Effectiveness of Pulse Methylprednisolone in Patients with Non-Human Immunodeficiency Virus Pneumocystis Pneumonia: A Multicentre, Retrospective Registry-based Cohort Study

Effectiveness of Pulse Methylprednisolone in Patients with Non-Human Immunodeficiency Virus Pneumocystis Pneumonia: A Multicentre, Retrospective Registry-based Cohort Study | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Effectiveness of Pulse Methylprednisolone in Patients with Non-Human Immunodeficiency Virus Pneumocystis Pneumonia: A Multicentre, Retrospective Registry-based Cohort Study Yasuhiro Morimoto, Hiroki Matsui, Haruka Fujioka, Yuya Homma, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-4781746/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 02 Nov, 2024 Read the published version in BMC Infectious Diseases → Version 1 posted 4 You are reading this latest preprint version Abstract Background A recent database study and meta-analysis reported that adjunctive glucocorticoid therapy reduces mortality in patients with non-human immunodeficiency virus-associated (non-HIV) Pneumocystis jirovecii pneumonia (PCP), having hypoxemia. However, the optimal glucocorticoid dose remains unclear. Our study aimed to evaluate the effectiveness of pulse methylprednisolone compared with mild-to-moderate steroid doses in patients with non-HIV PCP. Methods This multicentre retrospective cohort study included adults with non-HIV PCP receiving adjunctive steroids at three Japanese tertiary care hospitals from June 2006 to March 2021. Patients were categorised into pulse methylprednisolone and mild-to-moderate dose groups. Pulse methylprednisolone involved an initial intravenous infusion of 500–1000 mg methylprednisolone daily, while the mild-to-moderate dose was lower. Primary and secondary outcomes were 30-day and 180-day mortality rates from treatment initiation. Patient characteristics were adjusted using propensity score analysis with overlap weighting. Subgroup analysis focused on patients with respiratory failure. Results The study included 139 patients with non-HIV PCP: 55 in the pulse methylprednisolone group and 84 in the mild-to-moderate dose group. After adjusting for patient background, 30-day mortality (15.8% vs. 14.1%, P = 0.813) and 180-day mortality (33.7% vs. 25.3%, P = 0.367) did not differ significantly between groups. Subgroup analysis revealed no significant associations among patients with respiratory failure. Conclusions After adjusting for patient characteristics, no difference in prognosis was observed between pulse methylprednisolone and mild-to-moderate dose groups in patients with non-HIV PCP. A mild-to-moderate dose of adjunctive corticosteroid may suffice for treating non-HIV PCP. non-human immunodeficiency virus-infected patient pneumocystis pneumonia adjunctive corticosteroid treatment pulse methylprednisolone Figures Figure 1 Background Pneumocystis jirovecii pneumonia (PCP) is a life-threatening opportunistic infection occurring in patients with human immunodeficiency virus (HIV) infection and other immunocompromised states [ 1 ]. Owing to differences in pathophysiology, non-HIV-associated (non-HIV) PCP has been reported to cause a more severe inflammatory response and profound hypoxemia than in those with HIV [ 1 , 2 ]. The mortality rates in patients with non-HIV PCP (30–60%) have been reported to be higher than those in patients with HIV (10–20%) [ 1 ]. Recent epidemiological studies have shown an increasing trend in the incidence and mortality of non-HIV PCP [ 2 – 4 ]. The first-line antibiotic for treating PCP is trimethoprim-sulfamethoxazole [ 1 , 5 – 7 ]. Adjunctive steroids are recommended for patients experiencing hypoxemia, which is characterised by a partial pressure of oxygen < 70 mmHg and an alveolar-arterial oxygen gradient of ≥ 35 mmHg [ 5 , 7 ]. Previous randomised controlled trials and a meta-analysis have demonstrated that adjunctive corticosteroid treatment reduces the need for ventilation and mortality in patients with HIV-PCP with such hypoxemia [ 8 – 11 ]. However, limited data exist on the effectiveness of adjunctive glucocorticoid therapy in patients with non-HIV PCP [ 12 ]. A nationwide administrative claims database study and a meta-analysis have reported that adjunctive glucocorticoid therapy reduces mortality in patients with non-HIV PCP having respiratory failure [ 13 , 14 ]. Evidence supporting the efficacy of adjunctive glucocorticoid therapy in cases of respiratory failure is accumulating. However, the appropriate dosage of glucocorticoids has not been well studied. The nationwide database study suggested that low-dose corticosteroids (prednisone equivalents 17–36 mg/day) are associated with a lower risk of all-cause mortality in a subgroup of patients with respiratory failure [ 13 ]. In a subgroup analysis conducted in the recent meta-analysis [ 14 ], low-dose corticosteroids (equivalent to 1 mg/kg/day prednisone) were significantly associated with reduced mortality in patients with respiratory failure, while no significant association was found with high-dose corticosteroids (prednisone equivalents > 240 mg). However, these studies have limitations. The administrative claims data study lacks detailed patient severity information, such as lactate dehydrogenase and albumin levels, which have been reported to affect the prognosis of non-HIV PCP [ 15 ]. The meta-analysis only included one small observational study of 39 cases evaluating high-dose steroids without adjustment for patient backgrounds. Therefore, further large-scale research on dosage appropriateness based on real clinical practice data, with adjustments for patient backgrounds and severity information, is necessary. In this multicentre cohort study, our objective was to evaluate the efficacy of pulse methylprednisolone compared to mild-to-moderate steroid doses in patients with non-HIV PCP. We aimed to adjust for patient backgrounds and assess the primary endpoint of 30-day mortality. Material and Methods Study setting and population We conducted a multicentre, retrospective, observational cohort study comprising adult patients with clinically diagnosed non-HIV PCP treated with adjunctive corticosteroid therapy. Patients without HIV, diagnosed with PCP at Hospital A, Hospital B, and Hospital C between January 2006 and March 2021, were retrospectively enrolled (registry named RE-VISION-PCP: Registry to Provide New Evidence and Insights for the Management of Pneumocystis Pneumonia in Non-HIV-infected Patients). The study protocol was approved by the research ethics committees of Hospital A (#21-069-230801), Hospital B (#3584), and Hospital C (#21–58). As this was a retrospective study and patient data were anonymised, the requirement for written informed consent was waived. Based on the diagnostic guideline for non-HIV PCP and previous studies [ 16 – 19 ], we defined the diagnostic criteria for PCP as follows: 1) Host factors: This includes possible immunocompromised conditions other than HIV. 2) Clinical criteria: The presence of clinical symptoms consistent with PCP, such as dyspnoea, cough, fever, and hypoxemia, as well as identification of abnormal shadows (such as bilateral ground-glass opacities) on chest X-ray or chest computed tomography scans that indicate PCP. 3) Microbiological criteria: Detection of pneumocystis in respiratory specimens, such as sputum or bronchoalveolar lavage fluid, using conventional staining methods (Grocott methenamine silver or Diff-Quick staining) or deoxyribonucleic acid testing (loop-mediated isothermal amplification or polymerase chain reaction). Alternatively, elevated levels of β-D-glucan, along with a favourable response to standard therapy for PCP, can also be considered as part of the microbiological criteria. Serum concentrations of β-D-glucan were assessed using either the β-D-glucan test kit (Wako Pure Chemical Industries, Osaka, Japan) or the FUNGITEC G test MKII (Nissui Pharmaceutical, Tokyo, Japan). Elevated β-D-glucan levels were defined as > 5 pg/mL (β-D-glucan test; Wako assay) or > 20 pg/mL (FUNGITEC G-test KM assay) [ 20 , 21 ]. Notably, patients with PCP who received adjunctive corticosteroid therapy or any other treatment were included in the study. The exclusion criteria were as follows: 1) patients who did not receive adjunctive corticosteroid therapy. 2) patients who had missing data on the variables analysed. Exposure defined by steroid dosage Patients who participated in the study were grouped into two categories based on their steroid dosage: the pulse methylprednisolone group and the mild-to-moderate dose group. Pulse methylprednisolone was defined as an initial intravenous infusion of 500–1000 mg of methylprednisolone administered daily. Alternatively, the mild-to-moderate dose group was characterised by a steroid dose lower than that used in pulse methylprednisolone therapy. In the adjunctive steroid treatment of PCP for the mild-to-moderate dose group, the administration methods and durations typically follow international guidelines derived from research conducted on HIV-associated PCP [ 5 , 7 ]. The treatment regimen begins with administration of prednisone, or an equivalent dose of another corticosteroid, at 40 mg twice daily for the first 5 days, followed by 40 mg once daily from Days 6 to 11, and finally, a dosage of 20 mg daily through Day 21. Notably, treating physicians have the flexibility to adjust this regimen as needed. In the pulse methylprednisolone therapy group, an initial dose of 500–1000 mg is administered for the first 3 days, after which the established protocol for HIV-associated PCP continues from Day 4 onwards [ 5 , 7 ]. The entire course of steroid treatment spans 21 days, with modifications as determined by the treating physician. Outcomes The primary endpoint was the 30-day mortality rate from the start of the treatment. The secondary endpoint was the 180-day mortality rate after treatment initiation. Data collection The following data were retrospectively collected for each patient from their medical records: age, sex, weight, hospital, underlying diseases, immunosuppressive agents administration at diagnosis, laboratory results (platelet count; haemoglobin, serum albumin, lactate dehydrogenase, serum sodium, serum potassium, and creatinine levels; creatinine clearance), consciousness status, presence of hypotension, respiratory status (no oxygen support, oxygen support, and mechanical ventilation), initial treatment drugs (Trimethoprim-Sulfamethoxazole, pentamidine, and atovaquone), use of adjunctive glucocorticoid therapy (including pulse methylprednisolone administration), and 30- and 180-day mortality rates. Statistical analyses Descriptive statistics for baseline characteristics and outcomes were obtained for each group. As this was a retrospective cohort study, prior sample size calculations were not performed, and all available populations were enrolled. Because three cases had missing variables, a complete case analysis was performed, and the missing cases were addressed using a list-wise method. No loss to follow-up occurred for the 30-day mortality, which was the primary endpoint of the study. T-tests were used for continuous variables and χ-square tests for categorical variables to compare between groups. Propensity scores for pulse methylprednisolone were calculated to reduce the confounding effect of the application, and overlap weighting was performed using the propensity scores [ 22 ]. For propensity score calculation, a logistic regression model was constructed with pulse methylprednisolone as the dependent variable and age, sex, hospital, history of malignancy, serum albumin levels, lactate dehydrogenase levels, respiratory status, interstitial pneumonia, and creatinine clearance as explanatory variables. These explanatory variables were selected by considering results of clustering by hospital, prognostic factors for non-HIV PCP [ 6 , 15 ], and interstitial pneumonia complications. We assumed that pulse methylprednisolone therapy would be more likely to be selected in cases of interstitial pneumonia due to the suspicion of acute exacerbation of interstitial pneumonia as a potential differential diagnosis. This assumption is based on the common practice in Japan, where acute exacerbations of interstitial pneumonia are often treated with pulse methylprednisolone therapy. The decision to use this treatment approach is guided by the Japanese guidelines for idiopathic pulmonary fibrosis [ 23 ]. The balance of variables between the groups was evaluated using the standardised mean difference (SMD) between the variables. As per previous studies [ 24 ], the groups were considered balanced when the SMD was less than 0.1. Statistical analyses were conducted using the R software (version 4.3.0; R Development Core Team). Subgroup analysis The same methodology described previously was also used for the subgroup analysis, which was limited to patients with respiratory failure. Respiratory failure was defined as respiratory status requiring oxygen support or mechanical ventilation. This analysis was conducted based on prior studies demonstrating the benefits of adjunctive corticosteroid therapy in patients with non-HIV PCP and hypoxemia [ 13 , 14 ]. Results A flowchart of the study is shown in Fig. 1 . Data were collected from 164 patients diagnosed with non-HIV PCP. Twenty-two patients who did not receive adjunctive corticosteroid therapy and three patients with missing initial treatment types were excluded. Therefore, 139 patients with non-HIV PCP were included in this study and were categorised into two groups: 55 in the pulse methylprednisolone group and 84 in the mild-to-moderate dose group. In the subgroup analysis, 67 patients with respiratory failure were selected from the 139 patients with non-HIV PCP. The patients were classified into two groups: 32 in the pulse methylprednisolone group and 35 in the mild-to-moderate dose group. The unadjusted and adjusted baseline characteristics of the study participants are shown in Table 1 . In the unadjusted cohort, sex, weight, hospital, presence of malignancies, solid tumours, connective tissue disease, or interstitial pneumonia, and use of corticosteroids, immunosuppressants, biologics, or anticancer agents were imbalanced between the two groups because the SMD was > 0.1. Among the laboratory results, haemoglobin, serum albumin, lactate dehydrogenase, creatinine levels, hypotension, and respiratory status were imbalanced across the two groups. In the adjusted cohort, age, sex, hospital, presence of solid tumours, malignancies or interstitial pneumonia, haemoglobin, serum albumin, lactate dehydrogenase, serum sodium, creatinine clearance, hypotension, respiratory status, and mechanical ventilation were considered balanced since the SMD was < 0.1. Table 1 Baseline characteristics of participants Unadjusted cohort Adjusted cohort Variables Pulse methylprednisolone n = 55 Mild-to-moderate dose n = 84 SMD Pulse methylprednisolone n = 26.35 Mild-to-moderate dose n = 26.35 SMD Age (years) 70.67 (± 11.33) 70.21 (± 10.52) 0.042 70.52 (± 11.33) 70.52 (± 10.43) < 0.001 Female 25 (45.5) 50 (59.5) 0.285 12.7 (48.2) 12.7 (48.2) < 0.001 Weight (kg) 52.24 (± 10.80) 53.55 (± 11.99) 0.115 52.01 (± 10.92) 54.85 (± 12.22) 0.245 Hospital 0.280 < 0.001 Hospital A 35 (63.6) 49 (58.3) 17.2 (65.2) 17.2 (65.2) Hospital B 13 (23.6) 29 (34.5) 6.9 (26.1) 6.9 (26.1) Hospital C 7 (12.7) 6 (7.1) 2.3 (8.7) 2.3 (8.7) Underlying disease Malignancies 15 (27.3) 13 (15.5) 0.291 5.8 (22.1) 5.8 (22.1) < 0.001 Haematological malignancies 5 (9.1) 6 (7.1) 0.071 2.0 (7.4) 2.7 (10.4) 0.103 Solid tumours 11 (20.0) 8 (9.5) 0.299 4.1 (15.4) 3.4 (12.9) 0.072 Connective tissue disease 34 (61.8) 68 (81.0) 0.433 17.1 (65.0) 19.6 (74.3) 0.203 Interstitial pneumonia 23 (41.8) 13 (15.5) 0.609 7.6 (28.8) 7.6 (28.8) < 0.001 Immunosuppressive agents used Corticosteroid 35 (63.6) 58 (69.0) 0.115 16.3 (61.9) 19.4 (73.5) 0.250 Immunosuppressant 32 (58.2) 55 (65.5) 0.151 16.4 (62.1) 13.7 (51.9) 0.208 Biologics 9 (16.4) 22 (26.2) 0.242 6.3 (24.0) 4.9 (18.5) 0.135 Anticancer agent 12 (21.8) 4 (4.8) 0.519 4.4 (16.8) 1.5 (5.8) 0.351 Blood biochemistry Haemoglobin (g/dL) 11.22 (± 2.13) 11.57 (± 1.93) 0.170 11.27 (± 2.08) 11.36 (± 1.96) 0.045 Platelet count (×10⁴/µL) 21.69 (± 9.48) 22.55 (± 10.95) 0.085 21.19 (± 9.21) 22.70 (± 11.63) 0.145 Albumin (g/dL) 2.75 (± 0.64) 3.06 (± 0.61) 0.500 2.88 (± 0.66) 2.88 (± 0.59) < 0.001 Lactate dehydrogenase (IU/L) 440.15 (± 153.04) 386.81 (± 169.50) 0.330 413.88 (± 132.73) 413.88 (± 195.02) < 0.001 Serum sodium (mEq/L) 137.73 (± 4.89) 137.85 (± 3.68) 0.027 137.54 (± 4.64) 137.74 (± 4.24) 0.044 Serum potassium (mEq/L) 4.17 (± 0.59) 4.22 (± 0.46) 0.100 4.16 (± 0.59) 4.24 (± 0.46) 0.151 Creatinine (mg/dL) 0.99 (± 0.85) 1.10 (± 1.31) 0.101 1.03 (± 0.89) 1.32 (± 1.64) 0.223 Creatinine clearance (mL/min) 60.79 (± 29.37) 61.39 (± 28.16) 0.021 60.11 (± 30.67) 60.11 (± 30.80) < 0.001 Disturbed consciousness 1 (1.8) 1 (1.2) 0.052 0.2 (0.6) 0.6 (2.3) 0.140 Hypotension (systolic pressure < 90 mmHg) 2 (3.6) 1 (1.2) 0.160 0.4 (1.6) 0.5 (1.8) 0.014 Respiratory status 0.335 < 0.001 Without oxygen 23 (41.8) 49 (58.3) 12.2 (46.4) 12.2 (46.4) Administration of oxygen 31 (56.4) 34 (40.5) 13.8 (52.6) 13.8 (52.6) 1 − 4 L/min 11 (20.0) 28 (33.3) 4.5 (17.2) 10.6 (40.1) 5 − 10 L/min 12 (21.8) 1 (1.2) 5.6 (21.1) 0.7 (2.8) 11 − 15 L/min 8 (14.5) 5 (6.0) 3.8 (14.3) 2.5 (9.6) Mechanical ventilation 1 (1.8) 1 (1.2) 0.052 0.3 (1.1) 0.3 (1.1) < 0.001 Initial treatment 0.200 0.261 Trimethoprim-Sulfamethoxazole 51 (92.7) 73 (86.9) 24.7 (93.6) 22.7 (86.0) Pentamidine 1 (1.8) 2 (2.4) 0.4 (1.5) 0.6 (2.2) Atovaquone 3 (5.5) 9 (10.7) 1.3 (4.8) 3.1 (11.8) Categorical variables are presented as n (%), and continuous variables are presented as mean ± standard deviation. Abbreviations: SMD = standardised mean difference The clinical outcomes of the unadjusted and adjusted cohorts are summarised in Table 2 . In the unadjusted cohort, the 30-day mortality rates were 21.8% for the pulse methylprednisolone group and 8.3% for the mild-to-moderate dose group. The 180-day mortality rates were 41.8% in the pulse methylprednisolone group and 14.3% in the mild-to-moderate dose group. In the adjusted cohort, there were no significant differences (30-day mortality: 15.8%, pulse methylprednisolone group and 14.1% in the mild-to-moderate dose group; and 180-day mortality: 33.7%, pulse methylprednisolone group and 25.3%, mild-to-moderate dose group). Table 2 Summary of clinical outcomes Unadjusted cohort Adjusted cohort Variables Pulse methylprednisolone n = 55 Mild-to-moderate dose n = 84 P Pulse methylprednisolone n = 26.3 Mild-to-moderate dose n = 26.3 P Primary endpoint 30-day mortality 12 (21.8) 7 (8.3) 0.044 4.2 (15.8) 3.7 (14.1) 0.813 Secondary endpoint 180-day mortality 23 (41.8) 12 (14.3) 0.001 8.9 (33.7) 6.7 (25.3) 0.367 Categorical variables are presented as n (%). Subsequently, we performed a subgroup analysis of patients with respiratory failure. The unadjusted and adjusted baseline characteristics of the subgroups are presented in Table 3 . In the unadjusted cohort, sex, weight, hospital, presence of malignancies, haematological malignancies, solid tumours, connective tissue disease, or interstitial pneumonia, and the use of immunosuppressants, biologics, or anticancer agents were imbalanced. Among the laboratory results, haemoglobin, serum albumin, lactate dehydrogenase, serum sodium, creatinine, and creatinine clearance levels were imbalanced, as were disturbed consciousness and initial treatment. In the adjusted cohort, age, sex, hospital, presence of malignancies and interstitial pneumonia, use of immunosuppressants and biologics, haemoglobin, serum albumin, lactate dehydrogenase, serum sodium, serum potassium, creatinine clearance, respiratory status, and mechanical ventilation were balanced. Table 3 Baseline characteristics of patients in the subgroup analysis limited to respiratory failure Unadjusted cohort Adjusted cohort Variables Pulse methylprednisolone n = 32 Mild-to-moderate dose n = 35 SMD Pulse methylprednisolone n = 13.40 Mild-to-moderate dose n = 13.40 SMD Age (years) 71.56 (± 11.84) 71.46 (± 9.49) 0.010 71.85 (± 12.89) 71.85 (± 9.87) < 0.001 Female 14 (43.8) 19 (54.3) 0.212 6.0 (45.1) 6.0 (45.1) < 0.001 Weight (kg) 52.56 (± 9.76) 54.43 (± 12.16) 0.169 52.50 (± 10.45) 55.92 (± 12.20) 0.301 Hospital 0.249 < 0.001 Hospital A 27 (84.4) 28 (80.0) 11.3 (84.4) 11.3 (84.4) Hospital B 5 (15.6) 6 (17.1) 2.1 (15.6) 2.1 (15.6) Hospital C 0 (0.0) 1 (2.9) 0.0 (0.0) 0.0 (0.0) Underlying disease Malignancies 12 (37.5) 6 (17.1) 0.469 3.5 (25.8) 3.5 (25.8) < 0.001 Haematological malignancies 4 (12.5) 3 (8.6) 0.128 0.9 (6.8) 1.9 (14.1) 0.242 Solid tumours 9 (28.1) 3 (8.6) 0.522 2.7 (19.9) 1.6 (11.7) 0.228 Connective tissue disease 16 (50.0) 26 (74.3) 0.517 7.9 (59.0) 8.6 (64.3) 0.108 Interstitial pneumonia 10 (31.2) 7 (20.0) 0.260 3.1 (23.1) 3.1 (23.1) < 0.001 Immunosuppressive agents used Corticosteroid 24 (75.0) 26 (74.3) 0.016 11.2 (83.6) 9.1 (68.2) 0.367 Immunosuppressant 13 (40.6) 18 (51.4) 0.218 6.0 (44.7) 5.5 (41.1) 0.073 Biologics 2 (6.2) 6 (17.1) 0.344 1.3 (10.0) 1.6 (11.6) 0.051 Anticancer agent 10 (31.2) 2 (5.7) 0.697 2.9 (22.0) 1.0 (7.6) 0.413 Blood biochemistry Haemoglobin (g/dL) 11.21 (± 2.28) 11.57 (± 2.04) 0.167 11.46 (± 2.27) 11.33 (± 2.02) 0.063 Platelet count (×10⁴/µL) 22.54 (± 10.01) 21.63 (± 11.51) 0.085 23.02 (± 10.32) 20.80 (± 11.50) 0.203 Albumin (g/dL) 2.52 (± 0.49) 2.81 (± 0.61) 0.529 2.67 (± 0.48) 2.67 (± 0.57) < 0.001 Lactate dehydrogenase (IU/L) 458.38 (± 167.76) 377.00 (± 169.81) 0.482 427.95 (± 144.20) 427.95 (± 210.47) < 0.001 Serum sodium (mEq/L) 138.62 (± 5.53) 137.83 (± 4.15) 0.163 138.44 (± 4.63) 138.15 (± 4.24) 0.066 Serum potassium (mEq/L) 4.11 (± 0.65) 4.11 (± 0.40) 0.015 4.12 (± 0.61) 4.12 (± 0.41) 0.012 Creatinine (mg/dL) 0.89 (± 0.50) 1.35 (± 1.88) 0.333 0.97 (± 0.62) 1.53 (± 2.17) 0.356 Creatinine clearance (mL/min) 62.68 (± 28.42) 59.38 (± 30.07) 0.113 60.59 (± 29.82) 60.59 (± 31.88) < 0.001 Disturbed consciousness 0 (0.0) 1 (2.9) 0.243 0.0 (0.0) 0.5 (4.0) 0.290 Hypotension (systolic pressure < 90 mmHg) 1 (3.1) 1 (2.9) 0.016 0.2 (1.8) 0.5 (3.4) 0.100 Respiratory status 0.016 < 0.001 Administration of oxygen 32 (100.0) 35 (100.0) 13.4 (100.0) 13.4 (100.0) 1 − 4 L/min 11 (34.4) 28 (80.0) 4.2 (31.1) 9.5 (70.9) 5 − 10 L/min 12 (37.5) 1 (2.9) 5.0 (37.5) 0.6 (4.8) 11 − 15 L/min 8 (25.0) 5 (14.3) 3.9 (29.3) 3.0 (22.1) Mechanical ventilation 1 (3.1) 1 (2.9) 0.016 0.3 (2.1) 0.3 (2.1) < 0.001 Initial treatment 0.508 0.549 Trimethoprim-Sulfamethoxazole 32 (100.0) 31 (88.6) 13.4 (100.0) 11.6 (86.9) Pentamidine 0 (0.0) 0 (0.0) 0 (0.0) 0 (0.0) Atovaquone 0 (0.0) 4 (11.4) 0 (0.0) 1.8 (13.1) Categorical variables are presented as n (%), and continuous variables are presented as mean ± standard deviation. Abbreviations: SMD = standardised mean difference The clinical outcomes of both cohorts are shown in Table 4 . In the unadjusted cohort, the 30-day mortality rates were 25.0% for the pulse methylprednisolone group and 17.1% for the mild-to-moderate dose group. The 180-day mortality rates were 50.0% in the pulse methylprednisolone group and 25.7% in the mild-to-moderate dose group. No significant differences were observed between the two groups in the adjusted cohort (30-day mortality: 21.4%, pulse methylprednisolone group and 27.1%, mild-to-moderate dose group; and 180-day mortality: 43.9%, pulse methylprednisolone group and 35.7%, mild-to-moderate dose group). Table 4 Clinical outcomes of the subgroup analysis limited to respiratory failure Unadjusted cohort Adjusted cohort Variables Pulse methylprednisolone n = 32 Mild-to-moderate dose n = 35 P Pulse methylprednisolone n = 13.4 Mild-to-moderate dose n = 13.4 P Primary endpoint 30-day mortality 8 (25.0) 6 (17.1) 0.625 2.9 (21.4) 3.6 (27.1) 0.639 Secondary endpoint 180-day mortality 16 (50.0) 9 (25.7) 0.072 5.9 (43.9) 4.8 (35.7) 0.558 Categorical variables are presented as n (%) Discussion In this multicentre, retrospective, observational cohort study of patients with non-HIV PCP treated with adjunctive corticosteroid therapy, we evaluated the efficacy of pulse methylprednisolone compared to mild-to-moderate steroid doses. No significant differences were observed between the two groups in terms of the 30- or 180-day mortality rates after adjusting for patient background using the overlap weighting method with propensity scores. To our knowledge, this study is the first to compare pulse methylprednisolone with other doses for the treatment of non-HIV PCP using hospital-based detailed clinical information after adjusting for patient background. In contrast, some reports exist on the appropriateness of dosage and the effectiveness of adjunctive corticosteroid therapy in non-HIV PCP. Several randomised controlled trials and a meta-analysis have provided evidence that adjunctive corticosteroid therapy reduces the need for mechanical ventilation and mortality in patients with HIV-associated PCP and hypoxemia [ 8 – 11 ]. A Cochrane meta-analysis, which evaluated six randomised controlled trials on the efficacy of adjunctive steroids for moderate to severe HIV-associated PCP, found that compared to placebo, patients receiving adjunctive steroids had a lower risk of overall mortality at 1 month (risk ratio 0.56, 95% CI 0.32–0.98) and at 3–4 months (risk ratio 0.59, 95% CI 0.41–0.85) of follow-up [ 11 ]. Therefore, international guidelines recommend an initial dose of 80 mg/day of adjunctive corticosteroids for adult patients with moderate-to-severe HIV-associated PCP, defined as arterial oxygen partial pressure 35 mmHg on room air [ 7 , 11 , 25 ]. In contrast to HIV-associated PCP, there are limited data on the effectiveness of adjunctive corticosteroid therapy in patients with non-HIV-associated PCP. The American Thoracic Society’s Statement on the treatment of fungal infections in adult pulmonary patients recommends a corticosteroid treatment regimen for patients with moderate to severe non-HIV-associated PCP, similar to that used for HIV-associated PCP, as previously described [ 5 ]. However, this recommendation for adjunctive corticosteroid therapy in non-HIV PCP is primarily based on studies conducted in HIV-associated PCP [ 10 , 25 ], and there is a lack of solid evidence from randomised controlled trials specifically focusing on PCP in patients without HIV. The current recommendation lacks a robust foundation of evidence in the non-HIV population [ 26 ]. As discussed in the introduction, there is an increasing body of evidence supporting the effectiveness of adjunctive glucocorticoid treatment in patients with respiratory failure. However, the optimal dosage of glucocorticoids for PCP treatment in patients without HIV remains inadequately explored [ 13 , 14 ]. In this multicentre study, we found no significant difference in the 30- and 180-day mortality rates between pulse methylprednisolone and mild-to-moderate steroid doses after adjusting for patient background. Additionally, no significant association was observed in the subgroup analysis of patients with respiratory failure. These findings suggest that pulse methylprednisolone may not be necessary as an adjunctive steroid in non-HIV PCP, and mild-to-moderate steroid doses could be sufficient. Nevertheless, it is important to note that further large prospective cohort studies and randomised controlled trials are needed to confirm these results. The strength of this study lies in its multicentre design, which has a large number of patients adjusted for backgrounds. In clinical practice, higher doses of corticosteroids tend to be administered in more severe cases, and there may be a selection bias in patients treated with adjunctive corticosteroids. In this study, the respiratory status tended to be worse in the pulse methylprednisolone group between the two groups before adjustment for patient background. Patients with interstitial lung disease may also be more likely to be selected for pulse methylprednisolone therapy due to suspected acute exacerbations [ 23 ], potentially leading to patient background bias. Indeed, there were more patients with interstitial pneumonia in the pulse methylprednisolone group before adjusting for patient characteristics. In this study, patient characteristics, including interstitial pneumonia, respiratory status, and other prognostic factors (age, sex, history of malignancies, serum albumin levels, and serum lactate dehydrogenase levels) were adjusted using the overlap weighting method in propensity score analysis [ 15 ]. Our study had some limitations. First, this was a retrospective, observational study. Although we adjusted for confounding factors related to pulse methylprednisolone therapy and outcomes, such as interstitial pneumonia and prognostic factors, using propensity score analysis, we could not completely adjust for unknown confounding factors. Future prospective randomised trials are required to eliminate the influence of these confounders. Second, this study did not examine adverse events associated with corticosteroid use. Although the adverse events associated with systemic corticosteroid use (including hyperglycaemia, increased risk of coinfections, delirium, and ICU-acquired weakness) are generally recognised, data on the safety of adjunctive corticosteroid therapy for non-HIV PCP are lacking. The selection of the corticosteroid therapy dose should be based not only on the outcome but also on safety. Future studies are required to evaluate the safety of steroid use. Conclusions Pulse methylprednisolone therapy was not observed to be more effective than a mild-to-moderate dose regimen in the treatment of patients with non-HIV PCP after adjusting for patient characteristics. A mild-to-moderate dose of adjunctive corticosteroid may be sufficient for treating patients with non-HIV PCP. Further studies, including large-scale prospective cohort studies and randomised controlled studies, are required to confirm our results. Abbreviations HIV, human immunodeficiency virus; ICU, intensive care unit; PCP, Pneumocystis jirovecii pneumonia; SMD, standardised mean difference. Declarations Ethics approval and consent to participate The study protocol was approved by the research ethics committees of Hospital A (#21-069-230801), Hospital B (#3584), and Hospital C (#21-58). As this was a retrospective study and patient data were anonymised, the requirement for written informed consent was waived. Consent for publication : Not applicable Availability of data and materials Data pertaining to this study will be available by the corresponding author upon reasonable request. Competing interests Authors have no conflicts of interest to declare. Funding This study received no specific grants from any funding agency in the public, commercial, or not-for-profit sectors. Authors' contributions Conceptualisation: Y.M., H.M., S.O., K.N. Data curation: Y.M., H.M., S.O., K.N. Formal analysis: H.M. Investigation: Y.M., H.F., Y.H., T.N, S.O., D.S. Methodology: Y.M., H.M., S.O., K.N. Project administration: Y.M., S.O., K.N. Resources: Y.M., H.F., Y.H., T.N., A.O., H.I., S.O., T.M., D.S., W.T., Y.O., K.N. Software: H.M. Supervision: K.N. Validation: H.M., K.N. Visualisation: Y.M., H.M., K.N. Writing - original draft: Y.M. Writing - review & editing: Y.M., H.M., H.F., Y.H., T.N, A.O., H.I., S.O., T.M., D.S., W.T., Y.O., K.N. Acknowledgements We thank Editage (www.editage.jp) for English language editing. We thank all clinicians from the Department of Medical Oncology, Hematology/Oncology, and Rheumatology at Kameda Medical Center, Japan, for providing the case data. References Thomas Jr CF, Limper AH. Pneumocystis pneumonia. N Engl J Med. 2004;350:2487–98. Tasaka S, Tokuda H. Pneumocystis jirovecii pneumonia in non-HIV-infected patients in the era of novel immunosuppressive therapies. J Infect Chemother. 2012;18:793–806. Sepkowitz KA. Opportunistic infections in patients with and patients without acquired immunodeficiency syndrome. Clin Infect Dis. 2002;34:1098–107. Coyle PV, McCaughey C, Nager A, McKenna J, O’Neill H, Feeney SA, et al. Rising incidence of Pneumocystis jirovecii pneumonia suggests iatrogenic exposure of immune-compromised patients may be becoming a significant problem. J Med Microbiol. 2012;61:1009–15. Limper AH, Knox KS, Sarosi GA, Ampel NM, Bennett JE, Catanzaro A, et al. An Official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011;183:96–128. Maschmeyer G, Helweg-Larsen J, Pagano L, Robin C, Cordonnier C, Schellongowski P, et al. ECIL guidelines for treatment of Pneumocystis jirovecii pneumonia in non-HIV-infected haematology patients. J Antimicrob Chemother. 2016;71:2405-13. Guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Recommendations from the Centers for Disease Control and Prevention. The National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/pneumocystis?view=full. Accessed 8 March, 2024. Montaner JS, Lawson LM, Levitt N, Belzberg A, Schechter MT, Ruedy J. Corticosteroids prevent early deterioration in patients with moderately severe pneumocystis carinii pneumonia and the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1990;113:14–20. Gagnon S, Boota AM, Fischl MA, Baier H, Kirksey OW, La Voie L. Corticosteroids as adjunctive therapy for severe pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A double-blind, placebo-controlled trial. N Engl J Med. 1990;323:1444–50. Bozzette SA, Sattler FR, Chiu J, Wu AW, Gluckstein D, Kemper C, et al. A controlled trial of early adjunctive treatment with corticosteroids for pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative treatment group. N Engl J Med. 1990;323:1451–7. Ewald H, Raatz H, Boscacci R, Furrer H, Bucher HC, Briel M. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection. Cochrane Database Syst Rev. 2015;2015:CD006150. Delclaux C, Zahar JR, Amraoui G, Leleu G, Lebargy F, Brochard L, et al. Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in non-human immunodeficiency virus-infected patients: retrospective study of 31 patients. Clin Infect Dis. 1999;29:670–2. Inoue N, Fushimi K. Adjunctive corticosteroids decreased the risk of mortality of non-HIV Pneumocystis pneumonia. Int J Infect Dis. 2019;79:109–15. Ding L, Huang H, Wang H, He H. Adjunctive corticosteroids may be associated with better outcome for non-HIV Pneumocystis pneumonia with respiratory failure: a systemic review and meta-analysis of observational studies. Ann Intensive Care. 2020;10:34. Liu Y, Su L, Jiang S-J, Qu H. Risk factors for mortality from pneumocystis carinii pneumonia (PCP) in non-HIV patients: a meta-analysis. Oncotarget. 2017;8:59729–39. Lagrou K, Chen S, Masur H, Viscoli C, Decker CF, Pagano L, et al. Pneumocystis jirovecii disease: basis for the revised EORTC/MSGERC invasive fungal disease definitions in individuals without human immunodeficiency virus. Clin Infect Dis. 2021;72;Suppl 2:S114–20. Harigai M, Koike R, Miyasaka N. Pneumocystis pneumonia associated with infliximab in Japan. N Engl J Med. 2007;1:1874–6. Nakashima K, Aoshima M, Nakashita T, Hara M, Otsuki A, Noma S, et al. Low-dose trimethoprim-sulfamethoxazole treatment for pneumocystis pneumonia in non-human immunodeficiency virus-infected immunocompromised patients: a single-center retrospective observational cohort study. J Microbiol Immunol Infect. 2018;51:810–20. Nagai T, Matsui H, Fujioka H, Homma Y, Otsuki A, Ito H, et al. Low-dose vs conventional-dose trimethoprim-sulfamethoxazole treatment for pneumocystis pneumonia in patients not infected with HIV: A multicenter, retrospective observational cohort study. Chest. 2024;165:58-67. Del Corpo O, Butler-Laporte G, Sheppard DC, Cheng MP, McDonald EG, Lee TC. Diagnostic accuracy of serum (1-3)-beta-D-glucan for Pneumocystis jirovecii pneumonia: a systematic review and meta-analysis. Clin Microbiol Infect. 2020;26:1137–43. Taniguchi J, Nakashima K, Matsui H, Watari T, Otsuki A, Ito H, et al. Low cut-off value of serum (1,3)-beta-D-glucan for the diagnosis of Pneumocystis pneumonia in non-HIV patients: a retrospective cohort study. BMC Infect Dis. 2021;21:1200. Thomas LE, Li F, Pencina MJ. Overlap weighting: a propensity score method that mimics attributes of a randomized clinical trial. JAMA. 2020;323:2417–8. Homma S, Bando M, Azuma A, Sakamoto S, Sugino K, Ishii Y, et al. Japanese guideline for the treatment of idiopathic pulmonary fibrosis. Respir Investig. 2018;56:268–91. Austin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009;28:3083–107. National Institutes of Health-University of California Expert Panel for Corticosteroids as Adjunctive Therapy for Pneumocystis pneumonia. Consensus statement on the use of corticosteroids as adjunctive therapy for pneumocystis pneumonia in the acquired immunodeficiency syndrome. N Engl J Med. 1990;323:1500–4. McDonald EG, Butler-Laporte G, Del Corpo O, Hsu JM, Lawandi A, Senecal J, et al. On the treatment of Pneumocystis jirovecii pneumonia: current practice based on outdated evidence. Open Forum Infect Dis. 2021;8:ofab545. Additional Declarations No competing interests reported. Cite Share Download PDF Status: Published Journal Publication published 02 Nov, 2024 Read the published version in BMC Infectious Diseases → Version 1 posted Editorial decision: Revision requested 24 Jul, 2024 Editor assigned by journal 23 Jul, 2024 Submission checks completed at journal 23 Jul, 2024 First submitted to journal 22 Jul, 2024 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-4781746","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":331057501,"identity":"c96651e5-236e-46a0-a8ff-be96bc8030db","order_by":0,"name":"Yasuhiro Morimoto","email":"","orcid":"","institution":"Kameda Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Yasuhiro","middleName":"","lastName":"Morimoto","suffix":""},{"id":331057504,"identity":"e1911e26-09cf-440e-805c-11dc158a828e","order_by":1,"name":"Hiroki Matsui","email":"","orcid":"","institution":"the University of 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Center","correspondingAuthor":false,"prefix":"","firstName":"Tomohisa","middleName":"","lastName":"Watari","suffix":""},{"id":331057529,"identity":"8b0d59af-2d98-4c68-8b93-77456b949439","order_by":11,"name":"Yoshihito Otsuka","email":"","orcid":"","institution":"Kameda Medical Center","correspondingAuthor":false,"prefix":"","firstName":"Yoshihito","middleName":"","lastName":"Otsuka","suffix":""},{"id":331057531,"identity":"9f9198f9-b2f4-4e6a-bce7-3976a9267810","order_by":12,"name":"Kei Nakashima","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABE0lEQVRIie3QsUrEMBjA8a8c3FRwTSk0TyCkHJyT9S2cEwpmyYHjgcMFHG7xAU4C5yt4CJ0jGTr6ADpcEeri0FVw8GsHdWgrboL5DyGU70fSAPh8fzACgZ68dxuYAgdI2q92/wOB8BuZdYSPEuyTYEK36xiJ1pcax59otC7rfaUyeXPqKjwlSw51P4nDew0M6tSE6oiJIl/sHs8Yknw2t/0kIXgTDi7YgpoSUUwWO8NbYkUxRGilwYI72R681EhWMjWyGSUxCTS+mROG8DkSx2msxk+JroR2wFx+vXltSZnexurccjb8L6Qsq2dYuuPNg6yjt+KCUiPvmmaZJUOkzeKTfcW6SdY/2h/Vv5n2+Xy+/9AHHY9gy+SmA+sAAAAASUVORK5CYII=","orcid":"","institution":"Kameda Medical Center","correspondingAuthor":true,"prefix":"","firstName":"Kei","middleName":"","lastName":"Nakashima","suffix":""}],"badges":[],"createdAt":"2024-07-22 12:11:57","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-4781746/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-4781746/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12879-024-10151-3","type":"published","date":"2024-11-02T16:20:29+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":63278053,"identity":"9c17e741-355f-43a9-8599-2ff7609d3e44","added_by":"auto","created_at":"2024-08-26 12:32:54","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":56656,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eFlowchart showing study design and patient selection\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003ePCP, \u003cem\u003ePneumocystis jirovecii\u003c/em\u003e pneumonia; HIV, human immunodeficiency virus\u003c/p\u003e","description":"","filename":"Figure1TIFF20240616.png","url":"https://assets-eu.researchsquare.com/files/rs-4781746/v1/1493fe486767d054708dacc5.png"},{"id":68207256,"identity":"8dd0d60e-5ec1-43a4-9b49-e4fb92db62d5","added_by":"auto","created_at":"2024-11-04 16:36:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":920491,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-4781746/v1/1cfaf905-d130-41d4-9ece-e9e46a2a1931.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Effectiveness of Pulse Methylprednisolone in Patients with Non-Human Immunodeficiency Virus Pneumocystis Pneumonia: A Multicentre, Retrospective Registry-based Cohort Study","fulltext":[{"header":"Background","content":"\u003cp\u003e \u003cem\u003ePneumocystis jirovecii\u003c/em\u003e pneumonia (PCP) is a life-threatening opportunistic infection occurring in patients with human immunodeficiency virus (HIV) infection and other immunocompromised states [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Owing to differences in pathophysiology, non-HIV-associated (non-HIV) PCP has been reported to cause a more severe inflammatory response and profound hypoxemia than in those with HIV [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. The mortality rates in patients with non-HIV PCP (30\u0026ndash;60%) have been reported to be higher than those in patients with HIV (10\u0026ndash;20%) [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]. Recent epidemiological studies have shown an increasing trend in the incidence and mortality of non-HIV PCP [\u003cspan additionalcitationids=\"CR3\" citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe first-line antibiotic for treating PCP is trimethoprim-sulfamethoxazole [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan additionalcitationids=\"CR6\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Adjunctive steroids are recommended for patients experiencing hypoxemia, which is characterised by a partial pressure of oxygen\u0026thinsp;\u0026lt;\u0026thinsp;70 mmHg and an alveolar-arterial oxygen gradient of \u0026ge;\u0026thinsp;35 mmHg [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. Previous randomised controlled trials and a meta-analysis have demonstrated that adjunctive corticosteroid treatment reduces the need for ventilation and mortality in patients with HIV-PCP with such hypoxemia [\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. However, limited data exist on the effectiveness of adjunctive glucocorticoid therapy in patients with non-HIV PCP [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eA nationwide administrative claims database study and a meta-analysis have reported that adjunctive glucocorticoid therapy reduces mortality in patients with non-HIV PCP having respiratory failure [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. Evidence supporting the efficacy of adjunctive glucocorticoid therapy in cases of respiratory failure is accumulating. However, the appropriate dosage of glucocorticoids has not been well studied. The nationwide database study suggested that low-dose corticosteroids (prednisone equivalents 17\u0026ndash;36 mg/day) are associated with a lower risk of all-cause mortality in a subgroup of patients with respiratory failure [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e]. In a subgroup analysis conducted in the recent meta-analysis [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e], low-dose corticosteroids (equivalent to 1 mg/kg/day prednisone) were significantly associated with reduced mortality in patients with respiratory failure, while no significant association was found with high-dose corticosteroids (prednisone equivalents\u0026thinsp;\u0026gt;\u0026thinsp;240 mg). However, these studies have limitations. The administrative claims data study lacks detailed patient severity information, such as lactate dehydrogenase and albumin levels, which have been reported to affect the prognosis of non-HIV PCP [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The meta-analysis only included one small observational study of 39 cases evaluating high-dose steroids without adjustment for patient backgrounds. Therefore, further large-scale research on dosage appropriateness based on real clinical practice data, with adjustments for patient backgrounds and severity information, is necessary.\u003c/p\u003e \u003cp\u003eIn this multicentre cohort study, our objective was to evaluate the efficacy of pulse methylprednisolone compared to mild-to-moderate steroid doses in patients with non-HIV PCP. We aimed to adjust for patient backgrounds and assess the primary endpoint of 30-day mortality.\u003c/p\u003e"},{"header":"Material and Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003eStudy setting and population\u003c/h2\u003e \u003cp\u003eWe conducted a multicentre, retrospective, observational cohort study comprising adult patients with clinically diagnosed non-HIV PCP treated with adjunctive corticosteroid therapy. Patients without HIV, diagnosed with PCP at Hospital A, Hospital B, and Hospital C between January 2006 and March 2021, were retrospectively enrolled (registry named RE-VISION-PCP: Registry to Provide New Evidence and Insights for the Management of Pneumocystis Pneumonia in Non-HIV-infected Patients). The study protocol was approved by the research ethics committees of Hospital A (#21-069-230801), Hospital B (#3584), and Hospital C (#21\u0026ndash;58). As this was a retrospective study and patient data were anonymised, the requirement for written informed consent was waived.\u003c/p\u003e \u003cp\u003eBased on the diagnostic guideline for non-HIV PCP and previous studies [\u003cspan additionalcitationids=\"CR17 CR18\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], we defined the diagnostic criteria for PCP as follows: 1) Host factors: This includes possible immunocompromised conditions other than HIV. 2) Clinical criteria: The presence of clinical symptoms consistent with PCP, such as dyspnoea, cough, fever, and hypoxemia, as well as identification of abnormal shadows (such as bilateral ground-glass opacities) on chest X-ray or chest computed tomography scans that indicate PCP. 3) Microbiological criteria: Detection of pneumocystis in respiratory specimens, such as sputum or bronchoalveolar lavage fluid, using conventional staining methods (Grocott methenamine silver or Diff-Quick staining) or deoxyribonucleic acid testing (loop-mediated isothermal amplification or polymerase chain reaction). Alternatively, elevated levels of β-D-glucan, along with a favourable response to standard therapy for PCP, can also be considered as part of the microbiological criteria. Serum concentrations of β-D-glucan were assessed using either the β-D-glucan test kit (Wako Pure Chemical Industries, Osaka, Japan) or the FUNGITEC G test MKII (Nissui Pharmaceutical, Tokyo, Japan). Elevated β-D-glucan levels were defined as \u0026gt;\u0026thinsp;5 pg/mL (β-D-glucan test; Wako assay) or \u0026gt;\u0026thinsp;20 pg/mL (FUNGITEC G-test KM assay) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. Notably, patients with PCP who received adjunctive corticosteroid therapy or any other treatment were included in the study.\u003c/p\u003e \u003cp\u003eThe exclusion criteria were as follows: 1) patients who did not receive adjunctive corticosteroid therapy. 2) patients who had missing data on the variables analysed.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003eExposure defined by steroid dosage\u003c/h2\u003e \u003cp\u003ePatients who participated in the study were grouped into two categories based on their steroid dosage: the pulse methylprednisolone group and the mild-to-moderate dose group. Pulse methylprednisolone was defined as an initial intravenous infusion of 500\u0026ndash;1000 mg of methylprednisolone administered daily. Alternatively, the mild-to-moderate dose group was characterised by a steroid dose lower than that used in pulse methylprednisolone therapy. In the adjunctive steroid treatment of PCP for the mild-to-moderate dose group, the administration methods and durations typically follow international guidelines derived from research conducted on HIV-associated PCP [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The treatment regimen begins with administration of prednisone, or an equivalent dose of another corticosteroid, at 40 mg twice daily for the first 5 days, followed by 40 mg once daily from Days 6 to 11, and finally, a dosage of 20 mg daily through Day 21. Notably, treating physicians have the flexibility to adjust this regimen as needed. In the pulse methylprednisolone therapy group, an initial dose of 500\u0026ndash;1000 mg is administered for the first 3 days, after which the established protocol for HIV-associated PCP continues from Day 4 onwards [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]. The entire course of steroid treatment spans 21 days, with modifications as determined by the treating physician.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003eOutcomes\u003c/h2\u003e \u003cp\u003eThe primary endpoint was the 30-day mortality rate from the start of the treatment. The secondary endpoint was the 180-day mortality rate after treatment initiation.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003eData collection\u003c/h2\u003e \u003cp\u003eThe following data were retrospectively collected for each patient from their medical records: age, sex, weight, hospital, underlying diseases, immunosuppressive agents administration at diagnosis, laboratory results (platelet count; haemoglobin, serum albumin, lactate dehydrogenase, serum sodium, serum potassium, and creatinine levels; creatinine clearance), consciousness status, presence of hypotension, respiratory status (no oxygen support, oxygen support, and mechanical ventilation), initial treatment drugs (Trimethoprim-Sulfamethoxazole, pentamidine, and atovaquone), use of adjunctive glucocorticoid therapy (including pulse methylprednisolone administration), and 30- and 180-day mortality rates.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003eStatistical analyses\u003c/h2\u003e \u003cp\u003eDescriptive statistics for baseline characteristics and outcomes were obtained for each group. As this was a retrospective cohort study, prior sample size calculations were not performed, and all available populations were enrolled. Because three cases had missing variables, a complete case analysis was performed, and the missing cases were addressed using a list-wise method. No loss to follow-up occurred for the 30-day mortality, which was the primary endpoint of the study. T-tests were used for continuous variables and χ-square tests for categorical variables to compare between groups. Propensity scores for pulse methylprednisolone were calculated to reduce the confounding effect of the application, and overlap weighting was performed using the propensity scores [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. For propensity score calculation, a logistic regression model was constructed with pulse methylprednisolone as the dependent variable and age, sex, hospital, history of malignancy, serum albumin levels, lactate dehydrogenase levels, respiratory status, interstitial pneumonia, and creatinine clearance as explanatory variables. These explanatory variables were selected by considering results of clustering by hospital, prognostic factors for non-HIV PCP [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e], and interstitial pneumonia complications. We assumed that pulse methylprednisolone therapy would be more likely to be selected in cases of interstitial pneumonia due to the suspicion of acute exacerbation of interstitial pneumonia as a potential differential diagnosis. This assumption is based on the common practice in Japan, where acute exacerbations of interstitial pneumonia are often treated with pulse methylprednisolone therapy. The decision to use this treatment approach is guided by the Japanese guidelines for idiopathic pulmonary fibrosis [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eThe balance of variables between the groups was evaluated using the standardised mean difference (SMD) between the variables. As per previous studies [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e], the groups were considered balanced when the SMD was less than 0.1. Statistical analyses were conducted using the R software (version 4.3.0; R Development Core Team).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003eSubgroup analysis\u003c/h2\u003e \u003cp\u003eThe same methodology described previously was also used for the subgroup analysis, which was limited to patients with respiratory failure. Respiratory failure was defined as respiratory status requiring oxygen support or mechanical ventilation. This analysis was conducted based on prior studies demonstrating the benefits of adjunctive corticosteroid therapy in patients with non-HIV PCP and hypoxemia [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003c/div\u003e"},{"header":"Results","content":"\u003cp\u003eA flowchart of the study is shown in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. Data were collected from 164 patients diagnosed with non-HIV PCP. Twenty-two patients who did not receive adjunctive corticosteroid therapy and three patients with missing initial treatment types were excluded. Therefore, 139 patients with non-HIV PCP were included in this study and were categorised into two groups: 55 in the pulse methylprednisolone group and 84 in the mild-to-moderate dose group. In the subgroup analysis, 67 patients with respiratory failure were selected from the 139 patients with non-HIV PCP. The patients were classified into two groups: 32 in the pulse methylprednisolone group and 35 in the mild-to-moderate dose group.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eThe unadjusted and adjusted baseline characteristics of the study participants are shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e. In the unadjusted cohort, sex, weight, hospital, presence of malignancies, solid tumours, connective tissue disease, or interstitial pneumonia, and use of corticosteroids, immunosuppressants, biologics, or anticancer agents were imbalanced between the two groups because the SMD was \u0026gt;\u0026thinsp;0.1. Among the laboratory results, haemoglobin, serum albumin, lactate dehydrogenase, creatinine levels, hypotension, and respiratory status were imbalanced across the two groups. In the adjusted cohort, age, sex, hospital, presence of solid tumours, malignancies or interstitial pneumonia, haemoglobin, serum albumin, lactate dehydrogenase, serum sodium, creatinine clearance, hypotension, respiratory status, and mechanical ventilation were considered balanced since the SMD was \u0026lt;\u0026thinsp;0.1.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of participants\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnadjusted cohort\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eAdjusted cohort\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePulse methylprednisolone\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMild-to-moderate dose\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSMD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePulse methylprednisolone\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;26.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMild-to-moderate dose\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;26.35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSMD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70.67 (\u0026plusmn;\u0026thinsp;11.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.21 (\u0026plusmn;\u0026thinsp;10.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.042\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e70.52 (\u0026plusmn;\u0026thinsp;11.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e70.52 (\u0026plusmn;\u0026thinsp;10.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e25 (45.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e50 (59.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.285\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.7 (48.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.7 (48.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.24 (\u0026plusmn;\u0026thinsp;10.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53.55 (\u0026plusmn;\u0026thinsp;11.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52.01 (\u0026plusmn;\u0026thinsp;10.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e54.85 (\u0026plusmn;\u0026thinsp;12.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.245\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.280\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (58.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17.2 (65.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17.2 (65.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (23.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e29 (34.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.9 (26.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.9 (26.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7 (12.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.3 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.3 (8.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnderlying disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignancies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15 (27.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.291\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.8 (22.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.8 (22.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaematological malignancies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (9.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (7.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.071\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.0 (7.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.7 (10.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.103\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSolid tumours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8 (9.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.299\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.1 (15.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.4 (12.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConnective tissue disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e34 (61.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68 (81.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.433\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e17.1 (65.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19.6 (74.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.203\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterstitial pneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (41.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e13 (15.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.609\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.6 (28.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.6 (28.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunosuppressive agents used\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticosteroid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e35 (63.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e58 (69.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.3 (61.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e19.4 (73.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.250\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunosuppressant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (58.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e55 (65.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.151\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.4 (62.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13.7 (51.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.208\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiologics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (16.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22 (26.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.242\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.3 (24.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.9 (18.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.135\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnticancer agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (21.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.519\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.4 (16.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.5 (5.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.351\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood biochemistry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.22 (\u0026plusmn;\u0026thinsp;2.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.57 (\u0026plusmn;\u0026thinsp;1.93)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.170\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.27 (\u0026plusmn;\u0026thinsp;2.08)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.36 (\u0026plusmn;\u0026thinsp;1.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.045\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count (\u0026times;10⁴/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21.69 (\u0026plusmn;\u0026thinsp;9.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e22.55 (\u0026plusmn;\u0026thinsp;10.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e21.19 (\u0026plusmn;\u0026thinsp;9.21)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22.70 (\u0026plusmn;\u0026thinsp;11.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.145\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.75 (\u0026plusmn;\u0026thinsp;0.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.06 (\u0026plusmn;\u0026thinsp;0.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.500\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.88 (\u0026plusmn;\u0026thinsp;0.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.88 (\u0026plusmn;\u0026thinsp;0.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate dehydrogenase (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e440.15 (\u0026plusmn;\u0026thinsp;153.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e386.81 (\u0026plusmn;\u0026thinsp;169.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.330\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e413.88 (\u0026plusmn;\u0026thinsp;132.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e413.88 (\u0026plusmn;\u0026thinsp;195.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum sodium (mEq/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e137.73 (\u0026plusmn;\u0026thinsp;4.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e137.85 (\u0026plusmn;\u0026thinsp;3.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.027\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e137.54 (\u0026plusmn;\u0026thinsp;4.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e137.74 (\u0026plusmn;\u0026thinsp;4.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum potassium (mEq/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.17 (\u0026plusmn;\u0026thinsp;0.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.22 (\u0026plusmn;\u0026thinsp;0.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.100\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.16 (\u0026plusmn;\u0026thinsp;0.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.24 (\u0026plusmn;\u0026thinsp;0.46)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.151\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.99 (\u0026plusmn;\u0026thinsp;0.85)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.10 (\u0026plusmn;\u0026thinsp;1.31)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.101\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.03 (\u0026plusmn;\u0026thinsp;0.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.32 (\u0026plusmn;\u0026thinsp;1.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.223\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine clearance (mL/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60.79 (\u0026plusmn;\u0026thinsp;29.37)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61.39 (\u0026plusmn;\u0026thinsp;28.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.021\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60.11 (\u0026plusmn;\u0026thinsp;30.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e60.11 (\u0026plusmn;\u0026thinsp;30.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisturbed consciousness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2 (0.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.6 (2.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.140\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypotension (systolic pressure\u0026thinsp;\u0026lt;\u0026thinsp;90 mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (3.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.160\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4 (1.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.5 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.014\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.335\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWithout oxygen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (41.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e49 (58.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.2 (46.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e12.2 (46.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdministration of oxygen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e31 (56.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e34 (40.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.8 (52.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13.8 (52.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026thinsp;\u0026minus;\u0026thinsp;4 L/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (33.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.5 (17.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e10.6 (40.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u0026thinsp;\u0026minus;\u0026thinsp;10 L/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (21.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.6 (21.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.7 (2.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u0026thinsp;\u0026minus;\u0026thinsp;15 L/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (14.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (6.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.8 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.5 (9.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMechanical ventilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (1.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.052\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.3 (1.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInitial treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.200\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.261\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrimethoprim-Sulfamethoxazole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51 (92.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e73 (86.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e24.7 (93.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e22.7 (86.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePentamidine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (2.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.4 (1.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.6 (2.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtovaquone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3 (5.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (10.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.3 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.1 (11.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eCategorical variables are presented as n (%), and continuous variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: SMD\u0026thinsp;=\u0026thinsp;standardised mean difference\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe clinical outcomes of the unadjusted and adjusted cohorts are summarised in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. In the unadjusted cohort, the 30-day mortality rates were 21.8% for the pulse methylprednisolone group and 8.3% for the mild-to-moderate dose group. The 180-day mortality rates were 41.8% in the pulse methylprednisolone group and 14.3% in the mild-to-moderate dose group. In the adjusted cohort, there were no significant differences (30-day mortality: 15.8%, pulse methylprednisolone group and 14.1% in the mild-to-moderate dose group; and 180-day mortality: 33.7%, pulse methylprednisolone group and 25.3%, mild-to-moderate dose group).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eSummary of clinical outcomes\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnadjusted cohort\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eAdjusted cohort\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePulse methylprednisolone\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;55\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMild-to-moderate dose\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;84\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePulse methylprednisolone\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;26.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMild-to-moderate dose\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;26.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary endpoint\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30-day mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (21.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (8.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.044\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.2 (15.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.7 (14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.813\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary endpoint\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e180-day mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23 (41.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.001\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e8.9 (33.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.7 (25.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.367\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eCategorical variables are presented as n (%).\u003c/p\u003e \u003cp\u003eSubsequently, we performed a subgroup analysis of patients with respiratory failure. The unadjusted and adjusted baseline characteristics of the subgroups are presented in Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e. In the unadjusted cohort, sex, weight, hospital, presence of malignancies, haematological malignancies, solid tumours, connective tissue disease, or interstitial pneumonia, and the use of immunosuppressants, biologics, or anticancer agents were imbalanced. Among the laboratory results, haemoglobin, serum albumin, lactate dehydrogenase, serum sodium, creatinine, and creatinine clearance levels were imbalanced, as were disturbed consciousness and initial treatment. In the adjusted cohort, age, sex, hospital, presence of malignancies and interstitial pneumonia, use of immunosuppressants and biologics, haemoglobin, serum albumin, lactate dehydrogenase, serum sodium, serum potassium, creatinine clearance, respiratory status, and mechanical ventilation were balanced.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline characteristics of patients in the subgroup analysis limited to respiratory failure\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnadjusted cohort\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eAdjusted cohort\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePulse methylprednisolone\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMild-to-moderate dose\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eSMD\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePulse methylprednisolone\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;13.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMild-to-moderate dose\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;13.40\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003eSMD\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (years)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e71.56 (\u0026plusmn;\u0026thinsp;11.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e71.46 (\u0026plusmn;\u0026thinsp;9.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.010\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e71.85 (\u0026plusmn;\u0026thinsp;12.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e71.85 (\u0026plusmn;\u0026thinsp;9.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e14 (43.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e19 (54.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.212\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.0 (45.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.0 (45.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight (kg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52.56 (\u0026plusmn;\u0026thinsp;9.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e54.43 (\u0026plusmn;\u0026thinsp;12.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.169\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e52.50 (\u0026plusmn;\u0026thinsp;10.45)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e55.92 (\u0026plusmn;\u0026thinsp;12.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.301\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.249\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e27 (84.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.3 (84.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.3 (84.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.1 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.1 (15.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospital C\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnderlying disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMalignancies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.469\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.5 (25.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.5 (25.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaematological malignancies\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4 (12.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.128\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.9 (6.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.9 (14.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.242\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSolid tumours\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9 (28.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3 (8.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.522\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.7 (19.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.6 (11.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.228\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eConnective tissue disease\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (74.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.517\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.9 (59.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e8.6 (64.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.108\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInterstitial pneumonia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (31.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7 (20.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.260\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.1 (23.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.1 (23.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunosuppressive agents used\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCorticosteroid\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24 (75.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e26 (74.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.2 (83.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.1 (68.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.367\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eImmunosuppressant\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e13 (40.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e18 (51.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.218\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.0 (44.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.5 (41.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.073\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBiologics\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2 (6.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.344\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.3 (10.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.6 (11.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.051\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAnticancer agent\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e10 (31.2)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2 (5.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.697\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.9 (22.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.0 (7.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.413\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBlood biochemistry\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHaemoglobin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11.21 (\u0026plusmn;\u0026thinsp;2.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e11.57 (\u0026plusmn;\u0026thinsp;2.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.167\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.46 (\u0026plusmn;\u0026thinsp;2.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.33 (\u0026plusmn;\u0026thinsp;2.02)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.063\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePlatelet count (\u0026times;10⁴/\u0026micro;L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e22.54 (\u0026plusmn;\u0026thinsp;10.01)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.63 (\u0026plusmn;\u0026thinsp;11.51)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.085\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e23.02 (\u0026plusmn;\u0026thinsp;10.32)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e20.80 (\u0026plusmn;\u0026thinsp;11.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.203\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAlbumin (g/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2.52 (\u0026plusmn;\u0026thinsp;0.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.81 (\u0026plusmn;\u0026thinsp;0.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.529\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.67 (\u0026plusmn;\u0026thinsp;0.48)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.67 (\u0026plusmn;\u0026thinsp;0.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLactate dehydrogenase (IU/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e458.38 (\u0026plusmn;\u0026thinsp;167.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e377.00 (\u0026plusmn;\u0026thinsp;169.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.482\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e427.95 (\u0026plusmn;\u0026thinsp;144.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e427.95 (\u0026plusmn;\u0026thinsp;210.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum sodium (mEq/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e138.62 (\u0026plusmn;\u0026thinsp;5.53)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e137.83 (\u0026plusmn;\u0026thinsp;4.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.163\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e138.44 (\u0026plusmn;\u0026thinsp;4.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e138.15 (\u0026plusmn;\u0026thinsp;4.24)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.066\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSerum potassium (mEq/L)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4.11 (\u0026plusmn;\u0026thinsp;0.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.11 (\u0026plusmn;\u0026thinsp;0.40)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.015\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.12 (\u0026plusmn;\u0026thinsp;0.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.12 (\u0026plusmn;\u0026thinsp;0.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.012\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine (mg/dL)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0.89 (\u0026plusmn;\u0026thinsp;0.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.35 (\u0026plusmn;\u0026thinsp;1.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.333\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.97 (\u0026plusmn;\u0026thinsp;0.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.53 (\u0026plusmn;\u0026thinsp;2.17)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.356\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCreatinine clearance (mL/min)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e62.68 (\u0026plusmn;\u0026thinsp;28.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e59.38 (\u0026plusmn;\u0026thinsp;30.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.113\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e60.59 (\u0026plusmn;\u0026thinsp;29.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e60.59 (\u0026plusmn;\u0026thinsp;31.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisturbed consciousness\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.243\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.5 (4.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.290\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHypotension (systolic pressure\u0026thinsp;\u0026lt;\u0026thinsp;90 mmHg)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.2 (1.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.5 (3.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.100\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRespiratory status\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAdministration of oxygen\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.4 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e13.4 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e1\u0026thinsp;\u0026minus;\u0026thinsp;4 L/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e11 (34.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e28 (80.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.2 (31.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.5 (70.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e5\u0026thinsp;\u0026minus;\u0026thinsp;10 L/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e12 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.0 (37.5)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.6 (4.8)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e11\u0026thinsp;\u0026minus;\u0026thinsp;15 L/min\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5 (14.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.9 (29.3)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.0 (22.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMechanical ventilation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1 (3.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1 (2.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.016\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.3 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.3 (2.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eInitial treatment\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.508\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.549\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTrimethoprim-Sulfamethoxazole\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e31 (88.6)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.4 (100.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.6 (86.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePentamidine\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAtovaquone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4 (11.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0 (0.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.8 (13.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eCategorical variables are presented as n (%), and continuous variables are presented as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;standard deviation.\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eAbbreviations: SMD\u0026thinsp;=\u0026thinsp;standardised mean difference\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eThe clinical outcomes of both cohorts are shown in Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e. In the unadjusted cohort, the 30-day mortality rates were 25.0% for the pulse methylprednisolone group and 17.1% for the mild-to-moderate dose group. The 180-day mortality rates were 50.0% in the pulse methylprednisolone group and 25.7% in the mild-to-moderate dose group. No significant differences were observed between the two groups in the adjusted cohort (30-day mortality: 21.4%, pulse methylprednisolone group and 27.1%, mild-to-moderate dose group; and 180-day mortality: 43.9%, pulse methylprednisolone group and 35.7%, mild-to-moderate dose group).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClinical outcomes of the subgroup analysis limited to respiratory failure\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c4\" namest=\"c2\"\u003e \u003cp\u003eUnadjusted cohort\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c7\" namest=\"c5\"\u003e \u003cp\u003eAdjusted cohort\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVariables\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ePulse methylprednisolone\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMild-to-moderate dose\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePulse methylprednisolone\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;13.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003eMild-to-moderate dose\u003c/p\u003e \u003cp\u003en\u0026thinsp;=\u0026thinsp;13.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePrimary endpoint\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e30-day mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8 (25.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6 (17.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.625\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.9 (21.4)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.6 (27.1)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.639\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSecondary endpoint\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e180-day mortality\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16 (50.0)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9 (25.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.072\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.9 (43.9)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.8 (35.7)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.558\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"7\"\u003eCategorical variables are presented as n (%)\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eIn this multicentre, retrospective, observational cohort study of patients with non-HIV PCP treated with adjunctive corticosteroid therapy, we evaluated the efficacy of pulse methylprednisolone compared to mild-to-moderate steroid doses. No significant differences were observed between the two groups in terms of the 30- or 180-day mortality rates after adjusting for patient background using the overlap weighting method with propensity scores. To our knowledge, this study is the first to compare pulse methylprednisolone with other doses for the treatment of non-HIV PCP using hospital-based detailed clinical information after adjusting for patient background. In contrast, some reports exist on the appropriateness of dosage and the effectiveness of adjunctive corticosteroid therapy in non-HIV PCP.\u003c/p\u003e \u003cp\u003eSeveral randomised controlled trials and a meta-analysis have provided evidence that adjunctive corticosteroid therapy reduces the need for mechanical ventilation and mortality in patients with HIV-associated PCP and hypoxemia [\u003cspan additionalcitationids=\"CR9 CR10\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. A Cochrane meta-analysis, which evaluated six randomised controlled trials on the efficacy of adjunctive steroids for moderate to severe HIV-associated PCP, found that compared to placebo, patients receiving adjunctive steroids had a lower risk of overall mortality at 1 month (risk ratio 0.56, 95% CI 0.32\u0026ndash;0.98) and at 3\u0026ndash;4 months (risk ratio 0.59, 95% CI 0.41\u0026ndash;0.85) of follow-up [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Therefore, international guidelines recommend an initial dose of 80 mg/day of adjunctive corticosteroids for adult patients with moderate-to-severe HIV-associated PCP, defined as arterial oxygen partial pressure\u0026thinsp;\u0026lt;\u0026thinsp;70 mmHg or alveolar-arterial gradient\u0026thinsp;\u0026gt;\u0026thinsp;35 mmHg on room air [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eIn contrast to HIV-associated PCP, there are limited data on the effectiveness of adjunctive corticosteroid therapy in patients with non-HIV-associated PCP. The American Thoracic Society\u0026rsquo;s Statement on the treatment of fungal infections in adult pulmonary patients recommends a corticosteroid treatment regimen for patients with moderate to severe non-HIV-associated PCP, similar to that used for HIV-associated PCP, as previously described [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. However, this recommendation for adjunctive corticosteroid therapy in non-HIV PCP is primarily based on studies conducted in HIV-associated PCP [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e], and there is a lack of solid evidence from randomised controlled trials specifically focusing on PCP in patients without HIV. The current recommendation lacks a robust foundation of evidence in the non-HIV population [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. As discussed in the introduction, there is an increasing body of evidence supporting the effectiveness of adjunctive glucocorticoid treatment in patients with respiratory failure. However, the optimal dosage of glucocorticoids for PCP treatment in patients without HIV remains inadequately explored [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. In this multicentre study, we found no significant difference in the 30- and 180-day mortality rates between pulse methylprednisolone and mild-to-moderate steroid doses after adjusting for patient background. Additionally, no significant association was observed in the subgroup analysis of patients with respiratory failure. These findings suggest that pulse methylprednisolone may not be necessary as an adjunctive steroid in non-HIV PCP, and mild-to-moderate steroid doses could be sufficient. Nevertheless, it is important to note that further large prospective cohort studies and randomised controlled trials are needed to confirm these results.\u003c/p\u003e \u003cp\u003eThe strength of this study lies in its multicentre design, which has a large number of patients adjusted for backgrounds. In clinical practice, higher doses of corticosteroids tend to be administered in more severe cases, and there may be a selection bias in patients treated with adjunctive corticosteroids. In this study, the respiratory status tended to be worse in the pulse methylprednisolone group between the two groups before adjustment for patient background. Patients with interstitial lung disease may also be more likely to be selected for pulse methylprednisolone therapy due to suspected acute exacerbations [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], potentially leading to patient background bias. Indeed, there were more patients with interstitial pneumonia in the pulse methylprednisolone group before adjusting for patient characteristics. In this study, patient characteristics, including interstitial pneumonia, respiratory status, and other prognostic factors (age, sex, history of malignancies, serum albumin levels, and serum lactate dehydrogenase levels) were adjusted using the overlap weighting method in propensity score analysis [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eOur study had some limitations. First, this was a retrospective, observational study. Although we adjusted for confounding factors related to pulse methylprednisolone therapy and outcomes, such as interstitial pneumonia and prognostic factors, using propensity score analysis, we could not completely adjust for unknown confounding factors. Future prospective randomised trials are required to eliminate the influence of these confounders. Second, this study did not examine adverse events associated with corticosteroid use. Although the adverse events associated with systemic corticosteroid use (including hyperglycaemia, increased risk of coinfections, delirium, and ICU-acquired weakness) are generally recognised, data on the safety of adjunctive corticosteroid therapy for non-HIV PCP are lacking. The selection of the corticosteroid therapy dose should be based not only on the outcome but also on safety. Future studies are required to evaluate the safety of steroid use.\u003c/p\u003e"},{"header":"Conclusions","content":"\u003cp\u003ePulse methylprednisolone therapy was not observed to be more effective than a mild-to-moderate dose regimen in the treatment of patients with non-HIV PCP after adjusting for patient characteristics. A mild-to-moderate dose of adjunctive corticosteroid may be sufficient for treating patients with non-HIV PCP. Further studies, including large-scale prospective cohort studies and randomised controlled studies, are required to confirm our results.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eHIV, human immunodeficiency virus; ICU, intensive care unit; PCP, \u003cem\u003ePneumocystis jirovecii\u003c/em\u003e pneumonia; SMD, standardised mean difference.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe study protocol was approved by the research ethics committees of Hospital A (#21-069-230801), Hospital B (#3584), and Hospital C (#21-58). As this was a retrospective study and patient data were anonymised, the requirement for written informed consent was waived.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e: Not applicable\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eData pertaining to this study will be available by the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAuthors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study received no specific grants from any funding agency in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eConceptualisation: Y.M., H.M., S.O., K.N. Data curation: Y.M., H.M., S.O., K.N. Formal analysis: H.M. Investigation: Y.M., H.F., Y.H., T.N, S.O., D.S. Methodology: Y.M., H.M., S.O., K.N. Project administration: Y.M., S.O., K.N. Resources: Y.M., H.F., Y.H., T.N., A.O., H.I., S.O., T.M., D.S., W.T., Y.O., K.N. Software: H.M. Supervision: K.N. Validation: H.M., K.N. Visualisation: Y.M., H.M., K.N. Writing - original draft: Y.M. Writing - review \u0026amp; editing: Y.M., H.M., H.F., Y.H., T.N, A.O., H.I., S.O., T.M., D.S., W.T., Y.O., K.N.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u0026nbsp;\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe thank Editage (www.editage.jp) for English language editing. We thank all clinicians from the Department of Medical Oncology, Hematology/Oncology, and Rheumatology at Kameda Medical Center, Japan, for providing the case data.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eThomas Jr CF, Limper AH. Pneumocystis pneumonia. N Engl J Med. 2004;350:2487\u0026ndash;98.\u003c/li\u003e\n\u003cli\u003eTasaka S, Tokuda H. \u003cem\u003ePneumocystis jirovecii\u003c/em\u003e pneumonia in non-HIV-infected patients in the era of novel immunosuppressive therapies. J Infect Chemother. 2012;18:793\u0026ndash;806.\u003c/li\u003e\n\u003cli\u003eSepkowitz KA. Opportunistic infections in patients with and patients without acquired immunodeficiency syndrome. Clin Infect Dis. 2002;34:1098\u0026ndash;107.\u003c/li\u003e\n\u003cli\u003eCoyle PV, McCaughey C, Nager A, McKenna J, O\u0026rsquo;Neill H, Feeney SA, et al. Rising incidence of \u003cem\u003ePneumocystis jirovecii\u003c/em\u003e pneumonia suggests iatrogenic exposure of immune-compromised patients may be becoming a significant problem. J Med Microbiol. 2012;61:1009\u0026ndash;15.\u003c/li\u003e\n\u003cli\u003eLimper AH, Knox KS, Sarosi GA, Ampel NM, Bennett JE, Catanzaro A, et al. An Official American Thoracic Society statement: treatment of fungal infections in adult pulmonary and critical care patients. Am J Respir Crit Care Med. 2011;183:96\u0026ndash;128.\u003c/li\u003e\n\u003cli\u003eMaschmeyer G, Helweg-Larsen J, Pagano L, Robin C, Cordonnier C, Schellongowski P, et al. ECIL guidelines for treatment of \u003cem\u003ePneumocystis jirovecii\u003c/em\u003e pneumonia in non-HIV-infected haematology patients. J Antimicrob Chemother. 2016;71:2405-13.\u003c/li\u003e\n\u003cli\u003eGuidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV. Recommendations from the Centers for Disease Control and Prevention. The National Institutes of Health, and the HIV Medicine Association of the Infectious Diseases Society of America. https://clinicalinfo.hiv.gov/en/guidelines/hiv-clinical-guidelines-adult-and-adolescent-opportunistic-infections/pneumocystis?view=full. Accessed 8 March, 2024.\u003c/li\u003e\n\u003cli\u003eMontaner JS, Lawson LM, Levitt N, Belzberg A, Schechter MT, Ruedy J. Corticosteroids prevent early deterioration in patients with moderately severe pneumocystis carinii pneumonia and the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1990;113:14\u0026ndash;20.\u003c/li\u003e\n\u003cli\u003eGagnon S, Boota AM, Fischl MA, Baier H, Kirksey OW, La Voie L. Corticosteroids as adjunctive therapy for severe pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. A double-blind, placebo-controlled trial. N Engl J Med. 1990;323:1444\u0026ndash;50.\u003c/li\u003e\n\u003cli\u003eBozzette SA, Sattler FR, Chiu J, Wu AW, Gluckstein D, Kemper C, et al. A controlled trial of early adjunctive treatment with corticosteroids for pneumocystis carinii pneumonia in the acquired immunodeficiency syndrome. California Collaborative treatment group. N Engl J Med. 1990;323:1451\u0026ndash;7.\u003c/li\u003e\n\u003cli\u003eEwald H, Raatz H, Boscacci R, Furrer H, Bucher HC, Briel M. Adjunctive corticosteroids for Pneumocystis jiroveci pneumonia in patients with HIV infection. Cochrane Database Syst Rev. 2015;2015:CD006150.\u003c/li\u003e\n\u003cli\u003eDelclaux C, Zahar JR, Amraoui G, Leleu G, Lebargy F, Brochard L, et al. Corticosteroids as adjunctive therapy for severe Pneumocystis carinii pneumonia in non-human immunodeficiency virus-infected patients: retrospective study of 31 patients. Clin Infect Dis. 1999;29:670\u0026ndash;2.\u003c/li\u003e\n\u003cli\u003eInoue N, Fushimi K. Adjunctive corticosteroids decreased the risk of mortality of non-HIV Pneumocystis pneumonia. Int J Infect Dis. 2019;79:109\u0026ndash;15.\u003c/li\u003e\n\u003cli\u003eDing L, Huang H, Wang H, He H. Adjunctive corticosteroids may be associated with better outcome for non-HIV Pneumocystis pneumonia with respiratory failure: a systemic review and meta-analysis of observational studies. Ann Intensive Care. 2020;10:34.\u003c/li\u003e\n\u003cli\u003eLiu Y, Su L, Jiang S-J, Qu H. Risk factors for mortality from pneumocystis carinii pneumonia (PCP) in non-HIV patients: a meta-analysis. Oncotarget. 2017;8:59729\u0026ndash;39.\u003c/li\u003e\n\u003cli\u003eLagrou K, Chen S, Masur H, Viscoli C, Decker CF, Pagano L, et al. Pneumocystis jirovecii disease: basis for the revised EORTC/MSGERC invasive fungal disease definitions in individuals without human immunodeficiency virus. Clin Infect Dis. 2021;72;Suppl 2:S114\u0026ndash;20.\u003c/li\u003e\n\u003cli\u003eHarigai M, Koike R, Miyasaka N. Pneumocystis pneumonia associated with infliximab in Japan. N Engl J Med. 2007;1:1874\u0026ndash;6.\u003c/li\u003e\n\u003cli\u003eNakashima K, Aoshima M, Nakashita T, Hara M, Otsuki A, Noma S, et al. Low-dose trimethoprim-sulfamethoxazole treatment for pneumocystis pneumonia in non-human immunodeficiency virus-infected immunocompromised patients: a single-center retrospective observational cohort study. J Microbiol Immunol Infect. 2018;51:810\u0026ndash;20.\u003c/li\u003e\n\u003cli\u003eNagai T, Matsui H, Fujioka H, Homma Y, Otsuki A, Ito H, et al. Low-dose vs conventional-dose trimethoprim-sulfamethoxazole treatment for pneumocystis pneumonia in patients not infected with HIV: A multicenter, retrospective observational cohort study. Chest. 2024;165:58-67.\u003c/li\u003e\n\u003cli\u003eDel Corpo O, Butler-Laporte G, Sheppard DC, Cheng MP, McDonald EG, Lee TC. Diagnostic accuracy of serum (1-3)-beta-D-glucan for \u003cem\u003ePneumocystis jirovecii\u003c/em\u003e pneumonia: a systematic review and meta-analysis. Clin Microbiol Infect. 2020;26:1137\u0026ndash;43.\u003c/li\u003e\n\u003cli\u003eTaniguchi J, Nakashima K, Matsui H, Watari T, Otsuki A, Ito H, et al. Low cut-off value of serum (1,3)-beta-D-glucan for the diagnosis of Pneumocystis pneumonia in non-HIV patients: a retrospective cohort study. BMC Infect Dis. 2021;21:1200.\u003c/li\u003e\n\u003cli\u003eThomas LE, Li F, Pencina MJ. Overlap weighting: a propensity score method that mimics attributes of a randomized clinical trial. JAMA. 2020;323:2417\u0026ndash;8.\u003c/li\u003e\n\u003cli\u003eHomma S, Bando M, Azuma A, Sakamoto S, Sugino K, Ishii Y, et al. Japanese guideline for the treatment of idiopathic pulmonary fibrosis. Respir Investig. 2018;56:268\u0026ndash;91.\u003c/li\u003e\n\u003cli\u003eAustin PC. Balance diagnostics for comparing the distribution of baseline covariates between treatment groups in propensity-score matched samples. Stat Med. 2009;28:3083\u0026ndash;107.\u003c/li\u003e\n\u003cli\u003eNational Institutes of Health-University of California Expert Panel for Corticosteroids as Adjunctive Therapy for Pneumocystis pneumonia. Consensus statement on the use of corticosteroids as adjunctive therapy for pneumocystis pneumonia in the acquired immunodeficiency syndrome. N Engl J Med. 1990;323:1500\u0026ndash;4. \u003c/li\u003e\n\u003cli\u003eMcDonald EG, Butler-Laporte G, Del Corpo O, Hsu JM, Lawandi A, Senecal J, et al. On the treatment of Pneumocystis jirovecii pneumonia: current practice based on outdated evidence. Open Forum Infect Dis. 2021;8:ofab545.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"non-human immunodeficiency virus-infected patient, pneumocystis pneumonia, adjunctive corticosteroid treatment, pulse methylprednisolone","lastPublishedDoi":"10.21203/rs.3.rs-4781746/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-4781746/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eA recent database study and meta-analysis reported that adjunctive glucocorticoid therapy reduces mortality in patients with non-human immunodeficiency virus-associated (non-HIV) \u003cem\u003ePneumocystis jirovecii\u003c/em\u003e pneumonia (PCP), having hypoxemia. However, the optimal glucocorticoid dose remains unclear. Our study aimed to evaluate the effectiveness of pulse methylprednisolone compared with mild-to-moderate steroid doses in patients with non-HIV PCP.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e This multicentre retrospective cohort study included adults with non-HIV PCP receiving adjunctive steroids at three Japanese tertiary care hospitals from June 2006 to March 2021. Patients were categorised into pulse methylprednisolone and mild-to-moderate dose groups. Pulse methylprednisolone involved an initial intravenous infusion of 500\u0026ndash;1000 mg methylprednisolone daily, while the mild-to-moderate dose was lower. Primary and secondary outcomes were 30-day and 180-day mortality rates from treatment initiation. Patient characteristics were adjusted using propensity score analysis with overlap weighting. Subgroup analysis focused on patients with respiratory failure.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eThe study included 139 patients with non-HIV PCP: 55 in the pulse methylprednisolone group and 84 in the mild-to-moderate dose group. After adjusting for patient background, 30-day mortality (15.8% vs. 14.1%, P\u0026thinsp;=\u0026thinsp;0.813) and 180-day mortality (33.7% vs. 25.3%, P\u0026thinsp;=\u0026thinsp;0.367) did not differ significantly between groups. Subgroup analysis revealed no significant associations among patients with respiratory failure.\u003c/p\u003e\u003ch2\u003eConclusions\u003c/h2\u003e \u003cp\u003eAfter adjusting for patient characteristics, no difference in prognosis was observed between pulse methylprednisolone and mild-to-moderate dose groups in patients with non-HIV PCP. A mild-to-moderate dose of adjunctive corticosteroid may suffice for treating non-HIV PCP.\u003c/p\u003e","manuscriptTitle":"Effectiveness of Pulse Methylprednisolone in Patients with Non-Human Immunodeficiency Virus Pneumocystis Pneumonia: A Multicentre, Retrospective Registry-based Cohort Study","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-08-26 12:32:50","doi":"10.21203/rs.3.rs-4781746/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-07-24T06:57:34+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-07-23T11:43:08+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2024-07-23T11:42:47+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Infectious Diseases","date":"2024-07-22T12:10:35+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-infectious-diseases","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"infd","sideBox":"Learn more about [BMC Infectious Diseases](http://bmcinfectdis.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/infd","title":"BMC Infectious Diseases","twitterHandle":"#bmcinfectdis","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"6f3c51ee-1ecc-47cb-bc22-5894a790ede4","owner":[],"postedDate":"August 26th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-11-04T16:28:17+00:00","versionOfRecord":{"articleIdentity":"rs-4781746","link":"https://doi.org/10.1186/s12879-024-10151-3","journal":{"identity":"bmc-infectious-diseases","isVorOnly":false,"title":"BMC Infectious Diseases"},"publishedOn":"2024-11-02 16:20:29","publishedOnDateReadable":"November 2nd, 2024"},"versionCreatedAt":"2024-08-26 12:32:50","video":"","vorDoi":"10.1186/s12879-024-10151-3","vorDoiUrl":"https://doi.org/10.1186/s12879-024-10151-3","workflowStages":[]},"version":"v1","identity":"rs-4781746","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-4781746","identity":"rs-4781746","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}