Letter to the Editor
Continuous infusion of apomorphine in patients with advanced Parkinson's disease and different degrees of functional disability
Apomorfina en bomba de perfusión continua en pacientes con enfermedad de Parkinson avanzada con diferente grado de afectación funcional
G. Salazar
, J. Martín, M. Fragoso, M.A. Font
Corresponding author
Servicio de Neurología, Hospital Consorci Sanitari de Terrassa, Barcelona, Spain
Read
4357
Timeswas read the article
757
Total PDF
3600
Total HTML
Share statistics
array:25 [ "pii" => "S2173580817300056" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2015.10.003" "estado" => "S300" "fechaPublicacion" => "2017-07-01" "aid" => "807" "copyright" => "Sociedad Española de Neurología" "copyrightAnyo" => "2015" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2017;32:407-10" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1159 "formatos" => array:3 [ "EPUB" => 84 "HTML" => 840 "PDF" => 235 ] ] "Traduccion" => array:1 [ "es" => array:20 [ "pii" => "S0213485315002297" "issn" => "02134853" "doi" => "10.1016/j.nrl.2015.10.001" "estado" => "S300" "fechaPublicacion" => "2017-07-01" "aid" => "807" "copyright" => "Sociedad Española de Neurología" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2017;32:407-10" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 9480 "formatos" => array:3 [ "EPUB" => 114 "HTML" => 8709 "PDF" => 657 ] ] "es" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">CARTA AL EDITOR</span>" "titulo" => "Apomorfina en bomba de perfusión continua en pacientes con enfermedad de Parkinson avanzada con diferente grado de afectación funcional" "tienePdf" => "es" "tieneTextoCompleto" => "es" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "407" "paginaFinal" => "410" ] ] "titulosAlternativos" => array:1 [ "en" => array:1 [ "titulo" => "Continuous infusion of apomorphine in patients with advanced Parkinson's disease and different degrees of functional disability" ] ] "contieneTextoCompleto" => array:1 [ "es" => true ] "contienePdf" => array:1 [ "es" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figura 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1064 "Ancho" => 1578 "Tamanyo" => 113724 ] ] "descripcion" => array:1 [ "es" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Comparación de los porcentajes de mejoría en las variables de resultado según un grado de afectación funcional de los pacientes moderados (grupo A) y graves (grupo B). Los pacientes con afectación moderada experimentaron mayores mejorías en todas las escalas, alcanzando diferencia estadísticamente significativa en fluctuaciones motoras (FM), escala de Schwab y England (S&E), escala de movimientos anormales (AIMS), escala hospitalaria (HADS) de ansiedad (A) y depresión (D).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "G. Salazar, J. Martín, M. Fragoso, M.A. Font" "autores" => array:4 [ 0 => array:2 [ "nombre" => "G." "apellidos" => "Salazar" ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Martín" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Fragoso" ] 3 => array:2 [ "nombre" => "M.A." "apellidos" => "Font" ] ] ] ] ] "idiomaDefecto" => "es" "Traduccion" => array:1 [ "en" => array:9 [ "pii" => "S2173580817300056" "doi" => "10.1016/j.nrleng.2015.10.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580817300056?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213485315002297?idApp=UINPBA00004N" "url" => "/02134853/0000003200000006/v1_201707060041/S0213485315002297/v1_201707060041/es/main.assets" ] ] "itemSiguiente" => array:20 [ "pii" => "S2173580817300883" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2015.11.011" "estado" => "S300" "fechaPublicacion" => "2017-07-01" "aid" => "816" "copyright" => "Sociedad Española de Neurología" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2017;32:411-3" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 831 "formatos" => array:3 [ "EPUB" => 60 "HTML" => 554 "PDF" => 217 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Nilotinib as a risk factor for ischaemic stroke: a series of three cases" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "411" "paginaFinal" => "413" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Nilotinib como factor de riesgo de ictus isquémico. A propósito de 3 casos" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 861 "Ancho" => 1400 "Tamanyo" => 111858 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">MRA in patient 3 showed moderate stenosis (> 50%) of the right MCA (A) and right ICA occlusion due to dissection (B).</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "J.B. Gómez-Galván, S. Borrego, N. Tovar, L. Llull" "autores" => array:4 [ 0 => array:2 [ "nombre" => "J.B." "apellidos" => "Gómez-Galván" ] 1 => array:2 [ "nombre" => "S." "apellidos" => "Borrego" ] 2 => array:2 [ "nombre" => "N." "apellidos" => "Tovar" ] 3 => array:2 [ "nombre" => "L." "apellidos" => "Llull" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0213485315002467" "doi" => "10.1016/j.nrl.2015.11.003" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213485315002467?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580817300883?idApp=UINPBA00004N" "url" => "/21735808/0000003200000006/v1_201707180027/S2173580817300883/v1_201707180027/en/main.assets" ] "itemAnterior" => array:20 [ "pii" => "S2173580816301237" "issn" => "21735808" "doi" => "10.1016/j.nrleng.2016.11.001" "estado" => "S300" "fechaPublicacion" => "2017-07-01" "aid" => "810" "copyright" => "Sociedad Española de Neurología" "documento" => "simple-article" "crossmark" => 1 "licencia" => "http://creativecommons.org/licenses/by-nc-nd/4.0/" "subdocumento" => "cor" "cita" => "Neurologia. 2017;32:404-7" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:2 [ "total" => 1089 "formatos" => array:3 [ "EPUB" => 62 "HTML" => 750 "PDF" => 277 ] ] "en" => array:11 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Intravenous thrombolysis and thrombectomy in young patients with ischaemic stroke due to undetected atrial myxoma: Do recent clinical trials provide sufficient evidence to support reperfusion in these cases?" "tienePdf" => "en" "tieneTextoCompleto" => "en" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "404" "paginaFinal" => "407" ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Trombólisis intravenosa y trombectomía en paciente joven con ictus isquémico por mixoma auricular desconocido: ¿hay suficiente evidencia en los recientes ensayos clínicos de reperfusión para estos casos?" ] ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1422 "Ancho" => 1900 "Tamanyo" => 453252 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">(A) Simple cranial CT scan (axial slice). (B) Thoracic CT-angiography showing an intracardiac mass (M). (C) Thrombus in the left subclavian and vertebral arteries. (D) Artery angiogram (lateral projection) showing occlusion of the right internal carotid artery. (E) Left internal carotid artery angiogram (anteroposterior projection) displaying a thrombus at the bifurcation of the M2 segment of the left middle cerebral artery with considerable pial collateral circulation to the right hemisphere. (F) Angiogram of the right vertebral artery with retrograde flow from the left vertebral artery and occlusion of the P1 segment of the right posterior cerebral artery.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "E. Zapata-Arriaza, B. Pardo-Galiana, A. González-García, J. Montaner Villalonga" "autores" => array:4 [ 0 => array:2 [ "nombre" => "E." "apellidos" => "Zapata-Arriaza" ] 1 => array:2 [ "nombre" => "B." "apellidos" => "Pardo-Galiana" ] 2 => array:2 [ "nombre" => "A." "apellidos" => "González-García" ] 3 => array:2 [ "nombre" => "J." "apellidos" => "Montaner Villalonga" ] ] ] ] ] "idiomaDefecto" => "en" "Traduccion" => array:1 [ "es" => array:9 [ "pii" => "S0213485315002327" "doi" => "10.1016/j.nrl.2015.10.004" "estado" => "S300" "subdocumento" => "" "abierto" => array:3 [ "ES" => true "ES2" => true "LATM" => true ] "gratuito" => true "lecturas" => array:1 [ "total" => 0 ] "idiomaDefecto" => "es" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0213485315002327?idApp=UINPBA00004N" ] ] "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580816301237?idApp=UINPBA00004N" "url" => "/21735808/0000003200000006/v1_201707180027/S2173580816301237/v1_201707180027/en/main.assets" ] "en" => array:16 [ "idiomaDefecto" => true "cabecera" => "<span class="elsevierStyleTextfn">Letter to the Editor</span>" "titulo" => "Continuous infusion of apomorphine in patients with advanced Parkinson's disease and different degrees of functional disability" "tieneTextoCompleto" => true "saludo" => "Dear Editor:" "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "407" "paginaFinal" => "410" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "G. Salazar, J. Martín, M. Fragoso, M.A. Font" "autores" => array:4 [ 0 => array:4 [ "nombre" => "G." "apellidos" => "Salazar" "email" => array:1 [ 0 => "gsalaz64@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "J." "apellidos" => "Martín" ] 2 => array:2 [ "nombre" => "M." "apellidos" => "Fragoso" ] 3 => array:2 [ "nombre" => "M.A." "apellidos" => "Font" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Servicio de Neurología, Hospital Consorci Sanitari de Terrassa, Barcelona, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Apomorfina en bomba de perfusión continua en pacientes con enfermedad de Parkinson avanzada con diferente grado de afectación funcional" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1064 "Ancho" => 1578 "Tamanyo" => 110527 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Percentages of improvement in the outcome variables in patients with moderate (group A) and severe (group B) functional disability. Patients with moderate functional disability displayed more marked improvements in all areas; differences were statistically significant for motor fluctuations (MF), Schwab & England Activities of Daily Living Scale (S&E) rates, Abnormal Involuntary Movement Scale (AIMS) scores, and Hospital Anxiety and Depression Scale (HADS-A and HADS-B).</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Progression of Parkinson's disease (PD) is associated with significantly decreased mobility, increased risk of falls, and such non-motor symptoms as cognitive and psychotic disorders. The main phenotypic manifestations of advanced PD (APD) are motor fluctuations, severe dyskinesia, axial motor symptoms resistant to levodopa, and non-motor symptoms such as cognitive impairment.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">1</span></a> Conventional treatment, which fails to control symptoms satisfactorily in these patients, is usually administered to patients on H&Y stages 4 or 5. Approximately 50% of patients with PD display alterations characteristic of APD 5 years after clinical diagnosis; such alterations include motor fluctuations, non-motor symptoms, and treatment-induced dyskinesia.<a class="elsevierStyleCrossRef" href="#bib0085"><span class="elsevierStyleSup">2</span></a> Treatment with continuous infusion of apomorphine (CIA) has been found to effectively improve motor symptoms and overall function in patients with APD.<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">3–5</span></a> However, the literature provides little information on the effectiveness of CIA according to the degree of functional disability in these patients. With this in mind, we conducted an observational study to determine the effectiveness and tolerability of CIA in patients with APD and different degrees of functional disability. We believe that our partial results are worth publishing.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0005">Patients and methods</span><p id="par0010" class="elsevierStylePara elsevierViewall">We included consecutive patients with PD, diagnosed according to the Queen Square Brain Bank diagnostic criteria,<a class="elsevierStyleCrossRef" href="#bib0105"><span class="elsevierStyleSup">6</span></a> who were attended in the Parkinson's and movement disorders unit at Consorci Sanitari de Terrassa (Barcelona, Spain); all patients were in advanced stages of the disease. The included patients had motor and non-motor fluctuations and experienced disabling ‘off’ periods. These patients were offered initiation of treatment with continuous subcutaneous infusion of apomorphine in line with the indications listed on the summary of product characteristics.<a class="elsevierStyleCrossRef" href="#bib0110"><span class="elsevierStyleSup">7</span></a> All patients signed informed consent forms before inclusion. Our study was approved by the hospital's Clinical Research Ethics Committee.</p><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Assessment of functional disability and patient classification</span><p id="par0015" class="elsevierStylePara elsevierViewall">Participants were categorised in 2 groups: a) patients with APD and moderate functional disability, defined as rates of 60% to 80% on the Schwab & England Activities of Daily Living Scale (S&E) and H&Y stages 2 to 3 (group A); and b) patients with APD and severe functional impairment, defined as S&E rates <<span class="elsevierStyleHsp" style=""></span>60% and H&Y stages >3 (group B).</p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Procedure</span><p id="par0020" class="elsevierStylePara elsevierViewall">We tested CIA in all patients for 3 to 4 days. The initial infusion rate of apomorphine (Apomorfina Archimedes<span class="elsevierStyleSup">®</span> 10<span class="elsevierStyleHsp" style=""></span>mg/mL, infusion solution; Archimedes Pharma Ibérica S.L., Madrid, Spain), at a concentration of 5<span class="elsevierStyleHsp" style=""></span>mg/mL, was 0.20<span class="elsevierStyleHsp" style=""></span>mL/h. Infusion speed was adjusted according to clinical response in increments of 0.20<span class="elsevierStyleHsp" style=""></span>mL/h until either symptom control was achieved or patients displayed side effects. An infusion time of 12<span class="elsevierStyleHsp" style=""></span>hours/day was recommended for all patients; doses were subsequently adjusted during follow-up visits. Antiparkinsonian drugs administered before inclusion in the study were maintained during the initial phase and progressively adjusted or discontinued during follow-up according to each patient's clinical response. Previous treatments included levodopa, dopamine agonists (pramipexole and rotigotine), and pen-injected apomorphine (APO-go PEN<span class="elsevierStyleSup">®</span> 10<span class="elsevierStyleHsp" style=""></span>mg/mL; Britannia Pharmaceuticals Ltd., Newbury, UK); the latter was used as a rescue treatment. Patients were assessed at inclusion (before starting CIA) and during follow up (at 1, 3, 6, and 12 months).</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Outcome variables</span><p id="par0025" class="elsevierStylePara elsevierViewall">1) Patient diary of motor fluctuations, 2) Abnormal Involuntary Movement Scale (AIMS) for dyskinesia, 3) Schwab & England Activities of Daily Living Scale, and 4) Hospital Anxiety and Depression Scale (HADS).</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Statistical analysis</span><p id="par0030" class="elsevierStylePara elsevierViewall">We initially conducted a descriptive analysis. Continuous variables were expressed as means<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD and qualitative variables as frequencies and percentages. Given the small sample size, we used the non-parametric Friedman test followed by the Wilcoxon signed rank test for paired comparisons in order to analyse progression of the follow-up variables at different stages of the disease. The percentages of change between baseline status and status at 12 months were compared using the Mann–Whitney <span class="elsevierStyleItalic">U</span> test. We used R statistical software for analysis. Statistical significance was set at <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.05.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Results</span><p id="par0035" class="elsevierStylePara elsevierViewall">Twelve patients with APD were included in our study; 6 of them had moderate functional disability (group A) and the remaining 6 had severe functional disability (group B). Clinical and demographic characteristics of our sample are summarised in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. Before CIA was started, all patients were receiving levodopa dosed at 728<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>mg in group A and 925<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>100<span class="elsevierStyleHsp" style=""></span>mg in group B. All patients in group A and one patient in group B also received pramipexole, and 4 patients in group B received rotigotine (as patches). Use of dopamine agonists progressively decreased during follow-up; these drugs were finally discontinued in all patients in group A at 6 months. Only one patient in group B continued to receive rotigotine dosed at 4<span class="elsevierStyleHsp" style=""></span>mg.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0040" class="elsevierStylePara elsevierViewall">Levodopa doses were not changed significantly during the study period (12 months); however, the number and volume of rescue apomorphine injections did decrease progressively in both groups.</p><p id="par0045" class="elsevierStylePara elsevierViewall">Apomorphine infusion speed at the beginning of the follow-up period was 0.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.2<span class="elsevierStyleHsp" style=""></span>mL/h in group A and 0.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.2<span class="elsevierStyleHsp" style=""></span>mL/h in group B. Infusion speed was increased progressively in both groups until reaching 1.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.2<span class="elsevierStyleHsp" style=""></span>mL/h in group A and 0.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.1<span class="elsevierStyleHsp" style=""></span>mL/h in group B by the end of the study period.</p><p id="par0050" class="elsevierStylePara elsevierViewall">Regarding clinical variables, motor fluctuations in patients in group A had decreased by 63.9% at the last follow-up consultation. These fluctuations were reported to last approximately 2<span class="elsevierStyleHsp" style=""></span>hours of every 12<span class="elsevierStyleHsp" style=""></span>hours in the last follow-up visit, compared to 5.5<span class="elsevierStyleHsp" style=""></span>hours in the baseline consultation (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>). During this period, dyskinesia decreased by 85.7% according to the AIMS; significant improvements were also observed in S&E rates (28.6%) (<a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>).</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia><p id="par0055" class="elsevierStylePara elsevierViewall">Patients in group B also experienced improvements for all variables, although these were less marked. Motor fluctuations had decreased by 56.4% at 12 months of follow-up (from 7.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6<span class="elsevierStyleHsp" style=""></span>h/12<span class="elsevierStyleHsp" style=""></span>h to 3.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6<span class="elsevierStyleHsp" style=""></span>h/12<span class="elsevierStyleHsp" style=""></span>h); dyskinesia decreased by 74.0%, and S&E rates improved by 16.7%, with a mean independence rate of 70% at the end of the study period (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>).</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">Patients with moderate functional disability achieved higher percentages of improvement after 12 months of treatment with CIA than patients with severe functional disability for all tests; differences were statistically significant for AIMS scores and S&E rates (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>).</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0065" class="elsevierStylePara elsevierViewall">Regarding tolerance to treatment, 4 patients in group A had nausea, which was effectively controlled with 10<span class="elsevierStyleHsp" style=""></span>mg domperidone every 8<span class="elsevierStyleHsp" style=""></span>hours, with no need to reduce apomorphine doses. However, domperidone only achieved partial relief in 3 patients from group B who also experienced nausea; in these cases, symptoms were resolved by reducing the dose of CIA. None of the patients reported hallucinations, although 2 patients from group B experienced hypersexuality and delusion of jealousy; these symptoms improved when the dose was reduced, with no need for antipsychotics. Lastly, 4 patients developed small subcutaneous nodules<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">8</span></a> (fewer than 3 palpable nodules in the infusion area) and displayed few or no skin marks. Nodules were painless, measured 1<span class="elsevierStyleHsp" style=""></span>cm in diameter, showed no signs of local infection, and were largely inconsequential for patients and carers. Only 2 of these patients required treatment (anti-inflammatory ointments and ice) at the affected area.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">In the past few years, several studies have proved the effectiveness of CIA for improving motor and non-motor symptoms and quality of life in patients with APD.<a class="elsevierStyleCrossRefs" href="#bib0120"><span class="elsevierStyleSup">9–11</span></a> However, the published studies addressing the effectiveness of CIA in APD display heterogeneous criteria for when to start treatment in terms of time since diagnosis or symptom progression. The patients included in these studies have severely impaired functions<a class="elsevierStyleCrossRefs" href="#bib0090"><span class="elsevierStyleSup">3–5</span></a>; this seems to be linked to high rates of side effects or of loss of efficacy which lead to a short mean treatment duration (around 26 months) and treatment discontinuation.<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">12</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">In our study, we observed that patients with APD and moderate functional disability experienced greater overall improvement than did those with severe functional disability during a one-year follow-up period (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). This was true for scales measuring functional independence, motor fluctuations, dyskinesia, and emotional state.</p><p id="par0080" class="elsevierStylePara elsevierViewall">At the beginning of the study period, patients with severe functional disability showed poorer executive function, greater gait instability, and more marked overall cognitive impairment leading to a higher level of dependence. We hypothesise that this greater impairment at baseline in group B prevented patients from displaying the more marked functional improvements as seen in group A. Some researchers have recently suggested that CIA should be considered for patients in earlier stages of the disease than is generally contemplated in current clinical practice.<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">13–15</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">In our study, levodopa doses did not change significantly during the follow-up period; some dopamine agonists, however, were successfully discontinued. At the end of the follow-up period, patients with moderate functional disability were receiving higher apomorphine doses to control symptoms. One potential explanation is that, as a general rule, patients with more severe functional disability did not tolerate higher doses due to side effects, which were usually mild but nonetheless forced clinicians to administer lower doses. Lower doses are very probably responsible for the more discreet improvements in this group.</p><p id="par0090" class="elsevierStylePara elsevierViewall">This study has the limitations inherent to a single-centre observational study with a small sample size; its results, however, offer preliminary data on a topic that should be thoroughly addressed. Our results suggest new treatment options for patients with APD and moderate functional disability who are resistant to conventional treatment, and complement the results of other studies addressing treatment alternatives for APD. Greater overall impairment may reduce the benefits of treatment with CIA in APD. These findings suggest that CIA may be more beneficial for eligible patients with APC who have moderate functional and cognitive impairment and are not severely dependent. This idea should be explored further in studies with larger sample sizes and longer follow-up times to deliver more robust conclusions.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Funding</span><p id="par0095" class="elsevierStylePara elsevierViewall">This study was financed by <span class="elsevierStyleGrantSponsor" id="gs1">Joan Costa Roma Foundation</span>. Consorci Sanitari de Terrassa, Terrassa, Barcelona, Spain.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:5 [ 0 => array:3 [ "identificador" => "sec0005" "titulo" => "Patients and methods" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0010" "titulo" => "Assessment of functional disability and patient classification" ] 1 => array:2 [ "identificador" => "sec0015" "titulo" => "Procedure" ] 2 => array:2 [ "identificador" => "sec0020" "titulo" => "Outcome variables" ] 3 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical analysis" ] ] ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Results" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Discussion" ] 3 => array:2 [ "identificador" => "sec0040" "titulo" => "Funding" ] 4 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Salazar G, Martín J, Fragoso M, Font MA. Apomorfina en bomba de perfusión continua en pacientes con enfermedad de Parkinson avanzada con diferente grado de afectación funcional. Neurología. 2017;32:407–410.</p>" ] ] "multimedia" => array:4 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1064 "Ancho" => 1578 "Tamanyo" => 110527 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Percentages of improvement in the outcome variables in patients with moderate (group A) and severe (group B) functional disability. Patients with moderate functional disability displayed more marked improvements in all areas; differences were statistically significant for motor fluctuations (MF), Schwab & England Activities of Daily Living Scale (S&E) rates, Abnormal Involuntary Movement Scale (AIMS) scores, and Hospital Anxiety and Depression Scale (HADS-A and HADS-B).</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:1 [ "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="table-head " align="" valign="top" scope="col" style="border-bottom: 2px solid black"> \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group A<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6 \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Group B<br><span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>6 \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Sex (women/men) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3/3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1/5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Disease onset (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.9 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Age (years) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>3.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">78.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.5 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">H&Y stage \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">S&E score (mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD and <span class="elsevierStyleItalic">n</span> [%]) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">65.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.5<br>3 (60%)<br>3 (70%) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">46.7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.2<br>4 (50%)<br>2 (40%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Disease duration (years)<br>‘Off’ time (h/12<span class="elsevierStyleHsp" style=""></span>h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.9<br>5.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.9<br>7.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Levodopa \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">728<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>100 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">925<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>100 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">‘On’ time with dyskinesia (h/12<span class="elsevierStyleHsp" style=""></span>h) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.1 \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1460560.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Baseline demographic and clinical characteristics of patients with APD by degree of functional disability: moderate (Group A) and severe (Group B).</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:2 [ "leyenda" => "<p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Analysis performed using the Friedman test.</p><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">AIMS: Abnormal Involuntary Movement Scale; CIA: continuous infusion of apomorphine; MF: motor fluctuations; HADS: Hospital Anxiety (A) and Depression (D) Scale; S&E: Schwab & England Activities of Daily Living Scale.</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="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Mean</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Baseline (before CIA) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">3 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">6 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">12 months (end of study) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">% of improvement baseline – end of study \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span>-value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">MF in 12<span class="elsevierStyleHsp" style=""></span>h</td><td class="td" title="table-entry " align="left" valign="top">5.5<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">0.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">63.9% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.001* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">AIMS</td><td class="td" title="table-entry " align="left" valign="top">14<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">85.7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><.001* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">S&E rate</td><td class="td" title="table-entry " align="left" valign="top">70% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">90% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">28.6% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><.001* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">HADS</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">8.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">24.1% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.008* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">13<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">10.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">39.9% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.001* \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1460559.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Follow-up results for motor symptoms, non-motor symptoms, and emotional status in patients with moderate functional disability (group A).</p>" ] ] 3 => array:8 [ "identificador" => "tbl0015" "etiqueta" => "Table 3" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at3" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Analysis performed using the Friedman test.</p><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">AIMS: Abnormal Involuntary Movement Scale; CIA: continuous infusion of apomorphine; MF: motor fluctuations; HADS: Hospital Anxiety (A) and Depression (D) Scale; S&E: Schwab & England Activities of Daily Living Scale.</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="table-head " colspan="2" align="center" valign="top" scope="col" style="border-bottom: 2px solid black">Mean</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age at symptom onset (before CIA) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">3 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">6 months \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">12 months (end of study) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">% of improvement baseline – end of study \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black"><span class="elsevierStyleItalic">P</span>-value \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">MF in 12<span class="elsevierStyleHsp" style=""></span>h</td><td class="td" title="table-entry " align="left" valign="top">7.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.1 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">56.4% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.001* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">AIMS</td><td class="td" title="table-entry " align="left" valign="top">16<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">5.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">4.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">74.0% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.001* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " colspan="2" align="left" valign="top">S&E rate</td><td class="td" title="table-entry " align="left" valign="top">60% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">70% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">16.7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top"><.001* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="table-entry " rowspan="2" align="left" valign="top">HADS</td><td class="td" title="table-entry " align="left" valign="top">A \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">9.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">7.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">21.7% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.016* \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">D \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">19.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>8.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">14.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.2 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">12.9<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.5 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">32.1% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="char" valign="top">.001* \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1460561.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Follow-up results for motor symptoms, non-motor symptoms, and emotional status in patients with severe functional disability (group B).</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:15 [ 0 => array:3 [ "identificador" => "bib0080" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Advanced Parkinson's disease: clinical characteristics and treatment, Part I" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "J. Kulisevsky" 1 => "M.R. Luquin" 2 => "J.M. Arbelo" 3 => "J.A. Burguera" 4 => "F. Carrillo" 5 => "A. Castro" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.nrl.2013.05.001" "Revista" => array:6 [ "tituloSerie" => "Neurologia" "fecha" => "2013" "volumen" => "28" "paginaInicial" => "503" "paginaFinal" => "521" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23856182" "web" => "Medline" ] ] ] ] ] ] ] ] 1 => array:3 [ "identificador" => "bib0085" "etiqueta" => "2" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Progression of Parkinson's disease in the clinical phase: potential markers" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "W. Maetzler" 1 => "I. Liepelt" 2 => "D. Berg" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/S1474-4422(09)70291-1" "Revista" => array:6 [ "tituloSerie" => "Lancet Neurol" "fecha" => "2009" "volumen" => "8" "paginaInicial" => "1158" "paginaFinal" => "1171" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19909914" "web" => "Medline" ] ] ] ] ] ] ] ] 2 => array:3 [ "identificador" => "bib0090" "etiqueta" => "3" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Efficacy of long-term continuous subcutaneous apomorphine infusion in advanced Parkinson's disease with motor fluctuations: a multicenter study" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P.J. García Ruiz" 1 => "A. Sesar Ignacio" 2 => "B. Ares Pensado" 3 => "A. Castro García" 4 => "F. Alonso Frech" 5 => "M. Alvarez López" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/mds.22063" "Revista" => array:6 [ "tituloSerie" => "Mov Disord" "fecha" => "2008" "volumen" => "23" "paginaInicial" => "1130" "paginaFinal" => "1136" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/18442107" "web" => "Medline" ] ] ] ] ] ] ] ] 3 => array:3 [ "identificador" => "bib0095" "etiqueta" => "4" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Continuous subcutaneous apomorphine therapy improves dyskinesias in Parkinson's disease: a prospective study using single-dose challenges" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "R. Katzenschlager" 1 => "A. Hughes" 2 => "A. Evans" 3 => "A.J. Manson" 4 => "M. Hoffman" 5 => "L. Swinn" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/mds.20276" "Revista" => array:6 [ "tituloSerie" => "Mov Disord" "fecha" => "2005" "volumen" => "20" "paginaInicial" => "151" "paginaFinal" => "157" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15390035" "web" => "Medline" ] ] ] ] ] ] ] ] 4 => array:3 [ "identificador" => "bib0100" "etiqueta" => "5" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EuroInf: a multicenter comparative observational study of apomorphine and levodopa infusion in Parkinson's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "P. Martínez-Martín" 1 => "P. Reddy" 2 => "R. Katzenschlager" 3 => "A. Antonini" 4 => "A. Todorova" 5 => "P. Odin" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1002/mds.26067" "Revista" => array:6 [ "tituloSerie" => "Mov Disord" "fecha" => "2015" "volumen" => "30" "paginaInicial" => "510" "paginaFinal" => "516" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/25382161" "web" => "Medline" ] ] ] ] ] ] ] ] 5 => array:3 [ "identificador" => "bib0105" "etiqueta" => "6" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "EFNS/MDS-ES/ENS corrected recommendations for the diagnosis of Parkinson's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "A. Berardelli" 1 => "G.K. Wenning" 2 => "A. Antonini" 3 => "D. Berg" 4 => "B.R. Bloem" 5 => "V. Bonifati" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1111/ene.12022" "Revista" => array:6 [ "tituloSerie" => "Eur J Neurol" "fecha" => "2013" "volumen" => "20" "paginaInicial" => "16" "paginaFinal" => "34" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23279440" "web" => "Medline" ] ] ] ] ] ] ] ] 6 => array:3 [ "identificador" => "bib0110" "etiqueta" => "7" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "Available from: <span class="elsevierStyleInterRef" id="intr0010" href="http://www.aemps.gob.es/cima/pdfs/es/ft/72074/P_72074.pdf">http://www.aemps.gob.es/cima/pdfs/es/ft/72074/P_72074.pdf</span> [accessed May 2015]" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Ficha Técnica: Apomorfina Archimedes 10<span class="elsevierStyleHsp" style=""></span>mg/ml solución inyectable/para perfusión revista electrónica" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Libro" => array:1 [ "fecha" => "2013" ] ] ] ] ] ] 7 => array:3 [ "identificador" => "bib0115" "etiqueta" => "8" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Apomorphine nodules in Parkinson's disease: best practice considerations" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Todd" 1 => "C.A. James" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.12968/bjcn.2008.13.10.31182" "Revista" => array:6 [ "tituloSerie" => "Br J Community Nurs" "fecha" => "2008" "volumen" => "13" "paginaInicial" => "457" "paginaFinal" => "463" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19057470" "web" => "Medline" ] ] ] ] ] ] ] ] 8 => array:3 [ "identificador" => "bib0120" "etiqueta" => "9" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Subcutaneous apomorphine: an evidence-based review of its use in Parkinson's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:3 [ 0 => "D. Deleu" 1 => "Y. Hanssens" 2 => "M.G. Northway" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "Drugs Aging" "fecha" => "2004" "volumen" => "21" "paginaInicial" => "687" "paginaFinal" => "709" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/15323576" "web" => "Medline" ] ] ] ] ] ] ] ] 9 => array:3 [ "identificador" => "bib0125" "etiqueta" => "10" "referencia" => array:1 [ 0 => array:3 [ "comentario" => "7–8" "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Apomorphine in the treatment of Parkinson's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "P. Hagell" 1 => "P. Odin" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:6 [ "tituloSerie" => "J Neurosci Nurs" "fecha" => "2001" "volumen" => "33" "paginaInicial" => "21" "paginaFinal" => "34" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/11233359" "web" => "Medline" ] ] ] ] ] ] ] ] 10 => array:3 [ "identificador" => "bib0130" "etiqueta" => "11" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Continuous apomorphine infusion (CAI) and neuropsychiatric disorders in patients with advanced Parkinson's disease: a follow-up of two years" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "L. Morgante" 1 => "G. Basile" 2 => "A. Epifanio" 3 => "E. Spina" 4 => "A. Antonini" 5 => "F. Stocchi" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1016/j.archger.2004.04.039" "Revista" => array:6 [ "tituloSerie" => "Arch Gerontol Geriatr Suppl" "fecha" => "2004" "volumen" => "38" "numero" => "Suppl 9" "paginaInicial" => "291" "paginaFinal" => "296" ] ] ] ] ] ] 11 => array:3 [ "identificador" => "bib0135" "etiqueta" => "12" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "When the going gets tough: how to select patients with Parkinson's disease for advanced therapies" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "P.F. Worth" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1136/practneurol-2012-000463" "Revista" => array:6 [ "tituloSerie" => "Pract Neurol" "fecha" => "2013" "volumen" => "13" "paginaInicial" => "140" "paginaFinal" => "152" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23487815" "web" => "Medline" ] ] ] ] ] ] ] ] 12 => array:3 [ "identificador" => "bib0140" "etiqueta" => "13" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Subcutaneous continuous apomorphine infusion: treatment initiation and follow up" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "F.J. Grandas" 1 => "A. Sesar-Ignacio" ] ] ] ] ] "host" => array:1 [ 0 => array:1 [ "Revista" => array:7 [ "tituloSerie" => "Rev Neurol" "fecha" => "2012" "volumen" => "55" "numero" => "Suppl 1" "paginaInicial" => "S21" "paginaFinal" => "S24" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/23169229" "web" => "Medline" ] ] ] ] ] ] ] ] 13 => array:3 [ "identificador" => "bib0145" "etiqueta" => "14" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Apomorphine and levodopa infusion therapies for advanced Parkinson's disease: selection criteria and patient management" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "A. Antonini" 1 => "E. Tolosa" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1586/ern.09.48" "Revista" => array:6 [ "tituloSerie" => "Expert Rev Neurother" "fecha" => "2009" "volumen" => "9" "paginaInicial" => "859" "paginaFinal" => "867" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/19496689" "web" => "Medline" ] ] ] ] ] ] ] ] 14 => array:3 [ "identificador" => "bib0150" "etiqueta" => "15" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Subcutaneous infusions of apomorphine: a reappraisal of its therapeutic efficacy in advanced Parkinson's disease" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:1 [ 0 => "F. Grandas" ] ] ] ] ] "host" => array:1 [ 0 => array:2 [ "doi" => "10.1586/14737175.2013.839235" "Revista" => array:6 [ "tituloSerie" => "Expert Rev Neurother" "fecha" => "2013" "volumen" => "13" "paginaInicial" => "1343" "paginaFinal" => "1353" "link" => array:1 [ 0 => array:2 [ "url" => "https://www.ncbi.nlm.nih.gov/pubmed/24160681" "web" => "Medline" ] ] ] ] ] ] ] ] ] ] ] ] ] "idiomaDefecto" => "en" "url" => "/21735808/0000003200000006/v1_201707180027/S2173580817300056/v1_201707180027/en/main.assets" "Apartado" => array:4 [ "identificador" => "9409" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Letters to the editor" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/21735808/0000003200000006/v1_201707180027/S2173580817300056/v1_201707180027/en/main.pdf?idApp=UINPBA00004N&text.app=https://www.elsevier.es/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S2173580817300056?idApp=UINPBA00004N" ]
| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 October | 18 | 10 | 28 |
| 2024 September | 23 | 7 | 30 |
| 2024 August | 25 | 7 | 32 |
| 2024 July | 21 | 7 | 28 |
| 2024 June | 17 | 0 | 17 |
| 2024 May | 16 | 4 | 20 |
| 2024 April | 28 | 4 | 32 |
| 2024 March | 30 | 6 | 36 |
| 2024 February | 16 | 2 | 18 |
| 2024 January | 23 | 10 | 33 |
| 2023 December | 21 | 8 | 29 |
| 2023 November | 26 | 2 | 28 |
| 2023 October | 46 | 13 | 59 |
| 2023 September | 11 | 3 | 14 |
| 2023 August | 19 | 8 | 27 |
| 2023 July | 20 | 5 | 25 |
| 2023 June | 30 | 9 | 39 |
| 2023 May | 35 | 3 | 38 |
| 2023 April | 63 | 1 | 64 |
| 2023 March | 45 | 9 | 54 |
| 2023 February | 22 | 8 | 30 |
| 2023 January | 21 | 2 | 23 |
| 2022 December | 35 | 6 | 41 |
| 2022 November | 38 | 13 | 51 |
| 2022 October | 25 | 8 | 33 |
| 2022 September | 30 | 8 | 38 |
| 2022 August | 38 | 8 | 46 |
| 2022 July | 41 | 9 | 50 |
| 2022 June | 49 | 11 | 60 |
| 2022 May | 64 | 6 | 70 |
| 2022 April | 95 | 9 | 104 |
| 2022 March | 133 | 6 | 139 |
| 2022 February | 163 | 7 | 170 |
| 2022 January | 113 | 10 | 123 |
| 2021 December | 92 | 11 | 103 |
| 2021 November | 108 | 8 | 116 |
| 2021 October | 66 | 14 | 80 |
| 2021 September | 66 | 14 | 80 |
| 2021 August | 83 | 3 | 86 |
| 2021 July | 52 | 18 | 70 |
| 2021 June | 38 | 14 | 52 |
| 2021 May | 41 | 11 | 52 |
| 2021 April | 102 | 38 | 140 |
| 2021 March | 63 | 15 | 78 |
| 2021 February | 64 | 12 | 76 |
| 2021 January | 55 | 10 | 65 |
| 2020 December | 54 | 10 | 64 |
| 2020 November | 70 | 13 | 83 |
| 2020 October | 42 | 8 | 50 |
| 2020 September | 34 | 16 | 50 |
| 2020 August | 49 | 6 | 55 |
| 2020 July | 55 | 7 | 62 |
| 2020 June | 57 | 19 | 76 |
| 2020 May | 60 | 18 | 78 |
| 2020 April | 47 | 7 | 54 |
| 2020 March | 47 | 20 | 67 |
| 2020 February | 41 | 7 | 48 |
| 2020 January | 41 | 8 | 49 |
| 2019 December | 31 | 11 | 42 |
| 2019 November | 28 | 9 | 37 |
| 2019 October | 20 | 2 | 22 |
| 2019 September | 22 | 10 | 32 |
| 2019 August | 12 | 2 | 14 |
| 2019 July | 30 | 15 | 45 |
| 2019 June | 67 | 32 | 99 |
| 2019 May | 132 | 46 | 178 |
| 2019 April | 61 | 5 | 66 |
| 2019 March | 20 | 3 | 23 |
| 2019 February | 17 | 6 | 23 |
| 2019 January | 15 | 2 | 17 |
| 2018 December | 9 | 0 | 9 |
| 2018 November | 14 | 11 | 25 |
| 2018 October | 19 | 7 | 26 |
| 2018 September | 27 | 6 | 33 |
| 2018 August | 7 | 2 | 9 |
| 2018 July | 21 | 2 | 23 |
| 2018 June | 18 | 1 | 19 |
| 2018 May | 18 | 3 | 21 |
| 2018 April | 13 | 1 | 14 |
| 2018 March | 7 | 0 | 7 |
| 2018 February | 64 | 9 | 73 |
| 2018 January | 5 | 1 | 6 |
| 2017 December | 15 | 1 | 16 |
| 2017 November | 11 | 4 | 15 |
| 2017 October | 6 | 1 | 7 |
| 2017 September | 13 | 2 | 15 |
| 2017 August | 29 | 5 | 34 |
| 2017 July | 14 | 11 | 25 |
| 2017 June | 0 | 1 | 1 |
| 2017 May | 1 | 2 | 3 |
| 2017 April | 2 | 2 | 4 |
| 2017 March | 4 | 1 | 5 |
| 2017 February | 1 | 5 | 6 |
Show all
