Comparing drug interaction frequencies of various hepatitis C treatment regimens among monoinfected patients

array:24 ["pii" => "S1665268119300572" "issn" => "16652681" "doi" => "10.1016/j.aohep.2019.01.005" "estado" => "S300" "fechaPublicacion" => "2019-07-01" "aid" => "49" "copyright" => "Fundación Clínica Médica Sur, A.C." "copyrightAnyo" => "2019" "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2019;18:601-6" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 262 "formatos" => array:3 [ "EPUB" => 18 "HTML" => 136 "PDF" => 108 ] ] "itemSiguiente" => array:19 [ "pii" => "S1665268119300584" "issn" => "16652681" "doi" => "10.1016/j.aohep.2019.01.006" "estado" => "S300" "fechaPublicacion" => "2019-07-01" "aid" => "50" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2019;18:607-12" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 442 "formatos" => array:3 [ "EPUB" => 23 "HTML" => 275 "PDF" => 144 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Prognostic value of hepatic encephalopathy for survival of patients with liver failure: A systematic review and meta-analysis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "607" "paginaFinal" => "612" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1695 "Ancho" => 2083 "Tamanyo" => 168242 ] ] "descripcion" => array:1 [ "en" => "Literature search and study selection." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Hanqing Yu, Yu Chen, Ping Jiang" "autores" => array:3 [ 0 => array:2 [ "nombre" => "Hanqing" "apellidos" => "Yu" ] 1 => array:2 [ "nombre" => "Yu" "apellidos" => "Chen" ] 2 => array:2 [ "nombre" => "Ping" "apellidos" => "Jiang" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119300584?idApp=UINPBA00004N" "url" => "/16652681/0000001800000004/v3_201908230828/S1665268119300584/v3_201908230828/en/main.assets" ] "itemAnterior" => array:19 [ "pii" => "S1665268119300663" "issn" => "16652681" "doi" => "10.1016/j.aohep.2019.01.010" "estado" => "S300" "fechaPublicacion" => "2019-07-01" "aid" => "58" "copyright" => "Fundación Clínica Médica Sur, A.C." "documento" => "article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "fla" "cita" => "Ann Hepatol. 2019;18:595-600" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 844 "formatos" => array:3 [ "EPUB" => 36 "HTML" => 331 "PDF" => 477 ] ] "en" => array:12 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Endoscopic retrograde cholangiopancreatography versus surgery for choledocholithiasis – A meta-analysis" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "595" "paginaFinal" => "600" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 3953 "Ancho" => 1439 "Tamanyo" => 418420 ] ] "descripcion" => array:1 [ "en" => "Risk of bias summary. Captions: “+” – low risk of bias; “−” – high risk of bias; blank – unclear risk of bias." ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Fernando C. Schacher, Sofia M. Giongo, Fernanda J.P. Teixeira, Ângelo Z. Mattos" "autores" => array:4 [ 0 => array:2 [ "nombre" => "Fernando C." "apellidos" => "Schacher" ] 1 => array:2 [ "nombre" => "Sofia M." "apellidos" => "Giongo" ] 2 => array:2 [ "nombre" => "Fernanda J.P." "apellidos" => "Teixeira" ] 3 => array:2 [ "nombre" => "Ângelo Z." "apellidos" => "Mattos" ] ] ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119300663?idApp=UINPBA00004N" "url" => "/16652681/0000001800000004/v3_201908230828/S1665268119300663/v3_201908230828/en/main.assets" ] "en" => array:19 [ "idiomaDefecto" => true "cabecera" => "Original article" "titulo" => "Comparing drug interaction frequencies of various hepatitis C treatment regimens among monoinfected patients" "tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "601" "paginaFinal" => "606" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "Alisha Ahmed, Christopher Schriever, Nicholas Britt, Jenna Yager, Ronish Amin, Liam McGuey, Nimish Patel" "autores" => array:7 [ 0 => array:3 [ "nombre" => "Alisha" "apellidos" => "Ahmed" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "Christopher" "apellidos" => "Schriever" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "Nicholas" "apellidos" => "Britt" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "Jenna" "apellidos" => "Yager" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 4 => array:3 [ "nombre" => "Ronish" "apellidos" => "Amin" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 5 => array:3 [ "nombre" => "Liam" "apellidos" => "McGuey" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 6 => array:4 [ "nombre" => "Nimish" "apellidos" => "Patel" "email" => array:1 [ 0 => "patel.nimish@gmail.com" ] "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "e" "identificador" => "aff0025" ] 2 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:5 [ 0 => array:3 [ "entidad" => "Department of Pharmacy Practice, Albany College of Pharmacy & Health Sciences, Albany, NY, USA" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Pharmacy Practice, University of Illinois College of Pharmacy at Chicago, Rockford Campus, Rockford, IL, USA" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "University of Kansas, School of Pharmacy, Kansas City, KS, USA" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Department of Pharmacy, Samuel S. Stratton Veterans Affairs Medical Center, Albany, NY, USA" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA" "etiqueta" => "e" "identificador" => "aff0025" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author at: Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA" ] ] ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1203 "Ancho" => 2083 "Tamanyo" => 107584 ] ] "descripcion" => array:1 [ "en" => "Frequency of contraindicated drug–drug interactions between various HCV treatment regimens, stratified by use of ≥6 medications. EBV/GZR – elbasvir/grazoprevir; GLE/PIB – glecaprevir/pibrentasvir; LDV/SOF – ledipasvir/sofosbuvir and SOF/VEL – sofosbuvir/velpatasvir." ] ] ] "textoCompleto" => "1IntroductionCurrently, there are several therapeutic options available to treat chronic genotype 1 hepatitis C virus (HCV) infection. These include glecaprevir/pibrentasvir (GLE/PIB), grazoprevir/elbasvir (GZR/EBR), ledipasvir/sofosbuvir (LDV/SOF) and sofosbuvir/velpatasvir (SOF/VEL) <a class="elsevierStyleCrossRefs" href="#bib0110">[1–5]</a>. Each has demonstrated impressive rates of sustained virologic response in treatment recipients with low toxicity <a class="elsevierStyleCrossRefs" href="#bib0135">[6–10]</a>. While the safety and efficacy appear to be similar, some characteristics distinguishing these four regimens are not entirely clear, potentially complicating treatment selection by clinicians. One potential difference is the occurrence of contraindicated drug–drug interactions (XDDIs) with patients’ medications used to treat other medical conditions. In general, patients with chronic HCV infection are generally advanced in age and may have developed certain comorbidities necessitating medication therapy <a class="elsevierStyleCrossRef" href="#bib0160">[11]</a>. As a result, use of multiple medications simultaneously, otherwise known as polypharmacy, may create a therapeutic dilemma <a class="elsevierStyleCrossRefs" href="#bib0165">[12,13]</a>. Polypharmacy significantly elevates the risk of experiencing XDDIs and may impact clinical outcomes <a class="elsevierStyleCrossRefs" href="#bib0175">[14–16]</a>.Limited comparative data exist evaluating the potential risk of XDDIs between GLE/PIB, GZR/EBR, LDV/SOF and SOV/VEL. It is unclear which regimen is safest to administer to HCV-monoinfected patients who have a high probability of XDDIs due to age-related polypharmacy <a class="elsevierStyleCrossRef" href="#bib0175">[14]</a>. These issues also have important cost implications. The presence of XDDIs can potentially lead to dangerous health effects <a class="elsevierStyleCrossRefs" href="#bib0180">[15–17]</a>. In extreme scenarios, mitigation of XDDIs may require utilization of costly additional healthcare resources <a class="elsevierStyleCrossRef" href="#bib0195">[18]</a>. Third party payors can attempt to minimize patient harm and contain the potentially unnecessary expenditures by limiting formularies to anti-HCV medications with a low probability of XDDIs.Additionally, the proportion of patients who have XDDI to all HCV treatment regimens has not been defined. Understanding which patients have XDDIs to all anti-HCV regimens is crucial so appropriate modifications can be made to concomitant medications to facilitate prompt HCV treatment and prevent the consequences of untreated HCV infection <a class="elsevierStyleCrossRef" href="#bib0110">[1]</a>.The objectives of this study were to: (1) compare prevalence of contraindicated drug interactions (XDDIs) between GLE/PIB, GZR/EBR, LDV/SOF and SOF/VEL when added to the home medication profiles of patients with HCV monoinfection; (2) quantify the proportion of patients with XDDIs to all four HCV treatment regimens; and (3) determine clinical/demographic risk factors of having XDDIs to all four regimens.2Materials and methodsThe Institutional Review Board at the Stratton Veterans’ Affairs Medical Center approved this study with a waiver of informed consent.2.1Study design and populationWe performed a cross-sectional study among HCV monoinfected Veterans receiving care in Upstate New York Veterans’ Healthcare Administration between January 1, 2000 and December 31, 2013.Inclusion criteria were: (1) age ≥18 years; (2) HCV infection (International Classification of Diseases 9th Revision codes 070.41, 070.44, 070.51, 070.54, 070.70, and 070.71), confirmed by laboratory tests for either HCV RNA or anti-HCV; and (3) availability of medication list. The focus of this study was HCV monoinfection and therefore patients with hepatitis B or HIV coinfection were excluded.2.2Data collectionData were obtained from computerized medical records. Information abstracted from patients’ medical records included demographics, comorbidities, and most recent medication lists. The full list of covariates extracted from patients’ medical records is described elsewhere <a class="elsevierStyleCrossRef" href="#bib0200">[19]</a>. Home medications were initially categorized according to the World Health Organization Anatomical Therapeutic Chemical (ATC) classification system <a class="elsevierStyleCrossRef" href="#bib0205">[20]</a>. The ATC-categorized medications were subsequently collapsed into therapeutic classes based on distribution of medication use.2.3Outcome assessmentThe primary outcome was the occurrence of contraindicated drug–drug interactions (XDDIs) with the patient's home medication profile after the addition of each of the four HCV regimens evaluated: GLE/PIB, GZR/EBR, LDV/SOF, and SOF/VEL. The HCV treatment guidelines specifically list the University of Liverpool drug interaction website as a resource to evaluate drug–drug interactions <a class="elsevierStyleCrossRefs" href="#bib0110">[1,21]</a>. In the present study, this website was used to classify the type of drug–drug interaction (do not coadminister, potential interaction, no interaction expected, no clear data). Drug–drug interactions classified as “do not coadminister” were the only ones recorded and deemed contraindicated. The University of Liverpool drug interaction website only assesses drug–drug interactions where at least one of the medications used in the drug–drug combination is used to treat HCV infection <a class="elsevierStyleCrossRef" href="#bib0210">[21]</a>, and this study was limited to such interactions. Various XDDIs between non-HCV medications assessed by other drug interaction programs are described elsewhere <a class="elsevierStyleCrossRef" href="#bib0165">[12]</a>.2.4Statistical analysesTwo-way comparisons were performed using McNemar's test to assess the frequencies of XDDIs between each of the HCV regimens. Because of the multiple comparisons being made between each of the HCV regimen's prevalence of XDDIs in the bivariate analyses, a p-value of 0.0083, adjusted for multiple comparisons, was used to denote statistical significance (Kappa, κ, =6 possible combinations of comparisons between anti-HCV regimens divided by α of 0.05).To determine the predictors of having XDDIs to all four HCV treatment regimens, bivariate analyses were performed comparing presence of XDDIs to all regimens with clinical/demographic characteristics. Continuous variables were compared using student's t or Mann–Whitney U tests and categorical variables were compared using chi-square or Fisher's exact tests. Classification and regression tree (CART) analyses were performed to identify thresholds in continuous predictor variables associated with a significantly increased likelihood of having an XDDI to all four HCV treatment regimens when dichotomized around the threshold (i.e. CART identifies 6 as number of medications associated with XDDIs to all four regimens; patients are dichotomized into two groups – those using ≥6 or <6 medications; the percentage of patients with XDDIs to all four regimens differs significantly between those using ≥6 and <6 medications). Variables in the bivariate analyses with an associated p-value <0.25 were eligible for model entry into the multivariable logistic regression analyses. Using a backward, stepwise approach, the most parsimonious model contained variables that were significantly associated with XDDIs to all regimens. The only confounders retained in the model were those that changed the measure of association for the final predictor variables by more than 10%. The exponentiated beta coefficients from the final multivariable model were used to compute the predicted probabilities of having XDDIs to all four HCV treatment regimens when certain covariates were present or absent.3ResultsOf the 4047 patients evaluated, the majority were male (96.4%). Mean±standard deviation (SD) age was 59.8±7.6 years. Patients were using a median (interquartile range, IQR) of 7 (4–10) medications. The most commonly used medication classes were antihypertensives (77.1%), vitamins/supplements (70.1%), antidepressants (67.9%), and antiplatelet medications (62.9%).After adding each HCV regimen to the patients’ home medication profiles, there were 814 (20.1%) patients with XDDIs to at least one HCV regimen. The frequencies of XDDIs after the addition of each HCV regimen are in displayed <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>. The prevalence of XDDIs was highest for GLE/PIB (17.8%), followed by LDV/SOF (4.4%), SOF/VEL (2.8%), and EBV/GZR (2.8%). There were significant (p<0.0083) differences in two-way comparisons of the frequency of XDDIs between most pairings of HCV treatment regimens. The only exception to this was the comparison between SOF/VEL and EBV/GZR (p=0.85).<elsevierMultimedia ident="fig0005"></elsevierMultimedia>There were 95 (2.3%) patients with XDDIs to all four HCV regimens. Bivariate analyses comparing clinical/demographic characteristics between patients with and without XDDIs to all four HCV regimens is displayed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Variables significantly associated with XDDIs to all four HCV regimens were number of medications, use of anti-anxiety medications, anti-coagulants, anti-emetics, anti-epileptic medications, anti-psychotics, asthma/chronic obstructive pulmonary disorder medications, erythropoietin stimulating agents (ESAs) and years with HCV diagnosis. A CART-derived breakpoint was identified for number of concomitant medications associated with an increased risk of having an XDDI to all four regimens. This breakpoint was 6 medications. Patients using ≥6 concomitant medications had a significantly higher prevalence of XDDIs to all four regimens than patients below this threshold (3.1% versus 1.1%, p<0.001). The prevalence of XDDIs after the addition of each HCV regimen to the patients’ home medication profiles, stratified by use of <6 or ≥6 medications, is displayed in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>. The other CART-derived breakpoint identified was the number of years with chronic HCV infection. The prevalence of XDDIs was significantly higher for patients with an HCV diagnosis of at least 10 years compared to those with a more recent diagnosis <10 years prior (2.7% versus 1.7%, p=0.05).<elsevierMultimedia ident="tbl0005"></elsevierMultimedia>In multivariable analyses, variables independently associated with XDDIs involving all four HCV treatment regimens were use of ≥6 medications (odds ratio, OR: 2.85, 95% confidence interval, CI: 1.68–4.84, p<0.001) and having an HCV diagnosis ≥10 years (OR: 1.49, 95% CI: 0.93–2.40, p=0.10). The results of the multivariable analyses were used to determine the predicted probabilities of experiencing an XDDI to all four HCV treatment regimens given certain covariate patterns. The predicted probabilities of XDDIs to all four HCV treatment regimens is displayed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. The reference probability was 0.8% when neither covariate was present (covariate pattern 1.01), and rose to 3.5% when both covariates were present (covariate pattern 1.04).<elsevierMultimedia ident="tbl0010"></elsevierMultimedia>A second multivariable model was assessed where use of ≥6 medications was replaced with individual medication classes. In the second model, variables independently associated with XDDIs to all four HCV treatment regimens were: anti-coagulants (OR: 2.98, 95% CI: 1.35–6.54, p=0.007), anti-epileptic medications (OR: 80.26, 95% CI: 32.37–199.02, p<0.001), anti-psychotic medications (OR: 1.95, 95% CI: 1.24–3.06, p=0.004), ESAs (OR: 4.39, 95% CI: 1.26–15.36, p=0.02) and HCV infection ≥10 years (OR: 1.37, 95% CI: 0.83–2.268, p=0.22). The predicted probability of having an XDDI to all four HCV regimens when none of the covariates were present was 0.001% (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>, covariate pattern 2.01). Conversely, the predicted probability of having an XDDI to all four HCV regimens when all of the covariates were present was 72.7% (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>, covariate pattern 2.22).4DiscussionSeveral treatment options are available for patients with HCV infection <a class="elsevierStyleCrossRefs" href="#bib0110">[1–5]</a>. One potential distinguishing feature is the potential for XDDIs. Our study demonstrated differences in the frequency of XDDIs between the various HCV regimens (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The prevalence of XDDIs was highest for GLE/PIB (17.8%) followed distantly by LDV/SOF (4.4%) and the remaining two regimens (2.8%). The high frequency of XDDIs involving GLE/PIB was driven by statins and was not surprising given the ubiquity of statin use in the Veterans Affairs population. While most of the two-way comparisons between HCV treatment regimens were statistically significant, it is important to note that the absolute differences for some comparisons were as little as 1.6% (comparison of LDV/SOF versus SOF/VEL) and the number needed to avert one XDDI would be >60 patients. Conversely, there were comparisons with absolute differences as large as 15% (GLE/PIB versus SOF/VEL) and the number needed to avert one XDDI would be <7 patients.Another unique feature of our study was an examination of risk factors for having a XDDI to all four HCV treatment regimens. Understanding these risk factors is important because these patients would be ineligible for HCV treatment without modifying concomitant medication(s) used to treat comorbidities. Duration of HCV infection ≥10 years and use of ≥6 medications were variables that independently predicted having an XDDI to all four HCV treatment regimens. This is of important clinical significance because patients with HCV infection are often afflicted by a variety of age-related comorbidities and use of concomitant medications is common. It is also important because there are multiple clinicians involved in the care of patients with HCV infection. An awareness of the factors leading to XDDIs to all HCV regimens by both specialists and non-specialists can help facilitate patient care. We attempted to improve the granularity of the model by replacing use of 6 medications with individual medication classes. The medication classes that remained in the final model were anti-coagulants, anti-epileptic medications, anti-psychotic medications and ESAs. With the exception of anti-epileptic medications, these classes are not generally associated with XDDIs to the HCV regimens evaluated. However, their use appears to be more common among patients with an elevated probability of XDDIs to all four HCV regimens. Based on the results of this analysis, patients using these medication classes should be screened more aggressively for XDDIs when considering HCV treatment.Some limitations of the present study should be considered. First, the four HCV treatment regimens were added to the home medication profiles of patients with chronic HCV infection in a simulated fashion. The theoretical nature of the study allows for detection of XDDIs under different exposure scenarios while keeping all other covariates constant. If this investigation examined a population of individuals receiving each of these regimens, selective forces that led individuals to use one regimen over another would need to be controlled. Second, several drug interaction software programs exist. We chose to use University of Liverpool website since it is specifically mentioned as a resource in the HCV treatment guidelines <a class="elsevierStyleCrossRef" href="#bib0110">[1]</a>. It may not be intuitive to use this website for non-specialty clinicians screening for drug interactions since other commercially available programs exist. The use of a second interaction screening tool will almost always be necessary since the University of Liverpool website only detects interactions between drug–drug combinations where at least one agent is used to treat HCV infection <a class="elsevierStyleCrossRef" href="#bib0210">[21]</a>. It does not identify interactions that may exist between two non-HCV medications within a patient's home medication list. A formal comparison should be conducted between the University of Liverpool website and drug interaction software programs to ensure that sensitivity/specificity of detecting XDDIs is reasonable. Third, drug interaction programs are routinely updated and the severity of some drug interactions are downgraded from contraindicated to use with caution (e.g., ledipasvir and proton pump inhibitors when initially approved) <a class="elsevierStyleCrossRef" href="#bib0115">[2]</a>. The converse may occur where the severity of drug interactions is upgraded in response to emerging clinical data (e.g., sofosbuvir and amiodarone) <a class="elsevierStyleCrossRef" href="#bib0190">[17]</a>. Time since market entry could affect the prevalence of XDDIs detected, and future studies should attempt to control this factor. Fourth, the predictors of having XDDIs to all HCV treatment regimens may be surrogates for other factors which were not studied; future analyses should consider the role these other unmeasured factors might play. For instance, duration of HCV ≥10 years may be a proxy measure for age or advanced stage of disease and may reflect higher medication use. It could also indicate patients should be considered for treatment as early as possible to avoid issues related to managing XDDIs. Fifth, this study used the statistical tool CART to identify breakpoints in continuous variables associated with XDDIs to all four HCV regimens. It should be noted that CART identifies breakpoints that are specific to a population and the same breakpoint may not be observed in other populations with different distributions within continuous variables or frequency of outcome. Finally, this study was performed among predominantly male Veterans. A varied frequency of XDDIs may be expected in other populations with a different distribution of medication use. This is particularly important for females that may be using hormonal therapies, such as ethinyl estradiol, which is contraindicated with GLE/PIB.In summary, there were significant differences in the frequency of XDDIs between various HCV treatment regimens. Of the HCV regimens evaluated, XDDIs were significantly more frequent with GLE/PIB compared to other regimens. A very low percentage of patients had XDDIs to all four HCV regimens. This was driven primarily by a high volume of medication use and prolonged duration of chronic HCV infection. Clinicians prescribing HCV treatment should include drug interactions in the multiple considerations that are involved in selecting an HCV treatment regimen.AbbreviationsATCAnatomical Therapeutic ChemicalCARTclassification and regression treeCIconfidence intervalXDDIscontraindicated drug–drug interactionsESAserythropoietin stimulating agentsGLE/PIBglecaprevir/pibrentasvirGZR/EBRgrazoprevir/elbasvirHCVhepatitis CIQRinterquartile rangeLDV/SOFledipasvir/sofosbuvirORodds ratioSOF/VELsofosbuvir/velpatasvirSDstandard deviationFinancial supportThe work presented in this manuscript was partially funded by an investigator-initiated research grant from Gilead Sciences.Conflict of interestNP has received investigator-initiated research grant support from Gilead Sciences and Merck & Co. NP has received consultant honoraria from Gilead Sciences. None of the other authors have conflicts of interest to declare." "textoCompletoSecciones" => array:1 [ "secciones" => array:11 [ 0 => array:3 [ "identificador" => "xres1233316" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1145648" "titulo" => "Keywords" ] 2 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 3 => array:3 [ "identificador" => "sec0010" "titulo" => "Materials and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study design and population" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Data collection" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Outcome assessment" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Statistical analyses" ] ] ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Results" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Discussion" ] 6 => array:2 [ "identificador" => "sec0045" "titulo" => "Abbreviations" ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Financial support" ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Conflict of interest" ] 9 => array:2 [ "identificador" => "xack422292" "titulo" => "Acknowledgements" ] 10 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2018-07-12" "fechaAceptado" => "2018-11-30" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1145648" "palabras" => array:4 [ 0 => "Pharmacoepidemiology" 1 => "Medications" 2 => "Safety" 3 => "Antiviral" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "Introduction and ObjectivesFour regimens are recommended for treating hepatitis C (HCV) genotype 1 infection. Study aims were to (1) compare frequencies of contraindicated drug interactions (XDDIs) when each HCV regimen is added to medication profiles of HCV-monoinfected patients, (2) quantify the proportion of patients with XDDIs to all four regimens and (3) determine covariates independently associated with having a XDDI to all four regimens. Materials and methodsA cross-sectional study was performed within Upstate New York Veterans Healthcare Administration. Inclusion criteria: (1) age ≥18 years, (2) HCV monoinfection and (3) available medication list. Data extracted were: demographics, comorbidities, and medication list. Primary outcome was XDDIs involving patient's home medications and each HCV regimen. University of Liverpool drug interaction website was used to define XDDIs. Two-way comparisons of regimens were performed using McNemar's test where p<0.0083 was considered statistically significant. Multivariate regression analyses were performed to determine predictors. ResultsOf the 4047 subjects, mean±standard deviation age was 59.8±7.6. Median (interquartile range) number of medications used was 7 <a class="elsevierStyleCrossRefs" href="#bib0125">[4–11]</a>. Frequencies of XDDIs after the addition of each regimen ranged from 2.8% to 17.8% and were mostly statistically different from one another. There were 95 (2.3%) patients with XDDIs to all four regimens. Predictors of having XDDIs to all four regimens were ≥6 medications and HCV infection ≥10 years. ConclusionThe frequencies of XDDIs varied between HCV regimens. Number of medications and duration of HCV infection were predictors of having XDDIs to all four regimens." "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction and Objectives" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Materials and methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusion" ] ] ] ] "multimedia" => array:3 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1203 "Ancho" => 2083 "Tamanyo" => 107584 ] ] "descripcion" => array:1 [ "en" => "Frequency of contraindicated drug–drug interactions between various HCV treatment regimens, stratified by use of ≥6 medications. EBV/GZR – elbasvir/grazoprevir; GLE/PIB – glecaprevir/pibrentasvir; LDV/SOF – ledipasvir/sofosbuvir and SOF/VEL – sofosbuvir/velpatasvir." ] ] 1 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "All data presented as n (%) unless otherwise indicated.Legend: BPH – benign prostatic hyperplasia, COPD – chronic obstructive pulmonary disorder, CNS – central nervous system, HCV – hepatits C infection, IQR – interquartile range, SD – standard deviation." "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Covariate \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">XDDIs≤3 HCV regimens (n=3952) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">XDDIs to all 4 HCV regimens (n=95) \t\t\t\t\t\t\n \t\t\t\t\t\t</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">p-value \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Age, mean±SD \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">59.8±7.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58.4±8.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Sex, male \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3807 (96.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">93 (97.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.58 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">RaceAfrican AmericanHispanicCaucasianOther \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1131 (28.6)108 (2.7)2312 (58.5)401 (10.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">25 (26.3)1 (1.1)54 (56.8)15 (15.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.26 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Years with diagnosed HCV infection, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (8–14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 (10–15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.04 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HCV diagnosis ≥10 years \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2631 (66.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72 (75.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Number of comorbidities, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (5–10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (6–11) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.08 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Number of medications, median (IQR) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7 (4–10) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10 (6–15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Medications ≥6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2418 (61.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78 (82.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Analgesics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1863 (47.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54 (56.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.06 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-anginal medications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">186 (4.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">5 (5.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.80 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-anxiety medications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">783 (19.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 (35.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-arrhythmic medications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1948 (49.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">51 (53.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.40 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-coagulants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">151 (3.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9 (9.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.005 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-depressants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2674 (67.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">72 (75.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.09 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-emetics \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">166 (4.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (8.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.05 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-epileptic medications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">684 (17.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">90 (94.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-histamines \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">215 (56.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">48 (50.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.28 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-hypertensives \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3043 (77.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">79 (83.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-platelet medications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2493 (63.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54 (56.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.21 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Anti-psychotic medications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">670 (17.0) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 (38.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><0.001 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Asthma/COPD medications (inhaled) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">864 (21.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">30 (31.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.02 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">BPH medications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2123 (53.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58 (61.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">CNS stimulants \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1925 (48.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 (54.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.25 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Erectile dysfunction medications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2359 (59.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58 (61.1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.79 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Erythropoeitin stimulating agents \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">37 (0.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">4 (4.2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.002 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Gastroesophageal reflux disease medications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2824 (71.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">66 (69.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.67 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Insulin \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2128 (53.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">55 (57.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.43 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Lipid lowering medications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">960 (24.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (30.5) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.16 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Oral anti-diabetic medications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">505 (12.8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 (11.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.73 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Osteoporosis medications \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">1951 (49.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">52 (54.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">0.30 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2106811.png" ] ] ] ] "descripcion" => array:1 [ "en" => "Bivariate relationship between clinical/demographic covariates and presence of contraindicated drug–drug interactions to all four hepatitis C treatment regimens." ] ] 2 => array:8 [ "identificador" => "tbl0010" "etiqueta" => "Table 2" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at2" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:1 [ "tablatextoimagen" => array:1 [ 0 => array:1 [ "tablaImagen" => array:1 [ 0 => array:4 [ "imagenFichero" => "fx1.jpeg" "imagenAlto" => 3508 "imagenAncho" => 2281 "imagenTamanyo" => 414221 ] ] ] ] ] "descripcion" => array:1 [ "en" => "Predicted probabilities of contraindicated drug–drug interactions in presence of clinical/demographic covariates in multivariate models." ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:21 [ 0 => array:3 [ "identificador" => "bib0110" "etiqueta" => "[1]" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "American Association for the Study of Liver Diseases (AASLD) – Infectious Diseases Society of America (IDSA). Recommendations for testing, managing, and treating hepatitis C. <a target="_blank" href="http://www.hcvguidelines.org/">http://www.hcvguidelines.org</a> [accessed 22.12.18]." ] ] ] 1 => array:3 [ "identificador" => "bib0115" "etiqueta" => "[2]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Harvoni (ledipasvir/sofosbuvir) tablet package insert" ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2017" "editorial" => "Gilead Sciences" "editorialLocalizacion" => "Foster City, CA" ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0120" "etiqueta" => "[3]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Epclusa (velpatasvir/sofosbuvir) tablet package insert" ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2017" "editorial" => "Gilead Sciences" "editorialLocalizacion" => "Foster City, CA" ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0125" "etiqueta" => "[4]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Mavyret (glecaprevir/pibrentasvir) tablet package insert" ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2017" "editorial" => "AbbVie Inc" "editorialLocalizacion" => "North Chicago, IL" ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0130" "etiqueta" => "[5]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:1 [ "titulo" => "Zepatier (elbasvir/grazoprevir) tablet package insert" ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2017" "editorial" => "Merck & Co., Inc." "editorialLocalizacion" => "Whitehouse Station, NJ" ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0135" "etiqueta" => "[6]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1, 2, 4, 5, or 6 infection in adults with compensated cirrhosis (EXPEDITION-1): a single-arm, open-label, multicentre phase 3 trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "X. Forns" 1 => "S.S. Lee" 2 => "J. Valdes" 3 => "S. Lens" 4 => "R. Ghalib" 5 => "H. Aguilar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1473-3099(17)30496-6" "Revista" => array:4 [ "tituloSerie" => "Lancet Infect Dis" "fecha" => "2017" "paginaInicial" => "1062" "paginaFinal" => "1068" ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0140" "etiqueta" => "[7]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Afdhal" 1 => "K.R. Reddy" 2 => "D.R. Nelson" 3 => "E. Lawitz" 4 => "S.C. Gordon" 5 => "E. Schiff" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1316366" "Revista" => array:4 [ "tituloSerie" => "N Engl J Med" "fecha" => "2014" "paginaInicial" => "1483" "paginaFinal" => "1493" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0145" "etiqueta" => "[8]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Afdhal" 1 => "S. Zeuzem" 2 => "P. Kwo" 3 => "M. Chojkier" 4 => "N. Gitlin" 5 => "M. Puoti" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1402454" "Revista" => array:4 [ "tituloSerie" => "N Engl J Med" "fecha" => "2014" "paginaInicial" => "1889" "paginaFinal" => "1898" ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0150" "etiqueta" => "[9]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Sofosbuvir and Velpatasvir for HCV Genotype 1, 2, 4, 5, and 6 infection" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J.J. Feld" 1 => "I.M. Jacobson" 2 => "C. Hezode" 3 => "T. Asselah" 4 => "P.J. Ruane" 5 => "N. Gruener" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMoa1512610" "Revista" => array:5 [ "tituloSerie" => "N Engl J Med" "fecha" => "2015" "paginaInicial" => "2599" "paginaFinal" => "2607" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20018959" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0155" "etiqueta" => "[10]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Grazoprevir-Elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis c virus genotype 1, 4, or 6 infection: a randomized trial" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "S. Zeuzem" 1 => "R. Ghalib" 2 => "K.R. Reddy" 3 => "P.J. Pockros" 4 => "Z. Ben Ari" 5 => "Y. Zhao" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.7326/M15-0785" "Revista" => array:5 [ "tituloSerie" => "Ann Intern Med" "fecha" => "2015" "paginaInicial" => "1" "paginaFinal" => "13" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7985890" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0160" "etiqueta" => "[11]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Indications for testing among reported cases of HCV infection from enhanced hepatitis surveillance sites in the United States, 2004–2010" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "R. Mahajan" 1 => "S.J. Liu" 2 => "R.M. Klevens" 3 => "S.D. Holmberg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.2105/AJPH. 2013.301211" "Revista" => array:4 [ "tituloSerie" => "Am J Public Health" "fecha" => "2013" "paginaInicial" => "1445" "paginaFinal" => "1449" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0165" "etiqueta" => "[12]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "What is polypharmacy?. A systematic review of definitions" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:4 [ 0 => "N. Masnoon" 1 => "S. Shakib" 2 => "L. Kalisch-Ellett" 3 => "G.E. Caughey" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1186/s12877-017-0621-2" "Revista" => array:3 [ "tituloSerie" => "BMC Geriatr" "fecha" => "2017" "volumen" => "230" ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0170" "etiqueta" => "[13]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Polypharmacy: misleading, but manageable" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:5 [ 0 => "R.L. Bushardt" 1 => "E.B. Massey" 2 => "T.W. Simpson" 3 => "J.C. Ariail" 4 => "K.N. Simpson" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:4 [ "tituloSerie" => "Clin Interv Aging" "fecha" => "2008" "paginaInicial" => "383" "paginaFinal" => "389" ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0175" "etiqueta" => "[14]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Medication use and medical comorbidity in patients with chronic hepatitis C from a US commercial claims database: high utilization of drugs with interaction potential" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:6 [ 0 => "J.C. Lauffenburger" 1 => "C.L. Mayer" 2 => "R.L. Hawke" 3 => "K.L. Brouwer" 4 => "M.W. Fried" 5 => "J.F. Farley" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/MEG. 0000000000000152" "Revista" => array:5 [ "tituloSerie" => "Eur J Gastroenterol Hepatol" "fecha" => "2014" "paginaInicial" => "1073" "paginaFinal" => "1082" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8680907" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0180" "etiqueta" => "[15]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The impact of polypharmacy on patient outcomes in older adults with cancer" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "G. Nightingale" 1 => "E. Skonecki" 2 => "M.K. Boparai" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1097/PPO. 0000000000000277" "Revista" => array:4 [ "tituloSerie" => "Cancer J" "fecha" => "2017" "paginaInicial" => "211" "paginaFinal" => "218" ] ] ] ] ] ] 15 => array:3 [ "identificador" => "bib0185" "etiqueta" => "[16]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Clinical consequences of polypharmacy in elderly" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "R.L. Maher" 1 => "J. Hanlon" 2 => "E.R. Hajjar" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1517/14740338.2013.827660" "Revista" => array:4 [ "tituloSerie" => "Expert Opin Drug Saf" "fecha" => "2014" "paginaInicial" => "57" "paginaFinal" => "65" ] ] ] ] ] ] 16 => array:3 [ "identificador" => "bib0190" "etiqueta" => "[17]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Bradyarrhythmias associated with sofosbuvir treatment" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "D.M. Brainard" 1 => "J.G. McHutchison" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1056/NEJMc1505967" "Revista" => array:3 [ "tituloSerie" => "N Engl J Med" "fecha" => "2015" "paginaInicial" => "1888" ] ] ] ] ] ] 17 => array:3 [ "identificador" => "bib0195" "etiqueta" => "[18]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "How many potential drug–drug interactions cause adverse drug reactions in hospitalized patients?" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "C. Bucsa" 1 => "A. Farcas" 2 => "I. Cazacu" 3 => "D. Leucuta" 4 => "A. Achimas-Cadariu" 5 => "C. Mogosan" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.ejim.2012.09.011" "Revista" => array:4 [ "tituloSerie" => "Eur J Intern Med" "fecha" => "2013" "paginaInicial" => "27" "paginaFinal" => "33" ] ] ] ] ] ] 18 => array:3 [ "identificador" => "bib0200" "etiqueta" => "[19]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "A cross-sectional study comparing the frequency of drug interactions after adding simeprevir- or sofosbuvir-containing therapy to medication profiles of hepatitis C monoinfected patients" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "N. Patel" 1 => "M. Nasiri" 2 => "A. Koroglu" 3 => "S. Bliss" 4 => "M. Davis" 5 => "L.A. McNutt" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1007/s40121-015-0058-x" "Revista" => array:4 [ "tituloSerie" => "Infect Dis Ther" "fecha" => "2015" "paginaInicial" => "67" "paginaFinal" => "78" ] ] ] ] ] ] 19 => array:3 [ "identificador" => "bib0205" "etiqueta" => "[20]" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Anatomical therapeutic chemical classification system/defined daily dose index" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "World Health Organization. WHO Collaborating Centre for Drug Statistics Methodology" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2017" ] ] ] ] ] ] 20 => array:3 [ "identificador" => "bib0210" "etiqueta" => "[21]" "referencia" => array:1 [ 0 => array:1 [ "referenciaCompleta" => "Liverpool Drug Interactions Group. University of Liverpool. HEP drug interaction checker. <a target="_blank" href="http://hep-druginteractions.org/">http://hep-druginteractions.org</a> [accessed 22.12.18]." ] ] ] ] ] ] ] "agradecimientos" => array:1 [ 0 => array:4 [ "identificador" => "xack422292" "titulo" => "Acknowledgements" "texto" => "This material is based upon work partially supported by the Office of Research and Development, Department of Veterans Affairs. The contents of this report do not represent the views of the Department of Veterans Affairs or the United States Government." "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/16652681/0000001800000004/v3_201908230828/S1665268119300572/v3_201908230828/en/main.assets" "Apartado" => array:4 [ "identificador" => "78265" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/16652681/0000001800000004/v3_201908230828/S1665268119300572/v3_201908230828/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119300572?idApp=UINPBA00004N"]

Statistics

Original article

Alisha Ahmeda, Christopher Schrieverb, Nicholas Brittc, Jenna Yagera, Ronish Amina, Liam McGueya, Nimish Pateld,e,

Corresponding author

patel.nimish@gmail.com

Corresponding author at: Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA

a Department of Pharmacy Practice, Albany College of Pharmacy & Health Sciences, Albany, NY, USA

b Department of Pharmacy Practice, University of Illinois College of Pharmacy at Chicago, Rockford Campus, Rockford, IL, USA

c University of Kansas, School of Pharmacy, Kansas City, KS, USA

d Department of Pharmacy, Samuel S. Stratton Veterans Affairs Medical Center, Albany, NY, USA

e Skaggs School of Pharmacy & Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA, USA

Read

1989

Times
was read the article

511

Total PDF

1478

Total HTML

Share statistics

 array:24 [
  "pii" => "S1665268119300572"
  "issn" => "16652681"
  "doi" => "10.1016/j.aohep.2019.01.005"
  "estado" => "S300"
  "fechaPublicacion" => "2019-07-01"
  "aid" => "49"
  "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
  "copyrightAnyo" => "2019"
  "documento" => "article"
  "crossmark" => 1
  "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
  "subdocumento" => "fla"
  "cita" => "Ann Hepatol. 2019;18:601-6"
  "abierto" => array:3 [
    "ES" => true
    "ES2" => true
    "LATM" => true
  ]
  "gratuito" => true
  "lecturas" => array:2 [
    "total" => 262
    "formatos" => array:3 [
      "EPUB" => 18
      "HTML" => 136
      "PDF" => 108
    ]
  ]
  "itemSiguiente" => array:19 [
    "pii" => "S1665268119300584"
    "issn" => "16652681"
    "doi" => "10.1016/j.aohep.2019.01.006"
    "estado" => "S300"
    "fechaPublicacion" => "2019-07-01"
    "aid" => "50"
    "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Ann Hepatol. 2019;18:607-12"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 442
      "formatos" => array:3 [
        "EPUB" => 23
        "HTML" => 275
        "PDF" => 144
      ]
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Prognostic value of hepatic encephalopathy for survival of patients with liver failure&#58; A systematic review and meta-analysis"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "607"
          "paginaFinal" => "612"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0005"
          "etiqueta" => "Fig&#46; 1"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr1.jpeg"
              "Alto" => 1695
              "Ancho" => 2083
              "Tamanyo" => 168242
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Literature search and study selection&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Hanqing Yu, Yu Chen, Ping Jiang"
          "autores" => array:3 [
            0 => array:2 [
              "nombre" => "Hanqing"
              "apellidos" => "Yu"
            ]
            1 => array:2 [
              "nombre" => "Yu"
              "apellidos" => "Chen"
            ]
            2 => array:2 [
              "nombre" => "Ping"
              "apellidos" => "Jiang"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119300584?idApp=UINPBA00004N"
    "url" => "/16652681/0000001800000004/v3_201908230828/S1665268119300584/v3_201908230828/en/main.assets"
  ]
  "itemAnterior" => array:19 [
    "pii" => "S1665268119300663"
    "issn" => "16652681"
    "doi" => "10.1016/j.aohep.2019.01.010"
    "estado" => "S300"
    "fechaPublicacion" => "2019-07-01"
    "aid" => "58"
    "copyright" => "Fundaci&#243;n Cl&#237;nica M&#233;dica Sur&#44; A&#46;C&#46;"
    "documento" => "article"
    "crossmark" => 1
    "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/"
    "subdocumento" => "fla"
    "cita" => "Ann Hepatol. 2019;18:595-600"
    "abierto" => array:3 [
      "ES" => true
      "ES2" => true
      "LATM" => true
    ]
    "gratuito" => true
    "lecturas" => array:2 [
      "total" => 844
      "formatos" => array:3 [
        "EPUB" => 36
        "HTML" => 331
        "PDF" => 477
      ]
    ]
    "en" => array:12 [
      "idiomaDefecto" => true
      "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
      "titulo" => "Endoscopic retrograde cholangiopancreatography versus surgery for choledocholithiasis &#8211; A meta-analysis"
      "tienePdf" => "en"
      "tieneTextoCompleto" => "en"
      "tieneResumen" => "en"
      "paginas" => array:1 [
        0 => array:2 [
          "paginaInicial" => "595"
          "paginaFinal" => "600"
        ]
      ]
      "contieneResumen" => array:1 [
        "en" => true
      ]
      "contieneTextoCompleto" => array:1 [
        "en" => true
      ]
      "contienePdf" => array:1 [
        "en" => true
      ]
      "resumenGrafico" => array:2 [
        "original" => 0
        "multimedia" => array:7 [
          "identificador" => "fig0010"
          "etiqueta" => "Fig&#46; 2"
          "tipo" => "MULTIMEDIAFIGURA"
          "mostrarFloat" => true
          "mostrarDisplay" => false
          "figura" => array:1 [
            0 => array:4 [
              "imagen" => "gr2.jpeg"
              "Alto" => 3953
              "Ancho" => 1439
              "Tamanyo" => 418420
            ]
          ]
          "descripcion" => array:1 [
            "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Risk of bias summary&#46; Captions&#58; &#8220;&#43;&#8221; &#8211; low risk of bias&#59; &#8220;&#8722;&#8221; &#8211; high risk of bias&#59; blank &#8211; unclear risk of bias&#46;</p>"
          ]
        ]
      ]
      "autores" => array:1 [
        0 => array:2 [
          "autoresLista" => "Fernando C&#46; Schacher, Sofia M&#46; Giongo, Fernanda J&#46;P&#46; Teixeira, &#194;ngelo Z&#46; Mattos"
          "autores" => array:4 [
            0 => array:2 [
              "nombre" => "Fernando C&#46;"
              "apellidos" => "Schacher"
            ]
            1 => array:2 [
              "nombre" => "Sofia M&#46;"
              "apellidos" => "Giongo"
            ]
            2 => array:2 [
              "nombre" => "Fernanda J&#46;P&#46;"
              "apellidos" => "Teixeira"
            ]
            3 => array:2 [
              "nombre" => "&#194;ngelo Z&#46;"
              "apellidos" => "Mattos"
            ]
          ]
        ]
      ]
    ]
    "idiomaDefecto" => "en"
    "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119300663?idApp=UINPBA00004N"
    "url" => "/16652681/0000001800000004/v3_201908230828/S1665268119300663/v3_201908230828/en/main.assets"
  ]
  "en" => array:19 [
    "idiomaDefecto" => true
    "cabecera" => "<span class="elsevierStyleTextfn">Original article</span>"
    "titulo" => "Comparing drug interaction frequencies of various hepatitis C treatment regimens among monoinfected patients"
    "tieneTextoCompleto" => true
    "paginas" => array:1 [
      0 => array:2 [
        "paginaInicial" => "601"
        "paginaFinal" => "606"
      ]
    ]
    "autores" => array:1 [
      0 => array:4 [
        "autoresLista" => "Alisha Ahmed, Christopher Schriever, Nicholas Britt, Jenna Yager, Ronish Amin, Liam McGuey, Nimish Patel"
        "autores" => array:7 [
          0 => array:3 [
            "nombre" => "Alisha"
            "apellidos" => "Ahmed"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          1 => array:3 [
            "nombre" => "Christopher"
            "apellidos" => "Schriever"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">b</span>"
                "identificador" => "aff0010"
              ]
            ]
          ]
          2 => array:3 [
            "nombre" => "Nicholas"
            "apellidos" => "Britt"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">c</span>"
                "identificador" => "aff0015"
              ]
            ]
          ]
          3 => array:3 [
            "nombre" => "Jenna"
            "apellidos" => "Yager"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          4 => array:3 [
            "nombre" => "Ronish"
            "apellidos" => "Amin"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          5 => array:3 [
            "nombre" => "Liam"
            "apellidos" => "McGuey"
            "referencia" => array:1 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">a</span>"
                "identificador" => "aff0005"
              ]
            ]
          ]
          6 => array:4 [
            "nombre" => "Nimish"
            "apellidos" => "Patel"
            "email" => array:1 [
              0 => "patel.nimish@gmail.com"
            ]
            "referencia" => array:3 [
              0 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">d</span>"
                "identificador" => "aff0020"
              ]
              1 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">e</span>"
                "identificador" => "aff0025"
              ]
              2 => array:2 [
                "etiqueta" => "<span class="elsevierStyleSup">&#42;</span>"
                "identificador" => "cor0005"
              ]
            ]
          ]
        ]
        "afiliaciones" => array:5 [
          0 => array:3 [
            "entidad" => "Department of Pharmacy Practice&#44; Albany College of Pharmacy &#38; Health Sciences&#44; Albany&#44; NY&#44; USA"
            "etiqueta" => "a"
            "identificador" => "aff0005"
          ]
          1 => array:3 [
            "entidad" => "Department of Pharmacy Practice&#44; University of Illinois College of Pharmacy at Chicago&#44; Rockford Campus&#44; Rockford&#44; IL&#44; USA"
            "etiqueta" => "b"
            "identificador" => "aff0010"
          ]
          2 => array:3 [
            "entidad" => "University of Kansas&#44; School of Pharmacy&#44; Kansas City&#44; KS&#44; USA"
            "etiqueta" => "c"
            "identificador" => "aff0015"
          ]
          3 => array:3 [
            "entidad" => "Department of Pharmacy&#44; Samuel S&#46; Stratton Veterans Affairs Medical Center&#44; Albany&#44; NY&#44; USA"
            "etiqueta" => "d"
            "identificador" => "aff0020"
          ]
          4 => array:3 [
            "entidad" => "Skaggs School of Pharmacy &#38; Pharmaceutical Sciences&#44; University of California&#44; San Diego&#44; La Jolla&#44; CA&#44; USA"
            "etiqueta" => "e"
            "identificador" => "aff0025"
          ]
        ]
        "correspondencia" => array:1 [
          0 => array:3 [
            "identificador" => "cor0005"
            "etiqueta" => "&#8270;"
            "correspondencia" => "Corresponding author at&#58; Skaggs School of Pharmacy &#38; Pharmaceutical Sciences&#44; University of California&#44; San Diego&#44; La Jolla&#44; CA&#44; USA"
          ]
        ]
      ]
    ]
    "resumenGrafico" => array:2 [
      "original" => 0
      "multimedia" => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1203
            "Ancho" => 2083
            "Tamanyo" => 107584
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Frequency of contraindicated drug&#8211;drug interactions between various HCV treatment regimens&#44; stratified by use of &#8805;6 medications&#46; EBV&#47;GZR &#8211; elbasvir&#47;grazoprevir&#59; GLE&#47;PIB &#8211; glecaprevir&#47;pibrentasvir&#59; LDV&#47;SOF &#8211; ledipasvir&#47;sofosbuvir and SOF&#47;VEL &#8211; sofosbuvir&#47;velpatasvir&#46;</p>"
        ]
      ]
    ]
    "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">1</span><span class="elsevierStyleSectionTitle" id="sect0035">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Currently&#44; there are several therapeutic options available to treat chronic genotype 1 hepatitis C virus &#40;HCV&#41; infection&#46; These include glecaprevir&#47;pibrentasvir &#40;GLE&#47;PIB&#41;&#44; grazoprevir&#47;elbasvir &#40;GZR&#47;EBR&#41;&#44; ledipasvir&#47;sofosbuvir &#40;LDV&#47;SOF&#41; and sofosbuvir&#47;velpatasvir &#40;SOF&#47;VEL&#41; <a class="elsevierStyleCrossRefs" href="#bib0110">&#91;1&#8211;5&#93;</a>&#46; Each has demonstrated impressive rates of sustained virologic response in treatment recipients with low toxicity <a class="elsevierStyleCrossRefs" href="#bib0135">&#91;6&#8211;10&#93;</a>&#46; While the safety and efficacy appear to be similar&#44; some characteristics distinguishing these four regimens are not entirely clear&#44; potentially complicating treatment selection by clinicians&#46; One potential difference is the occurrence of contraindicated drug&#8211;drug interactions &#40;XDDIs&#41; with patients&#8217; medications used to treat other medical conditions&#46; In general&#44; patients with chronic HCV infection are generally advanced in age and may have developed certain comorbidities necessitating medication therapy <a class="elsevierStyleCrossRef" href="#bib0160">&#91;11&#93;</a>&#46; As a result&#44; use of multiple medications simultaneously&#44; otherwise known as polypharmacy&#44; may create a therapeutic dilemma <a class="elsevierStyleCrossRefs" href="#bib0165">&#91;12&#44;13&#93;</a>&#46; Polypharmacy significantly elevates the risk of experiencing XDDIs and may impact clinical outcomes <a class="elsevierStyleCrossRefs" href="#bib0175">&#91;14&#8211;16&#93;</a>&#46;</p><p id="par0010" class="elsevierStylePara elsevierViewall">Limited comparative data exist evaluating the potential risk of XDDIs between GLE&#47;PIB&#44; GZR&#47;EBR&#44; LDV&#47;SOF and SOV&#47;VEL&#46; It is unclear which regimen is safest to administer to HCV-monoinfected patients who have a high probability of XDDIs due to age-related polypharmacy <a class="elsevierStyleCrossRef" href="#bib0175">&#91;14&#93;</a>&#46; These issues also have important cost implications&#46; The presence of XDDIs can potentially lead to dangerous health effects <a class="elsevierStyleCrossRefs" href="#bib0180">&#91;15&#8211;17&#93;</a>&#46; In extreme scenarios&#44; mitigation of XDDIs may require utilization of costly additional healthcare resources <a class="elsevierStyleCrossRef" href="#bib0195">&#91;18&#93;</a>&#46; Third party payors can attempt to minimize patient harm and contain the potentially unnecessary expenditures by limiting formularies to anti-HCV medications with a low probability of XDDIs&#46;</p><p id="par0015" class="elsevierStylePara elsevierViewall">Additionally&#44; the proportion of patients who have XDDI to all HCV treatment regimens has not been defined&#46; Understanding which patients have XDDIs to all anti-HCV regimens is crucial so appropriate modifications can be made to concomitant medications to facilitate prompt HCV treatment and prevent the consequences of untreated HCV infection <a class="elsevierStyleCrossRef" href="#bib0110">&#91;1&#93;</a>&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">The objectives of this study were to&#58; &#40;1&#41; compare prevalence of contraindicated drug interactions &#40;XDDIs&#41; between GLE&#47;PIB&#44; GZR&#47;EBR&#44; LDV&#47;SOF and SOF&#47;VEL when added to the home medication profiles of patients with HCV monoinfection&#59; &#40;2&#41; quantify the proportion of patients with XDDIs to all four HCV treatment regimens&#59; and &#40;3&#41; determine clinical&#47;demographic risk factors of having XDDIs to all four regimens&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2</span><span class="elsevierStyleSectionTitle" id="sect0040">Materials and methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">The Institutional Review Board at the Stratton Veterans&#8217; Affairs Medical Center approved this study with a waiver of informed consent&#46;</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;1</span><span class="elsevierStyleSectionTitle" id="sect0045">Study design and population</span><p id="par0030" class="elsevierStylePara elsevierViewall">We performed a cross-sectional study among HCV monoinfected Veterans receiving care in Upstate New York Veterans&#8217; Healthcare Administration between January 1&#44; 2000 and December 31&#44; 2013&#46;</p><p id="par0035" class="elsevierStylePara elsevierViewall">Inclusion criteria were&#58; &#40;1&#41; age &#8805;18 years&#59; &#40;2&#41; HCV infection &#40;International Classification of Diseases 9th Revision codes 070&#46;41&#44; 070&#46;44&#44; 070&#46;51&#44; 070&#46;54&#44; 070&#46;70&#44; and 070&#46;71&#41;&#44; confirmed by laboratory tests for either HCV RNA or anti-HCV&#59; and &#40;3&#41; availability of medication list&#46; The focus of this study was HCV monoinfection and therefore patients with hepatitis B or HIV coinfection were excluded&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;2</span><span class="elsevierStyleSectionTitle" id="sect0050">Data collection</span><p id="par0040" class="elsevierStylePara elsevierViewall">Data were obtained from computerized medical records&#46; Information abstracted from patients&#8217; medical records included demographics&#44; comorbidities&#44; and most recent medication lists&#46; The full list of covariates extracted from patients&#8217; medical records is described elsewhere <a class="elsevierStyleCrossRef" href="#bib0200">&#91;19&#93;</a>&#46; Home medications were initially categorized according to the World Health Organization Anatomical Therapeutic Chemical &#40;ATC&#41; classification system <a class="elsevierStyleCrossRef" href="#bib0205">&#91;20&#93;</a>&#46; The ATC-categorized medications were subsequently collapsed into therapeutic classes based on distribution of medication use&#46;</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;3</span><span class="elsevierStyleSectionTitle" id="sect0055">Outcome assessment</span><p id="par0045" class="elsevierStylePara elsevierViewall">The primary outcome was the occurrence of contraindicated drug&#8211;drug interactions &#40;XDDIs&#41; with the patient&#39;s home medication profile after the addition of each of the four HCV regimens evaluated&#58; GLE&#47;PIB&#44; GZR&#47;EBR&#44; LDV&#47;SOF&#44; and SOF&#47;VEL&#46; The HCV treatment guidelines specifically list the University of Liverpool drug interaction website as a resource to evaluate drug&#8211;drug interactions <a class="elsevierStyleCrossRefs" href="#bib0110">&#91;1&#44;21&#93;</a>&#46; In the present study&#44; this website was used to classify the type of drug&#8211;drug interaction &#40;do not coadminister&#44; potential interaction&#44; no interaction expected&#44; no clear data&#41;&#46; Drug&#8211;drug interactions classified as &#8220;do not coadminister&#8221; were the only ones recorded and deemed contraindicated&#46; The University of Liverpool drug interaction website only assesses drug&#8211;drug interactions where at least one of the medications used in the drug&#8211;drug combination is used to treat HCV infection <a class="elsevierStyleCrossRef" href="#bib0210">&#91;21&#93;</a>&#44; and this study was limited to such interactions&#46; Various XDDIs between non-HCV medications assessed by other drug interaction programs are described elsewhere <a class="elsevierStyleCrossRef" href="#bib0165">&#91;12&#93;</a>&#46;</p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">2&#46;4</span><span class="elsevierStyleSectionTitle" id="sect0060">Statistical analyses</span><p id="par0050" class="elsevierStylePara elsevierViewall">Two-way comparisons were performed using McNemar&#39;s test to assess the frequencies of XDDIs between each of the HCV regimens&#46; Because of the multiple comparisons being made between each of the HCV regimen&#39;s prevalence of XDDIs in the bivariate analyses&#44; a <span class="elsevierStyleItalic">p</span>-value of 0&#46;0083&#44; adjusted for multiple comparisons&#44; was used to denote statistical significance &#40;Kappa&#44; <span class="elsevierStyleItalic">&#954;</span>&#44; &#61;6 possible combinations of comparisons between anti-HCV regimens divided by <span class="elsevierStyleItalic">&#945;</span> of 0&#46;05&#41;&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">To determine the predictors of having XDDIs to all four HCV treatment regimens&#44; bivariate analyses were performed comparing presence of XDDIs to all regimens with clinical&#47;demographic characteristics&#46; Continuous variables were compared using student&#39;s <span class="elsevierStyleItalic">t</span> or Mann&#8211;Whitney <span class="elsevierStyleItalic">U</span> tests and categorical variables were compared using chi-square or Fisher&#39;s exact tests&#46; Classification and regression tree &#40;CART&#41; analyses were performed to identify thresholds in continuous predictor variables associated with a significantly increased likelihood of having an XDDI to all four HCV treatment regimens when dichotomized around the threshold &#40;i&#46;e&#46; CART identifies 6 as number of medications associated with XDDIs to all four regimens&#59; patients are dichotomized into two groups &#8211; those using &#8805;6 or &#60;6 medications&#59; the percentage of patients with XDDIs to all four regimens differs significantly between those using &#8805;6 and &#60;6 medications&#41;&#46; Variables in the bivariate analyses with an associated <span class="elsevierStyleItalic">p</span>-value &#60;0&#46;25 were eligible for model entry into the multivariable logistic regression analyses&#46; Using a backward&#44; stepwise approach&#44; the most parsimonious model contained variables that were significantly associated with XDDIs to all regimens&#46; The only confounders retained in the model were those that changed the measure of association for the final predictor variables by more than 10&#37;&#46; The exponentiated beta coefficients from the final multivariable model were used to compute the predicted probabilities of having XDDIs to all four HCV treatment regimens when certain covariates were present or absent&#46;</p></span></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">3</span><span class="elsevierStyleSectionTitle" id="sect0065">Results</span><p id="par0060" class="elsevierStylePara elsevierViewall">Of the 4047 patients evaluated&#44; the majority were male &#40;96&#46;4&#37;&#41;&#46; Mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation &#40;SD&#41; age was 59&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;6 years&#46; Patients were using a median &#40;interquartile range&#44; IQR&#41; of 7 &#40;4&#8211;10&#41; medications&#46; The most commonly used medication classes were antihypertensives &#40;77&#46;1&#37;&#41;&#44; vitamins&#47;supplements &#40;70&#46;1&#37;&#41;&#44; antidepressants &#40;67&#46;9&#37;&#41;&#44; and antiplatelet medications &#40;62&#46;9&#37;&#41;&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">After adding each HCV regimen to the patients&#8217; home medication profiles&#44; there were 814 &#40;20&#46;1&#37;&#41; patients with XDDIs to at least one HCV regimen&#46; The frequencies of XDDIs after the addition of each HCV regimen are in displayed <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46; The prevalence of XDDIs was highest for GLE&#47;PIB &#40;17&#46;8&#37;&#41;&#44; followed by LDV&#47;SOF &#40;4&#46;4&#37;&#41;&#44; SOF&#47;VEL &#40;2&#46;8&#37;&#41;&#44; and EBV&#47;GZR &#40;2&#46;8&#37;&#41;&#46; There were significant &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0083&#41; differences in two-way comparisons of the frequency of XDDIs between most pairings of HCV treatment regimens&#46; The only exception to this was the comparison between SOF&#47;VEL and EBV&#47;GZR &#40;<span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;85&#41;&#46;</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">There were 95 &#40;2&#46;3&#37;&#41; patients with XDDIs to all four HCV regimens&#46; Bivariate analyses comparing clinical&#47;demographic characteristics between patients with and without XDDIs to all four HCV regimens is displayed in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>&#46; Variables significantly associated with XDDIs to all four HCV regimens were number of medications&#44; use of anti-anxiety medications&#44; anti-coagulants&#44; anti-emetics&#44; anti-epileptic medications&#44; anti-psychotics&#44; asthma&#47;chronic obstructive pulmonary disorder medications&#44; erythropoietin stimulating agents &#40;ESAs&#41; and years with HCV diagnosis&#46; A CART-derived breakpoint was identified for number of concomitant medications associated with an increased risk of having an XDDI to all four regimens&#46; This breakpoint was 6 medications&#46; Patients using &#8805;6 concomitant medications had a significantly higher prevalence of XDDIs to all four regimens than patients below this threshold &#40;3&#46;1&#37; versus 1&#46;1&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#46; The prevalence of XDDIs after the addition of each HCV regimen to the patients&#8217; home medication profiles&#44; stratified by use of &#60;6 or &#8805;6 medications&#44; is displayed in <a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#46; The other CART-derived breakpoint identified was the number of years with chronic HCV infection&#46; The prevalence of XDDIs was significantly higher for patients with an HCV diagnosis of at least 10 years compared to those with a more recent diagnosis &#60;10 years prior &#40;2&#46;7&#37; versus 1&#46;7&#37;&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;05&#41;&#46;</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0075" class="elsevierStylePara elsevierViewall">In multivariable analyses&#44; variables independently associated with XDDIs involving all four HCV treatment regimens were use of &#8805;6 medications &#40;odds ratio&#44; OR&#58; 2&#46;85&#44; 95&#37; confidence interval&#44; CI&#58; 1&#46;68&#8211;4&#46;84&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41; and having an HCV diagnosis &#8805;10 years &#40;OR&#58; 1&#46;49&#44; 95&#37; CI&#58; 0&#46;93&#8211;2&#46;40&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;10&#41;&#46; The results of the multivariable analyses were used to determine the predicted probabilities of experiencing an XDDI to all four HCV treatment regimens given certain covariate patterns&#46; The predicted probabilities of XDDIs to all four HCV treatment regimens is displayed in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#46; The reference probability was 0&#46;8&#37; when neither covariate was present &#40;covariate pattern 1&#46;01&#41;&#44; and rose to 3&#46;5&#37; when both covariates were present &#40;covariate pattern 1&#46;04&#41;&#46;</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0080" class="elsevierStylePara elsevierViewall">A second multivariable model was assessed where use of &#8805;6 medications was replaced with individual medication classes&#46; In the second model&#44; variables independently associated with XDDIs to all four HCV treatment regimens were&#58; anti-coagulants &#40;OR&#58; 2&#46;98&#44; 95&#37; CI&#58; 1&#46;35&#8211;6&#46;54&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;007&#41;&#44; anti-epileptic medications &#40;OR&#58; 80&#46;26&#44; 95&#37; CI&#58; 32&#46;37&#8211;199&#46;02&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;001&#41;&#44; anti-psychotic medications &#40;OR&#58; 1&#46;95&#44; 95&#37; CI&#58; 1&#46;24&#8211;3&#46;06&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;004&#41;&#44; ESAs &#40;OR&#58; 4&#46;39&#44; 95&#37; CI&#58; 1&#46;26&#8211;15&#46;36&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;02&#41; and HCV infection &#8805;10 years &#40;OR&#58; 1&#46;37&#44; 95&#37; CI&#58; 0&#46;83&#8211;2&#46;268&#44; <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>0&#46;22&#41;&#46; The predicted probability of having an XDDI to all four HCV regimens when none of the covariates were present was 0&#46;001&#37; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#44; covariate pattern 2&#46;01&#41;&#46; Conversely&#44; the predicted probability of having an XDDI to all four HCV regimens when all of the covariates were present was 72&#46;7&#37; &#40;<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>&#44; covariate pattern 2&#46;22&#41;&#46;</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleLabel">4</span><span class="elsevierStyleSectionTitle" id="sect0070">Discussion</span><p id="par0085" class="elsevierStylePara elsevierViewall">Several treatment options are available for patients with HCV infection <a class="elsevierStyleCrossRefs" href="#bib0110">&#91;1&#8211;5&#93;</a>&#46; One potential distinguishing feature is the potential for XDDIs&#46; Our study demonstrated differences in the frequency of XDDIs between the various HCV regimens &#40;<a class="elsevierStyleCrossRef" href="#fig0005">Fig&#46; 1</a>&#41;&#46; The prevalence of XDDIs was highest for GLE&#47;PIB &#40;17&#46;8&#37;&#41; followed distantly by LDV&#47;SOF &#40;4&#46;4&#37;&#41; and the remaining two regimens &#40;2&#46;8&#37;&#41;&#46; The high frequency of XDDIs involving GLE&#47;PIB was driven by statins and was not surprising given the ubiquity of statin use in the Veterans Affairs population&#46; While most of the two-way comparisons between HCV treatment regimens were statistically significant&#44; it is important to note that the absolute differences for some comparisons were as little as 1&#46;6&#37; &#40;comparison of LDV&#47;SOF versus SOF&#47;VEL&#41; and the number needed to avert one XDDI would be &#62;60 patients&#46; Conversely&#44; there were comparisons with absolute differences as large as 15&#37; &#40;GLE&#47;PIB versus SOF&#47;VEL&#41; and the number needed to avert one XDDI would be &#60;7 patients&#46;</p><p id="par0090" class="elsevierStylePara elsevierViewall">Another unique feature of our study was an examination of risk factors for having a XDDI to all four HCV treatment regimens&#46; Understanding these risk factors is important because these patients would be ineligible for HCV treatment without modifying concomitant medication&#40;s&#41; used to treat comorbidities&#46; Duration of HCV infection &#8805;10 years and use of &#8805;6 medications were variables that independently predicted having an XDDI to all four HCV treatment regimens&#46; This is of important clinical significance because patients with HCV infection are often afflicted by a variety of age-related comorbidities and use of concomitant medications is common&#46; It is also important because there are multiple clinicians involved in the care of patients with HCV infection&#46; An awareness of the factors leading to XDDIs to all HCV regimens by both specialists and non-specialists can help facilitate patient care&#46; We attempted to improve the granularity of the model by replacing use of 6 medications with individual medication classes&#46; The medication classes that remained in the final model were anti-coagulants&#44; anti-epileptic medications&#44; anti-psychotic medications and ESAs&#46; With the exception of anti-epileptic medications&#44; these classes are not generally associated with XDDIs to the HCV regimens evaluated&#46; However&#44; their use appears to be more common among patients with an elevated probability of XDDIs to all four HCV regimens&#46; Based on the results of this analysis&#44; patients using these medication classes should be screened more aggressively for XDDIs when considering HCV treatment&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">Some limitations of the present study should be considered&#46; First&#44; the four HCV treatment regimens were added to the home medication profiles of patients with chronic HCV infection in a simulated fashion&#46; The theoretical nature of the study allows for detection of XDDIs under different exposure scenarios while keeping all other covariates constant&#46; If this investigation examined a population of individuals receiving each of these regimens&#44; selective forces that led individuals to use one regimen over another would need to be controlled&#46; Second&#44; several drug interaction software programs exist&#46; We chose to use University of Liverpool website since it is specifically mentioned as a resource in the HCV treatment guidelines <a class="elsevierStyleCrossRef" href="#bib0110">&#91;1&#93;</a>&#46; It may not be intuitive to use this website for non-specialty clinicians screening for drug interactions since other commercially available programs exist&#46; The use of a second interaction screening tool will almost always be necessary since the University of Liverpool website only detects interactions between drug&#8211;drug combinations where at least one agent is used to treat HCV infection <a class="elsevierStyleCrossRef" href="#bib0210">&#91;21&#93;</a>&#46; It does not identify interactions that may exist between two non-HCV medications within a patient&#39;s home medication list&#46; A formal comparison should be conducted between the University of Liverpool website and drug interaction software programs to ensure that sensitivity&#47;specificity of detecting XDDIs is reasonable&#46; Third&#44; drug interaction programs are routinely updated and the severity of some drug interactions are downgraded from contraindicated to use with caution &#40;e&#46;g&#46;&#44; ledipasvir and proton pump inhibitors when initially approved&#41; <a class="elsevierStyleCrossRef" href="#bib0115">&#91;2&#93;</a>&#46; The converse may occur where the severity of drug interactions is upgraded in response to emerging clinical data &#40;e&#46;g&#46;&#44; sofosbuvir and amiodarone&#41; <a class="elsevierStyleCrossRef" href="#bib0190">&#91;17&#93;</a>&#46; Time since market entry could affect the prevalence of XDDIs detected&#44; and future studies should attempt to control this factor&#46; Fourth&#44; the predictors of having XDDIs to all HCV treatment regimens may be surrogates for other factors which were not studied&#59; future analyses should consider the role these other unmeasured factors might play&#46; For instance&#44; duration of HCV &#8805;10 years may be a proxy measure for age or advanced stage of disease and may reflect higher medication use&#46; It could also indicate patients should be considered for treatment as early as possible to avoid issues related to managing XDDIs&#46; Fifth&#44; this study used the statistical tool CART to identify breakpoints in continuous variables associated with XDDIs to all four HCV regimens&#46; It should be noted that CART identifies breakpoints that are specific to a population and the same breakpoint may not be observed in other populations with different distributions within continuous variables or frequency of outcome&#46; Finally&#44; this study was performed among predominantly male Veterans&#46; A varied frequency of XDDIs may be expected in other populations with a different distribution of medication use&#46; This is particularly important for females that may be using hormonal therapies&#44; such as ethinyl estradiol&#44; which is contraindicated with GLE&#47;PIB&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">In summary&#44; there were significant differences in the frequency of XDDIs between various HCV treatment regimens&#46; Of the HCV regimens evaluated&#44; XDDIs were significantly more frequent with GLE&#47;PIB compared to other regimens&#46; A very low percentage of patients had XDDIs to all four HCV regimens&#46; This was driven primarily by a high volume of medication use and prolonged duration of chronic HCV infection&#46; Clinicians prescribing HCV treatment should include drug interactions in the multiple considerations that are involved in selecting an HCV treatment regimen&#46;</p></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Abbreviations</span><p id="par0105" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleDefList"><span class="elsevierStyleDefTerm">ATC</span><span class="elsevierStyleDefDescription"><p id="par0110" class="elsevierStylePara elsevierViewall">Anatomical Therapeutic Chemical</p></span><span class="elsevierStyleDefTerm">CART</span><span class="elsevierStyleDefDescription"><p id="par0115" class="elsevierStylePara elsevierViewall">classification and regression tree</p></span><span class="elsevierStyleDefTerm">CI</span><span class="elsevierStyleDefDescription"><p id="par0120" class="elsevierStylePara elsevierViewall">confidence interval</p></span><span class="elsevierStyleDefTerm">XDDI</span><span class="elsevierStyleDefDescription"><p id="par0125" class="elsevierStylePara elsevierViewall">scontraindicated drug&#8211;drug interactions</p></span><span class="elsevierStyleDefTerm">ESAs</span><span class="elsevierStyleDefDescription"><p id="par0130" class="elsevierStylePara elsevierViewall">erythropoietin stimulating agents</p></span><span class="elsevierStyleDefTerm">GLE&#47;PIB</span><span class="elsevierStyleDefDescription"><p id="par0135" class="elsevierStylePara elsevierViewall">glecaprevir&#47;pibrentasvir</p></span><span class="elsevierStyleDefTerm">GZR&#47;EBR</span><span class="elsevierStyleDefDescription"><p id="par0140" class="elsevierStylePara elsevierViewall">grazoprevir&#47;elbasvir</p></span><span class="elsevierStyleDefTerm">HCV</span><span class="elsevierStyleDefDescription"><p id="par0145" class="elsevierStylePara elsevierViewall">hepatitis C</p></span><span class="elsevierStyleDefTerm">IQR</span><span class="elsevierStyleDefDescription"><p id="par0150" class="elsevierStylePara elsevierViewall">interquartile range</p></span><span class="elsevierStyleDefTerm">LDV&#47;SOF</span><span class="elsevierStyleDefDescription"><p id="par0155" class="elsevierStylePara elsevierViewall">ledipasvir&#47;sofosbuvir</p></span><span class="elsevierStyleDefTerm">OR</span><span class="elsevierStyleDefDescription"><p id="par0160" class="elsevierStylePara elsevierViewall">odds ratio</p></span><span class="elsevierStyleDefTerm">SOF&#47;VEL</span><span class="elsevierStyleDefDescription"><p id="par0165" class="elsevierStylePara elsevierViewall">sofosbuvir&#47;velpatasvir</p></span><span class="elsevierStyleDefTerm">SD</span><span class="elsevierStyleDefDescription"><p id="par0170" class="elsevierStylePara elsevierViewall">standard deviation</p></span></span></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Financial support</span><p id="par0175" class="elsevierStylePara elsevierViewall">The work presented in this manuscript was partially funded by an investigator-initiated research grant from <span class="elsevierStyleGrantSponsor" id="gs1">Gilead Sciences</span>&#46;</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Conflict of interest</span><p id="par0180" class="elsevierStylePara elsevierViewall">NP has received investigator-initiated research grant support from Gilead Sciences and Merck &#38; Co&#46; NP has received consultant honoraria from Gilead Sciences&#46; None of the other authors have conflicts of interest to declare&#46;</p></span></span>"
    "textoCompletoSecciones" => array:1 [
      "secciones" => array:11 [
        0 => array:3 [
          "identificador" => "xres1233316"
          "titulo" => "Abstract"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "abst0005"
              "titulo" => "Introduction and Objectives"
            ]
            1 => array:2 [
              "identificador" => "abst0010"
              "titulo" => "Materials and methods"
            ]
            2 => array:2 [
              "identificador" => "abst0015"
              "titulo" => "Results"
            ]
            3 => array:2 [
              "identificador" => "abst0020"
              "titulo" => "Conclusion"
            ]
          ]
        ]
        1 => array:2 [
          "identificador" => "xpalclavsec1145648"
          "titulo" => "Keywords"
        ]
        2 => array:2 [
          "identificador" => "sec0005"
          "titulo" => "Introduction"
        ]
        3 => array:3 [
          "identificador" => "sec0010"
          "titulo" => "Materials and methods"
          "secciones" => array:4 [
            0 => array:2 [
              "identificador" => "sec0015"
              "titulo" => "Study design and population"
            ]
            1 => array:2 [
              "identificador" => "sec0020"
              "titulo" => "Data collection"
            ]
            2 => array:2 [
              "identificador" => "sec0025"
              "titulo" => "Outcome assessment"
            ]
            3 => array:2 [
              "identificador" => "sec0030"
              "titulo" => "Statistical analyses"
            ]
          ]
        ]
        4 => array:2 [
          "identificador" => "sec0035"
          "titulo" => "Results"
        ]
        5 => array:2 [
          "identificador" => "sec0040"
          "titulo" => "Discussion"
        ]
        6 => array:2 [
          "identificador" => "sec0045"
          "titulo" => "Abbreviations"
        ]
        7 => array:2 [
          "identificador" => "sec0050"
          "titulo" => "Financial support"
        ]
        8 => array:2 [
          "identificador" => "sec0055"
          "titulo" => "Conflict of interest"
        ]
        9 => array:2 [
          "identificador" => "xack422292"
          "titulo" => "Acknowledgements"
        ]
        10 => array:1 [
          "titulo" => "References"
        ]
      ]
    ]
    "pdfFichero" => "main.pdf"
    "tienePdf" => true
    "fechaRecibido" => "2018-07-12"
    "fechaAceptado" => "2018-11-30"
    "PalabrasClave" => array:1 [
      "en" => array:1 [
        0 => array:4 [
          "clase" => "keyword"
          "titulo" => "Keywords"
          "identificador" => "xpalclavsec1145648"
          "palabras" => array:4 [
            0 => "Pharmacoepidemiology"
            1 => "Medications"
            2 => "Safety"
            3 => "Antiviral"
          ]
        ]
      ]
    ]
    "tieneResumen" => true
    "resumen" => array:1 [
      "en" => array:3 [
        "titulo" => "Abstract"
        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction and Objectives</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Four regimens are recommended for treating hepatitis C &#40;HCV&#41; genotype 1 infection&#46; Study aims were to &#40;1&#41; compare frequencies of contraindicated drug interactions &#40;XDDIs&#41; when each HCV regimen is added to medication profiles of HCV-monoinfected patients&#44; &#40;2&#41; quantify the proportion of patients with XDDIs to all four regimens and &#40;3&#41; determine covariates independently associated with having a XDDI to all four regimens&#46;</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Materials and methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">A cross-sectional study was performed within Upstate New York Veterans Healthcare Administration&#46; Inclusion criteria&#58; &#40;1&#41; age &#8805;18 years&#44; &#40;2&#41; HCV monoinfection and &#40;3&#41; available medication list&#46; Data extracted were&#58; demographics&#44; comorbidities&#44; and medication list&#46; Primary outcome was XDDIs involving patient&#39;s home medications and each HCV regimen&#46; University of Liverpool drug interaction website was used to define XDDIs&#46; Two-way comparisons of regimens were performed using McNemar&#39;s test where <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span>&#60;<span class="elsevierStyleHsp" style=""></span>0&#46;0083 was considered statistically significant&#46; Multivariate regression analyses were performed to determine predictors&#46;</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Of the 4047 subjects&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>standard deviation age was 59&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;6&#46; Median &#40;interquartile range&#41; number of medications used was 7 <a class="elsevierStyleCrossRefs" href="#bib0125">&#91;4&#8211;11&#93;</a>&#46; Frequencies of XDDIs after the addition of each regimen ranged from 2&#46;8&#37; to 17&#46;8&#37; and were mostly statistically different from one another&#46; There were 95 &#40;2&#46;3&#37;&#41; patients with XDDIs to all four regimens&#46; Predictors of having XDDIs to all four regimens were &#8805;6 medications and HCV infection &#8805;10 years&#46;</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusion</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">The frequencies of XDDIs varied between HCV regimens&#46; Number of medications and duration of HCV infection were predictors of having XDDIs to all four regimens&#46;</p></span>"
        "secciones" => array:4 [
          0 => array:2 [
            "identificador" => "abst0005"
            "titulo" => "Introduction and Objectives"
          ]
          1 => array:2 [
            "identificador" => "abst0010"
            "titulo" => "Materials and methods"
          ]
          2 => array:2 [
            "identificador" => "abst0015"
            "titulo" => "Results"
          ]
          3 => array:2 [
            "identificador" => "abst0020"
            "titulo" => "Conclusion"
          ]
        ]
      ]
    ]
    "multimedia" => array:3 [
      0 => array:7 [
        "identificador" => "fig0005"
        "etiqueta" => "Fig&#46; 1"
        "tipo" => "MULTIMEDIAFIGURA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "figura" => array:1 [
          0 => array:4 [
            "imagen" => "gr1.jpeg"
            "Alto" => 1203
            "Ancho" => 2083
            "Tamanyo" => 107584
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Frequency of contraindicated drug&#8211;drug interactions between various HCV treatment regimens&#44; stratified by use of &#8805;6 medications&#46; EBV&#47;GZR &#8211; elbasvir&#47;grazoprevir&#59; GLE&#47;PIB &#8211; glecaprevir&#47;pibrentasvir&#59; LDV&#47;SOF &#8211; ledipasvir&#47;sofosbuvir and SOF&#47;VEL &#8211; sofosbuvir&#47;velpatasvir&#46;</p>"
        ]
      ]
      1 => array:8 [
        "identificador" => "tbl0005"
        "etiqueta" => "Table 1"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at1"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:2 [
          "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">All data presented as <span class="elsevierStyleItalic">n</span> &#40;&#37;&#41; unless otherwise indicated&#46;</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Legend&#58; BPH &#8211; benign prostatic hyperplasia&#44; COPD &#8211; chronic obstructive pulmonary disorder&#44; CNS &#8211; central nervous system&#44; HCV &#8211; hepatits C infection&#44; IQR &#8211; interquartile range&#44; SD &#8211; standard deviation&#46;</p>"
          "tablatextoimagen" => array:1 [
            0 => array:2 [
              "tabla" => array:1 [
                0 => """
                  <table border="0" frame="\n
                  \t\t\t\t\tvoid\n
                  \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Covariate&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">XDDIs<span class="elsevierStyleHsp" style=""></span>&#8804;<span class="elsevierStyleHsp" style=""></span>3 HCV regimens &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>3952&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black">XDDIs to all 4 HCV regimens &#40;<span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>&#61;<span class="elsevierStyleHsp" style=""></span>95&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th><th class="td" title="\n
                  \t\t\t\t\ttable-head\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">p</span>-value&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Age&#44; mean<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>SD&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">59&#46;8<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>7&#46;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58&#46;4<span class="elsevierStyleHsp" style=""></span>&#177;<span class="elsevierStyleHsp" style=""></span>8&#46;0&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Sex&#44; male&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3807 &#40;96&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">93 &#40;97&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;58&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">RaceAfrican AmericanHispanicCaucasianOther&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1131 &#40;28&#46;6&#41;108 &#40;2&#46;7&#41;2312 &#40;58&#46;5&#41;401 &#40;10&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">25 &#40;26&#46;3&#41;1 &#40;1&#46;1&#41;54 &#40;56&#46;8&#41;15 &#40;15&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;26&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Years with diagnosed HCV infection&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;8&#8211;14&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">12 &#40;10&#8211;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;04&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">HCV diagnosis &#8805;10 years&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2631 &#40;66&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72 &#40;75&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Number of comorbidities&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;5&#8211;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;6&#8211;11&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;08&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Number of medications&#44; median &#40;IQR&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">7 &#40;4&#8211;10&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">10 &#40;6&#8211;15&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Medications &#8805;6&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2418 &#40;61&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">78 &#40;82&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Analgesics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1863 &#40;47&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54 &#40;56&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;06&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti-anginal medications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">186 &#40;4&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">5 &#40;5&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;80&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti-anxiety medications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">783 &#40;19&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">34 &#40;35&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti-arrhythmic medications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1948 &#40;49&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">51 &#40;53&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;40&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti-coagulants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">151 &#40;3&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">9 &#40;9&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;005&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti-depressants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2674 &#40;67&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">72 &#40;75&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;09&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti-emetics&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">166 &#40;4&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">8 &#40;8&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;05&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti-epileptic medications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">684 &#40;17&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">90 &#40;94&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti-histamines&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">215 &#40;56&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">48 &#40;50&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;28&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti-hypertensives&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">3043 &#40;77&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">79 &#40;83&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti-platelet medications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2493 &#40;63&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">54 &#40;56&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;21&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Anti-psychotic medications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">670 &#40;17&#46;0&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;38&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">&#60;0&#46;001&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Asthma&#47;COPD medications &#40;inhaled&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">864 &#40;21&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">30 &#40;31&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;02&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">BPH medications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2123 &#40;53&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58 &#40;61&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">CNS stimulants&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1925 &#40;48&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52 &#40;54&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;25&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Erectile dysfunction medications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2359 &#40;59&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">58 &#40;61&#46;1&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;79&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Erythropoeitin stimulating agents&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">37 &#40;0&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">4 &#40;4&#46;2&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;002&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Gastroesophageal reflux disease medications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2824 &#40;71&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">66 &#40;69&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;67&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Insulin&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">2128 &#40;53&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">55 &#40;57&#46;9&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;43&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Lipid lowering medications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">960 &#40;24&#46;3&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">29 &#40;30&#46;5&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;16&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Oral anti-diabetic medications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">505 &#40;12&#46;8&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">11 &#40;11&#46;6&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;73&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">Osteoporosis medications&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">1951 &#40;49&#46;4&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">52 &#40;54&#46;7&#41;&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td><td class="td" title="\n
                  \t\t\t\t\ttable-entry\n
                  \t\t\t\t  " align="left" valign="\n
                  \t\t\t\t\ttop\n
                  \t\t\t\t">0&#46;30&nbsp;\t\t\t\t\t\t\n
                  \t\t\t\t</td></tr></tbody></table>
                  """
              ]
              "imagenFichero" => array:1 [
                0 => "xTab2106811.png"
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Bivariate relationship between clinical&#47;demographic covariates and presence of contraindicated drug&#8211;drug interactions to all four hepatitis C treatment regimens&#46;</p>"
        ]
      ]
      2 => array:8 [
        "identificador" => "tbl0010"
        "etiqueta" => "Table 2"
        "tipo" => "MULTIMEDIATABLA"
        "mostrarFloat" => true
        "mostrarDisplay" => false
        "detalles" => array:1 [
          0 => array:3 [
            "identificador" => "at2"
            "detalle" => "Table "
            "rol" => "short"
          ]
        ]
        "tabla" => array:1 [
          "tablatextoimagen" => array:1 [
            0 => array:1 [
              "tablaImagen" => array:1 [
                0 => array:4 [
                  "imagenFichero" => "fx1.jpeg"
                  "imagenAlto" => 3508
                  "imagenAncho" => 2281
                  "imagenTamanyo" => 414221
                ]
              ]
            ]
          ]
        ]
        "descripcion" => array:1 [
          "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Predicted probabilities of contraindicated drug&#8211;drug interactions in presence of clinical&#47;demographic covariates in multivariate models&#46;</p>"
        ]
      ]
    ]
    "bibliografia" => array:2 [
      "titulo" => "References"
      "seccion" => array:1 [
        0 => array:2 [
          "identificador" => "bibs0015"
          "bibliografiaReferencia" => array:21 [
            0 => array:3 [
              "identificador" => "bib0110"
              "etiqueta" => "&#91;1&#93;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "American Association for the Study of Liver Diseases &#40;AASLD&#41; &#8211; Infectious Diseases Society of America &#40;IDSA&#41;&#46; Recommendations for testing&#44; managing&#44; and treating hepatitis C&#46; <a target="_blank" href="http://www.hcvguidelines.org/">http&#58;&#47;&#47;www&#46;hcvguidelines&#46;org</a> &#91;accessed 22&#46;12&#46;18&#93;&#46;"
                ]
              ]
            ]
            1 => array:3 [
              "identificador" => "bib0115"
              "etiqueta" => "&#91;2&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Harvoni &#40;ledipasvir&#47;sofosbuvir&#41; tablet package insert"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2017"
                        "editorial" => "Gilead Sciences"
                        "editorialLocalizacion" => "Foster City&#44; CA"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            2 => array:3 [
              "identificador" => "bib0120"
              "etiqueta" => "&#91;3&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Epclusa &#40;velpatasvir&#47;sofosbuvir&#41; tablet package insert"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2017"
                        "editorial" => "Gilead Sciences"
                        "editorialLocalizacion" => "Foster City&#44; CA"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            3 => array:3 [
              "identificador" => "bib0125"
              "etiqueta" => "&#91;4&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Mavyret &#40;glecaprevir&#47;pibrentasvir&#41; tablet package insert"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2017"
                        "editorial" => "AbbVie Inc"
                        "editorialLocalizacion" => "North Chicago&#44; IL"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            4 => array:3 [
              "identificador" => "bib0130"
              "etiqueta" => "&#91;5&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:1 [
                      "titulo" => "Zepatier &#40;elbasvir&#47;grazoprevir&#41; tablet package insert"
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:3 [
                        "fecha" => "2017"
                        "editorial" => "Merck &#38; Co&#46;&#44; Inc&#46;"
                        "editorialLocalizacion" => "Whitehouse Station&#44; NJ"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            5 => array:3 [
              "identificador" => "bib0135"
              "etiqueta" => "&#91;6&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Glecaprevir plus pibrentasvir for chronic hepatitis C virus genotype 1&#44; 2&#44; 4&#44; 5&#44; or 6 infection in adults with compensated cirrhosis &#40;EXPEDITION-1&#41;&#58; a single-arm&#44; open-label&#44; multicentre phase 3 trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "X&#46; Forns"
                            1 => "S&#46;S&#46; Lee"
                            2 => "J&#46; Valdes"
                            3 => "S&#46; Lens"
                            4 => "R&#46; Ghalib"
                            5 => "H&#46; Aguilar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/S1473-3099(17)30496-6"
                      "Revista" => array:4 [
                        "tituloSerie" => "Lancet Infect Dis"
                        "fecha" => "2017"
                        "paginaInicial" => "1062"
                        "paginaFinal" => "1068"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            6 => array:3 [
              "identificador" => "bib0140"
              "etiqueta" => "&#91;7&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ledipasvir and sofosbuvir for previously treated HCV genotype 1 infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Afdhal"
                            1 => "K&#46;R&#46; Reddy"
                            2 => "D&#46;R&#46; Nelson"
                            3 => "E&#46; Lawitz"
                            4 => "S&#46;C&#46; Gordon"
                            5 => "E&#46; Schiff"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1316366"
                      "Revista" => array:4 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2014"
                        "paginaInicial" => "1483"
                        "paginaFinal" => "1493"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            7 => array:3 [
              "identificador" => "bib0145"
              "etiqueta" => "&#91;8&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Ledipasvir and sofosbuvir for untreated HCV genotype 1 infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Afdhal"
                            1 => "S&#46; Zeuzem"
                            2 => "P&#46; Kwo"
                            3 => "M&#46; Chojkier"
                            4 => "N&#46; Gitlin"
                            5 => "M&#46; Puoti"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1402454"
                      "Revista" => array:4 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2014"
                        "paginaInicial" => "1889"
                        "paginaFinal" => "1898"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            8 => array:3 [
              "identificador" => "bib0150"
              "etiqueta" => "&#91;9&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Sofosbuvir and Velpatasvir for HCV Genotype 1&#44; 2&#44; 4&#44; 5&#44; and 6 infection"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "J&#46;J&#46; Feld"
                            1 => "I&#46;M&#46; Jacobson"
                            2 => "C&#46; Hezode"
                            3 => "T&#46; Asselah"
                            4 => "P&#46;J&#46; Ruane"
                            5 => "N&#46; Gruener"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMoa1512610"
                      "Revista" => array:5 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2015"
                        "paginaInicial" => "2599"
                        "paginaFinal" => "2607"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/20018959"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            9 => array:3 [
              "identificador" => "bib0155"
              "etiqueta" => "&#91;10&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Grazoprevir-Elbasvir combination therapy for treatment-naive cirrhotic and noncirrhotic patients with chronic hepatitis c virus genotype 1&#44; 4&#44; or 6 infection&#58; a randomized trial"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "S&#46; Zeuzem"
                            1 => "R&#46; Ghalib"
                            2 => "K&#46;R&#46; Reddy"
                            3 => "P&#46;J&#46; Pockros"
                            4 => "Z&#46; Ben Ari"
                            5 => "Y&#46; Zhao"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.7326/M15-0785"
                      "Revista" => array:5 [
                        "tituloSerie" => "Ann Intern Med"
                        "fecha" => "2015"
                        "paginaInicial" => "1"
                        "paginaFinal" => "13"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/7985890"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            10 => array:3 [
              "identificador" => "bib0160"
              "etiqueta" => "&#91;11&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Indications for testing among reported cases of HCV infection from enhanced hepatitis surveillance sites in the United States&#44; 2004&#8211;2010"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "R&#46; Mahajan"
                            1 => "S&#46;J&#46; Liu"
                            2 => "R&#46;M&#46; Klevens"
                            3 => "S&#46;D&#46; Holmberg"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.2105/AJPH. 2013.301211"
                      "Revista" => array:4 [
                        "tituloSerie" => "Am J Public Health"
                        "fecha" => "2013"
                        "paginaInicial" => "1445"
                        "paginaFinal" => "1449"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            11 => array:3 [
              "identificador" => "bib0165"
              "etiqueta" => "&#91;12&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "What is polypharmacy&#63;&#46; A systematic review of definitions"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:4 [
                            0 => "N&#46; Masnoon"
                            1 => "S&#46; Shakib"
                            2 => "L&#46; Kalisch-Ellett"
                            3 => "G&#46;E&#46; Caughey"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1186/s12877-017-0621-2"
                      "Revista" => array:3 [
                        "tituloSerie" => "BMC Geriatr"
                        "fecha" => "2017"
                        "volumen" => "230"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            12 => array:3 [
              "identificador" => "bib0170"
              "etiqueta" => "&#91;13&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Polypharmacy&#58; misleading&#44; but manageable"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:5 [
                            0 => "R&#46;L&#46; Bushardt"
                            1 => "E&#46;B&#46; Massey"
                            2 => "T&#46;W&#46; Simpson"
                            3 => "J&#46;C&#46; Ariail"
                            4 => "K&#46;N&#46; Simpson"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Revista" => array:4 [
                        "tituloSerie" => "Clin Interv Aging"
                        "fecha" => "2008"
                        "paginaInicial" => "383"
                        "paginaFinal" => "389"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            13 => array:3 [
              "identificador" => "bib0175"
              "etiqueta" => "&#91;14&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Medication use and medical comorbidity in patients with chronic hepatitis C from a US commercial claims database&#58; high utilization of drugs with interaction potential"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:6 [
                            0 => "J&#46;C&#46; Lauffenburger"
                            1 => "C&#46;L&#46; Mayer"
                            2 => "R&#46;L&#46; Hawke"
                            3 => "K&#46;L&#46; Brouwer"
                            4 => "M&#46;W&#46; Fried"
                            5 => "J&#46;F&#46; Farley"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/MEG. 0000000000000152"
                      "Revista" => array:5 [
                        "tituloSerie" => "Eur J Gastroenterol Hepatol"
                        "fecha" => "2014"
                        "paginaInicial" => "1073"
                        "paginaFinal" => "1082"
                        "link" => array:1 [
                          0 => array:2 [
                            "url" => "https://www.ncbi.nlm.nih.gov/pubmed/8680907"
                            "web" => "Medline"
                          ]
                        ]
                      ]
                    ]
                  ]
                ]
              ]
            ]
            14 => array:3 [
              "identificador" => "bib0180"
              "etiqueta" => "&#91;15&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "The impact of polypharmacy on patient outcomes in older adults with cancer"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "G&#46; Nightingale"
                            1 => "E&#46; Skonecki"
                            2 => "M&#46;K&#46; Boparai"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1097/PPO. 0000000000000277"
                      "Revista" => array:4 [
                        "tituloSerie" => "Cancer J"
                        "fecha" => "2017"
                        "paginaInicial" => "211"
                        "paginaFinal" => "218"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            15 => array:3 [
              "identificador" => "bib0185"
              "etiqueta" => "&#91;16&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Clinical consequences of polypharmacy in elderly"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:3 [
                            0 => "R&#46;L&#46; Maher"
                            1 => "J&#46; Hanlon"
                            2 => "E&#46;R&#46; Hajjar"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1517/14740338.2013.827660"
                      "Revista" => array:4 [
                        "tituloSerie" => "Expert Opin Drug Saf"
                        "fecha" => "2014"
                        "paginaInicial" => "57"
                        "paginaFinal" => "65"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            16 => array:3 [
              "identificador" => "bib0190"
              "etiqueta" => "&#91;17&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Bradyarrhythmias associated with sofosbuvir treatment"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:2 [
                            0 => "D&#46;M&#46; Brainard"
                            1 => "J&#46;G&#46; McHutchison"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1056/NEJMc1505967"
                      "Revista" => array:3 [
                        "tituloSerie" => "N Engl J Med"
                        "fecha" => "2015"
                        "paginaInicial" => "1888"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            17 => array:3 [
              "identificador" => "bib0195"
              "etiqueta" => "&#91;18&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "How many potential drug&#8211;drug interactions cause adverse drug reactions in hospitalized patients&#63;"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "C&#46; Bucsa"
                            1 => "A&#46; Farcas"
                            2 => "I&#46; Cazacu"
                            3 => "D&#46; Leucuta"
                            4 => "A&#46; Achimas-Cadariu"
                            5 => "C&#46; Mogosan"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1016/j.ejim.2012.09.011"
                      "Revista" => array:4 [
                        "tituloSerie" => "Eur J Intern Med"
                        "fecha" => "2013"
                        "paginaInicial" => "27"
                        "paginaFinal" => "33"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            18 => array:3 [
              "identificador" => "bib0200"
              "etiqueta" => "&#91;19&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "A cross-sectional study comparing the frequency of drug interactions after adding simeprevir- or sofosbuvir-containing therapy to medication profiles of hepatitis C monoinfected patients"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => true
                          "autores" => array:6 [
                            0 => "N&#46; Patel"
                            1 => "M&#46; Nasiri"
                            2 => "A&#46; Koroglu"
                            3 => "S&#46; Bliss"
                            4 => "M&#46; Davis"
                            5 => "L&#46;A&#46; McNutt"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:2 [
                      "doi" => "10.1007/s40121-015-0058-x"
                      "Revista" => array:4 [
                        "tituloSerie" => "Infect Dis Ther"
                        "fecha" => "2015"
                        "paginaInicial" => "67"
                        "paginaFinal" => "78"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            19 => array:3 [
              "identificador" => "bib0205"
              "etiqueta" => "&#91;20&#93;"
              "referencia" => array:1 [
                0 => array:2 [
                  "contribucion" => array:1 [
                    0 => array:2 [
                      "titulo" => "Anatomical therapeutic chemical classification system&#47;defined daily dose index"
                      "autores" => array:1 [
                        0 => array:2 [
                          "etal" => false
                          "autores" => array:1 [
                            0 => "World Health Organization&#46; WHO Collaborating Centre for Drug Statistics Methodology"
                          ]
                        ]
                      ]
                    ]
                  ]
                  "host" => array:1 [
                    0 => array:1 [
                      "Libro" => array:1 [
                        "fecha" => "2017"
                      ]
                    ]
                  ]
                ]
              ]
            ]
            20 => array:3 [
              "identificador" => "bib0210"
              "etiqueta" => "&#91;21&#93;"
              "referencia" => array:1 [
                0 => array:1 [
                  "referenciaCompleta" => "Liverpool Drug Interactions Group&#46; University of Liverpool&#46; HEP drug interaction checker&#46; <a target="_blank" href="http://hep-druginteractions.org/">http&#58;&#47;&#47;hep-druginteractions&#46;org</a> &#91;accessed 22&#46;12&#46;18&#93;&#46;"
                ]
              ]
            ]
          ]
        ]
      ]
    ]
    "agradecimientos" => array:1 [
      0 => array:4 [
        "identificador" => "xack422292"
        "titulo" => "Acknowledgements"
        "texto" => "<p id="par0185" class="elsevierStylePara elsevierViewall">This material is based upon work partially supported by the Office of Research and Development&#44; Department of Veterans Affairs&#46; The contents of this report do not represent the views of the Department of Veterans Affairs or the United States Government&#46;</p>"
        "vista" => "all"
      ]
    ]
  ]
  "idiomaDefecto" => "en"
  "url" => "/16652681/0000001800000004/v3_201908230828/S1665268119300572/v3_201908230828/en/main.assets"
  "Apartado" => array:4 [
    "identificador" => "78265"
    "tipo" => "SECCION"
    "en" => array:2 [
      "titulo" => "Original Articles"
      "idiomaDefecto" => true
    ]
    "idiomaDefecto" => "en"
  ]
  "PDF" => "https://static.elsevier.es/multimedia/16652681/0000001800000004/v3_201908230828/S1665268119300572/v3_201908230828/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/"
  "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1665268119300572?idApp=UINPBA00004N"
]

Article information

ISSN: 16652681
Original language: English

DOI:10.1016/j.aohep.2019.01.005

The statistics are updated each day

Year/Month	Html	Pdf	Total

2024 November	5	0	5
2024 October	30	9	39
2024 September	34	8	42
2024 August	21	1	22
2024 July	16	2	18
2024 June	14	6	20
2024 May	22	3	25
2024 April	25	19	44
2024 March	80	14	94
2024 February	33	4	37
2024 January	29	2	31
2023 December	19	2	21
2023 November	16	5	21
2023 October	29	5	34
2023 September	7	3	10
2023 August	11	7	18
2023 July	10	3	13
2023 June	23	5	28
2023 May	32	2	34
2023 April	44	1	45
2023 March	14	1	15
2023 February	17	5	22
2023 January	10	2	12
2022 December	14	5	19
2022 November	19	13	32
2022 October	12	6	18
2022 September	17	6	23
2022 August	20	8	28
2022 July	22	8	30
2022 June	17	4	21
2022 May	25	8	33
2022 April	44	12	56
2022 March	79	10	89
2022 February	80	8	88
2022 January	54	11	65
2021 December	29	8	37
2021 November	39	7	46
2021 October	18	11	29
2021 September	15	8	23
2021 August	15	5	20
2021 July	49	10	59
2021 June	17	11	28
2021 May	17	12	29
2021 April	43	29	72
2021 March	8	10	18
2021 February	6	4	10
2021 January	17	11	28
2020 December	8	5	13
2020 November	11	6	17
2020 October	11	7	18
2020 September	12	7	19
2020 August	15	8	23
2020 July	18	7	25
2020 June	17	6	23
2020 May	11	7	18
2020 April	6	3	9
2020 March	10	9	19
2020 February	9	9	18
2020 January	14	5	19
2019 December	9	8	17
2019 November	10	2	12
2019 October	24	8	32
2019 September	16	7	23
2019 August	30	12	42
2019 July	27	23	50
2019 June	3	14	17
2019 May	0	24	24

Show all

Indexed in:

Follow us:

Statistics

Indexed in:

Follow us:

Statistics

Subscribe to our newsletter