Prevalence and risk factors for severe linezolid-associated thrombocytopenia in pediatric patients: An analysis of a public database.

Linezolid is widely used in various clinical settings. Studies have revealed that it may cause thrombocytopenia in adults. However, the correlation between the use of linezolid and thrombocytopenia in pediatric patients is still unclear. This study aimed to identify the impact of Linezolid on the occurrence of thrombocytopenia in children. A retrospective observational study was conducted using data on patients treated with linezolid from the Pediatric Intensive Care clinical database. Univariate and multiple logistic regression analyses were performed to identify the risk factors of linezolid-related severe thrombocytopenia. A total of 134 patients were included. The prevalence of severe thrombocytopenia was 8.96% (12/134). Univariate analysis indicated that the severe thrombocytopenia group showed significantly higher proportion of concomitant carbapenem (75% vs 44.3%; P < .05) and piperacillin/tazobactam (25% vs 6.6%; P < .05) than that of the non-severe thrombocytopenia group. Multivariate analysis also revealed that the occurrence of severe thrombocytopenia was significantly associated with concurrent use of carbapenem (odd ratio = 4.058; 95% confidence interval: 1.012-16.274; P = .048) and piperacillin/tazobactam (odd ratio = 5.335; 95% confidence interval: 1.117-25.478; P = .036). 75% of patients (9/12) developed severe thrombocytopenia within the first 7 days of linezolid use. The concomitant use of carbapenem and piperacillin/tazobactam was associated with an increased probability of severe thrombocytopenia in pediatric patients undergoing linezolid treatment. Further prospective clinical studies are required, and more detailed mechanisms of blood toxicity in pediatric patients must be investigated.

Contamination of personal protective equipment and environmental surfaces in Fangcang shelter hospitals.

BACKGROUND: Fangcang shelter hospitals emerged as a new public health concept after COVID-19. Data regarding contamination of Fangcang shelter environments remains scarce. This study aims to investigate the extent of SARS-CoV-2 contamination on personal protective equipment and surfaces in Fangcang hospitals. METHODS: Between March and May 2022, during wave of omicron variant, a prospective study was conducted in 2 Fangcang hospitals in Shanghai, China. Swabs of personal protective equipment worn and environmental surfaces of contaminated areas, doffing rooms, and potentially contaminated areas were collected. SARS-CoV-2 RNA was detected by reverse transcription quantitative polymerase chain reaction. If viral RNA was detected, sampling was repeated after cleaning and disinfection. RESULTS: A total of 602 samples were collected. 13.3% of the personal protective equipment were contaminated. Positive rate was higher in the contaminated areas (48.4%) than in the doffing rooms (11.7%) and the potentially contaminated areas (0; P<.05). Contamination was highest in patient occupied areas (67.5%). After cleaning, samples taken at previously contaminated surfaces are all negative. CONCLUSIONS: SARS-CoV-2 RNA contamination is prevalent in Fangcang hospitals and healthcare workers are under risk of infection. Potentially contaminated areas and surfaces after cleaning and disinfection are negative, underlying the importance of infection control policy.

Improved stacking ensemble learning based on feature selection to accurately predict warfarin dose.

Background: With the rapid development of artificial intelligence, prediction of warfarin dose via machine learning has received more and more attention. Since the dose prediction involve both linear and nonlinear problems, traditional machine learning algorithms are ineffective to solve such problems at one time. Objective: Based on the characteristics of clinical data of Chinese warfarin patients, an improved stacking ensemble learning can achieve higher prediction accuracy. Methods: Information of 641 patients from southern China who had reached a steady state on warfarin was collected, including demographic information, medical history, genotype, and co-medication status. The dataset was randomly divided into a training set (90%) and a test set (10%). The predictive capability is evaluated on a new test set generated by stacking ensemble learning. Additional factors associated with warfarin dose were discovered by feature selection methods. Results: A newly proposed heuristic-stacking ensemble learning performs better than traditional-stacking ensemble learning in key metrics such as accuracy of ideal dose (73.44%, 71.88%), mean absolute errors (0.11 mg/day, 0.13 mg/day), root mean square errors (0.18 mg/day, 0.20 mg/day) and R2 (0.87, 0.82). Conclusions: The developed heuristic-stacking ensemble learning can satisfactorily predict warfarin dose with high accuracy. A relationship between hypertension, a history of severe preoperative embolism, and warfarin dose is found, which provides a useful reference for the warfarin dose administration in the future.

Prevalence and risk factors of trimethoprim/sulfamethoxazole-related acute kidney injury in pediatric patients: an observational study from a public database.

Background: Trimethoprim/sulfamethoxazole (TMP/SMZ) is widely used in various clinical settings. Studies have revealed that it may cause acute kidney injury (AKI) in adults. However, the correlation between the use of TMP/SMZ and renal injury in pediatric patients is still unclear. This study aimed to identify the impact of TMP/SMZ on the occurrence of AKI in children. Methods: A retrospective observational study was conducted using data of patients treated with TMP/SMZ from the Paediatric Intensive Care clinical database. A newly developed criterion was used for the diagnosis of AKI, and univariate and multiple logistic regression analyses were performed to identify the risk factors of TMP/SMZ-related renal injury. Results: A total of 113 patients were included. The prevalence of AKI was 21.2% (24/113). Univariate analysis indicated that the AKI group showed significantly higher baseline serum creatinine level (46.00 vs. 37.00 µmol/L; P=0.034) and in-hospital mortality rate [29.2% (7/24) vs. 9.0% (8/89); P=0.01] than that of the non-AKI group. Multivariate analysis revealed that the occurrence of AKI was significantly associated with increased baseline serum creatinine level [odds ratio (OR) =1.029; 95% CI: 1.006-1.053; P=0.014] and concurrent use of vancomycin (OR =5.349; 95% CI: 1.381-20.714; P=0.015). A proportion of 79.2% of patients (19/24) developed AKI within the first 10 days of TMP/SMZ use. Conclusions: Elevated baseline serum creatinine level (≥40.25 µmol/L) and concurrent use of vancomycin were associated with the development of AKI in young patients. Further large multi-center prospective studies are necessary to confirm these relationships and validate their clinical significance.

A retrospective study on the evaluation of the appropriateness of oral anticoagulant therapy for patients with atrial fibrillation.

BACKGROUND: The incidence of atrial fibrillation (AF) is increasing, and effective anticoagulation therapy can prevent adverse events. Selecting the appropriate OAC based on patient characteristics has become a challenge. Interventions are going to be a potential area of focus. OBJECTIVES: To explore the discrepancies between clinician prescriptions and recommended guidelines of oral anticoagulants (OACs) for patients with atrial fibrillation (AF), and to provide direction for improving anticoagulation strategies for treating patients with AF. MATERIALS AND METHODS: Data were collected from the electronic medical record system of Fuwai Yunnan Cardiovascular Hospital between July 2019 and January 2020. The suitability of prescribed OACs for patients with AF was assessed according to the Rules for Avoiding Prescription Inappropriateness, the prescribed medicine label, and any relevant antithrombotic guidelines for treating patients with AF. RESULTS: A total of 460 patients met the inclusion criteria. Of these, 53.7% received an appropriate prescription and 46.3% received an inappropriate prescription. Of the patients who received inappropriate prescriptions, 15.4% were prescribed without the presenting appropriate indicators, 1.3% were prescribed inappropriate drug selection, and 29.6% were prescribed inappropriate drug doses. For patients prescribed without providing appropriate indicators, 2.2% had no indication for medication and 13.3% had an indication for medication, but not a specific OAC. For patients with inappropriate drug selection, 1, 5 patients were on rivaroxaban, dabigatran respectively. The distribution of NOAC doses was as follows: dabigatran standard dose (45.2%), the low dose (54.8%). Rivaroxaban standard dose (58.9%), low dose (36.8%), high dose (4.3%). A total of 44 patients (9.6%) experienced bleeding events, 12 patients (2.6%) experienced embolic events, and 7 patients experienced other adverse events after dosing. CONCLUSIONS: In clinical practice, it is common for patients with AF to receive inappropriate prescriptions of OACs. Therefore there is a need to enhance anticoagulation management in patients with AF to improve the appropriate use of OACs.

Predictors of mortality in adult patients with methicillin-resistant Staphylococcus aureus bloodstream infection: a meta-analysis and systematic review.

BACKGROUND: Cases of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection have been increasing. Patients with MRSA bloodstream infection have a poor prognosis and high mortality rate. Identification of potential risk factors associated with MRSA bloodstream infection-related mortality may help improve patient outcomes. METHODS: Embase, PubMed, and the Cochrane Library databases were searched to identify articles describing predictors of mortality in patients with MRSA bloodstream infections. Two investigators independently assessed articles for inclusion and data extraction. RESULTS: Twenty observational studies were included in the analysis. Factors associated with higher mortality were development of severe sepsis or septic shock [odds ratio (OR): 4.56, 95% CI: 3.37-6.18], congestive heart failure (OR: 1.78, 95% CI: 1.27-2.50), liver cirrhosis (OR: 1.90, 95% CI: 1.27-2.65), malignancy (OR: 1.62, 95% CI: 1.33-1.98), infective endocarditis (OR: 2.05, 95% CI: 1.35-3.11), nosocomial infection (OR: 2.80, 95% CI: 1.41-5.55), intensive care unit admission (OR: 3.08, 95% CI: 1.49-6.36) and inappropriate empirical antimicrobial treatment (OR: 2.25, 95% CI: 1.16-4.36); removal of the eradicable foci was a protective factor (OR: 0.51, 95% CI: 0.40-0.63) The average APACHE II score at the time of diagnosis of MRSA bloodstream infection was considerably higher in patients who did not survive than in those who survived [weighted mean difference (WMD): 5.81, 95% CI: 3.03-8.59]. DISCUSSION: Patient condition, appropriate timing of antimicrobial treatment, surgical intervention and disease severity according to the APACHE II score are the most important risk factors for death in patients with MRSA bloodstream infections.

Predictors of mortality in patients with carbapenem-resistant Klebsiella pneumoniae infection: a meta-analysis and a systematic review.

BACKGROUND: Cases of carbapenem-resistant Klebsiella pneumoniae infection have been increasing. Patients with carbapenem-resistant Klebsiella pneumoniae infection have a poor prognosis and a high mortality rate. Identification of potential risk factors associated with carbapenem-resistant Klebsiella pneumoniae infection-related mortality may help improve patient outcomes. METHODS: Embase, PubMed, and the Cochrane Library databases were searched to identify articles describing predictors of mortality in patients with carbapenem-resistant Klebsiella pneumoniae infection. The quality of articles was assessed with the Newcastle-Ottawa Scale score (NOS). Review Manager was used for statistical analyses. RESULTS: Twenty-seven observational studies were included in the analysis. Factors associated with higher mortality were septic shock [odds ratio (OR): 4.41, 95% CI: 3.17-6.15], congestive heart failure (OR: 2.65, 95% CI: 1.71-4.13), chronic obstructive pulmonary disease (COPD; OR: 2.43, 95% CI: 1.87-3.15), chronic kidney disease (CKD; OR: 1.78, 95% CI: 1.43-2.22), diabetes mellitus (OR: 1.41, 95% CI: 1.16-1.72), mechanical ventilation (OR: 1.65, 95% CI: 1.25-2.18), and inappropriate empirical antimicrobial treatment (OR: 1.25, 95% CI: 1.03-1.52). The average Acute Physiology and Chronic Health Evaluation (APACHE) II score at the time of diagnosis of carbapenem-resistant Klebsiella pneumoniae infection was considerably higher in patients who did not survive than in those who survived (weighted mean difference: 5.86, 95% CI: 2.46-9.26). DISCUSSION: Patient condition, timing appropriate antimicrobial treatment, and disease severity according to the APACHE II score are the most important risk factors for death in patients with carbapenem-resistant Klebsiella pneumoniae infection. Our finding may help predict patients' outcomes and improve management for them. REGISTRATION NUMBER: 20210417EuEGX/INPLASY2020100037.

Rationale and design of a prospective, multicenter, cross-sectional study of appropriateness evaluation of the prescription of non-vitamin K antagonist oral anticoagulants for Chinese atrial fibrillation patients (Chi-NOACs-AF trial).

BACKGROUND: Non-vitamin K antagonist oral anticoagulants (NOACs) are alternative to vitamin K antagonists (VKAs) for stroke prevention in patients with atrial fibrillation (AF). Along with their widespread clinical use in China, the off-label use of NOACs is commonly seen in real-world practice, which could result in adverse drug events and poor clinical outcomes. However, guideline adherence and label adherence for NOAC prescriptions have not been well evaluated in a real-world setting in China. METHODS: Between January 2021 and June 2021, a total of 1,750 outpatients or inpatients with AF will be consecutively enrolled at 26 canters in China. Data on patient demographics, clinical characteristics, treatment strategies, and prescribing information related to anticoagulation therapy for patients with AF will be collected. Clinical pharmacists will evaluate the rationality of the anticoagulation regimens and NOAC prescriptions based on the guideline recommendations and drug labels that are approved by the National Medical Products Administration. The primary outcomes will be the prevalence of irrational anticoagulation strategies and the inappropriate NOAC prescriptions, as well as potential risk factors associated with inappropriate prescriptions in patients with AF. DISCUSSION: This study will be the first national, multicenter, prospective study performed by pharmacists to explore real-world data on the appropriateness of NOAC prescription in Chinese patients with AF. TRIAL REGISTRATION: The Chi-NOACs-AF trial (Trial number: ChiCTR2000035908).

Infection within 2 weeks before liver transplantation closely related to prognosis of posttransplant infection: A single-center retrospective observational study in China.

BACKGROUND: Infections still represent the main factors influencing morbidity and mortality following liver transplantation. This study aimed to evaluate the incidence and risk factors for infection and survival after liver transplantation. METHODS: We retrospectively examined medical records in 210 liver recipients who underwent liver transplantation between April 2015 and October 2017 in our hospital. Clinical manifestations and results of pathogen detection test were used to define infection. We analyzed the prevalence, risk factors and prognosis of patients with infection. RESULTS: The median follow-up was 214 days; the incidence of infection after liver transplantation was 46.7% (n = 98) which included pneumonia (43.4%), biliary tract infection (21.9%), peritonitis (21.4%) and bloodstream infection (7.6%). Among the pathogens in pneumonia, the most frequently isolated was Acinetobacter baumanii (23.5%) and Klebsiella pneumoniae (21.2%). Model for end-stage liver disease (MELD) score (OR = 1.083, 95% CI: 1.045-1.123; P < 0.001), biliary complication (OR = 4.725, 95% CI: 1.119-19.947; P = 0.035) and duration of drainage tube (OR = 1.040, 95% CI: 1.007-1.074; P = 0.017) were independent risk factors for posttransplant infection. All-cause mortality was 11.0% (n = 23). The prognostic factors for postoperative infection in liver recipients were prior-transplant infection, especially pneumonia within 2 weeks before transplantation. Kaplan-Meier curves of survival showed that recipients within 2 weeks prior infection had a significantly lower cumulative survival rate compared with those without infection (65.2% vs. 90.0%; hazard ratio: 4.480; P < 0.001). CONCLUSIONS: Infection, especially pneumonia within 2 weeks before transplantation, complication with impaired renal function and MELD score after 7 days of transplantation was an independent prognostic factor for postoperative infection in liver transplant recipients.

Improving Pulmonary Infection Diagnosis with Metagenomic Next Generation Sequencing.

Pulmonary infections are among the most common and important infectious diseases due to their high morbidity and mortality, especially in older and immunocompromised individuals. However, due to the limitations in sensitivity and the long turn-around time (TAT) of conventional diagnostic methods, pathogen detection and identification methods for pulmonary infection with greater diagnostic efficiency are urgently needed. In recent years, unbiased metagenomic next generation sequencing (mNGS) has been widely used to detect different types of infectious pathogens, and is especially useful for the detection of rare and newly emergent pathogens, showing better diagnostic performance than traditional methods. There has been limited research exploring the application of mNGS for the diagnosis of pulmonary infections. In this study we evaluated the diagnostic efficiency and clinical impact of mNGS on pulmonary infections. A total of 100 respiratory samples were collected from patients diagnosed with pulmonary infection in Shanghai, China. Conventional methods, including culture and standard polymerase chain reaction (PCR) panel analysis for respiratory tract viruses, and mNGS were used for the pathogen detection in respiratory samples. The difference in the diagnostic yield between conventional methods and mNGS demonstrated that mNGS had higher sensitivity than traditional culture for the detection of pathogenic bacteria and fungi (95% vs 54%; p<0.001). Although mNGS had lower sensitivity than PCR for diagnosing viral infections, it identified 14 viral species that were not detected using conventional methods, including multiple subtypes of human herpesvirus. mNGS detected viruses with a genome coverage >95% and a sequencing depth >100× and provided reliable phylogenetic and epidemiological information. mNGS offered extra benefits, including a shorter TAT. As a complementary approach to conventional methods, mNGS could help improving the identification of respiratory infection agents. We recommend the timely use of mNGS when infection of mixed or rare pathogens is suspected, especially in immunocompromised individuals and or individuals with severe conditions that require urgent treatment.

Rapid detection of respiratory organisms with FilmArray respiratory panel and its impact on clinical decisions in Shanghai, China, 2016-2018.

BACKGROUND: In this study, we evaluated the diagnostic potential and clinical impact of an automated multiplex PCR platform (the FilmArray Respiratory Panel; FA-RP), specially designed for pathogen detection in respiratory tract infections in adults with unexplained pneumonia (UP). METHODS: A total of 112 UP patients in Shanghai, China, were enrolled prospectively and assessed using the FA-RP from October 2016 to March 2018. We examined the test results and their influence on clinical decisions. Furthermore, as a control group, we retrospectively obtained the clinical data of 70 UP patients between October 2014 and March 2016 (before the FA-RP was available). The two patient groups were compared with respect to factors, including general antimicrobial use and defined daily dose (DDD) numbers. RESULTS: Between October 2016 and March 2018, the positive rate obtained using FA-RP for UP was 76.8%. The primary pathogens in adults with UP were Influenza A/B (47.3%, 53/112). Compared with the patients before FA-RP was available, patients who underwent FA-RP testing had higher rates of antiviral drug use and antibiotic de-escalation during clinical treatment. FA-RP significantly decreased the total DDDs of antibiotic or antifungal drugs DDDs by 7 days after admission (10.6 ± 2.5 vs 14.1 ± 8.8, P < .01). CONCLUSIONS: The FA-RP is a rapid and sensitive nucleic acid amplification test method for UP diagnosis in adults. The application of FA-RP may lead to a more accurately targeted antimicrobial treatment and reduced use of antibiotic/antifungal drugs.

Clinical Evaluation of Diagnosis Efficacy of Active Mycobacterium tuberculosis Complex Infection via Metagenomic Next-Generation Sequencing of Direct Clinical Samples.

Background: Tuberculosis (TB) is now the leading cause of death from infectious disease. Rapid screening and diagnostic methods for TB are urgently required. Rapid development of metagenomics next-generation sequencing (mNGS) in recent years showed promising and satisfying application of mNGS in several kinds of infectious diseases. However, research directly evaluating the ability of mNGS in TB infection is still scarce. Methods: We conducted an adult prospective study in mainland China to evaluate the diagnostic performance of mNGS for detection of Mycobacterium tuberculosis complex (MTB) in multiple forms of direct clinical samples compared with GeneXpert MTB/RIF assay (Xpert), traditional diagnostic methods, and the clinical final diagnosis. Results: Of 123 patients presenting with suspected active TB infection between June 1, 2017, and May 21, 2018, 105 patients underwent synchronous tuberculous testing with culture, Xpert, and mNGS on direct clinical samples including sputum, cerebrospinal fluids, pus, etc. During follow-up, 45 of 105 participants had clinical final diagnosis of active TB infection, including 13 pulmonary TB cases and 32 extrapulmonary TB cases. Compared to clinical final diagnosis, mNGS produced a sensitivity of 44% for all active TB cases, which was similar to Xpert (42%) but much higher than conventional methods (29%). With only one false-positive result, mNGS had a specificity of 98% in our study. mNGS yielded significantly much higher sensitivity in pre-treatment samples (76%) than post-treatment ones (31%) (P = 0.005), which was also true for Xpert and conventional methods. Combining Xpert and mNGS together, the study identified 27 of 45 active TB cases (60%), including all 13 conventional method-identified cases, and the result reached statistical significance compared to conventional methods (McNemar-test P < 0.001). Conclusions: mNGS had a similar diagnostic ability of MTB compared with Xpert and showed potential for a variety of clinical samples. Combined mNGS and Xpert showed an overall superior advantage over conventional methods and significantly improved the etiology diagnosis of both MTB and other pathogens. The result that anti-TB treatment significantly reduced diagnostic efficacy of culture, Xpert, and mNGS highlighted the importance of collecting samples before empirical treatment.

Rapid and precise diagnosis of disseminated T.marneffei infection assisted by high-throughput sequencing of multifarious specimens in a HIV-negative patient: a case report.

BACKGROUND: Talaromyces marneffei, is an opportunistic pathogenic fungus that is most commonly reported in Southeast Asia and disseminated T.marneffei infection predominantly occurs in patients with immunodeficiency. With a potential to invade multiple organs, it can be fatal for patients if diagnosis and treatment are delayed. In current clinical practice, the diagnosis of T.marneffei infection relies heavily on tissue culture and histologic analysis, which may suffer from limited positive rate and is sometimes time consuming. The rapid and accurate diagnosis of disseminated T.marneffei infection remains challenging. CASE PRESENTATION: A 22-year-old man gradually developed fever, cough, lower extremities weakness, jaundice and rash, for which a 3-month extensive investigation failed to reach a diagnosis. After admitted into our hospital, laboratory and radiological tests revealed multiple lesions in the patient's brain, spinal cord, and lungs. We performed next generation sequencing on the patient's skin tissue, bone marrow, blood and cerebrospinal fluid, which all identified numerous Talaromyces marneffei nucleotide sequences and leaded to the rapid diagnosis and treatment of disseminated T.marneffei infection. CONCLUSIONS: This case underline the clinical significance of T.marneffei as a possible pathogen in immune-competent patients. This successful application of the next generation sequencing assisting the rapid diagnosis of disseminated T.marneffei infection provides a new perspective in the clinical approach to the systematic fungi infections and highlights the potential of this technique in rapid etiological diagnosis.

A two-stage multi-view learning framework based computer-aided diagnosis of liver tumors with contrast enhanced ultrasound images.

OBJECTIVE: With the fast development of artificial intelligence techniques, we proposed a novel two-stage multi-view learning framework for the contrast-enhanced ultrasound (CEUS) based computer-aided diagnosis for liver tumors, which adopted only three typical CEUS images selected from the arterial phase, portal venous phase and late phase. MATERIALS AND METHODS: In the first stage, the deep canonical correlation analysis (DCCA) was performed on three image pairs between the arterial and portal venous phases, arterial and delayed phases, and portal venous and delayed phases respectively, which then generated total six-view features. While in the second stage, these multi-view features were then fed to a multiple kernel learning (MKL) based classifier to further promote the diagnosis result. Two MKL classification algorithms were evaluated in this MKL-based classification framework. We evaluated proposed DCCA-MKL framework on 93 lesions (47 malignant cancers vs. 46 benign tumors). RESULTS: The proposed DCCA-MKL framework achieved the mean classification accuracy, sensitivity, specificity, Youden index, false positive rate, and false negative rate of 90.41 ± 5.80%, 93.56 ± 5.90%, 86.89 ± 9.38%, 79.44 ± 11.83%, 13.11 ± 9.38% and 6.44 ± 5.90%, respectively, by soft margin MKL classifier. CONCLUSION: The experimental results indicate that the proposed DCCA-MKL framework achieves best performance for discriminating benign liver tumors from malignant liver cancers. Moreover, it is also proved that the three-phase CEUS image based CAD is feasible for liver tumors with the proposed DCCA-MKL framework.

Human African Trypanosomiasis in Emigrant Returning to China from Gabon, 2017.

Human African trypanosomiasis is endemic to parts of sub-Saharan Africa and should be considered in the differential diagnosis of patients who have visited or lived in Africa. We report a 2017 case of stage 2 Trypanosoma brucei gambiense disease in an emigrant who returned to China from Gabon.