Original Article
Adjunctive Corticosteroids for Pneumocystis jirovecii Pneumonia in Non-HIV-Infected Patients: A Systematic Review and Meta-Analysis of Observational Studies
Tratamiento complementario con corticoides en la neumonía por Pneumocystis jirovecii en pacientes no infectados por VIH: revisión sistemática y metanálisis de los estudios observacionales
a Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, Saitama, Japan
b Department of Pulmonary Medicine, University of Tsukuba, Graduate School of Comprehensive Human Science, Ibaraki, Japan
c Department of Hygiene and Public Health, Teikyo University, School of Medicine, Tokio, Japan
d Nagasaki University, Nagasaki, Japan
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Respiratory command derives from inputs from both the motor cortex and the medulla. These commands are integrated at the spinal level and transmitted to the muscular effectors of the respiratory system. The subsequent activation of the respiratory muscles will generate afferent inputs that are fed back to the respiratory command centres and the somatosensory cortex. The comparison of the corollary discharge and the ensuing afferent feedback may cause a mismatch, and dyspnoea will occur when a negative affective sensation is attributed to this mismatch by the limbic cortex, which will also be influenced and modulated by memory and the prevailing environment.</p> <p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Adapted from Laviolette L, Laveneziana P. The European Respiratory Journal. 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Kawana, Shigeru Kohno" "autores" => array:4 [ 0 => array:4 [ "nombre" => "Yuji" "apellidos" => "Fujikura" "email" => array:1 [ 0 => "fujikura@ndmc.ac.jp" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:3 [ "nombre" => "Toshie" "apellidos" => "Manabe" "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">b</span>" "identificador" => "aff0010" ] 1 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">c</span>" "identificador" => "aff0015" ] ] ] 2 => array:3 [ "nombre" => "Akihiko" "apellidos" => "Kawana" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">a</span>" "identificador" => "aff0005" ] ] ] 3 => array:3 [ "nombre" => "Shigeru" "apellidos" => "Kohno" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">d</span>" "identificador" => "aff0020" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Division of Infectious Diseases and Respiratory Medicine, Department of Internal Medicine, National Defense Medical College, Saitama, Japan" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Department of Pulmonary Medicine, University of Tsukuba, Graduate School of Comprehensive Human Science, Ibaraki, Japan" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Department of Hygiene and Public Health, Teikyo University, School of Medicine, Tokio, Japan" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "Nagasaki University, Nagasaki, Japan" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Tratamiento complementario con corticoides en la neumonía por <span class="elsevierStyleItalic">Pneumocystis jirovecii</span> en pacientes no infectados por VIH: revisión sistemática y metanálisis de los estudios observacionales" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Fig. 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 2140 "Ancho" => 3442 "Tamanyo" => 295859 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Primary outcome: mortality. (a) Mortality, (b) funnel plot for mortality.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Introduction</span><p id="par0005" class="elsevierStylePara elsevierViewall"><span class="elsevierStyleItalic">Pneumocystis jirovecii</span> pneumonia (PJP) is life-threatening opportunistic infection affecting immunocompromised individuals.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">1</span></a> CD4+ T-cells play crucial roles in host defense against <span class="elsevierStyleItalic">P. jirovecii</span> in response to antigens and the production of interferon-gamma.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">2</span></a> CD4+ T-cells are especially suppressed in cases of advanced human immunodeficiency virus (HIV) infection; however, other causes of immunosuppression are frequently observed in clinical settings, such as continuous corticosteroid use, hematological malignancies, solid organ tumors, and organ transplants.<a class="elsevierStyleCrossRefs" href="#bib0130"><span class="elsevierStyleSup">3,4</span></a> PJP is most common in patients with HIV; however, PJP in non-HIV patients should not be overlooked, particularly in immunocompromised patients.</p><p id="par0010" class="elsevierStylePara elsevierViewall">The epidemiology and clinical presentations differ between HIV and non-HIV patients. PJP in non-HIV patients occurs at older age, with higher neutrophil levels and a lower density of <span class="elsevierStyleItalic">P. jirovecii</span> in bronchoalveolar lavage compared with HIV patients.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">5</span></a> Furthermore, the onset of respiratory failure is abrupt in non-HIV patients, whereas it is slower in HIV patients.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">1</span></a> Overall, the outcome of PJP is less favorable in non-HIV than HIV-infected patients due to a variety of underlying medical conditions.<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">The therapeutic strategy for PJP has been widely studied, especially in HIV-infected individuals. Sulfamethoxazole-trimethoprim is generally adminstered,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">6</span></a> and HIV-PJP patients with substantial hypoxemia are prescribed concurrent adjunctive corticosteroids, based on randomized controlled trials from 1990.<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">7</span></a> Recently, a meta-analysis and systematic review showed that adjunctive corticosteroid treatment had a beneficial effect on mortality in patients with hypoxemia (arterial oxygen partial pressure >70<span class="elsevierStyleHsp" style=""></span>mmHg or an alveolar-arterial gradient <35<span class="elsevierStyleHsp" style=""></span>mmHg on room air).<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">8</span></a></p><p id="par0020" class="elsevierStylePara elsevierViewall">The value of adjunctive corticosteroid in non-HIV-PJP patients, however, remains unclear. Although several observational studies have been published, they do not show a definitive effect on outcome. There have been no randomized controlled studies conducted to date; this might due to variations in underlying diseases and pathophysiology, and the relative rarity of non-HIV-PJP cases. However, since the pathophysiology of non-HIV-PJP patients differs from HIV-infected PJP patients, there may be factors associated with the use of adjunctive corticosteroids that affect the clinical course.</p><p id="par0025" class="elsevierStylePara elsevierViewall">We conducted a systematic review and meta-analysis of published observational studies focusing on adjunctive corticosteroids in non-HIV-PJP patients.</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Methods</span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Study Search</span><p id="par0030" class="elsevierStylePara elsevierViewall">A literature search was performed by 2 investigators (YF and TM) who independently searched PubMed and the Cochrane Database of Systematic Reviews for eligible articles published from 1949 to June 2015. We used free search terms, MeSH terms, and combinations of search terms “<span class="elsevierStyleItalic">Pneumocystis</span>”, “pneumonia, <span class="elsevierStyleItalic">Pneumocystis</span> [MeSH]”, “<span class="elsevierStyleItalic">Pneumocystis</span> infections [MeSH]”, “<span class="elsevierStyleItalic">Pneumocystis carinii</span> [MeSH]”, “<span class="elsevierStyleItalic">Pneumocystis jirovecii</span> [MeSH]”, “PCP”, “PJP”, AND “non-HIV”, “non-AIDS”, “non-HIV-infected”, “HIV-uninfected”, “AIDS uninfected”, “HIV-negative”, AND “steroids”, “corticosteroids”, “hydroxycorticosteroids”, “glucocorticoids”, “prednisolone”, “hydroxycortisone”, and “hydrocortisone”, with language restricted to English.</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Eligibility Criteria and Outcome Measures</span><p id="par0035" class="elsevierStylePara elsevierViewall">Studies that met the eligibility criteria were included in the meta-analysis. (1) Study design: randomized controlled trials (RCT) and observational studies; (2) population: non-HIV patients with PJP; (3) intervention: administration of adjunctive corticosteroids; (4) comparison intervention: no adjunctive corticosteroids or no increase in corticosteroid use, according to each study definition; (5) outcome variables: mortality as primary endpoint, and intubation rate (or need for mechanical ventilation) as the secondary endpoint. In addition, for the studies in patients with hypoxemia, we also focused on mortality due to severe hypoxemia (PaO<span class="elsevierStyleInf">2</span> <70<span class="elsevierStyleHsp" style=""></span>mmHg) in non-HIV cases of PJP. We excluded articles that did not define HIV status in the study population or did not extract exact data for evaluation.</p></span><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Statistical Analysis</span><p id="par0040" class="elsevierStylePara elsevierViewall">Meta-analysis was performed according to PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis)<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">9</span></a> and MOOSE (Meta-analysis Of Observational Studies in Epidemiology) recommendations.<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">10</span></a> Data were analyzed using Review Manager (RevMan) 5.3.5 (Cochrane Collaboration, Copenhagen) and R version 3.2.3 (R Foundation for Statistical Computing, Vienna, Austria) software with an open source statistical package for meta-analysis. A random effect model was used to aggregate data, and the odds ratio (OR) was used in summary. The heterogeneity of original studies was evaluated with <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span> statistics. Significance levels were two-tailed in all analyses, and <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>.05 was considered significant. A funnel plot examined publication bias.</p></span></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Results</span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Search Results and Study Characteristics</span><p id="par0045" class="elsevierStylePara elsevierViewall">Following discussions between the 2 reviewers, 7 observational studies<a class="elsevierStyleCrossRefs" href="#bib0170"><span class="elsevierStyleSup">11–17</span></a> were collected by systematic searches according to the PRISMA statement (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). The reviewers were in complete agreement about the search performed and data extracted. Of the 82 studies screened, 7 were included in a qualitative synthesis.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0050" class="elsevierStylePara elsevierViewall"><a class="elsevierStyleCrossRef" href="#tbl0005">Table 1</a> shows the characteristics of the studies included. There were no RCTs, and all studies were retrospective observational. The underlying diseases leading to immunosuppression varied widely, but malignancies – especially hematological diseases – were often recorded. Other background patient information is described in <a class="elsevierStyleCrossRef" href="#tbl0010">Table 2</a>. Corticosteroids were used in 38.6%–80% of patients, and other immunosuppressants were commonly administrated at the time of PJP diagnosis. Notably, prophylaxis against <span class="elsevierStyleItalic">P. jirovecii</span> was less common in non-HIV patients.</p><elsevierMultimedia ident="tbl0005"></elsevierMultimedia><elsevierMultimedia ident="tbl0010"></elsevierMultimedia></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Primary Outcome</span><p id="par0055" class="elsevierStylePara elsevierViewall">Mortality data were available for all studies. The pooled OR for mortality with adjunctive corticosteroids estimated from the results of the 7 observational studies was 1.26 (95% confidence interval [95% CI], 0.60–2.67, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.54, <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>46%, <span class="elsevierStyleItalic">P</span> for heterogeneity<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.08), which shows no effective outcome for the use of adjunctive corticosteroids in non-HIV patients (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>a). Some conflicting results were found, and moderate heterogeneity was observed. A funnel plot for the OR for mortality is shown in <a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>b. The slight lack of symmetry among studies indicates a potential publication bias, but this did not reach statistical significance (Egger's test, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.230).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0060" class="elsevierStylePara elsevierViewall">In the subgroup analysis, the mortality of non-HIV-PJP patients with significant hypoxemia (PaO<span class="elsevierStyleInf">2</span> <70<span class="elsevierStyleHsp" style=""></span>mmHg) was not reduced via adjunctive corticosteroids (<a class="elsevierStyleCrossRef" href="#fig0015">Fig. 3</a>).</p><elsevierMultimedia ident="fig0015"></elsevierMultimedia></span><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Secondary Outcome</span><p id="par0065" class="elsevierStylePara elsevierViewall">The need for intubation or mechanical ventilation was evaluated in 2 studies, which yielded a pooled OR of 1.34 (95% CI 0.44–4.11, <span class="elsevierStyleItalic">P</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.60, <span class="elsevierStyleItalic">I</span><span class="elsevierStyleSup">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0%, <span class="elsevierStyleItalic">P</span> for heterogeneity<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>.35) (<a class="elsevierStyleCrossRef" href="#fig0020">Fig. 4</a>).</p><elsevierMultimedia ident="fig0020"></elsevierMultimedia></span></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Discussion</span><p id="par0070" class="elsevierStylePara elsevierViewall">In this meta-analysis, no proof that adjunctive corticosteroids have beneficial effects on mortality in HIV-negative patients with PJP was found, and no statistically significant differences in mortality rate were found between non-HIV-PJP patients with hypoxemia (PaO<span class="elsevierStyleInf">2</span> <70<span class="elsevierStyleHsp" style=""></span>mmHg) vs. HIV patients.<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">8</span></a> Furthermore, treatment had no effect on the need for intubation or mechanical ventilation, which, according to previous studies, are prognostic factors of clinical course.<a class="elsevierStyleCrossRefs" href="#bib0205"><span class="elsevierStyleSup">18,19</span></a></p><p id="par0075" class="elsevierStylePara elsevierViewall">Although a randomized clinical trial has showed that administration of corticosteroids significantly reduced the relative risk of death in HIV-infected patients with PJP and substantial hypoxemia,<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">8</span></a> all published observational studies for non-HIV-infected patients have failed to show differences in mortality. Moreover, the results of Delclaux,<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">12</span></a> Bollee,<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">14</span></a> and Moon<a class="elsevierStyleCrossRef" href="#bib0190"><span class="elsevierStyleSup">15</span></a> show that adjunctive corticosteroids might have a mildly beneficial effect on mortality, while Kim<a class="elsevierStyleCrossRef" href="#bib0195"><span class="elsevierStyleSup">16</span></a> (reporting the largest number of subjects) found that corticosteroids had a negative effect. These results suggest that pathophysiological differences play a role in the disparity between HIV-PJP and non-HIV-PJP patients.</p><p id="par0080" class="elsevierStylePara elsevierViewall">Corticosteroids are concurrently used with anti-pneumocystis treatment in HIV patients with severe hypoxemia and attenuate transient excessive inflammation associated with drug-induced death from the eradication of <span class="elsevierStyleItalic">Pneumocystis jiroveciii</span>,<a class="elsevierStyleCrossRef" href="#bib0145"><span class="elsevierStyleSup">6</span></a> which may improve the clinical course. Generally, HIV-infected patients with PJP have a high burden of <span class="elsevierStyleItalic">P. jirovecii</span> in the lung.<a class="elsevierStyleCrossRef" href="#bib0140"><span class="elsevierStyleSup">5</span></a> One possible explanation for the lack of effect on mortality among non-HIV-PJP patients might be that the low numbers of microbes in the lung limit the potential benefits.<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">12</span></a></p><p id="par0085" class="elsevierStylePara elsevierViewall">Corticosteroid administration, meanwhile, is a major risk factor in the promotion of PJP,<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">20</span></a> especially in cases of long-term use in non-HIV patients.<a class="elsevierStyleCrossRef" href="#bib0130"><span class="elsevierStyleSup">3</span></a> Prior use of corticosteroids may alter the response to adjunctive corticosteroid treatment, that is, corticosteroids do not have a strong anti-inflammatory effect in PJP patients who have already taken these drugs. Indeed, a previous report revealed that prior corticosteroids use showed a trend toward an increase in mortality among non-HIV patients with PJP.<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">21</span></a></p><p id="par0090" class="elsevierStylePara elsevierViewall">Several additional findings from this review are noteworthy. First, the overall mortality rate of PJP in non-HIV patients was 32.8% among all subjects, which exceeds the rate reported in HIV patients with PJP.<a class="elsevierStyleCrossRef" href="#bib0120"><span class="elsevierStyleSup">1</span></a> These results might depend on the medical background of the patients rather than the severity of PJP or the pathophysiology of <span class="elsevierStyleItalic">P. jirovecii</span>; however, early diagnosis and treatment are necessary, because delays have been identified as prognostic factors in PJP.<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">22</span></a></p><p id="par0095" class="elsevierStylePara elsevierViewall">Second, prophylaxis for <span class="elsevierStyleItalic">P. jirovecii</span> was administered infrequently in all studies. A recent meta-analysis of PJP prevention in non-HIV immunocompromised patients<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">23</span></a> indicated an increased need for prophylactic anti-pneumocystis agents. Emphasis should therefore be placed on prophylaxis in patients receiving long-term corticosteroids or other immunosuppressive agents due to the high mortality rate associated with PJP.</p><p id="par0100" class="elsevierStylePara elsevierViewall">Some limitations to this systematic review should be mentioned. First, although publication bias did not reach statistical significance in our meta-analysis, all studies were retrospective and observational in design; thus, the true effects on mortality cannot be ascertained due to the potential for confounding bias. The possibility that adjunctive corticosteroids are administered more frequently in severely ill patients cannot be ruled out, and this might have underestimated the effect of this therapy. However, it might be difficult to conduct a randomized controlled trial, because there are fewer non-HIV-PJP patients and adjunctive corticosteroids are regarded as the standard treatment for PJP by many clinicians regardless of HIV status. From this point of view, our meta-analysis shows a strong trend among non-HIV-PJP patients. Second, the studies available are heterogeneous. Non-HIV-PJP patients constitute a heterogeneous group, which makes stratified subgroup analysis difficult. Statistical significance might not be attainable due to the inconsistent characteristics of non-HIV patients. In addition, the definition of adjunctive corticosteroids was not uniform in the studies included. Insufficient doses of corticosteroids could affect clinical outcome.</p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Conclusions</span><p id="par0105" class="elsevierStylePara elsevierViewall">Although purely observational studies were included, this meta-analysis showed that adjunctive corticosteroids did not improve the outcome of PJP in non-HIV patients. However, this result needs to be confirmed by a randomized controlled trial.</p></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Authorship</span><p id="par0110" class="elsevierStylePara elsevierViewall">Yuji Fujikura: literature search, data collection, analysis of data, manuscript preparation.</p><p id="par0115" class="elsevierStylePara elsevierViewall">Toshie Manabe: literature search, data collection, analysis of data, review of manuscript.</p><p id="par0120" class="elsevierStylePara elsevierViewall">Akihiko Kawana: review of manuscript.</p><p id="par0125" class="elsevierStylePara elsevierViewall">Shigeru Kohno: study design, review of manuscript.</p></span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Conflicts of Interest</span><p id="par0130" class="elsevierStylePara elsevierViewall">The authors state that they have no conflict of interests.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:12 [ 0 => array:3 [ "identificador" => "xres798275" "titulo" => "Abstract" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec796262" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres798274" "titulo" => "Resumen" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec796263" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:3 [ "identificador" => "sec0010" "titulo" => "Methods" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0015" "titulo" => "Study Search" ] 1 => array:2 [ "identificador" => "sec0020" "titulo" => "Eligibility Criteria and Outcome Measures" ] 2 => array:2 [ "identificador" => "sec0025" "titulo" => "Statistical Analysis" ] ] ] 6 => array:3 [ "identificador" => "sec0030" "titulo" => "Results" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0035" "titulo" => "Search Results and Study Characteristics" ] 1 => array:2 [ "identificador" => "sec0040" "titulo" => "Primary Outcome" ] 2 => array:2 [ "identificador" => "sec0045" "titulo" => "Secondary Outcome" ] ] ] 7 => array:2 [ "identificador" => "sec0050" "titulo" => "Discussion" ] 8 => array:2 [ "identificador" => "sec0055" "titulo" => "Conclusions" ] 9 => array:2 [ "identificador" => "sec0060" "titulo" => "Authorship" ] 10 => array:2 [ "identificador" => "sec0065" "titulo" => "Conflicts of Interest" ] 11 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2016-03-29" "fechaAceptado" => "2016-06-13" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec796262" "palabras" => array:5 [ 0 => "Corticosteroids" 1 => "Immunocompromised host" 2 => "Pneumocystis pneumonia" 3 => "<span class="elsevierStyleItalic">Pneumocystis jirovecii</span>" 4 => "Review" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec796263" "palabras" => array:5 [ 0 => "Corticoides" 1 => "Huésped inmunocomprometido" 2 => "Neumonía por <span class="elsevierStyleItalic">Pneumocystis</span>" 3 => "<span class="elsevierStyleItalic">Pneumocystis jirovecii</span>" 4 => "Revisión" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:3 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0010">Introduction</span><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">The clinical benefits of adjunctive corticosteroids for <span class="elsevierStyleItalic">Pneumocystis jirovecii</span> pneumonia in patients not infected with the human immunodeficiency virus (HIV) has not been evaluated by meta-analysis.</p></span> <span id="abst0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0015">Methods</span><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">We conducted a systematic review of published studies describing the effects of adjunctive corticosteroids on outcome in non-HIV <span class="elsevierStyleItalic">P. jirovecii</span> pneumonia patients. Two investigators independently searched the PubMed and Cochrane databases for eligible articles written in English. A meta-analysis was performed using a random-effects model for measuring mortality as the primary outcome, and the need for intubation or mechanical ventilation as the secondary outcome.</p></span> <span id="abst0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0020">Results</span><p id="spar0015" class="elsevierStyleSimplePara elsevierViewall">Seven observational studies were eligible. In these studies, adjunctive corticosteroids did not affect mortality in non-HIV patients (odds ratio [OR] 1.26; 95% CI 0.60–2.67) and there was no beneficial effect in patients with severe hypoxemia (PaO<span class="elsevierStyleInf">2</span> <70<span class="elsevierStyleHsp" style=""></span>mmHg) (OR 0.90; 95% CI 0.44–1.83). No significant effect on the secondary outcome was observed (OR 1.34; 95% CI 0.44–4.11).</p></span> <span id="abst0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conclusions</span><p id="spar0020" class="elsevierStyleSimplePara elsevierViewall">Although the studies were observational, meta-analysis showed that adjunctive corticosteroids did not improve the outcome of <span class="elsevierStyleItalic">P. jirovecii</span> pneumonia in non-HIV patients. The results warrant a randomized controlled trial.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0005" "titulo" => "Introduction" ] 1 => array:2 [ "identificador" => "abst0010" "titulo" => "Methods" ] 2 => array:2 [ "identificador" => "abst0015" "titulo" => "Results" ] 3 => array:2 [ "identificador" => "abst0020" "titulo" => "Conclusions" ] ] ] "es" => array:3 [ "titulo" => "Resumen" "resumen" => "<span id="abst0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Introducción</span><p id="spar0025" class="elsevierStyleSimplePara elsevierViewall">Los beneficios clínicos del tratamiento complementario con corticoides de la neumonía por <span class="elsevierStyleItalic">Pneumocystis jirovecii (P. jirovecii)</span> en pacientes no infectados por el virus de la inmunodeficiencia humana (VIH) no se han evaluado mediante metanálisis.</p></span> <span id="abst0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">Métodos</span><p id="spar0030" class="elsevierStyleSimplePara elsevierViewall">Realizamos una revisión sistemática de los estudios publicados que describen los efectos del tratamiento complementario con corticoides sobre la evolución de pacientes con neumonía por <span class="elsevierStyleItalic">P. jirovecii</span> no infectados por VIH. Dos investigadores hicieron búsquedas independientes de artículos elegibles escritos en inglés en las bases de datos PubMed y Cochrane. Se efectuó un metanálisis con un modelo de efectos aleatorios para determinar la mortalidad como variable principal, y la necesidad de intubación o ventilación mecánica como variable secundaria.</p></span> <span id="abst0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Resultados</span><p id="spar0035" class="elsevierStyleSimplePara elsevierViewall">Siete estudios observacionales resultaron elegibles. En ellos, el tratamiento complementario con corticoides no afectó a la mortalidad en los pacientes no infectados por VIH (<span class="elsevierStyleItalic">odss ratio</span> [OR] 1,26; IC 95% 0,60–2,67) y no tuvo ningún efecto beneficioso para los pacientes con hipoxemia intensa (PaO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>70<span class="elsevierStyleHsp" style=""></span>mmHg) (OR 0,90; IC 95% 0,44–1,83). No se observó ningún efecto significativo sobre la variable secundaria (OR 1,34; IC 95% 0,44–4,11).</p></span> <span id="abst0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Conclusiones</span><p id="spar0040" class="elsevierStyleSimplePara elsevierViewall">Aunque los estudios eran observacionales, el metanálisis mostró que el tratamiento complementario con corticoides no mejoraba la evolución de los pacientes con neumonía por <span class="elsevierStyleItalic">P. jirovecii</span> no infectados por VIH. Estos resultados justifican la realización de un ensayo controlado aleatorizado.</p></span>" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "abst0025" "titulo" => "Introducción" ] 1 => array:2 [ "identificador" => "abst0030" "titulo" => "Métodos" ] 2 => array:2 [ "identificador" => "abst0035" "titulo" => "Resultados" ] 3 => array:2 [ "identificador" => "abst0040" "titulo" => "Conclusiones" ] ] ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Fujikura Y, Manabe T, Kawana A, Kohno S. Tratamiento complementario con corticoides en la neumonía por <span class="elsevierStyleItalic">Pneumocystis jirovecii</span> en pacientes no infectados por VIH: revisión sistemática y metanálisis de los estudios observacionales. Arch Bronconeumol. 2017;53:55–61.</p>" ] ] "multimedia" => array:6 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Fig. 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 1595 "Ancho" => 2717 "Tamanyo" => 222515 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0045" class="elsevierStyleSimplePara elsevierViewall">PRISMA flow diagram.</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" => 2140 "Ancho" => 3442 "Tamanyo" => 295859 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0050" class="elsevierStyleSimplePara elsevierViewall">Primary outcome: mortality. (a) Mortality, (b) funnel plot for mortality.</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" => 651 "Ancho" => 3441 "Tamanyo" => 172547 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0055" class="elsevierStyleSimplePara elsevierViewall">Mortality in patients with severe hypoxemia (PaO<span class="elsevierStyleInf">2</span> <70<span class="elsevierStyleHsp" style=""></span>mmHg).</p>" ] ] 3 => array:7 [ "identificador" => "fig0020" "etiqueta" => "Fig. 4" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr4.jpeg" "Alto" => 601 "Ancho" => 3450 "Tamanyo" => 159879 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0060" class="elsevierStyleSimplePara elsevierViewall">Secondary outcome: need for intubation or mechanical ventilation.</p>" ] ] 4 => array:8 [ "identificador" => "tbl0005" "etiqueta" => "Table 1" "tipo" => "MULTIMEDIATABLA" "mostrarFloat" => true "mostrarDisplay" => false "detalles" => array:1 [ 0 => array:3 [ "identificador" => "at1" "detalle" => "Table " "rol" => "short" ] ] "tabla" => array:2 [ "leyenda" => "<p id="spar0070" class="elsevierStyleSimplePara elsevierViewall">PSL, prednisolone; mPSL, methyl-prednisolone; PJP, <span class="elsevierStyleItalic">Pneumocystis jirovecii</span> pneumonia.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study (Author, Year) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Country \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Center \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Age criteria \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Inclusion criteria \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">No. of patients (experimental vs control) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Underlying diseases (case) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Definition of adjunctive corticosteroids \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Outcome \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Selected outcome for our study \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pareja, 1998 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">USA \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Single \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">All confirmed cases of non-HIV PJP with PaO<span class="elsevierStyleInf">2</span> <65<span class="elsevierStyleHsp" style=""></span>mmHg or oxygen saturation <90% \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">30 (16 vs. 14) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Organ transplant (13), collagen-vascular diseases (9), malignancy (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">>2-fold increase or >PSL 60<span class="elsevierStyleHsp" style=""></span>mg daily \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mortality, intubation, duration of mechanical ventilation, ICU admission, supplemental oxygen requirement, hospitalization \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mortality (including subgroup analysis), need for intubation or mechanical ventilation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Delclaux, 1999 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">France \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Multi \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">All confirmed cases of non-HIV PJP with PaO<span class="elsevierStyleInf">2</span> <70<span class="elsevierStyleHsp" style=""></span>mmHg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">31 (23 vs. 8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hematological malignancies (24), vasculitis (3), solid tumors (2), others (2) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">De novo: >1<span class="elsevierStyleHsp" style=""></span>mg/kg of PSL, or mPSL 240<span class="elsevierStyleHsp" style=""></span>mg for 3 days, followed by 120<span class="elsevierStyleHsp" style=""></span>mg, 60<span class="elsevierStyleHsp" style=""></span>mg each for 3 days (or treatment period) Rescue: >3-fold increase \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mortality, intubation \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mortality (including subgroup analysis), need for intubation or mechanical ventilation \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Roblot, 2003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">France \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Multi \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥18 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">All confirmed cases of non-HIV PJP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">60 (35 vs. 25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hematological malignancies (60) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Not described) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mortality \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mortality \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bollee, 2007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">France \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Single \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Adult) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">All confirmed cases of non-HIV PJP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">56 (21 vs. 35) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hematological malignancies (44), Solid cancers (9), Miscellaneous (3), Marchiafava-Micheli anemia (1), Fanconi syndrome (1), Kaposi sarcoma (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">1<span class="elsevierStyleHsp" style=""></span>mg/kg or 30<span class="elsevierStyleHsp" style=""></span>mg increase in the daily steroids \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mortality \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mortality \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Moon, 2011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Korea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Single \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">≥16 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">All confirmed cases of non-HIV PJP with PaO<span class="elsevierStyleInf">2</span> ≤70<span class="elsevierStyleHsp" style=""></span>mmHg or AaDO<span class="elsevierStyleInf">2</span> ≥35<span class="elsevierStyleHsp" style=""></span>mmHg \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">88 (59 vs. 29) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Solid organ transplant (26), hematological malignancies (26), non-hematological malignancies (12), interstitial lung diseases (9), connective tissue diseases (7), others (8) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top"><72<span class="elsevierStyleHsp" style=""></span>hours of initiating PJP treatment, 40<span class="elsevierStyleHsp" style=""></span>mg twice daily for 5 days, then tapered \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mortality, respiratory failure \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mortality (including subgroup analysis) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kim, 2014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Korea \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Multi \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">All \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">All confirmed cases of non-HIV PJP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">173 (152 vs. 21) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hematological malignancies (81), solid tumors (38), organ transplantations (17), others (rheumatoid arthritis, dermatologic, glomerulonephritis, Henoch-Schonlein purpura) (37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Not described) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mortality \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mortality \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kofteridis, 2014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Greece \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Single \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Adult) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">All confirmed cases of non-HIV PJP \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">62 (50 vs. 12) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Hematological malignancies (31), solid tumors (16), chronic inflammatory diseases (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Not described) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mortality \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Mortality \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1338919.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0065" class="elsevierStyleSimplePara elsevierViewall">Characteristics of Observational Studies Included.</p>" ] ] 5 => 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="spar0080" class="elsevierStyleSimplePara elsevierViewall">PSL, prednisolone; IQR, inter-quartile range; PCP, <span class="elsevierStyleItalic">Pneumocystis jirovecii</span> pneumonia.</p>" "tablatextoimagen" => array:1 [ 0 => array:2 [ "tabla" => array:1 [ 0 => """ <table border="0" frame="\n \t\t\t\t\tvoid\n \t\t\t\t" class=""><thead title="thead"><tr title="table-row"><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Study (Author, Year) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Daily PSL use (case) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">Other immunosuppressants (case) \t\t\t\t\t\t\n \t\t\t\t</th><th class="td" title="table-head " align="left" valign="top" scope="col" style="border-bottom: 2px solid black">PCP prophylaxis \t\t\t\t\t\t\n \t\t\t\t</th></tr></thead><tbody title="tbody"><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Pareja, 1998 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">17.2<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>12.8<span class="elsevierStyleHsp" style=""></span>mg (24) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">FK506 (6), cyclosporine (2), methotrexate (2), fludarabine (1) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">No prophylaxis \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Delclaux, 1999 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Not described) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Not described) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Not described) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Roblot, 2003 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">52.6<span class="elsevierStyleHsp" style=""></span>mg<span class="elsevierStyleHsp" style=""></span>±<span class="elsevierStyleHsp" style=""></span>44.0<span class="elsevierStyleHsp" style=""></span>mg (25) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Chemotherapy (49) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">3 (0.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Bollee, 2007 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Long-term steroids (24), PSL 30<span class="elsevierStyleHsp" style=""></span>mg (IQR 15–45<span class="elsevierStyleHsp" style=""></span>mg), average 6.5 months \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Long-term steroids<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>chemotherapy/immunosuppressive agents (12), discontinuous steroids<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>chemotherapy/immunosuppressive agents (8), chemotherapy and/or immunosuppressive agents (15) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 (10.7%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Moon, 2011 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Corticosteroids, dose not described (34) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">T-cell immunosuppressant (31), anticancer agents (37) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">(Not described) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kim, 2014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Corticosteroids, within 2 weeks, dose not described (128) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Chemotherapeutic agents (107) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">6 (3.5%) \t\t\t\t\t\t\n \t\t\t\t</td></tr><tr title="table-row"><td class="td-with-role" title="table-entry ; entry_with_role_rowhead " align="left" valign="top">Kofterideis, 2014 \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Corticosteroid, dose not described (30) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">Chemotherapy (26), steroids<span class="elsevierStyleHsp" style=""></span>+<span class="elsevierStyleHsp" style=""></span>chemotherapy (17) \t\t\t\t\t\t\n \t\t\t\t</td><td class="td" title="table-entry " align="left" valign="top">21 (35%) \t\t\t\t\t\t\n \t\t\t\t</td></tr></tbody></table> """ ] "imagenFichero" => array:1 [ 0 => "xTab1338918.png" ] ] ] ] "descripcion" => array:1 [ "en" => "<p id="spar0075" class="elsevierStyleSimplePara elsevierViewall">Treatment Profiles of Patients in Studies.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:23 [ 0 => array:3 [ "identificador" => "bib0120" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Pneumocystis pneumonia" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "C.F. 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We would like to thank all members of the Committee.</p>" "vista" => "all" ] ] ] "idiomaDefecto" => "en" "url" => "/15792129/0000005300000002/v2_201702040101/S1579212916301872/v2_201702040101/en/main.assets" "Apartado" => array:4 [ "identificador" => "9374" "tipo" => "SECCION" "en" => array:2 [ "titulo" => "Original Articles" "idiomaDefecto" => true ] "idiomaDefecto" => "en" ] "PDF" => "https://static.elsevier.es/multimedia/15792129/0000005300000002/v2_201702040101/S1579212916301872/v2_201702040101/en/main.pdf?idApp=UINPBA00003Z&text.app=https://archbronconeumol.org/" "EPUB" => "https://multimedia.elsevier.es/PublicationsMultimediaV1/item/epub/S1579212916301872?idApp=UINPBA00003Z" ]
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