Antibiotics prior to age 2 years have limited association with preschool growth trajectory.

BACKGROUND: Prior studies of early antibiotic use and growth have shown mixed results, primarily on cross-sectional outcomes. This study examined the effect of oral antibiotics before age 24 months on growth trajectory at age 2-5 years. METHODS: We captured oral antibiotic prescriptions and anthropometrics from electronic health records through PCORnet, for children with ≥1 height and weight at 0-12 months of age, ≥1 at 12-30 months, and ≥2 between 25 and 72 months. Prescriptions were grouped into episodes by time and by antimicrobial spectrum. Longitudinal rate regression was used to assess differences in growth rate from 25 to 72 months of age. Models were adjusted for sex, race/ethnicity, steroid use, diagnosed asthma, complex chronic conditions, and infections. RESULTS: 430,376 children from 29 health U.S. systems were included, with 58% receiving antibiotics before 24 months. Exposure to any antibiotic was associated with an average 0.7% (95% CI 0.5, 0.9, p < 0.0001) greater rate of weight gain, corresponding to 0.05 kg additional weight. The estimated effect was slightly greater for narrow-spectrum (0.8% [0.6, 1.1]) than broad-spectrum (0.6% [0.3, 0.8], p < 0.0001) drugs. There was a small dose response relationship between the number of antibiotic episodes and weight gain. CONCLUSION: Oral antibiotic use prior to 24 months of age was associated with very small changes in average growth rate at ages 2-5 years. The small effect size is unlikely to affect individual prescribing decisions, though it may reflect a biologic effect that can combine with others.

Clinical Characterization of Children Presenting to the Hospital with Enterovirus D68 Infection During the 2014 Outbreak in St. Louis.

BACKGROUND: The largest known outbreak of enterovirus D68 (EV-D68) infections occurred during 2014. The goal of our study is to characterize the illness severity and clinical presentation of children infected with EV-D68 in comparison to non-EV-D68-human rhinoviruses/enteroviruses (HRV/EV). METHOD: Our study is a retrospective analysis of severity level, charges and length of stay of children who presented to St. Louis Children's Hospital from August 8, 2014 to October 31, 2014 and tested positive for EV-D68 in comparison to non-EV-D68-HRV/EV-infected patients. Chart review was performed for all EV-D68-infected patients and age and severity matched non-EV-D68-HRV/EV-infected patients. RESULT: There was a striking increase in hospital census in August of 2014 in our hospital with simultaneous increase in the number of patients with EV-D68 infection. There was no significant difference in severity of illness, length of stay or total charges between EV-D68-infected and non-EV-D68-HRV/EV-infected children. EV-D68 infection was characterized by presenting complaints of difficulty breathing (80%) and wheezing (67%) and by findings of tachypnea (65%), wheezing (71%) and retractions (65%) on examination. The most common interventions were albuterol (79%) and corticosteroid (68%) treatments, and the most common discharge diagnosis was asthma exacerbation (55%). CONCLUSION: EV-D68 caused a significant outbreak in 2014 with increased hospital admissions and associated increased charges. There was no significant difference in severity of illness caused by EV-D68 compared with non-EV-D68-HRV/EV infections suggesting that the impact from EV-D68 was because of increased number of infected children presenting to the hospital and not necessarily due to increased severity of illness.

An evolving paradigm for the workup and management of high-risk cutaneous squamous cell carcinoma.

BACKGROUND: No established standard of care exists for aggressive cutaneous squamous cell carcinoma (CSCC). OBJECTIVE: We sought to establish an aggressive CSCC management protocol by reviewing high-risk CSCC (HCSCC) and very high-risk CSCC (VCSCC) cases at our institution. METHODS: This was a retrospective review of all CSCC cases treated at our institution. RESULTS: A total of 27 patients were identified of 1591 cases treated between 2000 and 2011. Four patients with HCSCC received surgery alone and 1 received surgery and radiation. All remain disease free (median follow-up 5 years). Among patients with VCSCC, 4 received surgery alone: 1 (25%) showing a complete response and 3 (75%) showing disease progression. Eleven received surgery and radiation: 4 (36.4%) with complete response (median follow-up 3 years) and 7 (63.6%) with disease progression (median time to recurrence 6 months). Six received surgery and cetuximab: 3 (50%) had a complete response (median follow-up 3 years), 2 (33%) had disease progression, and 1 (14%) could not be assessed because of inability to tolerate infusions. One patient received surgery, cetuximab, and radiation, and remains disease-free after 4 years. LIMITATIONS: Lack of randomization, blinding, a true control arm, or standardization of treatment protocols are limitations. CONCLUSIONS: Patients with very HCSCC may have improved outcomes with surgery and adjuvant cetuximab.

The role of targeted molecular inhibitors in the management of advanced nonmelanoma skin cancer.

Surgical treatment remains the standard of care for nonmelanoma skin cancer and is successful for the vast majority of patients with these tumors. The treatment of patients with metastatic or unresectable nonmelanoma skin cancer, however, has until recently been based solely on traditional methods of chemotherapy and radiation. However, these methods have high rates of treatment failure, morbidity, and mortality, and alternative treatment modalities for patients with aggressive or advanced disease are needed. As in other areas of cancer therapeutics, recent research elucidating the molecular basis of cancer development, and the subsequent arrival of targeted molecular inhibitors for cancer therapy, have been met with much excitement. In this review, we seek to illuminate recent developments and future possibilities in the use of targeted molecular inhibitors for treatment of advanced squamous cell carcinoma, basal cell carcinoma, and dermatofibrosarcoma protuberans.

Product mass transfer resistance directly determined during freeze-drying cycle runs using tunable diode laser absorption spectroscopy (TDLAS) and pore diffusion model.

The pore diffusion model is used to express the dry layer mass transfer resistance, [Formula: see text], as a function of the ratio r(e)/?, where r(e) is the effective pore radius and ? is the tortuosity factor of the dry layer. Using this model, the effective pore radius of the dry layer can be estimated from the sublimation rate and product temperature profiles measured during primary drying. Freeze-drying cycle runs were performed using the LyoStar II dryer (FTS Systems), with real-time sublimation rate profiles during freeze drying continuously measured by tunable diode laser absorption spectroscopy (TDLAS). The formulations chosen for demonstration of the proposed approach include 5% mannitol, 5% sucrose, 5% lactose, 3% mannitol plus 2% sucrose, and a parenteral nutrition formulation denoted VitaM12. The three different methods used for determination of the product resistance are: (1) Using both the sublimation rate and product temperature profiles, (2) using the sublimation rate profile alone, and (3) using the product temperate profile alone. Unlike the second and third methods, the computation procedure of first method does not need solution of the complex heat and mass transfer equations.