Prevalence and Characteristics of Diagnostic Error in Pediatric Critical Care: A Multicenter Study.

OBJECTIVES: Effective interventions to prevent diagnostic error among critically ill children should be informed by diagnostic error prevalence and etiologies. We aimed to determine the prevalence and characteristics of diagnostic errors and identify factors associated with error in patients admitted to the PICU. DESIGN: Multicenter retrospective cohort study using structured medical record review by trained clinicians using the Revised Safer Dx instrument to identify diagnostic error (defined as missed opportunities in diagnosis). Cases with potential errors were further reviewed by four pediatric intensivists who made final consensus determinations of diagnostic error occurrence. Demographic, clinical, clinician, and encounter data were also collected. SETTING: Four academic tertiary-referral PICUs. PATIENTS: Eight hundred eighty-two randomly selected patients 0-18 years old who were nonelectively admitted to participating PICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Of 882 patient admissions, 13 (1.5%) had a diagnostic error up to 7 days after PICU admission. Infections (46%) and respiratory conditions (23%) were the most common missed diagnoses. One diagnostic error caused harm with a prolonged hospital stay. Common missed diagnostic opportunities included failure to consider the diagnosis despite a suggestive history (69%) and failure to broaden diagnostic testing (69%). Unadjusted analysis identified more diagnostic errors in patients with atypical presentations (23.1% vs 3.6%, p = 0.011), neurologic chief complaints (46.2% vs 18.8%, p = 0.024), admitting intensivists greater than or equal to 45 years old (92.3% vs 65.1%, p = 0.042), admitting intensivists with more service weeks/year (mean 12.8 vs 10.9 wk, p = 0.031), and diagnostic uncertainty on admission (77% vs 25.1%, p < 0.001). Generalized linear mixed models determined that atypical presentation (odds ratio [OR] 4.58; 95% CI, 0.94-17.1) and diagnostic uncertainty on admission (OR 9.67; 95% CI, 2.86-44.0) were significantly associated with diagnostic error. CONCLUSIONS: Among critically ill children, 1.5% had a diagnostic error up to 7 days after PICU admission. Diagnostic errors were associated with atypical presentations and diagnostic uncertainty on admission, suggesting possible targets for intervention.

Molecular predictors of resistance training outcomes in young untrained female adults.

We sought to determine if the myofibrillar protein synthetic (MyoPS) response to a naïve resistance exercise (RE) bout, or chronic changes in satellite cell number and muscle ribosome content, were associated with hypertrophic outcomes in females or differed in those who classified as higher (HR) or lower (LR) responders to resistance training (RT). Thirty-four untrained college-aged females (23.4 ± 3.4 kg/m2) completed a 10-wk RT protocol (twice weekly). Body composition and leg imaging assessments, a right leg vastus lateralis biopsy, and strength testing occurred before and following the intervention. A composite score, which included changes in whole body lean/soft tissue mass (LSTM), vastus lateralis (VL) muscle cross-sectional area (mCSA), midthigh mCSA, and deadlift strength, was used to delineate upper and lower HR (n = 8) and LR (n = 8) quartiles. In all participants, training significantly (P < 0.05) increased LSTM, VL mCSA, midthigh mCSA, deadlift strength, mean muscle fiber cross-sectional area, satellite cell abundance, and myonuclear number. Increases in LSTM (P < 0.001), VL mCSA (P < 0.001), midthigh mCSA (P < 0.001), and deadlift strength (P = 0.001) were greater in HR vs. LR. The first-bout 24-hour MyoPS response was similar between HR and LR (P = 0.367). While no significant responder × time interaction existed for muscle total RNA concentrations (i.e., ribosome content) (P = 0.888), satellite cell abundance increased in HR (P = 0.026) but not LR (P = 0.628). Pretraining LSTM (P = 0.010), VL mCSA (P = 0.028), and midthigh mCSA (P < 0.001) were also greater in HR vs. LR. Female participants with an enhanced satellite cell response to RT, and more muscle mass before RT, exhibited favorable resistance training adaptations.NEW & NOTEWORTHY This study continues to delineate muscle biology differences between lower and higher responders to resistance training and is unique in that a female population was interrogated. As has been reported in prior studies, increases in satellite cell numbers are related to positive responses to resistance training. Satellite cell responsivity, rather than changes in muscle ribosome content per milligrams of tissue, may be a more important factor in delineating resistance-training responses in women.

Sex differences in muscle activity emerge during sustained low-intensity contractions but not during intermittent low-intensity contractions.

Sex differences in motor performance may arise depending on the mode of contraction being performed. In particular, contractions that are held for long durations, rather than contractions that are interspersed with rest periods, may induce greater levels of fatigue in men compared to women. The purpose of this study was to examine fatigue responses in a cohort of healthy men (n = 7, age [mean] = 21.6 ± [SD] 1.1 year) and women (n = 7, age: 22.0 ± 2.0 year) during sustained isometric and intermittent isometric contractions. Two contraction protocols were matched for intensity (20% MVC) and total contraction time (600-s). Biceps brachii EMG and elbow flexion torque steadiness were examined throughout each protocol, and motor nerve stimulation was used to quantify central and peripheral fatigue. Overall, there were few sex-related differences in the fatigue responses during intermittent contractions. However, men exhibited progressively lower maximal torque generation (39% versus 27% decrease), progressively greater muscle activity (220% versus 144% increase), progressively greater declines in elbow flexion steadiness (354% versus 285% decrease), and progressively greater self-perception of fatigue (Borg scale: 8.8 ± 1.2 versus 6.3 ± 1.1) throughout the sustained contractions. The mechanism underlying fatigue responses had a muscle component, as voluntary activation of the biceps brachii did not differ between sexes, but the amplitude of resting twitches decreased throughout the sustained contractions (m: 32%, w: 10% decrease). As generating large sustained forces causes a progressive increase in intramuscular pressure and mechanical occlusion-which has the effect of enhancing metabolite accumulation and peripheral fatigue-it is likely that the greater maximal strength of men contributed to their exacerbated levels of fatigue.

Critical Care in the Pediatric Emergency Department.

In caring for critically ill children, recognition and management often begins in the pediatric emergency department. A seamless transition in care is needed to ensure appropriate care to the sickest of children. This review covers the management of critically ill children in the pediatric emergency department beyond the initial stabilization for conditions such as acute respiratory failure and pediatric acute respiratory distress syndrome, traumatic brain injury, status epilepticus, congenital heart disease, and metabolic emergencies.

Risk Factors for Failed Tracheal Intubation in Pediatric and Neonatal Critical Care Specialty Transport.

Abstract Objective. Nearly 200,000 pediatric and neonatal transports occur in the United States each year with some patients requiring tracheal intubation. First-pass intubation rates in both pediatric and adult transport literature are variable as are the factors that influence intubation success. This study sought to determine risk factors for failed tracheal intubation in neonatal and pediatric transport. Methods. A retrospective chart review was performed over a 2.5-year period. Data were collected from a hospital-based neonatal/pediatric critical care transport team that transports 2,500 patients annually, serving 12,000 square miles. Patients were eligible if they were transported and tracheally intubated by the critical care transport team. Patients were categorized into two groups for data analysis: (1) no failed intubation attempts and (2) at least one failed intubation attempt. Data were tabulated using Epi Info Version 3.5.1 and analyzed using SPSSv17.0. Results. A total of 167 patients were eligible for enrollment and were cohorted by age (48% pediatric versus 52% neonatal). Neonates were more likely to require multiple attempts at intubation when compared to the pediatric population (69.6% versus 30.4%, p = 0.001). Use of benzodiazepines and neuromuscular blockade was associated with increased successful first attempt intubation rates (p = 0.001 and 0.008, respectively). Use of opiate premedication was not associated with first-attempt intubation success. The presence of comorbid condition(s) was associated with at least one failed intubation attempt (p = 0.006). Factors identified with increasing odds of at least one intubation failure included, neonatal patients (OR 3.01), tracheal tube size ≤ 2.5 mm (OR 3.78), use of an uncuffed tracheal tube (OR 6.85), and the presence of a comorbid conditions (OR 2.64). Conclusions. There were higher rates of tracheal intubation failure in transported neonates when compared to pediatric patients. This risk may be related to the lack of benzodiazepine and neuromuscular blocking agents used to facilitate intubation. The presence of a comorbid condition is associated with a higher risk of tracheal intubation failure.

Immortalized chick embryo cell line adapted to serum-free growth conditions and capable of replicating human and reassortant H5N1 influenza strains for vaccine production.

The current process of influenza vaccine production can take 6-9 months and is dependent on the availability of embryonated eggs. Additionally, this process selects for receptor-binding variants with reduced antigenicity and requires significant downstream production for purification. We have established an immortalized chick embryo cell line, termed PBS-12SF, which is adapted to growth in serum free conditions, and is capable of replicating human and reassortant H5N1 influenza strains to high titers. In many cases, PBS-12SF cells produced higher growth titers of influenza virus than those of primary chick embryo kidney (CEK) cells, Madin-Darby Canine Kidney (MDCK) cells and African green monkey kidney cells (Vero). Additionally, in PBS-12SF cell cultures, influenza virus is released into the culture fluid without need for exogenous proteases, which can simplify downstream processing for vaccine production.

High titer growth of human and avian influenza viruses in an immortalized chick embryo cell line without the need for exogenous proteases.

The current method of growing influenza virus for vaccine production is through the use of embryonated chicken eggs. This manufacturing system yields a low concentration of virus per egg, requires significant downstream production for purification, and demands a considerable amount of time for production. We have demonstrated an immortalized chick embryo cell line, termed PBS-1, is capable of growing unmodified recent isolates of human and avian influenza A and B viruses to extremely high titers. In many cases, PBS-1 cells out perform primary chick embryo kidney (CEK) cells, Madin-Darby Canine Kidney (MDCK) cells and African green monkey kidney cells (Vero) in growth of recent influenza isolates. PBS-1 cells are free of any exogenous agents, are non-tumorigenic, and are readily adaptable to a variety of culture conditions, including growth on microcarrier beads. Influenza viruses grown in PBS-1 cells are released into the culture fluid without the need for exogenous proteases, thus simplifying downstream processing. In addition to offering a significant improvement in vaccine production, PBS-1 cells should prove valuable in diagnostics and as a cell line of choice for influenza virus research.