Ethanol lock therapy (ELT) can be used in patients with an indwelling central line to assist in the prevention of central venous catheter (CVC)–associated infections. However, its efficacy has not been consistently demonstrated in the pediatric population. The primary objective of this review and meta-analysis was to determine the efficacy and safety of ELT in prevention of central line–associated bloodstream infection (CLABSI) in the pediatric population. A search was conducted with the PubMed, CINAHL, PSCYInfo, Cochrane Library, and Academic Search Premier databases from inception through January 21, 2022. Studies were included if they reported incidence of CVC-related infections with ELT in pediatric patients. Meta-analyses used random-effects models according to the heterogeneity of all included studies. Of 736 studies, 25 met inclusion criteria for review and 10 for inclusion in the meta-analysis. Meta-analysis with pre- and post-ELT treatment showed that use of ELT significantly decreased mean CVC-related infections when compared with pre-treatment with no ELT with a mean difference of −5.79 (95% CI, −9.08 to −2.51; p < 0.001). The number of CVC infections also significantly decreased (OR, 0.42; 95% CI, 0.23–0.75; p = 0.004). Increased risk of thrombosis and increased frequency of catheter breakage, repair, and replacement were noted in several studies. Ethanol lock therapy is effective in preventing infection related to central venous catheter use in pediatric patients. Further study is warranted to determine the optimal protocol for, and incidence of, adverse events related to use of ELT.
Type B lactic acidosis can occur secondary to several factors, including thiamine deficiency, and is not as common as type A. Recognizing thiamine deficiency–associated lactic acidosis is challenging because serum thiamine concentrations are not routinely obtained, and a thorough and specific history is necessary for clinicians to suspect thiamine deficiency as a root cause. Furthermore, the appropriate dose and duration of thiamine treatment are not well defined. Untreated thiamine deficiency–associated lactic acidosis can lead to critical illness requiring lifesaving extracorporeal therapies. Additionally, if thiamine and glucose are not administered in an appropriate sequence, Wernicke encephalopathy or Korsakoff syndrome may occur. This review aims to summarize therapeutic treatment for thiamine deficiency–associated lactic acidosis, based on case reports/series and nutritional guidance. After a literature search of the PubMed database, 63 citations met inclusion criteria, of which 21 involved pediatric patients and are the focus of this review. Citations describe dosing regimens ranging from 25 to 1000 mg of intravenous (IV) thiamine as a single dose, or multiple daily doses for several days. Specific guidance for critically ill adults recommends a thiamine range of 100 mg IV once daily to 400 mg IV twice daily. Although there are no specific recommendations for the pediatric population, given the relative safety of thiamine administration, its low cost, and our review of the literature, treatment with thiamine 100 to 200 mg IV at least once is supported, with ongoing daily doses based on clinical response of the patient, regardless of age.
We estimated the effect of early initiation of dual therapy vs monotherapy on drug administration and related outcomes in mechanically ventilated, critically ill children. We used the electronic medical record at a single tertiary medical center to conduct an active comparator, new user cohort study. We included children <18 years of age who were exposed to a sedative or analgesic within 6 hours of intubation. We used stabilized inverse probability of treatment weighting to account for confounding at baseline. We estimated the average effect of initial dual therapy vs monotherapy on outcomes including cumulative opioid, benzodiazepine, and dexmedetomidine dosing; sedation scores; time to double the opioid or benzodiazepine infusion rate; initiation of neuromuscular blockade within the first 7 days of follow-up; time to extubation; and 7-day all-cause in-hospital death. The cohort included 640 patients. Children receiving dual therapy received 0.03 mg/kg (95% CI, 0.02–0.04) more dexmedetomidine over the first 7 days after initiation of mechanical ventilation than did monotherapy patients. Dual therapy patients had similar sedation scores, time to double therapy, initiation of neuromuscular blockade, and time to extubation as monotherapy patients. Dual therapy patients had a lower incidence of death. In this study, initial dual therapy compared with monotherapy does not reduce overall drug administration during mechanical ventilation. The identified effect of dual therapy on mortality deserves further investigation.OBJECTIVE
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The Advisory Committee on Immunization Practices recommends the pneumococcal polysaccharide vaccine (PPSV23) following the pneumococcal conjugate vaccine (PCV13) for pediatric patients aged 2 to 18 years with high-risk medical conditions. The PPSV23 is not a routine immunization for all pediatric patients and children who meet criteria for high-risk conditions may not consistently receive the PPSV23 vaccine, despite current recommendations. The goal of this study was to determine PPSV23 vaccination rates in the high-risk pediatric patients with type 1 or type 2 diabetes. A single-center retrospective cohort study was conducted. Patients were included if they were 2 to 18 years of age on January 1, 2019, with a diagnosis of diabetes, and had ≥1 encounters within the health care system in 2019. The primary outcome was PPSV23 vaccination rates in the high-risk diabetic pediatric population. Secondary outcomes included identifying missed opportunities for vaccinations and the incidence of invasive pneumococcal infections. A total of 366 patients met criteria for study inclusion. Patients had a mean age of 13.3 years and were predominantly white (69.8%). A total of 32 (8.7%) patients had documentation of PPSV23 vaccination. Baseline characteristics were comparable between the two groups. There were 32 cases of pneumonia charted before patients received the PPSV23 and one case reported after patients received the PPSV23 vaccination. PPSV23 vaccination rates were low in this high-risk diabetic pediatric group, with many documented missed opportunities for vaccination. This may be attributed to the vaccine not being a routinely recommended for all pediatric patients.OBJECTIVE
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The purpose of this study was to evaluate phytonadione in children with septic shock with disseminated intravascular coagulopathy (DIC). The primary objective was to identify the number of patients with an international normalized ratio (INR), defined as ≤1.2, following phytonadione. Secondary objectives were to compare patients who achieved a normalized INR versus those with INR >1.2 and to determine factors associated with a normalized INR. A retrospective study of children <18 years of age receiving phytonadione from October 1, 2013, to August 31, 2020, with a diagnosis of septic shock, were included. Data collection included demographics, phytonadione regimen, INR values, Pediatric Index of Mortality 2 (PIM2) and Pediatric Risk of Mortality III (PRISM III) scores, fresh frozen plasma (FFP) and cryoprecipitate use. A logistic regression model and generalized linear model were used to explore factors associated with a normalized INR and evaluate phytonadione dosing. Data for initial phytonadione course for 156 patients were evaluated. Sixty-six (42.3%) patients had a normalized INR. Most patients (n = 145; 92.9%) received ≤3 phytonadione doses, with the largest reduction in INR occurring after the second dose. In the logistic regression model, baseline INR, FFP, cryoprecipitate, vasopressors, PIM2, PRISM III, or cumulative phytonadione dose were not associated with achieving a normalized INR. Less than half of patients achieved a normalized INR. The median cumulative dose of phytonadione and receipt of FFP or cryoprecipitate was not associated with an increased odds of a normalized INR. Future studies are needed to further explore phytonadione use in children with sepsis-induced coagulopathy.OBJECTIVES
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Vancomycin 24-hour area under the curve over minimum inhibitory concentration (AUC/MIC) monitoring has been recommended over trough-based monitoring in pediatric patients. This study compared the proportion of target attainment between vancomycin AUC/MIC and trough-based methods, and identified risk factors for subtherapeutic initial extrapolated targets. This was a retrospective, observational study conducted at KK Women’s and Children’s Hospital (KKH), Singapore. Patients aged 1 month to 18 years with stable renal function who received intravenous vancomycin between January 2014 and October 2017, with at least 2 vancomycin serum concentrations obtained after the first dose of vancomycin, were included. Using a pharmacokinetic software, namely Adult and Pediatric Kinetics (APK), initial extrapolated steady-state troughs and 24-hour AUC were determined by using a one-compartmental model. Statistical tests included Wilcoxon rank sum test, McNemar test, logistic regression, and classification and regression tree (CART) analysis. Of the 82 pediatric patients included, a significantly larger proportion of patients achieved therapeutic targets when the AUC/MIC-based method (24, 29.3%) was used than with the trough-based method (9, 11.0%; p < 0.01). Patients with estimated glomerular filtration rate (eGFR) ≥60 mL/min/1.73 m2 or with age <13 years had an increased risk of obtaining subtherapeutic targets. However, empiric vancomycin doses of 60 mg/kg/day would be sufficient to achieve serum therapeutic targets, using the AUC/MIC-based method. The AUC/MIC-based vancomycin monitoring may be preferred because a larger proportion of patients could achieve initial therapeutic targets. Future prospective studies with larger sample size will be required to determine the optimal vancomycin strategy for pediatric patients.OBJECTIVES
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Cefepime and ceftazidime are alternatives to cefotaxime for management of Gram-negative infections in neonates. The objective was to evaluate neonatal outcomes when receiving cefepime or ceftazidime. This was a single center, retrospective analysis of neonates exposed to at least 24 hours of cefepime or ceftazidime between June 1, 2018, and June 1, 2021. The primary outcome was incidence of culture-positive, late-onset sepsis after initial exposure. Secondary outcomes included culture-negative, respiratory, urinary tract, and resistant infections; necrotizing enterocolitis; length of stay; age at discharge; mortality; and adverse effects. A total of 105 neonates were included (cefepime, n = 50; ceftazidime, n = 55). Baseline characteristics were similar except more cumulative days of antibiotics (25.0 [IQR, 9.3–47.0] versus 9.0 [IQR, 4.0–23.5], p = 0.01), central line days (11.0 [IQR, 6.0–40.0] versus 6.5 [IQR, 0.0–11.5], p = 0.001), and ventilator days (13.0 [IQR, 2.3–48.0] versus 4.0 [IQR, 0.0–25.0], p = 0.02) were found in the cefepime group than in the ceftazidime group. There was no difference in culture-positive sepsis after the initial antibiotic course (8.0% versus 3.6%, p = 0.42). Statistical differences were seen in select secondary outcomes including treated respiratory infections (16.0% versus 1.8%, p = 0.01), length of stay greater than 30 days (72.0% versus 50.9%, p = 0.03), and mortality (26.0% versus 9.1%, p = 0.02). These differences were not observed in analyses adjusted for ventilator days. This analysis found no difference in culture-positive sepsis in neonates exposed to cefepime versus ceftazidime. Moreover, there were no differences in secondary outcomes in adjusted analyses. Further research is needed to assess neonatal outcomes in a larger analysis.OBJECTIVES
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To assess the incidence of intracranial hemorrhage (ICH), including intraventricular hemorrhage, in infants receiving 4.2% or 8.4% sodium bicarbonate. This is a single-center retrospective chart review of neonates and infants with a gestational age (GA) >32 weeks and a postnatal age <2 months who received sodium bicarbonate in an intensive care unit at an academic tertiary children’s hospital. The primary outcome was the incidence of ICH in patients with baseline and follow-up head imaging. The secondary outcome was the incidence of ICH on follow-up head imaging, with or without baseline head imaging. There were 351 patients screened, with 135 meeting inclusion criteria. Of these, 84% were born ≥37 weeks GA. Forty-two met the criteria for the primary outcome. Study participants were further subdivided into 3 groups based on the concentration of sodium bicarbonate received: only 4.2%, only 8.4%, or a mixed group that received at least 1 dose each of 4.2% and 8.4%. Intracranial hemorrhage was noted in 1 patient in each group: 8.3%, 5.6%, and 8.3%, respectively (p = 1.00). For the secondary outcome, 11 ICHs were seen on head imaging: 11.3%, 3.8%, and 10%, respectively. There was no statistically significant difference in the incidence of ICH (p = 0.325). The incidence of ICH in term neonates and infants was not significantly different in those receiving 4.2% vs 8.4% sodium bicarbonate. Although additional studies are needed, this study suggests it may be possible to safely expand the use of 8.4% in neonates/infants ≥37 weeks GA. These results should not be applied to preterm neonates (<37 weeks GA and/or <1500 g) or neonates with additional ICH risk factors.OBJECTIVE
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Venous thromboembolism (VTE) is a leading cause of hospital-acquired morbidity for pediatric patients. Pharmacological thromboprophylaxis increases the risk of adverse events such as bleeding complications. There exists a need for a universal VTE risk assessment tool to aid in thromboprophylaxis prescribing while minimizing the risk of adverse events. The objective of this study is to investigate if implementation of a VTE risk assessment tool is associated with a change in the rate of thromboprophylaxis prescribing. This retrospective study evaluated the change in thromboprophylaxis prescribing pre and post implementation of a VTE risk assessment tool. Patients were excluded if they were pregnant, diagnosed with VTE ≤48 hours of admission, presented with VTE symptoms, or if they were diagnosed with multisystem inflammatory syndrome in children (MIS-C) or coronavirus disease (COVID-19). A total of 186 pediatric patients were included in this study. Thromboprophylaxis was prescribed in 16/93 (17.12%) and 75/93 (80.6%) patients in the pre- and post-implementation group, respectively (95% CI, 0.523–0.745; p < 0.001). No VTE events occurred in either group. Bleeding complications occurred in 3.2% and 7.5% of patients in the pre- and post-implementation groups, respectively. The risk tool was used in 80.6% of patients; providers used the tool correctly in 48% of patients and incorrectly in 52% of patients. Implementation of a VTE risk assessment tool was associated with a statistically significant change in the rate of thromboprophylaxis prescribing. Incorrect use may be minimized by providing provider reeducation and making modifications to the order set.OBJECTIVE
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Capillary leak syndrome (CLS) is a well-known phenomenon that has been reported commonly in association with septic shock, polytrauma, and pancreatitis in intensive care settings. In the hematologic literature, it has been reported following granulocyte colony-stimulating factor (G-CSF), granulocyte-macrophage colony-stimulating factor, tumor necrosis factor, interleukin 2, and interleukin 4 infusions; and autologous and allogenic bone marrow transplantations in both pediatric as well as adult populations. Only a few cases of CLS have been reported in the pediatric population following G-CSF. We report here a case of a 9-year-old female who developed CLS within 60 minutes of receiving the first dose of G-CSF that was successfully treated with immediate symptomatic management.
This case report describes a 14-year-old male with signs and symptoms of drug-induced hepatotoxicity after receiving azithromycin and lisdexamfetamine dimesylate. The patient was admitted to the hospital and a liver biopsy revealed findings suggestive of drug-induced hepatitis. In this patient, it is unclear whether 1 agent individually or a combination of azithromycin and lisdexamfetamine was the cause of hepatitis. Although hepatotoxicity has been reported with azithromycin and other macrolide antibiotics in adults, such a condition has yet to be reported in pediatrics. In light of this report, providers should be aware of a potentially rare reaction of acute hepatitis when combining azithromycin and lisdexamfetamine in pediatric patients.
The pharmaceutical industry including small and large organizations and biotech as well as other stakeholders in the health arena are increasingly aware of the benefits of working together in the precompetitive phase to address common problems. While they rightly remain focused on developing their own independent products and services in healthy competition, there is an increased awareness of the need to improve precompetitive efficiency by identifying and addressing common issues. A major challenge is defining the domain of precompetitive research. The basic biology, the understanding of disease, biomarkers of prognosis, and even drug responses allCompetition – How, Why, etc.
Necrotizing enterocolitis (NEC) is a serious gastrointestinal disease that can be seen in premature infants with high risk for morbidity and mortality. There is currently no US Food and Drug Administration (FDA) medication approved for the prevention of NEC. Despite great heterogeneity among available studies, large meta-analyses of clinical trials have demonstrated the efficacy of multiple-strain probiotics in reducing NEC and all-cause mortality. In 2020, Medical City Dallas’s Level IV neonatal intensive care unit (NICU) implemented a probiotic protocol for NEC prevention. As a result, a reduction in NEC was observed, with no occurrence of probiotic-related sepsis.