&#237;vel Superior (CAPES).</p>
      </ack>
    </back>
  </sub-article>
</article>
