Research Letter
Comparison of cardiotoxicity between N-methyl-glucamine and miltefosine in the treatment of American cutaneous leishmaniasis
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Cover; 2. Summary; 3. What is isotretinoin? ; 4. What is severe inflammatory acne? 5. What should I tell my physician before using isotretinoin? 6. How should I take isotretinoin? ; 7. What should I avoid while using isotretinoin? ; 8. What are the most common side effects of isotretinoin? ; 9. What should I immediately tell my physician while using isotretinoin? ; 10. Teratogenicity; 11. Laboratory tests; 12. Safe drug storage; 13. Frequently asked questions; 14. 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two capsules a day - for 28 days), followed by a weekly ECG in the Dermatology Service between 2008 and 2013.</p><p id="par0025" class="elsevierStylePara elsevierViewall">The inclusion criteria were: patients treated for ACL, aged between 18 and 85 years and the exclusion criteria were: pregnant women, patients with chronic kidney or liver disease, severe heart disease or other diseases, or receiving drugs that could interfere with the ECG. The patients were not taking any other medications at the time and had not been treated for ACL in the past 6 months.</p><p id="par0030" class="elsevierStylePara elsevierViewall">The included patients were divided into two groups: 1 - treated with NMG; 2 - treated with Miltefosine (M).</p><p id="par0035" class="elsevierStylePara elsevierViewall">The relative risk and the percentage of alterations in the EGC during treatment (heart rhythm and rate, P-wave, QRS complex, RR interval, presence or absence of arrhythmias, and QTc interval) were compared in the groups. For the heart rate, the range between 60 bpm and 100 bpm was considered normal, and the limit of 440 milliseconds for QTc for both sexes (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">The variables were expressed as frequency and the comparison between the groups was done using the Chi-squared test, or Fisher’s exact test when more than 20% of the cells showed an expected frequency < 5. A p-value < 0.05 was considered significant. A multivariate model was employed and the relative risk with a 95% confidence interval was calculated to analyze the intensity of the association between each independent variable and the proportion of adverse effects.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The medical records of 111 patients were analyzed and the epidemiological and electrocardiographic data of 53 individuals were recovered, of which 38 were treated with NMG and 15 with M.</p><p id="par0050" class="elsevierStylePara elsevierViewall">The mean age in the NMG group was 48.4 ± 16.29 years, while in the M group it was 58.4 ± 9.16 years, showing a difference between the groups (p = 0.033). In the NMG group, 23 individuals (60.5%) and in the M group, 7 individuals (46.7) were males (p = 0.37).</p><p id="par0055" class="elsevierStylePara elsevierViewall">On the seventh day of treatment (D7), 11.4% of the members of the NMG group and 33.3% of the M group had QT-interval prolongation. On the fourteenth day (D14), 26.6% of the NMG group had QT-interval prolongation, but none in the M group had it. The trend continued on the twenty-first day (D21), as 35.3% of the NMG group had an altered QTc, while there were no changes in group M. As for the heart rate, 28.9% of patients in the NMG group and 26.6 % of the M group had bradycardia during treatment.</p><p id="par0060" class="elsevierStylePara elsevierViewall">Before treatment, 16 (21%) of the patients in the NMG group and 37.5% of the M group had bradycardia (RR = 0.59; 95% CI 0.17 to 1.99); (p = 0.44). The QTc was altered in 13.51% of the NMG group and 6.66% of the M group (RR = 2.02, 95% CI 0.26 to 15.93; p = 0.5495).</p><p id="par0065" class="elsevierStylePara elsevierViewall">The only significant difference between the groups was demonstrated on the seventh day of treatment when patients treated with M more frequently showed QTc >440 (RR = 0.25; 95% CI 0.07 to 0.94); p = 0.04 (<a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>).</p><p id="par0070" class="elsevierStylePara elsevierViewall">Previous studies have already shown that miltefosine can increase the QT interval during treatment when compared to basal values.<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> The QT-interval prolongation (QT ≥ 440 ms), which translates into a marked increase in the action potential leading to inhomogeneity of the ventricular electrical matrix, favors the occurrence of reentry phenomena, in addition to favoring early diastolic depolarization and “triggered” activity. This QT-interval prolongation is associated with <span class="elsevierStyleItalic">Torsades de pointes</span>, a polymorphic ventricular tachycardia, which can exhibit degeneration into ventricular fibrillation, configuring the arrhythmic mechanism of sudden death.<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3,9</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Contrary to the expectations, a greater proportion of patients who used miltefosine had QTc > 440 ms on the seventh day of treatment, but this difference was not maintained in the second and third weeks.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Aging is a factor related to electrocardiographic alterations and the patients in group M had a higher mean age.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a> However, on the other hand, these alterations were already present in the pre-treatment period, which leads us to believe that age did not play a determining role in the alterations. Another limitation is the performance of multiple tests, which can increase the rate of type 1 errors.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Considering the result that suggests M cardiotoxicity in the context of the current trend in the treatment of ACL with the association of potentially cardiotoxic drugs (antimonials, amphotericin), this finding should be better studied in regimens with drug combinations. This seems to be the first study that demonstrated the presence of ECG alterations caused by M ​​over the course of treatment.<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> These findings, however, have an exploratory characteristic and deserve to be confirmed by studies with a larger number of patients.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Financial support</span><p id="par0090" class="elsevierStylePara elsevierViewall">Financial support from the <span class="elsevierStyleGrantSponsor" id="gs0005">Brazilian Society of Dermatology</span>(Sociedade Brasileira de Dermatologia, SBD) through Funaderme and from the <span class="elsevierStyleGrantSponsor" id="gs0010">Research Support Foundation of the Distrito Federal</span>(Fundação de Apoio à Pesquisa do Distrito Federal - FAP-DF), number <span class="elsevierStyleGrantNumber" refid="gs0010">0193.001447 / 2016.</span></p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Authors’ contributions</span><p id="par0095" class="elsevierStylePara elsevierViewall">Daniel Holanda Barroso: Drafting and editing of the manuscript; collection, analysis, and interpretation of data.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Ciro Martins Gomes: Critical review of the manuscript; collection, analysis, and interpretation of data. Antônia Marilene da Silva: Drafting and editing of the manuscript; collection, analysis, and interpretation of data.</p><p id="par0105" class="elsevierStylePara elsevierViewall">Raimunda Nonata Ribeiro Sampaio: Collection, analysis, and interpretation of data; drafting and editing of the manuscript; critical review of the manuscript.</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Conflicts of interest</span><p id="par0110" class="elsevierStylePara elsevierViewall">None declared.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:2 [ "identificador" => "sec0005" "titulo" => "Financial support" ] 1 => array:2 [ "identificador" => "sec0010" "titulo" => "Authors’ contributions" ] 2 => array:2 [ "identificador" => "sec0015" "titulo" => "Conflicts of interest" ] 3 => array:2 [ "identificador" => "xack545993" "titulo" => "Acknowledgments" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2020-11-29" "fechaAceptado" => "2021-02-26" "NotaPie" => array:2 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0010">How to cite this article: Barroso DH, Gomes CM, Silva AM, Sampaio RNR. Comparison of cardiotoxicity between N-methyl-glucamine and miltefosine in the treatment of American cutaneous leishmaniasis. An Bras Dermatol. 2021;96:502–4.</p>" ] 1 => array:2 [ "etiqueta" => "☆☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">Study conducted at the Hospital Universitário de Brasília and Laboratory of Dermatomycology, Faculdade de Medicina, Universidade de Brasília, Brasília, DF, Brazil.</p>" ] ] "multimedia" => array:1 [ 0 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at0005" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:3 [ "leyenda" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">CI, Confidence Interval; RR, Relative Risk.</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"> \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 " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Bradycardia</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">QTC >440</th><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " colspan="2" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Arrhythmias<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a></th></tr><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"> \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">RR (95% IC) \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 \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">RR (95% IC) \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 \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">RR (95% IC) \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 \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 " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Day 7</span></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">NMG \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">1.14 (0.31–4.23) \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">0.87 \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 (0.07–0.94) \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><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">0.85 (0.08–8.74) \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">0.87 \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">M \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">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"> \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">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"> \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">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"> \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 " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Day 14</span></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">NMG \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">0.53 (0.07–3.66) \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><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">6.58 (0.41–105.36) \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">0.18 \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">1.93 (0.10–37.44) \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">0.66 \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">M \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">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"> \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">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"> \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">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"> \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 " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Day 21</span></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">NMG \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">1.94 (0.12–31.74) \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">0.64 \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">7.22 (0.45–115.33) \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><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">2.94 (0.16–55.31) \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">0.47 \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">M \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">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"> \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">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"> \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">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"> \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 " colspan="7" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Day 28</span></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">NMG \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">0.36 (0.03–4.54) \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">0.53 \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">0.54 (0.04–7.25) \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">0.70 \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">0.13 (0.006–2.86) \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">0.20 \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">M \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">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"> \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">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"> \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">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"> \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab2657894.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Arrhythmias found: isolated ventricular extrasystoles.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Relative risks comparing patients treated with NMG and M.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:11 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Manual de Vigilância e Controle da Leishmaniose Tegumentar Americana atualizada" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "Ministério da Saúde" 1 => "Departamento de Vigilância Epidemiológica" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:3 [ "fecha" => "2017" "editorial" => "Ministério da Saúde" "editorialLocalizacion" => "Brasília" ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0010" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Electrocardiographic alterations during treatment of mucocutaneous leishmaniasis with meglumine antimoniate and allopurinol" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "G. 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| Year/Month | Html | Total | |
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| 2024 November | 21 | 11 | 32 |
| 2024 October | 137 | 71 | 208 |
| 2024 September | 143 | 79 | 222 |
| 2024 August | 201 | 126 | 327 |
| 2024 July | 207 | 100 | 307 |
| 2024 June | 168 | 64 | 232 |
| 2024 May | 129 | 56 | 185 |
| 2024 April | 122 | 78 | 200 |
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| 2024 February | 142 | 79 | 221 |
| 2024 January | 118 | 47 | 165 |
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| 2023 November | 93 | 83 | 176 |
| 2023 October | 65 | 76 | 141 |
| 2023 September | 61 | 83 | 144 |
| 2023 August | 62 | 35 | 97 |
| 2023 July | 57 | 30 | 87 |
| 2023 June | 61 | 40 | 101 |
| 2023 May | 49 | 21 | 70 |
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| 2022 May | 36 | 54 | 90 |
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| 2022 January | 58 | 77 | 135 |
| 2021 December | 49 | 54 | 103 |
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