A Process Improvement Project to Increase Compliance With Cephalosporin-based Surgical Antimicrobial Prophylaxis in Children With Non-severe Penicillin Allergies.

BACKGROUND/PURPOSE: Cephalosporins are considered safe and first-line prophylaxis in children with non-severe penicillin allergies. However, use of second-line agents is common and is primarily driven by poor allergic response documentation and misunderstanding of cross-reactivity risk. The goal of this project was to improve compliance with cephalosporin prophylaxis through improved documentation and targeted educational efforts. METHODS: A multidisciplinary working group including representatives from allergy, surgery, infectious disease, and pharmacy developed staged interventions to facilitate compliance with cephalosporin prophylaxis. These included: (1) caregiver outreach to clarify incomplete allergy documentation, (2) a decision-support algorithm for prophylaxis use in penicillin-allergic patients, (3) standardized educational resources for surgical faculty and rotating trainees, (4) email reminders with prophylaxis recommendations sent out prior to scheduled cases, and (5) EMR-based decision support during antibiotic ordering. Rates of complete allergy documentation and cephalosporin utilization were compared for general surgery procedures between a 12-month pre-intervention and 14-month post-intervention period. RESULTS: 578 patients with penicillin allergies recorded in the EMR were included (301 pre-intervention and 277 post-intervention), 54.0% of which received prophylaxis. Compared to the pre-intervention period, complete documentation of allergic reactions increased from 57.1% to 84.2% (p < 0.001) following implementation of all interventions. Appropriate prophylaxis utilization increased from 34.5% to 88.5% following implementation of all interventions (p < 0.001), and evidence of a stepwise increase in appropriate utilization was evident with each intervention stage. Persistent compliance failures during the post-implementation period were most commonly associated with urgent and emergent add-on cases. No adverse events or allergic responses were reported before or after project implementation. CONCLUSIONS: Compliance with cephalosporin prophylaxis significantly improved following a multidisciplinary effort targeting education, allergy documentation, and clinical support at the point of care. Ongoing efforts include postoperative audits within 24 h for noncompliant cases in order to identify barriers and improve compliance for urgent and emergent add-on cases. LEVEL OF EVIDENCE: III. TYPE OF STUDY: Prospective.

The effects of prism adaptation on daily life activities in patients with visuospatial neglect: a systematic review.

Studies that have investigated prism adaptation (PA) effects on symptoms of visuospatial neglect have primarily used neuropsychological tests as outcome measures. An important question that remains to be answered is whether PA effects translate into improvements in patients' daily life activities. In the present review, we examined systematically the evidence for the effect of PA treatment on daily life activities in patients with neglect. Two authors independently assessed the methodological quality of 25 intervention and 1 follow-up studies using validated scales. PA effects were evaluated for reading/writing, activities of daily living (ADL) direct tests, ADL questionnaires, and navigation tests. Studies were evaluated as being of excellent (n = 1), good (n = 12), fair (n = 10), or poor (n = 3) quality. Among the 26 articles, a total of 32 measurements showed significant PA effects (one measurement from a study of excellent quality, 17 from studies of good quality, 10 from studies of fair quality, four from studies of poor quality), whereas non-significant effects were found in 15 measurements (two from a study of excellent quality, three from studies of good quality, eight from studies of fair quality, two from studies of poor quality). There is some evidence suggesting that PA can improve daily functioning, particularly as measured by reading/writing and ADL direct tests. The impact of several variables on PA effects should be investigated further including sample heterogeneity and time since injury.

The influence of Trp53 in the dose response of radiation-induced apoptosis, DNA repair and genomic stability in murine haematopoietic cells.

Apoptotic and DNA damage endpoints are frequently used as surrogate markers of cancer risk, and have been well-studied in the Trp53+/- mouse model. We report the effect of differing Trp53 gene status on the dose response of ionizing radiation exposures (0.01-2 Gy), with the unique perspective of determining if effects of gene status remain at extended time points. Here we report no difference in the dose response for radiation-induced DNA double-strand breaks in bone marrow and genomic instability (MN-RET levels) in peripheral blood, between wild-type (Trp53+/+) and heterozygous (Trp53+/-) mice. The dose response for Trp53+/+ mice showed higher initial levels of radiation-induced lymphocyte apoptosis relative to Trp53+/- between 0 and 1 Gy. Although this trend was observed up to 12 hours post-irradiation, both genotypes ultimately reached the same level of apoptosis at 14 hours, suggesting the importance of late-onset p53-independent apoptotic responses in this mouse model. Expected radiation-induced G1 cell cycle delay was observed in Trp53+/+ but not Trp53+/-. Although p53 has an important role in cancer risk, we have shown its influence on radiation dose response can be temporally variable. This research highlights the importance of caution when using haematopoietic endpoints as surrogates to extrapolate radiation-induced cancer risk estimation.

Development of a new computerized prism adaptation procedure for visuo-spatial neglect.

BACKGROUND: Prism adaptation (PA) is a promising rehabilitation technique for visuo-spatial neglect. However, PA effects are often inconsistent across studies and the clinical application of this technique has been limited. The purpose of the present studies was to validate an easily standardized, home-friendly, and game-like PA technique (Peg-the-Mole) with healthy participants as a first step toward clinical development. NEW METHOD: In study 1, we used Peg-the-Mole with 32 participants wearing prism or sham goggles to investigate whether this procedure can induce significant after-effects on midline judgment and pointing tasks. In study 2, we compared Peg-the-Mole to a typical PA protocol in 42 participants for after-effects and level of enjoyment and to determine if the after-effects generalize to a throwing task. RESULTS AND COMPARISON WITH EXISTING METHOD: Study 1 showed that Peg-the-Mole induced significant after-effects on all outcome measures. Study 2 demonstrated that after-effects induced by Peg-the-Mole were equivalent to those induced by the typical PA procedure on all outcome measures. Peg-the-Mole was rated as more enjoyable than the typical procedure. CONCLUSIONS: Peg-the-Mole is a new computerized PA procedure that can be easily standardized and successfully used to induce significant after-effects. The present findings demonstrate that alterations can be made to the typical PA procedure to make it easier to use and more enjoyable, factors that could increase treatment availability, adherence and intensity.

Radiation-induced DNA damage and the relative biological effectiveness of 18F-FDG in wild-type mice.

Clinically, the most commonly used positron emission tomography (PET) radiotracer is the glucose analog 2-[(18)F] fluoro-2-deoxy-D-glucose ((18)F-FDG), however little research has been conducted on the biological effects of (18)F-FDG injections. The induction and repair of DNA damage and the relative biological effectiveness (RBE) of radiation from (18)F-FDG relative to 662 keV γ-rays were investigated. The study also assessed whether low-dose radiation exposure from (18)F-FDG was capable of inducing an adaptive response. DNA damage to the bone marrow erythroblast population was measured using micronucleus formation and lymphocyte γH2A.X levels. To test the RBE of (18)F-FDG, mice were injected with a range of activities of (18)F-FDG (0-14.80 MBq) or irradiated with Cs-137 γ-rays (0-100 mGy). The adaptive response was investigated 24h after the (18)F-FDG injection by 1 Gy in vivo challenge doses for micronucleated reticulocyte (MN-RET) formation or 1, 2 and 4 Gy in vitro challenges doses for γH2A.X formation. A significant increase in MN-RET formation above controls occurred following injection activities of 3.70, 7.40 or 14.80 MBq (P < 0.001) which correspond to bone marrow doses of ~35, 75 and 150 mGy, respectively. Per unit dose, the Cs-137 radiation exposure induced significantly more damage than the (18)F-FDG injections (RBE = 0.79 ± 0.04). A 20% reduction in γH2A.X fluorescence was observed in mice injected with a prior adapting low dose of 14.80 MBq (18)F-FDG relative to controls (P < 0.019). A 0.74 MBq (18)F-FDG injection, which gives mice a dose approximately equal to a typical human PET scan, did not cause a significant increase in DNA damage nor did it generate an adaptive response. Typical (18)F-FDG injection activities used in small animal imaging (14.80 MBq) resulted in a decrease in DNA damage, as measured by γH2A.X formation, below spontaneous levels observed in control mice. The (18)F-FDG RBE was <1.0, indicating that the mixed radiation quality and/or low dose rate from PET scans is less damaging than equivalent doses of gamma radiation.

Low-dose radiation from 18F-FDG PET does not increase cancer frequency or shorten latency but reduces kidney disease in cancer-prone Trp53+/- mice.

There is considerable interest in the health effects associated with low-level radiation exposure from medical imaging procedures. Concerns in the medical community that increased radiation exposure from imaging procedures may increase cancer risk among patients are confounded by research showing that low-dose radiation exposure can extend lifespan by increasing the latency period of some types of cancer. The most commonly used radiopharmaceutical for positron emission tomography (PET) scans is 2-[(18)F] fluoro-2-deoxy-d-glucose ((18)F-FDG), which exposes tissue to a low-dose, mixed radiation quality: 634 keV ß+ and 511 keV γ-rays. The goal of this research was to investigate how modification of cancer risk associated with exposure to low-dose ionising radiation in cancer-prone Trp53+/- mice is influenced by radiation quality from PET. At 7-8 weeks of age, Trp53+/- female mice were exposed to one of five treatments: 0 Gy, 10 mGy γ-rays, 10 mGy (18)F-FDG, 4 Gy γ-rays, 10 mGy (18)F-FDG + 4 Gy γ-rays (n > 185 per group). The large 4-Gy radiation dose significantly reduced the lifespan by shortening the latency period of cancer and significantly increasing the number of mice with malignancies, compared with unirradiated controls. The 10 mGy γ-rays and 10 mGy PET doses did not significantly modify the frequency or latency period of cancer relative to unirradiated mice. Similarly, the PET scan administered prior to a large 4-Gy dose did not significantly modify the latency or frequency of cancer relative to mice receiving a dose of only 4 Gy. The relative biological effectiveness of radiation quality from (18)F-FDG, with respect to malignancy, is approximately 1. However; when non-cancer endpoints were studied, it was found that the 10-mGy PET group had a significant reduction in kidney lesions (P < 0.021), indicating that a higher absorbed dose (20 ± 0.13 mGy), relative to the whole-body average, which occurs in specific tissues, may not be detrimental.

Quantifying murine bone marrow and blood radiation dose response following (18)F-FDG PET with DNA damage biomarkers.

The purpose of this study was to quantify the poorly understood radiation doses to murine bone marrow and blood from whole-body fluorine 18 ((18)F)-fluorodeoxyglucose (FDG) positron emission tomography (PET), by using specific biomarkers and comparing with whole body external low dose exposures. Groups of 3-5 mice were randomly assigned to 10 groups, each receiving either a different activity of (18)F-FDG: 0-37MBq or whole body irradiated with corresponding doses of 0-300mGy X-rays. Blood samples were collected at 24h and at 43h for reticulocyte micronucleus assays and QPCR analysis of gene expression in peripheral blood leukocytes. Blood and bone marrow dose estimates were calculated from injected activities of (18)F-FDG and were based on a recommended ICRP model. Doses to the bone marrow corresponding to 33.43mGy and above for internal (18)F-FDG exposure and to 25mGy and above for external X-ray exposure, showed significant increases in radiation-induced MN-RET formation relative to controls (P<0.05). Regression analysis showed that both types of exposure produced a linear response with linear regression analysis giving R(2) of 0.992 and 0.999 for respectively internal and external exposure. No significant difference between the two data sets was found with a P-value of 0.493. In vivo gene expression dose-responses at 24h for Bbc3 and Cdkn1 were similar for (18)F-FDG and X-ray exposures, with significant modifications occurring for doses over 300mGy for Bbc3 and at the lower dose of 150mGy for Cdkn1a. Both leucocyte gene expression and quantification of MN-RET are highly sensitive biomarkers for reliable estimation of the low doses delivered in vivo to, respectively, blood and bone marrow, following (18)F-FDG PET.