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class="elsevierStyleTextfn">Original Article</span>" "titulo" => "Respiratory Center Function and Its Impact in Obesity Hypoventilation Syndrome Treatment" "tienePdf" => "en" "tieneTextoCompleto" => "en" "tieneResumen" => array:2 [ 0 => "en" 1 => "en" ] "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "497" "paginaFinal" => "501" ] ] "contieneResumen" => array:1 [ "en" => true ] "contieneTextoCompleto" => array:1 [ "en" => true ] "contienePdf" => array:1 [ "en" => true ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0010" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 649 "Ancho" => 1333 "Tamanyo" => 46153 ] ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "Inés Ruiz Álvarez, Ramón Fernández Álvarez, Gemma Rubinos Cuadrado, María José Vázquez López, Marta García Clemente" "autores" => array:5 [ 0 => array:2 [ "nombre" => "Inés" "apellidos" => "Ruiz Álvarez" ] 1 => array:2 [ "nombre" => "Ramón" "apellidos" => "Fernández Álvarez" ] 2 => array:2 [ "nombre" => "Gemma" "apellidos" => "Rubinos Cuadrado" ] 3 => array:2 [ "nombre" => "María José" "apellidos" => "Vázquez López" ] 4 => array:2 [ "nombre" => "Marta" "apellidos" => "García Clemente" ] ] ] ] "resumen" => array:1 [ 0 => array:3 [ "titulo" => "Graphical abstract" "clase" => "graphical" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall"><elsevierMultimedia ident="fig0010"></elsevierMultimedia></p></span>" ] ] ] "idiomaDefecto" => "en" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S0300289623001710?idApp=UINPBA00003Z" "url" => "/03002896/0000005900000008/v3_202311210631/S0300289623001710/v3_202311210631/en/main.assets" ] "itemAnterior" => array:18 [ "pii" => "S0300289623001631" "issn" => "03002896" "doi" => 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Wijkstra, Hélène Prigent, Jean-Louis Pepin, Frederic Lofaso, Charles Khouri, Jean-Christian Borel" "autores" => array:19 [ 0 => array:3 [ "nombre" => "Mathieu" "apellidos" => "Delorme" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] ] ] 1 => array:3 [ "nombre" => "Antoine" "apellidos" => "Leotard" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] ] ] 2 => array:3 [ "nombre" => "Marius" "apellidos" => "Lebret" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Claire" "apellidos" => "Lefeuvre" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">e</span>" "identificador" => "aff0025" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">f</span>" "identificador" => "aff0030" ] ] ] 4 => array:3 [ "nombre" => "Anda" "apellidos" => "Hazenberg" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">h</span>" "identificador" => "aff0040" ] ] ] 5 => array:3 [ "nombre" => "Mercedes" "apellidos" => "Pallero" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">i</span>" "identificador" => "aff0045" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">j</span>" "identificador" => "aff0050" ] ] ] 6 => array:3 [ "nombre" => "Annabel H." "apellidos" => "Nickol" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">k</span>" "identificador" => "aff0055" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">l</span>" "identificador" => "aff0060" ] ] ] 7 => array:3 [ "nombre" => "Liam M." "apellidos" => "Hannan" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">m</span>" "identificador" => "aff0065" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">n</span>" "identificador" => "aff0070" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">o</span>" "identificador" => "aff0075" ] ] ] 8 => array:3 [ "nombre" => "Matthias" "apellidos" => "Boentert" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">p</span>" "identificador" => "aff0080" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">q</span>" "identificador" => "aff0085" ] ] ] 9 => array:3 [ "nombre" => "Aycan" "apellidos" => "Yüksel" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">r</span>" "identificador" => "aff0090" ] ] ] 10 => array:3 [ "nombre" => "Wolfram" "apellidos" => "Windisch" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">s</span>" "identificador" => "aff0095" ] ] ] 11 => array:3 [ "nombre" => "Mark E." "apellidos" => "Howard" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">n</span>" "identificador" => "aff0070" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">o</span>" "identificador" => "aff0075" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">t</span>" "identificador" => "aff0100" ] ] ] 12 => array:3 [ "nombre" => "Nicholas" "apellidos" => "Hart" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">u</span>" "identificador" => "aff0105" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">v</span>" "identificador" => "aff0110" ] ] ] 13 => array:3 [ "nombre" => "Peter J." "apellidos" => "Wijkstra" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">g</span>" "identificador" => "aff0035" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">h</span>" "identificador" => "aff0040" ] ] ] 14 => array:3 [ "nombre" => "Hélène" "apellidos" => "Prigent" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">w</span>" "identificador" => "aff0115" ] ] ] 15 => array:3 [ "nombre" => "Jean-Louis" "apellidos" => "Pepin" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">x</span>" "identificador" => "aff0120" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">y</span>" "identificador" => "aff0125" ] ] ] 16 => array:3 [ "nombre" => "Frederic" "apellidos" => "Lofaso" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 17 => array:3 [ "nombre" => "Charles" "apellidos" => "Khouri" "referencia" => array:3 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">x</span>" "identificador" => "aff0120" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">z</span>" "identificador" => "aff0130" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] ] ] 18 => array:4 [ "nombre" => "Jean-Christian" "apellidos" => "Borel" "email" => array:1 [ 0 => "j.borel@agiradom.com" ] "referencia" => array:4 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">x</span>" "identificador" => "aff0120" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">aa</span>" "identificador" => "aff0135" ] 2 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">1</span>" "identificador" => "fn0005" ] 3 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:27 [ 0 => array:3 [ "entidad" => "Université Paris-Saclay, UVSQ, ERPHAN, Versailles, France" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "AFM-Téléthon, Direction des Actions Médicales, Evry, France" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Service de Physiologie et explorations fonctionnelles, GHU APHP – Paris Saclay – Hôpital Raymond Poincaré (APHP), Garches, France" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Université Paris-Saclay, UVSQ, INSERM U1179, Equipe 3 «END:ICAP», Versailles, France" "etiqueta" => "d" "identificador" => "aff0020" ] 4 => array:3 [ "entidad" => "Neurology Department, Raymond Poincaré University Hospital, Garches, APHP, France" "etiqueta" => "e" "identificador" => "aff0025" ] 5 => array:3 [ "entidad" => "Nord-Est-Ile-de-France Neuromuscular Reference Center, FHU PHENIX, France" "etiqueta" => "f" "identificador" => "aff0030" ] 6 => array:3 [ "entidad" => "University of Groningen, University Medical Center Groningen, Department of Pulmonology and Tuberculosis, Department of Home Mechanical Ventilation, Groningen, The Netherlands" "etiqueta" => "g" "identificador" => "aff0035" ] 7 => array:3 [ "entidad" => "University of Groningen, University Medical Center Groningen, GRIAC Research Institute, The Netherlands" "etiqueta" => "h" "identificador" => "aff0040" ] 8 => array:3 [ "entidad" => "Respiratory Medicine Department, Hospital Universitari Vall d’Hebron, Barcelona, Spain" "etiqueta" => "i" "identificador" => "aff0045" ] 9 => array:3 [ "entidad" => "CIBER de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III, Madrid, Spain" "etiqueta" => "j" "identificador" => "aff0050" ] 10 => array:3 [ "entidad" => "Oxford Centre for Respiratory Medicine, Oxford University Hospital NHS Foundation Trust, Oxford, UK" "etiqueta" => "k" "identificador" => "aff0055" ] 11 => array:3 [ "entidad" => "The Royal Brompton Hospital, London, UK" "etiqueta" => "l" "identificador" => "aff0060" ] 12 => array:3 [ "entidad" => "Department of Respiratory Medicine, Northern Health, Melbourne, Victoria, Australia" "etiqueta" => "m" "identificador" => "aff0065" ] 13 => array:3 [ "entidad" => "Institute for Breathing and Sleep, Melbourne, Australia" "etiqueta" => "n" "identificador" => "aff0070" ] 14 => array:3 [ "entidad" => "Dept of Medicine, Dentistry and Health Sciences, University of Melbourne, Melbourne, Australia" "etiqueta" => "o" "identificador" => "aff0075" ] 15 => array:3 [ "entidad" => "Department of Neurology, Münster University Hospital (UKM), Münster, Germany" "etiqueta" => "p" "identificador" => "aff0080" ] 16 => array:3 [ "entidad" => "Department of Medicine, UKM-Marienhospital Steinfurt, Steinfurt, Germany" "etiqueta" => "q" "identificador" => "aff0085" ] 17 => array:3 [ "entidad" => "Ufuk University, Faculty of Medicine, Rıdvan Ege Hospital, Department of Pulmonology and Tuberculosis, Ankara, Turkey" "etiqueta" => "r" "identificador" => "aff0090" ] 18 => array:3 [ "entidad" => "Cologne Merheim Hospital, Department of Pneumology, Kliniken der Stadt Köln, gGmbH, Witten/Herdecke University, Germany" "etiqueta" => "s" "identificador" => "aff0095" ] 19 => array:3 [ "entidad" => "Turner Institute for Brain and Mental Health, Monash University, Melbourne, Australia" "etiqueta" => "t" "identificador" => "aff0100" ] 20 => array:3 [ "entidad" => "Lane Fox Clinical Respiratory Physiology Research Centre, Guy's and St Thomas’ NHS Foundation Trust, London, UK" "etiqueta" => "u" "identificador" => "aff0105" ] 21 => array:3 [ "entidad" => "Centre for Human and Applied Physiological Science, King's College London, London, UK" "etiqueta" => "v" "identificador" => "aff0110" ] 22 => array:3 [ "entidad" => "FHU Phenix – GHU APHP – Paris Saclay – Hôpital Raymond Poincaré (APHP), Garches, France" "etiqueta" => "w" "identificador" => "aff0115" ] 23 => array:3 [ "entidad" => "HP2 (Hypoxia and Physio-Pathologies) Laboratory, Inserm (French National Institute of Health and Medical Research), University Grenoble Alpes, Grenoble, France" "etiqueta" => "x" "identificador" => "aff0120" ] 24 => array:3 [ "entidad" => "EFCR (Cardiovascular and Respiratory Function) Laboratory, Grenoble Alpes University Hospital, Grenoble, France" "etiqueta" => "y" "identificador" => "aff0125" ] 25 => array:3 [ "entidad" => "Centre Régional de pharmacovigilance, Centre d’Investigation Clinique, CHU Grenoble Alpes, France" "etiqueta" => "z" "identificador" => "aff0130" ] 26 => array:3 [ "entidad" => "Research and Development Department, AGIR à dom Association, Meylan, France" "etiqueta" => "aa" "identificador" => "aff0135" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "resumenGrafico" => array:2 [ "original" => 1 "multimedia" => array:5 [ "identificador" => "fig0020" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => false "mostrarDisplay" => true "figura" => array:1 [ 0 => array:4 [ "imagen" => "fx1.jpeg" "Alto" => 754 "Ancho" => 1333 "Tamanyo" => 176869 ] ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall">Treatment of chronic respiratory failure with long-term home noninvasive ventilation (NIV) to reduce symptom load and improve survival in patients with slowly progressive neuromuscular and chest wall disorders (NMD, CWD) is part of standard clinical practice.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">1,2</span></a> Guideline criteria for NIV initiation in stable restrictive lung disease is targeted toward relief of symptoms, which is achieved by treating nocturnal hypoventilation and chronic respiratory hypercapnia with home NIV.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">2–5</span></a> Targeted reduction of carbon dioxide is one of the main goals of NIV.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a> This implies a combination of sufficient ventilatory support to treat alveolar hypoventilation, and sufficient usage of this treatment.</p><p id="par0010" class="elsevierStylePara elsevierViewall">In chronic obstructive pulmonary disease (COPD), a common indication for home NIV, the concept of “high-intensity” NIV has led to a paradigm shift over the past decade and is gaining growing consideration.<a class="elsevierStyleCrossRefs" href="#bib0235"><span class="elsevierStyleSup">7–11</span></a> High-intensity NIV can be defined as a strategy that consists of adjusting ventilator parameters with the specific goal of reducing transcutaneous carbon dioxide (TcCO<span class="elsevierStyleInf">2</span>) and arterial partial pressure of carbon dioxide (PaCO<span class="elsevierStyleInf">2</span>) by setting sufficient levels of pressure support (PS) (or tidal volume, V<span class="elsevierStyleInf">T</span>) and back-up respiratory rate (BURR).<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">12–15</span></a> Current clinical practice guidelines clearly state that NIV should be set with the aim of reducing or normalising PaCO<span class="elsevierStyleInf">2</span> levels in individuals with COPD.<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">10,11</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">However, data suggest that NIV may not always effectively improve PaCO<span class="elsevierStyleInf">2</span> levels and reverse hypoventilation-related symptoms.<a class="elsevierStyleCrossRefs" href="#bib0280"><span class="elsevierStyleSup">16–18</span></a> For instance, 12–40% of individuals with NMD have residual hypercapnia under NIV; furthermore, residual hypercapnia is associated with negative outcomes.<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">19</span></a> Despite these findings, the concept of using higher levels of NIV intensity in individuals with NMD and CWD has never really been discussed and deserves to be evaluated.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">Our aim was to determine the extent to which, during the initial period of NIV initiation, the intensity of NIV parameters influences PaCO<span class="elsevierStyleInf">2</span> levels in individuals with chronic respiratory failure due to slowly progressive NMD or CWD. Given the small number of studies that have addressed this question, and given the heterogeneity of published data regarding participants’ diagnoses and ventilatory modes used, we undertook a systematic review with meta-analysis of individual participant data (IPD).</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Methods</span><p id="par0025" class="elsevierStylePara elsevierViewall">This systematic review and meta-analysis is reported according to the Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data (PRISMA-IPD) statement.<a class="elsevierStyleCrossRef" href="#bib0305"><span class="elsevierStyleSup">21</span></a> The study protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO, CRD42021245121: <a href="http://www.crd.york.ac.uk/prospero/">www.crd.york.ac.uk/prospero/</a>).</p><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Search strategy and selection criteria</span><p id="par0030" class="elsevierStylePara elsevierViewall">Relevant articles indexed between 1 January 2000 and 31 December 2020 were sought in Medline, Embase, and the Cochrane Central Register of Controlled Trials. Search terms were chosen to identify studies that investigated any NIV-related intervention conducted in adult participants with slowly progressive NMD or CWD. Additional details regarding the search strategy are provided in <a class="elsevierStyleCrossRef" href="#sec0115">supplementary material</a>.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Study inclusion criteria</span><p id="par0035" class="elsevierStylePara elsevierViewall">Inclusion criteria were pre-defined in the registered study protocol and applied at the study level. They included: (i) controlled or non-controlled trials, and cohort studies that included individuals with slowly progressive NMD or CWD who were naïve to long-term NIV at the time of study enrolment, (ii) studies in which participants were treated either with pressure-cycled or volume-targeted pressure support modes (<span class="elsevierStyleItalic">hybrid</span> modes) and in which NIV settings were reported, (iii) studies with a timeframe of at least 4 weeks, (iv) studies that reported PaCO<span class="elsevierStyleInf">2</span> levels at baseline and study endpoint.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Study and data selection process</span><p id="par0040" class="elsevierStylePara elsevierViewall">The titles and abstracts of studies identified from the search were independently screened by two investigators (MD and AL) using <a href="http://www.covidence.org/">www.covidence.org</a>. The selected full-text articles were then reviewed for eligibility by the same investigators and discrepancies were settled by discussion. If consensus could not be reached, a third investigator (J-CB) resolved the disagreement. The corresponding authors of each eligible study were contacted by email and asked if they would accept to share participant data. Authors were asked to complete a standardised datasheet that included the variables listed in <a class="elsevierStyleCrossRef" href="#sec0115">Supplementary Tables 1 and 2</a>, and <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. No aggregate data were sought.</p><p id="par0045" class="elsevierStylePara elsevierViewall">The risk of bias of the studies included in the meta-analysis of IPD was assessed with the revised Cochrane collaboration risk-of-bias tool for randomized trials (RoB 2),<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">22</span></a> and with the Newcastle–Ottawa quality assessment scale for cohort studies.<a class="elsevierStyleCrossRef" href="#bib0315"><span class="elsevierStyleSup">23</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Outcomes</span><p id="par0050" class="elsevierStylePara elsevierViewall">Outcomes were defined <span class="elsevierStyleItalic">a priori</span> in the registered protocol. The primary outcome was diurnal PaCO<span class="elsevierStyleInf">2</span> level at study endpoints, as reported by the authors in the published materials. Diurnal PaO<span class="elsevierStyleInf">2</span>, daily NIV usage, interface type, nocturnal oxygenation and sleep quality at study endpoints were planned to be considered as secondary outcomes.</p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Deviations from the study protocol</span><p id="par0055" class="elsevierStylePara elsevierViewall">As PS and BURR were the primary interventions evaluated in this review, studies that reported interventions with volume-cycled modes were not planned to be eligible for inclusion. However, two selected studies reported data from participants treated with both pressure-cycled and volume-cycled modes, and individual participant data were provided.<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">24,25</span></a> We therefore decided to include these data in the analysis. We processed them together with data from the hybrid modes, in which inspiratory support is also defined by <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>. Hence, the level of <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> setting, in mL/kg of predicted body weight (<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T,PBW</span>),<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">26</span></a> was added to the data analysis.</p></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Data synthesis and analysis</span><p id="par0060" class="elsevierStylePara elsevierViewall">All analyses were conducted according to the predefined statistical analysis plan outlined in the protocol. Given the low rate of missing data, we performed a complete case analysis. One outlier with a baseline PaCO<span class="elsevierStyleInf">2</span> level<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>15<span class="elsevierStyleHsp" style=""></span>kPa was excluded from the analysis of PaCO<span class="elsevierStyleInf">2</span> and two outliers with a PaO<span class="elsevierStyleInf">2</span> level<span class="elsevierStyleHsp" style=""></span>><span class="elsevierStyleHsp" style=""></span>16<span class="elsevierStyleHsp" style=""></span>kPa at study endpoints were excluded from the analysis of PaO<span class="elsevierStyleInf">2</span>.</p><p id="par0065" class="elsevierStylePara elsevierViewall">Diurnal PaCO<span class="elsevierStyleInf">2</span> level at study endpoints was analysed using a generalised linear mixed model with a random intercept for study. In the base model, baseline PaCO<span class="elsevierStyleInf">2</span>, daily NIV usage at study endpoints, and disease category (NMD <span class="elsevierStyleItalic">versus</span> CWD) were included as fixed effects. Then, all other variables were tested one by one and included in the final model if <span class="elsevierStyleItalic">p</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>0.2 and the rate of missing data was<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>10%. Lastly, the impact of ventilatory parameters (PS, <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> and BURR) was tested. We defined NIV intensity as the product of PS and BURR for pressure-cycled modes, and the product of V<span class="elsevierStyleInf">T</span> and BURR for volume-cycled and hybrid modes. We used the <span class="elsevierStyleItalic">Z</span>-scores of these values to obtain a unified measure of NIV intensity regardless of the NIV mode. By definition, mean NIV intensity of the whole cohort corresponds to a <span class="elsevierStyleItalic">Z</span>-score of 0. We defined the mean – 1SD, mean, mean<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>1SD, and mean<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>2SD of NIV intensity <span class="elsevierStyleItalic">Z</span>-scores as <span class="elsevierStyleItalic">low</span>, <span class="elsevierStyleItalic">medium</span>, <span class="elsevierStyleItalic">high</span> and <span class="elsevierStyleItalic">very high</span> NIV intensity. A conversion chart between ventilatory parameters and NIV intensity <span class="elsevierStyleItalic">Z</span>-scores is presented in <a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>. Interactions between NIV intensity, disease category and baseline PaCO<span class="elsevierStyleInf">2</span> level were also tested.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0070" class="elsevierStylePara elsevierViewall">For secondary outcomes (PaO<span class="elsevierStyleInf">2</span> and daily NIV usage), the same approach was used for the construction of the final model. Finally, to investigate the relation between interface type and NIV intensity, we identified NIV intensity as the dependent variable, and we included interface type as a fixed effect in the base model, along with baseline PaCO<span class="elsevierStyleInf">2</span> level, disease category and daily NIV usage.</p><p id="par0075" class="elsevierStylePara elsevierViewall">In the final models, the following assumptions were verified: linearity, absence of collinearity in the predictors, homoscedasticity, normality of residuals, absence of influential data points and independence. All statistical analyses were performed with <span class="elsevierStyleItalic">R</span> and Jamovi (Gamjl package), and <span class="elsevierStyleItalic">R</span> packages lmer4 and lmerTest.</p></span></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Results</span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Study selection and collection of IPD</span><p id="par0080" class="elsevierStylePara elsevierViewall">The flow-diagram of study inclusions is shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>. Of the 16 eligible studies identified, 7 authors were able to share IPD.<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">24,25,27–31</span></a> The main characteristics of the studies for which IPD were provided and of the studies for which IPD were not provided, based on the published materials, are displayed in <a class="elsevierStyleCrossRef" href="#sec0115">supplementary Table 3</a>. Of the 7 studies included in this meta-analysis, data from 192 individual participants who met the inclusion criteria were provided by the authors. We excluded 11 participants for whom insufficient data were provided for NIV settings at study endpoints, and 5 participants for whom information about diagnosis was not clear. Thus, the meta-analysis was carried out on data from 176 participants from the 7 studies: 113 with NMD, and 63 with CWD.</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Study and participants characteristics</span><p id="par0085" class="elsevierStylePara elsevierViewall">The main characteristics of the studies included are reported in <a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a>. The primary timeframe for PaCO<span class="elsevierStyleInf">2</span> evaluation was 3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1 months for three studies,<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">27–29</span></a> 6 months for three studies,<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">24,25,30</span></a> and 12 months for one study.<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a></p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><p id="par0090" class="elsevierStylePara elsevierViewall">The baseline characteristics of study participants are presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. Mean PaCO<span class="elsevierStyleInf">2</span> level before starting NIV was 6.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.4<span class="elsevierStyleHsp" style=""></span>kPa; 124 (70.5%) participants had a baseline PaCO<span class="elsevierStyleInf">2</span> level ≥6.0<span class="elsevierStyleHsp" style=""></span>kPa, 65 (57.5%) with NMD and 59 (93.7%) with CWD. Mean FVC was 49.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>19.6%; 102 (58.0%) participants had baseline FVC<span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>50% predicted, 52 (46.0%) with NMD and 50 (79.4%) with CWD. Additional information is provided in <a class="elsevierStyleCrossRef" href="#sec0115">supplementary Tables 1 and 2</a>.</p><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Risk of bias and IPD integrity</span><p id="par0095" class="elsevierStylePara elsevierViewall">The risk of bias assessment identified some concerns in five of the included studies,<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">25,27,28,30,31</span></a> and the remaining two studies were found to have a low risk of bias.<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">24,29</span></a> The most common concerns for the RCTs related to insufficient information about concealment of the intervention and/or the number of dropouts. Concerns for the cohort studies related to the lack of a control group. Details of the risk of bias analysis are provided in <a class="elsevierStyleCrossRef" href="#sec0115">supplementary Fig. 1</a>. The IPD provided were consistent with published aggregate data.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">NIV settings</span><p id="par0100" class="elsevierStylePara elsevierViewall">The main NIV settings at study endpoints are presented in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. Six of the included studies explicitly mentioned that the ventilatory parameter adjustment (PS or <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>) was guided by a balance between the individual's tolerance and an effective reduction in daytime PaCO<span class="elsevierStyleInf">2</span> level or mean nocturnal TcCO<span class="elsevierStyleInf">2</span>.<a class="elsevierStyleCrossRefs" href="#bib0320"><span class="elsevierStyleSup">24,25,27,29–31</span></a> The remaining study reported that adjustments were mainly driven by the presence of residual sleep-disordered breathing.<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a> Four of the included studies reported on the strategy used to adjust the backup respiratory rate; it was commonly set about two cycles below the individual's spontaneous awake respiratory rate.<a class="elsevierStyleCrossRefs" href="#bib0325"><span class="elsevierStyleSup">25,28–30</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">Ventilation for pressure-cycled modes was set with a mean PS of 12.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.3<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O (range: 2–28<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O). Volume-cycled and hybrid modes were set with a mean target <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> of 621<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>159<span class="elsevierStyleHsp" style=""></span>mL, corresponding to 10.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.0<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleInf">PBW</span><span class="elsevierStyleSup">−1</span> (range: 4.9–22.8<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleInf">PBW</span><span class="elsevierStyleSup">−1</span>). Mean BURR was 15.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.9<span class="elsevierStyleHsp" style=""></span>breaths/min, ranging from 8 to 24<span class="elsevierStyleHsp" style=""></span>breaths/min. Overall NIV intensity <span class="elsevierStyleItalic">Z</span>-scores ranged from −1.7 to 4.2, and mean values were higher for the CWD (0.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.0) than the NMD (−0.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>0.8) group (<a class="elsevierStyleCrossRef" href="#sec0115">supplementary Fig. 2</a>).</p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Primary outcome: effects of NIV settings on PaCO<span class="elsevierStyleInf">2</span> level</span><p id="par0110" class="elsevierStylePara elsevierViewall">The results of the final multivariate models for PaCO<span class="elsevierStyleInf">2</span> are presented in <a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>. NIV intensity <span class="elsevierStyleItalic">per se</span> was not significantly associated with PaCO<span class="elsevierStyleInf">2</span> level at study endpoints. A lower PaCO<span class="elsevierStyleInf">2</span> level at study endpoints was independently associated with a lower baseline PaCO<span class="elsevierStyleInf">2</span> level and greater amount of daily NIV usage. These results held true when considering PS (or <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>) and BURR separately.</p><elsevierMultimedia ident="tbl0015"></elsevierMultimedia><p id="par0115" class="elsevierStylePara elsevierViewall">In addition, a multiple interaction associated with a lower PaCO<span class="elsevierStyleInf">2</span> level at study endpoints was identified, including a higher baseline PaCO<span class="elsevierStyleInf">2</span> level, diagnosis of CWD, and higher NIV intensity (<a class="elsevierStyleCrossRef" href="#tbl0015">Table 3</a>). Indeed, as shown in <a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>, the reduction of PaCO<span class="elsevierStyleInf">2</span> between baseline and study endpoints was greater for higher baseline PaCO<span class="elsevierStyleInf">2</span> levels, and this reduction was associated with higher NIV intensity only in CWD.</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia><p id="par0120" class="elsevierStylePara elsevierViewall">In a sensitivity analysis, we included only patients with baseline PaCO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>kPa and re-ran the final multivariate regression model. The results confirmed that NIV intensity <span class="elsevierStyleItalic">per se</span> was not associated with PaCO<span class="elsevierStyleInf">2</span> at study endpoints (<a class="elsevierStyleCrossRef" href="#sec0115">supplementary Table 4</a>).</p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Secondary outcomes: effects of NIV settings on PaO<span class="elsevierStyleInf">2</span>, daily NIV usage, and interface type</span><p id="par0125" class="elsevierStylePara elsevierViewall">A higher PaO<span class="elsevierStyleInf">2</span> level at study endpoints was independently and positively associated with a higher baseline PaO<span class="elsevierStyleInf">2</span> level and greater amount of daily NIV usage, but negatively associated with NIV intensity (<a class="elsevierStyleCrossRef" href="#sec0115">supplementary Table 5</a>). The multiple interaction between baseline PaO<span class="elsevierStyleInf">2</span> level, disease category and NIV intensity was also significant: the improvement in PaO<span class="elsevierStyleInf">2</span> level between baseline and study endpoints was more pronounced with lower baseline PaO<span class="elsevierStyleInf">2</span> levels, and this improvement was associated with higher NIV intensity in CWD. Unexpectedly, in CWD with elevated baseline PaO<span class="elsevierStyleInf">2</span> level, a higher NIV intensity resulted in a reduction in PaO<span class="elsevierStyleInf">2</span> between baseline and study endpoints (<a class="elsevierStyleCrossRef" href="#sec0115">supplementary Fig. 3</a>).</p><p id="par0130" class="elsevierStylePara elsevierViewall">Daily NIV usage at study endpoints was not associated with NIV intensity. Greater amount of daily NIV usage was independently associated with being male, and with longer study duration (<a class="elsevierStyleCrossRef" href="#sec0115">supplementary Table 6</a>). No significant association was found between NIV intensity and interface type (<a class="elsevierStyleCrossRef" href="#sec0115">supplementary Table 7</a>). Finally, owing to the high rate of missing data, nocturnal oxygenation and sleep quality at study endpoints could not be analysed (<a class="elsevierStyleCrossRef" href="#sec0115">supplementary Table 2</a>).</p></span></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Discussion</span><p id="par0135" class="elsevierStylePara elsevierViewall">The primary aim of this systematic review with meta-analysis of IPD was to evaluate the effect of NIV intensity on PaCO<span class="elsevierStyleInf">2</span> level in individuals with slowly progressive NMD or CWD initiated on long-term home NIV. We used an original method involving the <span class="elsevierStyleItalic">Z</span>-score principle, which allowed us, based on the included studies, to define the intensity of NIV regardless of the ventilatory mode. In the whole study sample, NIV intensity was not significantly associated with PaCO<span class="elsevierStyleInf">2</span> level at study endpoints. However, the effects of NIV intensity differed between the underlying disease categories: no significant effect of NIV intensity was found for NMD, whereas in CWD with the most severe baseline hypercapnia, higher NIV intensities were associated with greater reductions in PaCO<span class="elsevierStyleInf">2</span> levels. Neither daily NIV usage nor interface type were associated with NIV intensity.</p><p id="par0140" class="elsevierStylePara elsevierViewall">The severity of the respiratory impairment at the time of NIV initiation could explain the discrepancy in the effect of NIV intensity on PaCO<span class="elsevierStyleInf">2</span> level at study endpoints between participants with NMD and CWD. Participants with NMD had moderate impairment of respiratory function and gas exchange at baseline. It is therefore conceivable that they had no major impairment of thoraco-pulmonary compliance or neural respiratory drive. Moreover, patients with NMD are often closely monitored in specialised centres; therefore, respiratory failure is managed early. Participants may have had other symptoms for which the use of NIV was indicated, such as nocturnal hypercapnia or hypoxemia, orthopnoea or reduced muscle strength.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">2</span></a> Consequently, the change in PaCO<span class="elsevierStyleInf">2</span> level was achieved even with low intensity NIV. These results contrast with those of a recent retrospective study by our group that suggested that higher levels of ventilatory support were associated with lower nocturnal TcCO<span class="elsevierStyleInf">2</span> in individuals with NMD.<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">20</span></a> However, the participants in that study had been treated with NIV for more than 8 years on average and therefore likely had more advanced disease. Additionally, the analysis was based on nocturnal, rather than diurnal evaluation of PCO<span class="elsevierStyleInf">2</span>, which may also explain the stronger relationship between NIV intensity and PCO<span class="elsevierStyleInf">2</span>.</p><p id="par0145" class="elsevierStylePara elsevierViewall">In the present meta-analysis, respiratory function and gas exchange at baseline were more impaired in the individuals with CWD than in those with NMD. In CWD, increasing NIV intensity could compensate for reduced compliance, which is a major determinant of alveolar hypoventilation in these disorders.<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">32,33</span></a> Although the model showed that NIV intensity was associated with a greater improvement in hypoventilation in the individuals with CWD with the highest levels of hypercapnia, a paradoxical effect of NIV intensity might occur in those with moderate or no hypercapnia; in this situation, the benefits of NIV intensity may be limited.</p><p id="par0150" class="elsevierStylePara elsevierViewall">It is noteworthy that the sensitivity analysis including only patients with diurnal hypercapnia (PaCO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>6<span class="elsevierStyleHsp" style=""></span>kPa) at treatment initiation did not alter the direction of the results of our main analysis, thereby supporting the validity of our findings regardless of baseline PaCO<span class="elsevierStyleInf">2</span>.</p><p id="par0155" class="elsevierStylePara elsevierViewall">Our results also support evidence that the amount of daily NIV usage is an essential determinant of improvement in daytime PaCO<span class="elsevierStyleInf">2</span> level.<a class="elsevierStyleCrossRefs" href="#bib0370"><span class="elsevierStyleSup">34–37</span></a> This finding highlights the importance of encouraging good adherence to treatment to obtain sufficient daily usage, at least during the first months, rather than immediately increasing NIV intensity to reduce PaCO<span class="elsevierStyleInf">2</span> levels. Close follow-up, for instance by telemonitoring or with specific procedures such as polysomnography-directed titration, could be useful to increase daily NIV usage in the initial phase of treatment.<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">29,38</span></a></p><p id="par0160" class="elsevierStylePara elsevierViewall">Finally, our results did not show any association between NIV intensity and the type of mask used (nasal <span class="elsevierStyleItalic">vs</span>. oronasal) in either NMD or CWD. This contrasts with the results of a recent meta-analysis in individuals with COPD or OHS that showed that the inspiratory positive airway pressure level tended to be higher (1.42 [−0.04, 2.88]<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O) in individuals fitted with an oronasal mask.<a class="elsevierStyleCrossRef" href="#bib0395"><span class="elsevierStyleSup">39</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">This meta-analysis has several limitations. First, among the 16 studies that fulfilled our inclusion criteria, only 7 authors shared their IPD. The studies for which we did not obtain IPD were older, and alteration of FVC at the time of NIV initiation was significantly more pronounced, which likely reflects the current trend to introduce NIV at earlier stages of disease progression.<a class="elsevierStyleCrossRefs" href="#bib0210"><span class="elsevierStyleSup">2,3</span></a> Although these considerations may have induced a selection bias, it should be noted that very few studies restricted their inclusion criteria to our population of interest. Consequently, our research question could not be addressed with aggregated data, which made it necessary to obtain IPD. The resulting sample size was therefore limited and, even though this meta-analysis gathered one of the largest datasets analysed in such a population,<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">16</span></a> it may have been underpowered and so the results must be interpreted cautiously, particularly the modelling of the highest NIV intensity levels for which the confidence intervals were quite large.</p><p id="par0170" class="elsevierStylePara elsevierViewall">Second, we combined data from prospective cohort studies and RCTs, which could have led to heterogeneity in the results. However, in the multivariate models, study design was not significantly associated with any of the outcomes of interest. In addition, in the RCTs, we only used data from the individuals who received treatment, and no control groups were available in the cohort studies. Therefore, we cannot differentiate between the effect of the natural course of the diseases and the effect of NIV. Although we tried to minimize this bias by testing and adjusting for participants’ baseline characteristics (especially baseline PaCO<span class="elsevierStyleInf">2</span>), we cannot exclude the presence of residual and unmeasured confounding.</p><p id="par0175" class="elsevierStylePara elsevierViewall">Third, the data provided did not allow us to conclude on the effect of NIV intensity on nocturnal variables, especially nocturnal hypoventilation, which is a very common and important indication for ventilation in these disorders.<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">2</span></a> The effect of NIV intensity on nocturnal symptoms should be evaluated in clinical trials, particularly in this population in which improving sleep quality (as well as health-related quality-of-life) is a major target of long-term home NIV.<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">6</span></a></p><p id="par0180" class="elsevierStylePara elsevierViewall">Finally, the NIV parameters by which we defined “<span class="elsevierStyleItalic">high</span>” levels of NIV intensity are notably lower than what is encountered in other aetiologies such as COPD.<a class="elsevierStyleCrossRefs" href="#bib0260"><span class="elsevierStyleSup">12–15,40</span></a> Nevertheless, these values reflect what is actually documented in the literature in this heterogeneous population, and should be further investigated.</p></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Conclusion</span><p id="par0185" class="elsevierStylePara elsevierViewall">This meta-analysis found no significant effects of NIV intensity on PaCO<span class="elsevierStyleInf">2</span> levels in individuals with NMD or CWD initiated on long-term home NIV. More specifically, the effects of NIV intensity at the time of treatment initiation are not uniform across populations; higher NIV intensities may be of benefit to individuals with CWD and the most severe levels of baseline hypercapnia. Importantly, the amount of daily NIV usage, whatever the settings, appears to be a decisive independent factor in determining NIV effectiveness on gas exchange. During the early period of NIV implementation, achieving sufficient therapy usage seems to be a consideration that likely should prevail over the intensity of settings to increase alveolar ventilation. Further prospective studies should be conducted to confirm these results.</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Authors’ contributions</span><p id="par0190" class="elsevierStylePara elsevierViewall">MD, AL, ML, CK and J-CB contributed to the conception and design of the study. All the authors have written or edited the manuscript.</p><p id="par0195" class="elsevierStylePara elsevierViewall">AH, MP, AHN, LMH, MB, AY, MEH, NH and PJW provided complete IPD from their respective studies. Each co-author made substantial contributions to the manuscript; drafted sections of the manuscript and revised it critically for important intellectual content; provided final approval of the version to be published; agreed to be accountable for all aspects of the manuscript and to ensure that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.</p></span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Patients’ consent for publication</span><p id="par0200" class="elsevierStylePara elsevierViewall">Not required.</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0135">Data sharing</span><p id="par0205" class="elsevierStylePara elsevierViewall">No data are available. All the de-identified individual participant data collected in this systematic review and meta-analysis must be requested from each author individually.</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0140">Funding</span><p id="par0210" class="elsevierStylePara elsevierViewall">The authors do not declare a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.</p></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0145">Conflict of interests</span><p id="par0215" class="elsevierStylePara elsevierViewall">MD reports personal fees from Air Liquide Medical Systems, Breas Medical AB, and ResMed SAS, outside the submitted work; AL reports consulting fees from Air Liquide Medical Systems, outside the submitted work; ML is a part time employee of Air Liquide Medical Systems, outside the submitted work; AH reports grants from ZonMw VIMP, outside the submitted work; WW reports grants and personal fees from Löwenstein Medical, Germany, grants from Philips Respironics, USA, and personal fees from Sentec, Switzerland, outside the submitted work: LH and MEH report in-kind support from Philips Respironics to his research institute, outside the submitted work; PJW reports personal fees from Philips Respironics, outside the submitted work; HP reports personal fees from ASV Santé, SOS Oxygène, ISIS Medical, Breas Medical, ResMed, Sanofi – Genzyme, and Sanofi – Biogen, outside the submitted work; J-CB is employed by AGIR à dom (French home care provider), outside the submitted work. The other authors have no conflicts of interest to disclose.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:15 [ 0 => array:3 [ "identificador" => "xres2019684" "titulo" => "Graphical abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:3 [ "identificador" => "xres2019683" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] 2 => array:2 [ "identificador" => "xpalclavsec1729201" "titulo" => "Keywords" ] 3 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 4 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Search strategy and selection criteria" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Study inclusion criteria" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Study and data selection process" ] 3 => array:2 [ "identificador" => "sec0030" "titulo" => "Outcomes" ] 4 => array:2 [ "identificador" => "sec0035" "titulo" => "Deviations from the study protocol" ] 5 => array:2 [ "identificador" => "sec0040" "titulo" => "Data synthesis and analysis" ] ] ] 5 => array:3 [ "identificador" => "sec0045" "titulo" => "Results" "secciones" => array:6 [ 0 => array:2 [ "identificador" => "sec0050" "titulo" => "Study selection and collection of IPD" ] 1 => array:2 [ "identificador" => "sec0055" "titulo" => "Study and participants characteristics" ] 2 => array:2 [ "identificador" => "sec0060" "titulo" => "Risk of bias and IPD integrity" ] 3 => array:2 [ "identificador" => "sec0065" "titulo" => "NIV settings" ] 4 => array:2 [ "identificador" => "sec0070" "titulo" => "Primary outcome: effects of NIV settings on PaCO level" ] 5 => array:2 [ "identificador" => "sec0075" "titulo" => "Secondary outcomes: effects of NIV settings on PaO, daily NIV usage, and interface type" ] ] ] 6 => array:2 [ "identificador" => "sec0080" "titulo" => "Discussion" ] 7 => array:2 [ "identificador" => "sec0085" "titulo" => "Conclusion" ] 8 => array:2 [ "identificador" => "sec0090" "titulo" => "Authors’ contributions" ] 9 => array:2 [ "identificador" => "sec0095" "titulo" => "Patients’ consent for publication" ] 10 => array:2 [ "identificador" => "sec0100" "titulo" => "Data sharing" ] 11 => array:2 [ "identificador" => "sec0105" "titulo" => "Funding" ] 12 => array:2 [ "identificador" => "sec0110" "titulo" => "Conflict of interests" ] 13 => array:2 [ "identificador" => "xack705216" "titulo" => "Acknowledgements" ] 14 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2023-02-28" "fechaAceptado" => "2023-05-05" "PalabrasClave" => array:1 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1729201" "palabras" => array:5 [ 0 => "Noninvasive ventilation" 1 => "Neuromuscular diseases" 2 => "Chest wall disorders" 3 => "Meta-analysis" 4 => "Systematic review" ] ] ] ] "tieneResumen" => true "resumen" => array:1 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Introduction</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Home noninvasive ventilation (NIV), targeting a reduction of carbon dioxide with a combination of sufficient inspiratory support and backup-rate improves outcomes in patients with chronic obstructive pulmonary disease. The aim of this systematic review with individual participant data (IPD) meta-analysis was to evaluate the effects of intensity of home NIV on respiratory outcomes in individuals with slowly progressive neuromuscular (NMD) or chest-wall disorders (CWD).</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Methods</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Controlled, non-controlled and cohort studies indexed between January-2000 and December-2020 were sought from Medline, Embase and the Cochrane Central Register. Outcomes were diurnal PaCO<span class="elsevierStyleInf">2</span>, PaO<span class="elsevierStyleInf">2</span>, daily NIV usage, and interface type (PROSPERO-CRD 42021245121). NIV intensity was defined according to the <span class="elsevierStyleItalic">Z</span>-score of the product of pressure support (or tidal volume) and backup-rate.</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Results</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">16 eligible studies were identified; we obtained IPD for 7 studies (176 participants: 113-NMD; 63-CWD). The reduction in PaCO<span class="elsevierStyleInf">2</span> was greater with higher baseline PaCO<span class="elsevierStyleInf">2</span>. NIV intensity <span class="elsevierStyleItalic">per se</span> was not associated with improved PaCO<span class="elsevierStyleInf">2</span> except in individuals with CWD and the most severe baseline hypercapnia. Similar results were found for PaO<span class="elsevierStyleInf">2</span>. Daily NIV usage was associated with improvement in gas exchange but not with NIV intensity. No association between NIV intensity and interface type was found.</p></span> <span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Conclusion</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Following home NIV initiation in NMD or CWD patients, no relationship was observed between NIV intensity and PaCO<span class="elsevierStyleInf">2</span>, except in individuals with the most severe CWD. The amount of daily NIV usage, rather than intensity, is key to improving hypoventilation in this population during the first few months after introduction of therapy.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0010" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0015" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0020" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0025" "titulo" => "Conclusion" ] ] ] ] "NotaPie" => array:1 [ 0 => array:3 [ "etiqueta" => "1" "nota" => "<p class="elsevierStyleNotepara" id="npar0015">MD and AL are joint first authors. CK and J-CB are joint senior authors.</p>" "identificador" => "fn0005" ] ] "apendice" => array:1 [ 0 => array:1 [ "seccion" => array:1 [ 0 => array:4 [ "apendice" => "<p id="par0230" class="elsevierStylePara elsevierViewall">The following are the supplementary data to this article:<elsevierMultimedia ident="upi0005"></elsevierMultimedia></p>" "etiqueta" => "Appendix A" "titulo" => "Supplementary data" "identificador" => "sec0120" ] ] ] ] "multimedia" => array:8 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 764 "Ancho" => 2341 "Tamanyo" => 158968 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Values of NIV intensity <span class="elsevierStyleItalic">Z</span>-scores according to backup respiratory rate for pressure-cycled modes (panel A), and for volume-cycled and hybrid modes (panel B). Noninvasive ventilation (NIV) intensity was defined as the product of pressure support (PS) and backup respiratory rate (BURR) for pressure-cycled modes, and of tidal volume (<span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>) and BURR for volume-cycled and hybrid modes. <span class="elsevierStyleItalic">Z</span>-scores represent the number of standard deviations above or below the mean NIV intensity used in the included studies. For pressure-cycled modes (panel A), the combination of a BURR set at 14<span class="elsevierStyleHsp" style=""></span>breaths/min and a PS set at 10<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O corresponds to a <span class="elsevierStyleItalic">Z</span>-score of 0 (<span class="elsevierStyleItalic">medium</span> NIV intensity). The combination of a BURR set at 14<span class="elsevierStyleHsp" style=""></span>breaths/min and a PS set at 20<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O corresponds to a <span class="elsevierStyleItalic">Z</span>-score of 2 (<span class="elsevierStyleItalic">very high</span> NIV intensity). For volume-cycled or hybrid modes (panel B), the combination of a BURR set at 18<span class="elsevierStyleHsp" style=""></span>breaths/min and a <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> set at 5<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleInf">PBW</span><span class="elsevierStyleSup">−1</span> corresponds to <span class="elsevierStyleItalic">Z</span>-score of −1 (<span class="elsevierStyleItalic">low</span> NIV intensity). The combination of a BURR set at 18<span class="elsevierStyleHsp" style=""></span>breaths/min and a <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span> set at 15<span class="elsevierStyleHsp" style=""></span>mL<span class="elsevierStyleHsp" style=""></span>kg<span class="elsevierStyleInf">PBW</span><span class="elsevierStyleSup">−1</span> corresponds to a <span class="elsevierStyleItalic">Z</span>-score of 1 (<span class="elsevierStyleItalic">high</span> NIV intensity). BURR, backup respiratory rate; NIV, noninvasive ventilation; PS, pressure support.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 3474 "Ancho" => 2508 "Tamanyo" => 374207 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Preferred Reporting Items for Systematic Review and Meta-Analyses of Individual Participant Data (PRISMA-IPD) flow diagram.</p>" ] ] 2 => array:7 [ "identificador" => "fig0015" "etiqueta" => "Fig. 3" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr3.jpeg" "Alto" => 1171 "Ancho" => 2341 "Tamanyo" => 165652 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Model of the difference in PaCO<span class="elsevierStyleInf">2</span> levels between baseline and study endpoints according to baseline PaCO<span class="elsevierStyleInf">2</span>, disease category, and NIV intensity. The figure shows the difference in PaCO<span class="elsevierStyleInf">2</span> levels between baseline and study endpoints, and final marginal means of the model according to baseline PaCO<span class="elsevierStyleInf">2</span>, disease category, and NIV intensity. The values presented were adjusted for variables included in the final model, <span class="elsevierStyleItalic">i.e.</span> daily NIV usage, sex, and study design. <span class="elsevierStyleItalic">Low, medium, high</span> and <span class="elsevierStyleItalic">very high</span> NIV intensity correspond to a <span class="elsevierStyleItalic">Z</span>-score of −1, 0, 1 and 2, respectively. CWD, chest wall disorders; NIV, noninvasive ventilation; NMD, neuromuscular disorders.</p>" ] ] 3 => 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:3 [ "leyenda" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">CWD, chest wall disorder; HRQoL, health-related quality of life; NIV, noninvasive ventilation; NMD, neuromuscular disorder; PSG, polysomnography; PVA, patient-ventilator asynchrony; RCT, randomised controlled trial.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="\n \t\t\t\t\ttable-head\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t" scope="col" style="border-bottom: 2px solid black">Study \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">Location \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">Design \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">Population \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">Sample size included in the meta-analysis (<span class="elsevierStyleItalic">n</span>) \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">Primary outcome of the study \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">Primary timeframe (months) \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">Intervention/comparator \t\t\t\t\t\t\n \t\t\t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t ; entry_with_role_rowhead " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Nickol et al. (2005)<a class="elsevierStyleCrossRef" href="#bib0335"><span class="elsevierStyleSup">27</span></a> \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">United Kingdom \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">Cohort study \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">NMD/CWD<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">19 \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">PaCO<span class="elsevierStyleInf">2</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prospective follow up of patients initiated on long-term NIV \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">Pallero et al. (2014)<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">24</span></a> \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">Spain \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">RCT (parallel groups) \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">NMD/CWD<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 \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">PaCO<span class="elsevierStyleInf">2</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Ambulatory NIV initiation vs. Hospital NIV initiation \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">Hazenberg et al. (2014)<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">25</span></a> \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">The Netherlands \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">RCT (parallel groups) \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">NMD/CWD<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38 \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">PaCO<span class="elsevierStyleInf">2</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Home NIV initiation vs. Hospital NIV initiation \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">Boentert et al. (2016)<a class="elsevierStyleCrossRef" href="#bib0340"><span class="elsevierStyleSup">28</span></a> \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">Germany \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">Cohort study \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">NMD \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13 \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">Sleep disordered breathing \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">3–4 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Prospective follow up of patients initiated on long-term NIV \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">Hannan et al. (2019)<a class="elsevierStyleCrossRef" href="#bib0345"><span class="elsevierStyleSup">29</span></a> \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">Australia \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">RCT (parallel groups) \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">NMD/CWD<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">PVA and arousal indices \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">2–3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Daytime NIV titration<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>PSG vs. control (daytime NIV titration<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>sham PSG) \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">van den Biggelaar et al. (2020)<a class="elsevierStyleCrossRef" href="#bib0350"><span class="elsevierStyleSup">30</span></a> \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">The Netherlands \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">RCT (parallel groups) \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">NMD/CWD<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 \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">PaCO<span class="elsevierStyleInf">2</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">Home NIV initiation vs. Hospital NIV initiation \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">Yüksel et al. (2020)<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">31</span></a> \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">Turkey \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">Cohort study \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">NMD/CWD<a class="elsevierStyleCrossRef" href="#tblfn0005"><span class="elsevierStyleSup">a</span></a> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">11 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t">HRQoL \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12 \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">Prospective follow up of patients initiated on long-term NIV \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab3351586.png" ] ] ] "notaPie" => array:1 [ 0 => array:3 [ "identificador" => "tblfn0005" "etiqueta" => "a" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">The study included NMD/CWD participants, among other disease categories.</p>" ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">Characteristics of the included studies.</p>" ] ] 4 => 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="spar0060" class="elsevierStyleSimplePara elsevierViewall">Data are mean<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>SD or <span class="elsevierStyleItalic">n</span> (%). BMI, body mass index; EPAP, expiratory positive airway pressure; FVC, forced vital capacity; NIV, noninvasive ventilation; PS, pressure support; PBW, predicted body weight; RR, respiratory rate; <span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf">T</span>, tidal volume.</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="" 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"><span class="elsevierStyleItalic">N</span> participants; <span class="elsevierStyleItalic">n</span> studies \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">Missing data (%) \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">All participants <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>176 \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">Neuromuscular disorders <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>113 \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">Chest wall disorders <span class="elsevierStyleItalic">n</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>63 \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" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">Baseline characteristics</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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Age, y</span> \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"><span class="elsevierStyleItalic">176; 7</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">0.0</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">58.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>14.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">56.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>13.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">62.4<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>15.4 \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Female sex, n (%)</span> \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"><span class="elsevierStyleItalic">176; 7</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">0.0</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">78 (44.3) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">44 (38.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 (54.0) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">BMI, kg.m</span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">-2</span></span> \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"><span class="elsevierStyleItalic">176; 7</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">0.0</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">27.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">28.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.8 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>6.1 \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">FVC, % predicted</span> \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"><span class="elsevierStyleItalic">175; 7</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">0.0</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">49.0<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>19.6 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>20.3 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">38.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.9 \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">PaCO</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">, kPa</span> \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"><span class="elsevierStyleItalic">176; 7</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">0.0</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.6<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="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">6.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.1 \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">7.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>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="\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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">PaO</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">, kPa</span> \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"><span class="elsevierStyleItalic">176; 7</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">0.0</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.2<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.7 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>1.7 \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleVsp" style="height:0.5px"></span></td></tr><tr title="table-row"><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " colspan="6" align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleBold">NIV settings at study endpoints</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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">NIV mode, n (%)</span> \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"><span class="elsevierStyleItalic">176; 7</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">0.0</span> \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="" 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="" 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="" 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 " align="left" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Pressure-cycled \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"><span class="elsevierStyleItalic">82; 6</span> \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="" 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">82 (46.6) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">53 (46.9) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">29 (46.0) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Volume-cycled \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"><span class="elsevierStyleItalic">94; 4</span> \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="" 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">94 (53.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">60 (53.1) \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">34 (54.0) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Volumetric modes \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"><span class="elsevierStyleItalic">40; 2</span> \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="" 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">40 (22.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">14 (12.4) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">26 (41.3) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleHsp" style=""></span>Hybrid modes \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"><span class="elsevierStyleItalic">54; 3</span> \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="" 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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">54 (30.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">46 (40.7) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">8 (12.7) \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">PS, cmH</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">2</span></span><span class="elsevierStyleItalic">O</span> \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"><span class="elsevierStyleItalic">82; 6</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">0.0</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">12.4<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="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.9<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="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">15.1<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>5.6 \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">V</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">T</span></span><span class="elsevierStyleItalic">, mL.kg</span><span class="elsevierStyleInf"><span class="elsevierStyleItalic">PBW</span></span><span class="elsevierStyleSup"><span class="elsevierStyleItalic">-1</span></span> \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"><span class="elsevierStyleItalic">93; 4</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">1.1</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">10.8<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.0 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">9.3<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>2.9 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n \t\t\t\t\ttable-entry\n \t\t\t\t " align="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t">13.6<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>4.4 \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"><span class="elsevierStyleHsp" style=""></span><span class="elsevierStyleItalic">Backup RR, bpm</span> \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"><span class="elsevierStyleItalic">157; 6</span> \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="char" valign="\n \t\t\t\t\ttop\n \t\t\t\t"><span class="elsevierStyleItalic">10.8</span> \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="\n