Serotype distribution and antimicrobial resistance of pediatric Streptococcus pneumoniae isolated from inpatients and outpatients at Beijing Children's Hospital.

BACKGROUND: Understanding the epidemiology of Streptococcus pneumoniae (S. pneumoniae) isolates is important for pneumonia treatment and prevention. This research aimed to explore the epidemiological characteristics of S. pneumoniae isolated from pediatric inpatients and outpatients during the same period. METHODS: S. pneumoniae were isolated from unsterile samples of inpatients and outpatients younger than five years old between March 2013 and February 2014. The serotypes were determined using diagnostic pneumococcal antisera. The resistance of each strain to 13 antibiotics was tested using either the E-test or the disc diffusion method. The Sequence Types (STs) were analyzed via Multilocus Sequence Typing (MLST). RESULTS: The dominant serotypes obtained from inpatients were 19F (32.9 %), 19A (20.7 %), 23F (10.7 %), 6A (10.0 %), and 14 (8.6 %), while those from outpatients were 19F (13.6 %), 23F (12.9 %), 6A (10.0 %), 6B (10.0 %), and 19A (7.9 %). The coverage rates of 13-valent Pneumococcal Conjugate Vaccine (PCV) formulations were high in both groups. The nonsusceptibility to penicillin, cefuroxime, imipenem, erythromycin, and trimethoprim-sulfamethoxazole among the inpatient isolates was 7.1 %, 92.8 %, 65.7 %, 100 %, and 85.0 %, respectively, while that among the outpatient isolates was 0.7 %, 50.0 %, 38.6 %, 96.4 %, and 65.7 %, respectively. There were 45 and 81 STs detected from the pneumococci isolated from inpatients and outpatients, respectively. CC271 was common among both inpatients and outpatients (43.6 % and 14.3 %). CONCLUSIONS: Pneumococcal vaccine-related serotypes are prevalent among both inpatients and outpatients, especially among inpatients, who exhibit more severe antibiotic resistance. Therefore, universal immunization with PCV13 would decrease the hospitalization rate due to S. pneumoniae and the antibiotic resistance rate of S. pneumoniae.

Repeated atrial arrhythmia induced by cochineal red poisoning: A case report.

BACKGROUND: Cochineal red is an organic compound widely used in food, cosmetics, pharmaceuticals, textiles, and other fields due to its excellent safety profile. Poisoning caused by eating foods containing cochineal red is rare, and repeated atrial arrhythmia due to cochineal red poisoning is even rarer. CASE SUMMARY: An 88-year-old Asian female patient was admitted to hospital due to a disturbance of consciousness. Twelve hours prior to presentation, the patient consumed 12 eggs containing cochineal red over a period of 2 h. At presentation, the patient was in a coma and had a score of 6 on the Glasgow Coma Scale (E2 + VT + M4). The patient's skin and mucous membranes were pink. Electrocardiography (ECG) revealed rapid atrial fibrillation without any signs of ischemia. We prescribed cedilan and fluid replacement for arrhythmia correction. Shortly after admission, the atrial fibrillation corrected to a normal sinus rhythm. On the day 2 of admission, the patient had a sudden atrial flutter accompanied by hemodynamic instability and rapidly declining arterial oxygen saturation between 85% and 90%. The sinus rhythm returned to normal after two electrical cardioversions. Six days after admission, the skin color of the patient returned to normal, and the ECG results were normal. The patient was transferred out of the intensive care unit and eventually discharged after 12 d in hospital. At the 2-mo follow-up visit, the patient was in good health with no recurrence of arrhythmia. CONCLUSION: Although cochineal red is a safe, natural food additive, excessive consumption or occupational exposure can induce cardiac arrhythmias.

Etiology and clinical features of children with bronchiectasis in China: A 10-year multicenter retrospective study.

INTRODUCTION: The current study aims to investigate the etiology spectrum and the clinical characteristics of bronchiectasis in Chinese children. METHODS: The study is designed as a multicenter retrospective study. 193 cases were enrolled in 13 centers in China between 2008 and 2017. The inclusive cases must meet the clinical as well as the HRCT criteria. Only if both two radiologists confirmed the diagnosis, the case could be enrolled. The cases that could not provide clinical and imageology data were excluded. The data were entered into the specialized system and then analyzed. RESULTS: One hundred sixty-nine cases (87%) were found to have the underlying etiology. Post-infective (46%), primary immunodeficiency (14%), and PCD (13%) were the common causes. All cases came from 28 provinces in Mainland China. The median age of symptom onset was 5.8 (2.0, 8.9) years. The median age of diagnosis was 8.4 (4.5, 11.6) years. The main symptoms were cough, sputum expectoration, and fever during the exacerbation. Nineteen percent of patients suffered from limited exercise tolerance. Clubbing was found in 17% of cases. Nearly 30% of patients presented growth limitations. On the HRCT findings, 126 cases had diffused bronchiectasis, and bilateral involvement was found in 94 cases. The lower lobes and right middle lobes were most commonly involved. Approximately 30% of cultures of sputum and bronchoalveolar lavage were positive. CONCLUSION: A majority of cases could be found the underlying etiology. Post-infective, primary immunodeficiency, and PCD were the most common causes. Some clinical figures might indicate a specific etiology.

Diagnosis, treatment, and prevention of monkeypox in children: an experts' consensus statement.

Monkeypox is a zoonotic disease. Since the first human monkeypox case was detected in 1970, it has been prevalent in some countries in central and western Africa. Since May 2022, monkeypox cases have been reported in more than 96 non-endemic countries and regions worldwide. As of September 14, 2022, there have been more than 58,200 human monkeypox cases, and there is community transmission. The cessation of smallpox vaccination in 1980, which had some cross-protection with monkeypox, resulted in a general lack of immunity to monkeypox, which caused global concern and vigilance. As of September 14, 2022, there are four monkeypox cases in China, including three in Taiwan province and one in Hong Kong city. Previous foreign studies have shown that children are vulnerable to monkeypox and are also at high risk for severe disease or complications. In order to improve pediatricians' understanding of monkeypox and achieve early detection, early diagnosis, early treatment,  and early disposal, we have organized national authoritative experts in pediatric infection, respiratory, dermatology, critical care medicine, infectious diseases, and public health and others to formulate this expert consensus, on the basis of the latest "Clinical management and infection prevention and control for monkeypox" released by The World Health Organization, the "guidelines for diagnosis and treatment of monkeypox (version 2022)" issued by National Health Commission of the People's Republic of China and other relevant documents. During the development of this consensus, multidisciplinary experts have repeatedly demonstrated the etiology, epidemiology, transmission, clinical manifestations, laboratory examinations, diagnosis, differential diagnosis, treatment, discharge criteria, prevention, disposal process, and key points of prevention and control of suspected and confirmed cases.

Acute respiratory distress syndrome following multiple wasp stings treated with extracorporeal membrane oxygenation: A case report.

BACKGROUND: It is necessary for clinicians to be aware of a rare but possible acute respiratory distress syndrome (ARDS) complication caused by multiple wasp stings. Severe ARDS has a high mortality rate but no specific pharmacotherapies have been identified to date. This case study presents the first case of severe ARDS caused by multiple wasp stings, treated successfully with extracorporeal membrane oxygenation (ECMO). It also emphasizes the effectiveness of early ECMO treatment for severe ARDS with persistent hypoxemia. CASE SUMMARY: A 24-year-old woman was admitted to the emergency department after being stung by more than 10 wasps within a 30-min period, with clinical symptoms of multiple rashes, dizziness, chest tightness, nausea, and vomiting. On the 2nd day of admission, the patient developed progressive dyspnea. The patient was diagnosed with ARDS based on clinical manifestations and lung computed tomography (CT) scan. Because of the progressive dyspnea, the intensive care unit physician performed endotracheal intubation and continued to provide ventilator support, but the patient's respiratory distress worsened, as indicated by the ratio of arterial partial pressure of oxygen to fraction of inspired oxygen. Veno-venous ECMO was initiated for 6 d. On day 7 of admission, ECMO was stopped. On the 11th day of admission, CT scan of the lungs revealed significant reduction of ground-glass opacities and consolidations. After about 2 wk, the patient recovered completely from ARDS and was discharged to home. At the 2-mo follow-up, the patient was in good health with no recurrence of dyspnea nor chest tightness. CONCLUSION: ARDS complication caused by multiple wasp stings may be fatal when mechanical ventilation becomes dangerous due to persistent hypoxemia and despite optimization of ARDS management. We propose that the early implementation of ECMO is a relatively effective treatment, although the evidence is relatively limited.

Camrelizumab-induced anaphylactic shock in an esophageal squamous cell carcinoma patient: A case report and review of literature.

BACKGROUND: Camrelizumab (SHR-1210), an immune checkpoint inhibitor, is clinically used as a therapeutic option for various types of tumors. However, reports of adverse reactions associated with camrelizumab are gradually increasing. Anaphylactic shock due to camrelizumab has not been reported previously, until now. We report here, for the first time, a case of anaphylactic shock associated with camrelizumab in a patient with esophageal squamous cell carcinoma. CASE SUMMARY: An 84-year-old male esophageal cancer patient received radiotherapy and chemotherapy 11 years ago. He was diagnosed with advanced esophageal squamous cell carcinoma with liver metastasis (TxN1M1) and received the first immunotherapy (camrelizumab 200 mg/each time, once every 3 wk) dose in December 2020, with no adverse reactions. Three weeks later, a generalized rash was noted on the chest and upper limbs; palpitations and breathing difficulties with a sense of dying occurred 10 min after the patient had been administered with the second camrelizumab therapy. Electrocardiograph monitoring revealed a 70 beats/min pulse rate, 69/24 mmHg (1 mmHg = 0.133 kPa) blood pressure, 28 breaths/min respiratory rate, and 86% pulse oximetry in room air. The patient was diagnosed with anaphylactic shock and was managed with intravenous fluid, adrenaline, dexamethasone sodium phosphate, calcium glucosate, and noradrenaline. Approximately 2 h after treatment, the patient's anaphylactic shock symptoms had been completely relieved. CONCLUSION: Due to the widespread use of camrelizumab, attention should be paid to anti-programmed cell death 1 antibody therapy-associated hypersensitivity or anaphylactic shock.

Simplified Chinese version of the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire: cross-cultural adaptation, reliability, and validity for patients with cervical spondylotic myelopathy.

PURPOSE: This study aimed to validate the simplified Chinese version of the Japanese Orthopaedic Association Cervical Myelopathy Evaluation Questionnaire (JOACMEQ) for Chinese patients with cervical spondylotic myelopathy (CSM). METHODS: The construct validity was conducted using confirmatory factor analysis (CFA). The convergent validity was based on factor loading, composite reliability (CR), and Pearson correlation coefficients (r). Internal consistency reliability was evaluated using Cronbach's α, test-retest reliability using intraclass correlation coefficients (ICC), and the ceiling and floor effects were also examined. RESULTS: A total of 168 native Chinese-speaking patients were enrolled. The CFA indicated that construct validity did not meet the preset criteria to be considered as good. Except for Q 4-1, the factor loading was higher than the standard of 0.5, and the CR values ranged from 0.70 to 0.85. Strong to moderate correlations were found between other scales and the simplified Chinese JOACMEQ. The scale showed good internal consistency reliability (Cronbach's α 0.639-0.821), and test-retest reliability (ICC 0.760-0.916). Moreover, the ceiling effect was displayed from Q1 to Q4. CONCLUSIONS: This study indicates that the simplified Chinese JOACMEQ is a reliable and valid measure of the functional status among Chinese patients with CSM.IMPLICATIONS FOR REHABILITATIONThe JOACMEQ was translated into the simplified Chinese and culturally adapted for Chinese-speaking patients with CSM for the first time.The simplified JOACMEQ demonstrated an excellent level of internal consistency and good test-retest reliability.The simplified Chinese JOACMEQ was reliable and valid for the measurement of the functional status among the patients with CSM.

Population pharmacokinetics-pharmacodynamics of ceftazidime in neonates and young infants: Dosing optimization for neonatal sepsis.

Ceftazidime is a third-generation cephalosporin with high activity against many pathogens. But the ambiguity and diversity of the dosing regimens in neonates and young infants impair access to effective treatment. Thus, we conducted a population pharmacokinetic study of ceftazidime in this vulnerable population and recommended a model-based dosage regimen to optimize sepsis therapy. Totally 146 neonates and young infants (gestational age (GA): 36-43.4 weeks, postnatal age (PNA): 1-81 days, current weight (CW): 900-4500 g) were enrolled based on inclusion and exclusion criteria. Ceftazidime bloods samples (203) were obtained using the opportunistic sampling strategy and determined by the high-performance liquid chromatography. The population pharmacokinetic-pharmacodynamic analysis was conducted by nonlinear mixed effects model (NONMEM). A one-compartment model with first-order elimination best described the pharmacokinetic data. Covariate analysis showed the significance of GA, PNA, and CW on developmental pharmacokinetics. Monte Carlo simulation was performed based on above covariates and minimum inhibitory concentration (MIC). In the newborns with PNA ≤ 3 days (MIC=8 mg/L), the dose regimen was 25 mg/kg twice daily (BID). For the newborns with PNA > 3 days (MIC=16 mg/L), the optimal dose was 30 mg/kg three times daily (TID) for those with GA ≤ 37 weeks and 40 mg/kg TID for those with GA > 37 weeks. Overall, on the basis of the developmental population pharmacokinetic-pharmacodynamic analysis covering the whole range of neonates and young infants, the evidence-based ceftazidime dosage regimens were proposed to optimize neonatal early-onset and late-onset sepsis therapy.

Drug Clearance in Neonates: A Combination of Population Pharmacokinetic Modelling and Machine Learning Approaches to Improve Individual Prediction.

BACKGROUND: Population pharmacokinetic evaluations have been widely used in neonatal pharmacokinetic studies, while machine learning has become a popular approach to solving complex problems in the current era of big data. OBJECTIVE: The aim of this proof-of-concept study was to evaluate whether combining population pharmacokinetic and machine learning approaches could provide a more accurate prediction of the clearance of renally eliminated drugs in individual neonates. METHODS: Six drugs that are primarily eliminated by the kidneys were selected (vancomycin, latamoxef, cefepime, azlocillin, ceftazidime, and amoxicillin) as 'proof of concept' compounds. Individual estimates of clearance obtained from population pharmacokinetic models were used as reference clearances, and diverse machine learning methods and nested cross-validation were adopted and evaluated against these reference clearances. The predictive performance of these combined methods was compared with the performance of two other predictive methods: a covariate-based maturation model and a postmenstrual age and body weight scaling model. Relative error was used to evaluate the different methods. RESULTS: The extra tree regressor was selected as the best-fit machine learning method. Using the combined method, more than 95% of predictions for all six drugs had a relative error of < 50% and the mean relative error was reduced by an average of 44.3% and 71.3% compared with the other two predictive methods. CONCLUSION: A combined population pharmacokinetic and machine learning approach provided improved predictions of individual clearances of renally cleared drugs in neonates. For a new patient treated in clinical practice, individual clearance can be predicted a priori using our model code combined with demographic data.

Endoscopic retrograde cholangiopancreatography in the treatment of pancreaticopleural fistula in children.

BACKGROUND: Pancreaticopleural fistula (PPF) is a rare disease, especially in children. Conservative treatment and surgery are traditional therapies, but surgery is invasive. The emergence of endoscopic retrograde cholangiopancreatography (ERCP) has provided a new noninvasive treatment for PPF and may become the first choice for children with PPF. AIM: To explore the treatment response to ERCP for PPF in children. METHODS: Seven children with PPF were hospitalized in the Gastroenterology Department of Beijing Children's Hospital from December 2007 to May 2019. Data on these seven patients' clinical characteristics, diagnosis, treatments, and outcomes were analyzed, and their treatment responses following surgery and ERCP were compared. The correlation between the length of hospital stay and conservative treatment was analyzed. Peer-reviewed articles written in English and Chinese published from January 2009 to December 2019 were obtained from various open data sources and reviewed. RESULTS: The seven patients comprised three boys and four girls with a mean age of 6.57 ± 3.26 years. The main symptoms were chest tightness and pain (n = 4), intermittent fever (n = 3), dyspnea (n = 3), and abdominal pain (n = 1), and all patients had bloody pleural effusion. All seven patients were diagnosed with PPF by magnetic resonance cholangiopancreatography, and all were initially treated conservatively for a mean of 34.67 ± 22.03 d with a poor response. Among five patients who underwent ERCP, one required surgery because of intubation failure; thus, the success rate of ERCP was 80%. Two patients were successfully treated with surgery (100%). The postoperative hospital stay of the two patients treated by surgery was 20 and 30 d, respectively (mean of 25 d), and that of the four patients treated by ERCP ranged from 12 to 30 d (mean of 19.25 ± 8.85 d). The recovery time after ERCP was short [time to oral feeding, 4-6 d (mean, 5.33 ± 1.15 d); duration of closed thoracic drainage, 2-22 d (mean, 13.3 d)]. Analysis of previous cases of PPF published worldwide during the past decade showed that the treatment success rate of ERCP is not lower than that of surgery. There was no significant difference in the postoperative hospital stay between surgery (16 ± 10.95 d) and ERCP (18.7 ± 6.88 d, P > 0.05). A positive linear correlation was found between the overall hospital stay and ERCP intervention time (R 2 = 0.9992). CONCLUSION: ERCP is recommended as the first-choice treatment for PPF in children. ERCP should be performed as early as possible if conditions permit.

A comparison between the low back pain scales for patients with lumbar disc herniation: validity, reliability, and responsiveness.

BACKGROUND: Although the Japanese Orthopedic Association Back Pain Evaluation Questionnaire (JOABPEQ), Numerical Pain Rating Scale (NPRS), Oswestry Disability Index (ODI), Roland Morris Disability Questionnaire (RMDQ), and Short Form 36 Health Survey (SF-36) has shown a preferable psychometric properties in patients with low back pain (LBP), but no study has yet determined these in conservative treatment of patients with lumbar disc herniation (LDH). Thus the current study aimed to compare those scales in LDH patients receiving conservative treatment to select the better option to assess the severity of disease. METHODS: LDH patients were invited to complete the JOABPEQ, NPRS, ODI, RMDQ, and SF-36 twice. The internal consistency was evaluated by the Cronbach's α. Test-retest reliability was tested by the intraclass correlation coefficient (ICC). The relationships of these scales were evaluated by the Pearson correlation coefficients (r). The responsiveness was operationalised using the receiver operating characteristic (ROC) curve, as well as the comparison of smallest detectable change (SDC), minimum important change (MIC). RESULTS: A total of 353 LDH patients were enrolled. Four subscales of the Chinese JOABPEQ were over 0.70, then the ICCs for the test-retest reliability were over 0.75. For functional status, remarked negative correlations could be seen between JOABPEQ Q2-Q4 and ODI, as well as RMDQ (r = - 0.634 to - 0.752). For general health status, remarkable positive correlations could also be seen between Q5 Mental health and SF-36 PCS (r = 0.724) as well as SF-36 MCS (r = 0.736). Besides, the area under of the curves (AUC) of the JOABPEQ ranged from 0.743 to 0.827, indicating acceptale responsiveness, as well as the NPRS, ODI, and RMDQ. CONCLUSION: NPRS, and ODI or RMDQ is recommended in studies related to LDH patients, while if the quality of life also is needed to observe, the NPRS, and JOABPEQ would be more appropriate rather than SF-36.

Reappraisal of the Optimal Dose of Meropenem in Critically Ill Infants and Children: a Developmental Pharmacokinetic-Pharmacodynamic Analysis.

Data of developmental pharmacokinetics (PK) of meropenem in critically ill infants and children with severe infections are limited. We assessed the population PK and defined the appropriate regimen to optimize treatment in this population based on developmental PK-pharmacodynamic (PD) analysis. Blood samples were collected from pediatric intensive care unit patients with severe infection treated with standard dosage regimens for meropenem. Population PK data were analyzed using NONMEM software. Fifty-seven patients (mean age, 2.96 years [range, 0.101 to 14.4]; mean body weight, 15.8 kg [range, 5.0 to 65.0]) were included. A total of 135 meropenem concentrations were obtainable for population PK modeling. The median number of samples per patients was 2 (range, 1 to 4). A two-compartment model with first-order elimination was optimal for PK modeling. Weight and creatinine clearance (estimated by the Schwartz formula) were significantly correlated with the PK parameters of meropenem. The probabilities of target attainment for pathogens with low MICs of 1 and 2 µg/ml were 87.5% and 68.6% following administration of 40 mg/kg/dose (every 8 h [q8h]) as a 4-h infusion and 98.0% and 73.3% with high MICs of 4 and 8 µg/ml following administration of 110 mg/kg/day as a continuous infusion in critically ill infants and children under 70% fT>MIC (the free time during which the plasma concentration of meropenem exceeds the MIC), respectively. The standard dosage regimens for meropenem did not meet an appropriate PD target, and an optimal dosing regimen was established in critically ill infants and children. (This study has been registered at ClinicalTrials.gov under identifier NCT03643497.).

Population pharmacokinetics and dose optimization of ceftriaxone for children with community-acquired pneumonia.

PURPOSE: To assess ceftriaxone population pharmacokinetics in a large pediatric population and describe the proper dose for establishing an optimized antibiotic regimen. METHODS: From pediatric patients using ceftriaxone, blood samples were obtained and the concentration was measured using high-performance liquid chromatography ultraviolet detection. The NONMEM software program was used for population pharmacokinetic analysis, for which data from 99 pediatric patients (2 to 12 years old) was collected and 175 blood concentrations were obtained. RESULTS: The best fit with the data was shown by the one-compartment model with first-order elimination. According to covariate analysis, weight had a significant impact on the clearance of ceftriaxone. Using Monte Carlo simulation, in a pediatric population with community-acquired pneumonia, a dose regimen of 100 mg/kg every 24 h produced satisfactory target attainment rates while remaining within the required minimum inhibitory concentration (2 mg/L). CONCLUSION: Population pharmacokinetics of ceftriaxone was evaluated in children and an optimum dosing regimen was constructed on the basis of the pharmacokinetics-pharmacodynamics model-based approach.