Consensus for antifungal stewardship in China (2024 edition).

Background: Invasive fungal disease (IFD) has become a serious threat to human health in China and around the world, with high mortality and morbidity. Currently, the misdiagnosis rate of IFD is extremely high, compounded with the low quality of prescription antifungals and the high incidence of adverse events associated with IFD treatment, resulting in lengthy hospitalization, low clinical response, and high disease burden, which have become serious challenges in clinical practice. Antifungal stewardship (AFS) can not only significantly increase the early diagnosis rate of IFD, reduce inappropriate utilization of antifungal drugs, improve patient prognosis, but can also improve therapeutic safety and reduce healthcare expenses. Thus, it is urgent to identify key AFS metrics suitable for China's current situation. Methods: Based on metrics recommended by international AFS consensuses, combined with the current situation of China and the clinical experience of authoritative experts in various fields, several metrics were selected, and experts in the fields of respiratory diseases, hematology, intensive care units (ICUs), dermatology, infectious diseases, microbiology laboratory and pharmacy were invited to assess AFS metrics by the Delphi method. Consensus was considered to be reached with an agreement level of ≥80% for the metric. Results: Consensus was reached for 24 metrics, including right patient metrics (n=4), right time metrics (n=3), and right use metrics (n=17). Right use metrics were further subdivided into drug choice (n=8), drug dosage (n=4), drug de-escalation (n=1), drug duration (n=2), and drug consumption (n=2) metrics. Forty-six authoritative experts assessed and reviewed the above metrics, and a consensus was reached with a final agreement level of ≥80% for 22 metrics. Conclusions: This consensus is the first to propose a set of AFS metrics suitable for China, which helps to establish AFS standards in China and is also the first AFS consensus in Asia, and may improve the standard of clinical diagnosis and treatment of IFD, and guide hospitals to implement AFS, ultimately promoting the rational use of antifungal drugs and improving patient prognosis.

Indirubin-3'-monoxime exhibits potent antiviral and anti-inflammatory effects against human adenoviruses in vitro and in vivo.

Human adenovirus (HAdV) infection is a major cause of respiratory disease, yet no antiviral drugs have been approved for its treatment. Herein, we evaluated the antiviral and anti-inflammatory effects of cyclin-dependent protein kinase (CDK) inhibitor indirubin-3'-monoxime (IM) against HAdV infection in cells and a transgenic mouse model. After evaluating its cytotoxicity, cytopathic effect reduction, antiviral replication kinetics, and viral yield reduction assays were performed to assess the anti-HAdV activity of IM. Quantitative real-time polymerase chain reaction (qPCR), quantitative reverse transcription PCR (qRT-PCR), and western blotting were used to assess the effects of IM on HAdV DNA replication, transcription, and protein expression, respectively. IM significantly inhibited HAdV DNA replication as well as E1A and Hexon transcription, in addition to significantly suppressing the phosphorylation of the RNA polymerase II C-terminal domain (CTD). IM mitigated body weight loss, reduced viral burden, and lung injury, decreasing cytokine and chemokine secretion to a greater extent than cidofovir. Altogether, IM inhibits HAdV replication by downregulating CTD phosphorylation to suppress viral infection and corresponding innate immune reactions as a promising therapeutic agent.

A multicenter prospective study of comprehensive metagenomic and transcriptomic signatures for predicting outcomes of patients with severe community-acquired pneumonia.

BACKGROUND: Severe community-acquired pneumonia (SCAP) results in high mortality as well as massive economic burden worldwide, yet limited knowledge of the bio-signatures related to prognosis has hindered the improvement of clinical outcomes. Pathogen, microbes and host are three vital elements in inflammations and infections. This study aims to discover the specific and sensitive biomarkers to predict outcomes of SCAP patients. METHODS: In this study, we applied a combined metagenomic and transcriptomic screening approach to clinical specimens gathered from 275 SCAP patients of a multicentre, prospective study. FINDINGS: We found that 30-day mortality might be independent of pathogen category or microbial diversity, while significant difference in host gene expression pattern presented between 30-day mortality group and the survival group. Twelve outcome-related clinical characteristics were identified in our study. The underlying host response was evaluated and enrichment of genes related to cell activation, immune modulation, inflammatory and metabolism were identified. Notably, omics data, clinical features and parameters were integrated to develop a model with six signatures for predicting 30-day mortality, showing an AUC of 0.953 (95% CI: 0.92-0.98). INTERPRETATION: In summary, our study linked clinical characteristics and underlying multi-omics bio-signatures to the differential outcomes of patients with SCAP. The establishment of a comprehensive predictive model will be helpful for future improvement of treatment strategies and prognosis with SCAP. FUNDING: National Natural Science Foundation of China (No. 82161138018), Shanghai Municipal Key Clinical Specialty (shslczdzk02202), Shanghai Top-Priority Clinical Key Disciplines Construction Project (2017ZZ02014), Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Diseases (20dz2261100).

Aetiology of severe community acquired pneumonia in adults identified by combined detection methods: a multi-centre prospective study in China.

Severe Community Acquired Pneumonia (SCAP) challenges public health globally. Considerable improvements in molecular pathogen testing emerged in the last few years. Our prospective study combinedly used traditional culture, antigen tests, PCR and mNGS in SCAP pathogen identification with clinical outcomes. From June 2018 to December 2019, we conducted a multi-centre prospective study in 17 hospitals of SCAP patients within 48 hours of emergency room stay or hospitalization in China. All clinical data were uploaded into an online database. Blood, urine and respiratory specimens were collected for routine culture, antigen detection, PCR and mNGS as designed appropriately. Aetiology confirmation was made by the local attending physician group and scientific committee according to microbiological results, clinical features, and response to the treatment. Two hundred seventy-five patients were included for final analysis. Combined detection methods made identification rate up to 74.2% (222/299), while 14.4% (43/299) when only using routine cultures and 40.8% (122/299) when not using mNGS. Influenza virus (23.2%, 46/198), S. pneumoniae (19.6%, 39/198), Enterobacteriaceae (14.6%, 29/198), Legionella pneumophila (12.6%, 25/198), Mycoplasma pneumoniae (11.1%, 22/198) were the top five common pathogens. The in-hospital mortality of patients with pathogen identified and unidentified was 21.7% (43/198) and 25.9% (20/77), respectively. In conclusion, early combined detection increased the pathogen identification rate and possibly benefitted survival. Influenza virus, S. pneumoniae, Enterobacteriaceae was the leading cause of SCAP in China, and there was a clear seasonal distribution pattern of influenza viruses. Physicians should be aware of the emergence of uncommon pathogens, including Chlamydia Psittaci and Leptospira.

A case-control study of human immunodeficiency virus-negative patients with cryptococcemia and cryptococcal meningitis in a Chinese tertiary care hospital during 10 years.

OBJECTIVE: This study aimed to characterize patients with cryptococcemia and compare the clinical features of cryptococcemia and cryptococcal meningitis. METHODS: This was a retrospective, case-control study. We retrospectively identified blood cultures with Cryptococcus spp. growth. Controls were hospitalized patients who suffered from cryptococcal meningitis, but did not experience cryptococcemia. Controls and cases were matched by admission date, age, sex, and body weight. Clinical information was analyzed by two independent reviewers. RESULTS: Eight patients with cryptococcemia and eight patients with cryptococcal meningitis were included. They were all negative for human immunodeficiency virus. The most common underlying disease was primary nephrotic syndrome. All patients presented with fever. The incidence of headache, nausea/vomiting, seizures, and cough/expectoration was significantly lower in patients with cryptococcemia than in those with cryptococcal meningitis. All clinical strains of Cryptococcus, except for one, were sensitive to fluconazole, voriconazole, itraconazole, amphotericin B, and flucytosine in vitro. The rate of receiving an amphotericin B-containing regimen was significantly higher in patients with cryptococcal meningitis than in those with cryptococcemia. In-hospital mortality was significantly higher in cryptococcemia cases compared with cryptococcal meningitis cases. CONCLUSION: Cryptococcemia is an unusual infection characterized by a high mortality. Cryptococcemia requires early identification and prompt antifungal therapy.

The safety and efficacy of endobronchialvalve therapy in patients with advanced heterogeneous emphysema versus standard medical care: A meta-analysis.

BACKGROUND: Endobronchial valves had been utilized for many years to treat patients with advanced emphysema, despite unfavorable results. In this meta-analysis, we aimed to assess the efficacy and safety of the use of endobronchial valves in patients with heterogeneous advanced emphysema. METHODS: We performed systematic database searches to identify clinical trials that met all our inclusion criteria. Direct-comparison and mixed-treatment-comparison (MTC) meta-analyses were conducted to estimate the mean difference or odds ratio of outcomes. Each outcome was analyzed with Review Manager 5 statistical software. RESULTS: Eight prospective clinical trials assessing this therapy were retrieved, with a total of 744 patients. Outcomes, including the forced expiratory volume in 1 second (FEV1), 6-minute walk test (6MWT), and St. George's Respiratory Questionnaire (SGRQ), were analyzed, and the odds ratio of reported complications related to endobronchial valve therapy was calculated. Significant improvement in the mean difference of FEV1 (5.61 [4.42, 6.80]), 6MWT (25.75 [12.30, 39.20]), and SGRQ (-10.96 [-13.88, -8.05]) was observed after endobronchial valve treatment. Moreover, the rate of adverse events related to endobronchial valves was low. CONCLUSIONS: Endobronchial valve treatment offers benefits in terms of lung function and quality of life. Endobronchial valve treatment is feasible and safe for patients with advanced heterogeneous emphysema, especially those with no evidence of collateral ventilation.

Diagnosis and treatment of community-acquired pneumonia in adults: 2016 clinical practice guidelines by the Chinese Thoracic Society, Chinese Medical Association.

Community-acquired pneumonia (CAP) in adults is an infectious disease with high morbidity in China and the rest of the world. With the changing pattern in the etiological profile of CAP and advances in medical techniques in diagnosis and treatment over time, Chinese Thoracic Society of Chinese Medical Association updated its CAP guideline in 2016 to address the standard management of CAP in Chinese adults. Extensive and comprehensive literature search was made to collect the data and evidence for experts to review and evaluate the level of evidence. Corresponding recommendations are provided appropriately based on the level of evidence. This updated guideline covers comprehensive topics on CAP, including aetiology, antimicrobial resistance profile, diagnosis, empirical and targeted treatments, adjunctive and supportive therapies, as well as prophylaxis. The recommendations may help clinicians manage CAP patients more effectively and efficiently. CAP in pediatric patients and immunocompromised adults is beyond the scope of this guideline. This guideline is only applicable for the immunocompetent CAP patients aged 18 years and older. The recommendations on selection of antimicrobial agents and the dosing regimens are not mandatory. The clinicians are recommended to prescribe and adjust antimicrobial therapies primarily based on their local etiological profile and results of susceptibility testing, with reference to this guideline.

Macrolide-resistant Mycoplasma pneumoniae prevalence and clinical aspects in adult patients with community-acquired pneumonia in China: a prospective multicenter surveillance study.

BACKGROUND: Drug resistant Mycoplasma pneumoniae (MP) is a rising issue in the management of community-acquired pneumonia (CAP). Epidemiological monitoring is essential for identifying resistant patterns of MP isolates against various antibiotics in adult CAP patients. METHODS: This is a prospectively designed multicenter study conducted on adult patients with CAP visiting six teaching hospitals in the cities of Beijing, Shanghai and Guangzhou between September 2010 and June 2012. RESULTS: A total of 520 adult patients (mean age: 45.7±26.2 years) with CAP visiting teaching hospitals in the cities of Beijing, Shanghai and Guangzhou were included. Of the 520 patients, only 75 (14.42%) were confirmed MP positive by means of culture and real-time PCR methods. Quinolones were the most common initially prescribed antimicrobial, followed by ß-lactams and ß-lactams plus quinolones. Macrolide resistance was as high as 80% and 72% against erythromycin (ERY) and azithromycin (AZM) respectively, which were associated with the A2063G transition mutation in domain V of the 23S ribosomal RNA (rRNA) gene. Six strains with mild to moderate ERY-resistant level were still susceptible to AZM. Tetracycline (TET), minocycline (MIN) and quinolones [moxifloxacin (MOX) and fluoroquinolones] had no signs of resistance. CONCLUSIONS: High resistance was observed with macrolides, whereas, none of the MP strains were resistant to fluoroquinolones and TET. Hence, macrolide resistant MP (MRMP)_infections could be well treated with fluoroquinolones. However, few isolated strains had minimal inhibitory concentration (MIC) values on the edge of resistance to quinolones, alarming a quinolone-resistant MP in the near future.

Perfluorocarbon reduces cell damage from blast injury by inhibiting signal paths of NF-κB, MAPK and Bcl-2/Bax signaling pathway in A549 cells.

BACKGROUND AND OBJECTIVE: Blast lung injury is a common type of blast injury and has very high mortality. Therefore, research to identify medical therapies for blast injury is important. Perfluorocarbon (PFC) is used to improve gas exchange in diseased lungs and has anti-inflammatory functions in vitro and in vivo. The aim of this study was to determine whether PFC reduces damage to A549 cells caused by blast injury and to elucidate its possible mechanisms of action. STUDY DESIGN AND METHODS: A549 alveolar epithelial cells exposed to blast waves were treated with and without PFC. Morphological changes and apoptosis of A549 cells were recorded. PCR and enzyme-linked immunosorbent assay (ELISA) were used to measure the mRNA or protein levels of IL-1ß, IL-6 and TNF-α. Malondialdehyde (MDA) levels and superoxide dismutase (SOD) activity levels were detected. Western blot was used to quantify the expression of NF-κB, Bax, Bcl-2, cleaved caspase-3 and MAPK cell signaling proteins. RESULTS: A549 cells exposed to blast wave shrank, with less cell-cell contact. The morphological change of A549 cells exposed to blast waves were alleviated by PFC. PFC significantly inhibited the apoptosis of A549 cells exposed to blast waves. IL-1ß, IL-6 and TNF-α cytokine and mRNA expression levels were significantly inhibited by PFC. PFC significantly increased MDA levels and decreased SOD activity levels. Further studies indicated that NF-κB, Bax, caspase-3, phospho-p38, phosphor-ERK and phosphor-JNK proteins were also suppressed by PFC. The quantity of Bcl-2 protein was increased by PFC. CONCLUSION: Our research showed that PFC reduced A549 cell damage caused by blast injury. The potential mechanism may be associated with the following signaling pathways: 1) the signaling pathways of NF-κB and MAPK, which inhibit inflammation and reactive oxygen species (ROS); and 2) the signaling pathways of Bcl-2/Bax and caspase-3, which inhibit apoptosis.

Metastatic pulmonary calcification misdiagnosed as a fungal infection: A case report.

Metastatic pulmonary calcification is a rare lesion, characterized by calcium salt depositing in normal lung tissue. The clinical profile of a case of metastatic pulmonary calcification following renal transplantation was described. A computed tomography scan of the chest revealed ground-glass opacities in bilateral lungs and a node exhibiting a halo in the right upper lobe, which were suspected aspergillus infection. Following examination and therapy, the results of lung biopsy revealed metastatic pulmonary calcification. Although metastatic pulmonary calcification was reported in renal failure patients previously, metastatic pulmonary calcification with cavity lesions has never, to the best of our knowledge, been previously reported. The aim of the present report was to improve the understanding of metastatic pulmonary calcification.

Healthcare-associated Pneumonia: Clinical Features and Retrospective Analysis Over 10 Years.

BACKGROUND: Healthcare-associated pneumonia (HCAP) is associated with drug-resistant pathogens and high mortality, and there is no clear evidence that this is due to inappropriate antibiotic therapy. This study was to elucidate the clinical features, pathogens, therapy, and outcomes of HCAP, and to clarify the risk factors for drug-resistant pathogens and prognosis. METHODS: Retrospective observational study among hospitalized patients with HCAP over 10 years. The primary outcome was 30-day all-cause hospital mortality after admission. Demographics (age, gender, clinical features, and comorbidities), dates of admission, discharge and/or death, hospitalization costs, microbiological results, chest imaging studies, and CURB-65 were analyzed. Antibiotics, admission to Intensive Care Unit (ICU), mechanical ventilation, and pneumonia prognosis were recorded. Patients were dichotomized based on CURB-65 (low- vs. high-risk). RESULTS: Among 612 patients (mean age of 70.7 years), 88.4% had at least one comorbidity. Commonly detected pathogens were Acinetobacter baumannii, Pseudomonas aeruginosa, and coagulase-negative staphylococci. Initial monotherapy with ß-lactam antibiotics was the most common initial therapy (50%). Mean age, length of stay, hospitalization expenses, ICU admission, mechanical ventilation use, malignancies, and detection rate for P. aeruginosa, and Staphylococcus aureus were higher in the high-risk group compared with the low-risk group. CURB-65 ≥3, malignancies, and mechanical ventilation were associated with an increased mortality. Logistic regression analysis showed that cerebrovascular diseases and being bedridden were independent risk factors for HCAP. CONCLUSION: Initial treatment of HCAP with broad-spectrum antibiotics could be an appropriate approach. CURB-65 ≥3, malignancies, and mechanical ventilation may result in an increased mortality.

[Bibliometric analysis of bacterial quantitative proteomics in English literatures].

OBJECTIVE: To analyze the worldwide advances on bacterial quantitative proteomics over the past fifteen years with bibliometric approach. METHODS: Literature retrieval was conducted throughout the databases of Pubmed, Embase and Science citation index (SCI), using "bacterium" and "quantitative proteomics" as the key words. The deadline is July 2013. We sorted and analyzed these articles with Endnote X6 from the aspects of published year, the first author, name of journal, published institution, cited frequency and publication type. RESULTS: 932 English articles were included in our research after deleting the duplicates. The first article on bacterial quantitative proteomics was reported in 1999. The maximal publications were 163 related articles in 2012. Up till July 2013, authors from more than 23 countries and regions have published articles in this field. China ranks the fourth. The main publication type is original articles. The most frequently cited article is entitled with "Absolute quantification of proteins by LCMSE: a virtue of parallel MS acquisition" by Silva JC, Gorenstein MV, Li GZ, et al in Mol Cell Proteomics 2006. The most productive author is Smith RD from Biological Sciences Division, Pac. Northwest National Laboratory. The top journal publishing bacterial quantitative proteomics is Proteomics. CONCLUSION: More and more researchers pay attention to quantitative proteomics which will be widely used in bacteriology.

Community-acquired necrotizing pneumonia caused by methicillin-resistant Staphylococcus aureus producing Panton-Valentine leukocidin in a Chinese teenager: case report and literature review.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA) has now been established as an important community-acquired pathogen. Although necrotizing pneumonia caused by community-acquired MRSA (CA-MRSA) strains producing Panton-Valentine leukocidin (PVL) has been reported with increasing frequency in many countries, it has been reported in only a few children younger than 1 year of age in Mainland China. METHODS: We describe a case of life-threatening necrotizing pneumonia due to PVL-positive CA-MRSA in a 15-year-old previously healthy female who presented with high fever, shivering, a dry cough, and dyspnea. Details of the clinical outcomes, microbiological data, and therapies for this patient were collected and compared with those of cases reported in the literature on CA-MRSA. RESULTS: Computed tomography (CT) findings showed cavitary consolidations in both lungs and bilateral pleural effusion. MRSA strains isolated from the patient's sputum and pleural fluid were susceptible to most non-ß-lactam antimicrobial agents except for clindamycin and erythromycin. Both of these isolates tested positive for the mecA gene as well as PVL genes, and were identified as ST59-MRSA-SCCmec type IV-spa type t437. The patient was treated successfully with linezolid, fosfomycin, and teicoplanin. CONCLUSIONS: To our knowledge, this is the first report from Mainland China of necrotizing pneumonia due to PVL-positive CA-MRSA among those aged older than 1 year. CA-MRSA necrotizing pneumonia should be considered in the differential diagnosis of severe community-acquired pneumonia, particularly in previously healthy individuals.

Immediate and long-term results of bronchial artery embolization for hemoptysis due to benign versus malignant pulmonary diseases.

BACKGROUND: Bronchial artery embolization (BAE) is widely used for the treatment of hemoptysis. The immediate and long-term results of BAE for hemoptysis in patients with benign and malignant pulmonary diseases were inconsistent in previous studies and were thus investigated. METHODS: This was a retrospective review of the clinical records of 154 patients (108 with benign disease and 46 with malignant disease) who received BAE for hemoptysis from January 2005 to June 2011 at the Chinese People's Liberation Army General Hospital. RESULTS: Immediate cessation of hemoptysis was achieved in 98 patients with benign disease (90.7%) and 42 patients with malignancy (91.3%). The long-term control rate of hemoptysis in patients with benign disease was 74.3% (80/108) at 1 year, significantly higher than in patients with cancer (16/46, 35.5%, P < 0.01). The worst outcomes in the benign and malignant groups were observed in patients with aspergilloma and squamous cell lung cancer, respectively. The average number of abnormal vessels on bronchial arteriography was higher in the benign group than in the malignant group (3 ± 1.3 versus 2 ± 1.1, respectively, P < 0.01). Moreover, recurrent hemoptysis was independently associated with the presence of massive hemoptysis and bronchial-pulmonary artery shunt in both groups (P < 0.05). CONCLUSIONS: BAE is a relatively safe procedure for patients with hemoptysis. Immediate control of hemoptysis with BAE is achieved in most cases, but the long-term hemoptysis control rate is worse in malignant lung diseases than in benign conditions, especially among patients with squamous cell lung cancer.

Comparative evaluation of thrombocytopenia in adult patients receiving linezolid or glycopeptides in a respiratory intensive care unit.

Linezolid is an oxazolidinone antibiotic agent, active against gram-positive bacteria that are resistant to traditional antibiotics, including glycopeptides. Linezolid is generally well tolerated, but has been associated with hematologic adverse effects such as thrombocytopenia. The primary objective of this study was to compare the incidence of thrombocytopenia between patients receiving linezolid or glycopeptides in different age groups. The secondary objective was to assess the association between the time-to-event and occurrence of thrombocytopenia. This retrospective study reviewed the medical records of patients who were treated with linezolid or glycopeptides (vancomycin or teicoplanin) between January 2010 and June 2013 in a respiratory intensive care unit. Data were extracted from the patients' electronic medical records, which were obtained from a central database in the hospital, and multivariate analyses were performed. In total, the study included 225 patients who received linezolid or glycopeptides. The cumulative probability of thrombocytopenia was higher in the patients receiving linezolid than in those receiving glycopeptides (P<0.05), however the cumulative probability of thrombocytopenia did not differ significantly between patients receiving linezolid or glycopeptides in the subgroup whose age was <65 years (P>0.05). With a treatment duration of ≥7 days, the incidence of thrombocytopenia and the mean platelet count reduction in the patients receiving linezolid was significantly higher than in those receiving glycopeptides (P<0.05). No significant difference was identified in the mean platelet counts between the patients receiving linezolid and those receiving glycopeptides. In conclusion, it was identified that patients in a respiratory intensive care unit, aged ≥65 years or with a treatment duration of ≥7 days who were treated with linezolid were more likely to develop thrombocytopenia than patients of the same subgroup who were treated with glycopeptides.

Prognosis and weaning of elderly multiple organ dysfunction syndrome patients with invasive mechanical ventilation.

BACKGROUND: Elderly multiple organ dysfunction syndrome (MODS) patients receiving invasive mechanical ventilation have poor prognosis in intensive care units (ICUs). We studied the usefulness of four commonly used severity scores and extrapulmonary factors that affected weaning to predict outcome of such patients. METHODS: Clinical data of 197 patients on admission to ICUs (from January 2009 to June 2012) were used retrospectively. The Acute Physiology and Chronic Health Evaluation (APACHE) II, APACHE III, Sample Acute Physiological Score (SAPS) II and MODS scores were calculated. All the patients were grouped into survivors and nonsurvivors according to the prognosis. Patients, who weaned from ventilator (n = 154), were subdivided into a successful weaning group and a failed weaning group. The receiver operating characteristic (ROC) curves and Logistic regression was used for prognostic and weaning assessment. RESULTS: Based on the outcomes, the areas under the ROC of APACHE II, APACHE III, SAPS II, and MODS were 0.837, 0.833, 0.824, and 0.837, respectively. The Logistic regression analysis revealed that the odds ratio (OR) of underlying lung diseases, serum albumin and creatinine, and the number of organ failures was 2.374, 0.920, 1.003, and 1.547. APACHE II scores on admission performed excellent (ROC: 0.921) on the weaning assessments. CONCLUSIONS: APACHE II and MODS systems were marginally better for evaluating the prognosis of elderly MODS patients who received invasive mechanical ventilation. Underlying lung diseases, serum albumin, serum creatinine and the number of organ failures were independent prognostic factors. Using the APACHE II scores on admission before weaning may increase the likelihood of successful weaning. (ClinicalTrial.gov identifier NCT01802983).