Background The high prevalence of medication use increases the potential for medication overdoses, especially among children. Purpose This paper describes the burden of unintentional pediatric ...medication overdoses in order to target new prevention efforts. Methods Data were analyzed in 2007 and 2008 from the National Electronic Injury Surveillance System, collected January 1, 2004, through December 31, 2005, to estimate the number of emergency department visits resulting from unintentional medication overdoses among children aged ≤18 years in the U.S. These data were analyzed by patient demographics, overdose cause, and implicated products, and compared to visits for nonpharmaceutical consumer product poisonings. Results Based on 3034 cases, an estimated 71,224 emergency department visits for medication overdoses were made annually by children aged ≤18 years, representing 68.9% of emergency department visits for unintentional pediatric poisonings. The rate of unintentional poisonings from medications was twice the rate of those from nonpharmaceutical consumer products (9.2 visits per 10,000 individuals per year 95% CI=7.3, 11.0 vs 4.2 per 10,000 individuals per year 95% CI=3.3, 5.0). Four fifths (82.2%) of visits for medication overdoses were from unsupervised ingestions (children accessing medications on their own); medication errors and misuse resulted in 14.3% of visits. Most visits (81.3%) involved children aged ≤5 years, and commonly available over-the-counter medications were implicated in one third (33.9%) of visits. Conclusions Medication overdoses among children, notably unsupervised ingestions, represent a substantial burden in terms of emergency department visits and hospitalizations. New efforts to prevent pediatric medication overdoses are needed.
Background & Aims: Celiac disease is an immune-mediated enteropathy triggered by gliadin, a component of the grain protein gluten. Gliadin induces an MyD88-dependent zonulin release that leads to ...increased intestinal permeability, a postulated early element in the pathogenesis of celiac disease. We aimed to establish the molecular basis of gliadin interaction with intestinal mucosa leading to intestinal barrier impairment. Methods: α-Gliadin affinity column was loaded with intestinal mucosal membrane lysates to identify the putative gliadin-binding moiety. In vitro experiments with chemokine receptor CXCR3 transfectants were performed to confirm binding of gliadin and/or 26 overlapping 20mer α-gliadin synthetic peptides to the receptor. CXCR3 protein and gene expression were studied in intestinal epithelial cell lines and human biopsy specimens. Gliadin-CXCR3 interaction was further analyzed by immunofluorescence microscopy, laser capture microscopy, real-time reverse-transcription polymerase chain reaction, and immunoprecipitation/Western blot analysis. Ex vivo experiments were performed using C57BL/6 wild-type and CXCR3−/− mouse small intestines to measure intestinal permeability and zonulin release. Results: Affinity column and colocalization experiments showed that gliadin binds to CXCR3 and that at least 2 α-gliadin 20mer synthetic peptides are involved in this binding. CXCR3 is expressed in mouse and human intestinal epithelia and lamina propria. Mucosal CXCR3 expression was elevated in active celiac disease but returned to baseline levels following implementation of a gluten-free diet. Gliadin induced physical association between CXCR3 and MyD88 in enterocytes. Gliadin increased zonulin release and intestinal permeability in wild-type but not CXCR3−/− mouse small intestine. Conclusions: Gliadin binds to CXCR3 and leads to MyD88-dependent zonulin release and increased intestinal permeability.
In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are ...posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.
The past decade has brought increasing coverage in the medical literature and lay media of the potential association between low-level radiation from diagnostic imaging and an increased lifetime ...cancer risk. Both physician and public opinion increasingly favour a greater discussion of benefit and risk with patients and their families when such imaging is being considered. Particular attention has been directed towards CT, its use in children and the emergency department setting. We will review the evolution of radiation dose awareness and knowledge among emergency physicians (EPs) alongside the parallel increase in public awareness. We will then discuss expectations for risk disclosure and the challenges faced by EPs and radiologists as we strive to provide this in a clinically balanced and meaningful way.
We evaluated the clinical impact of germ-line BRCA1/2 mutations in patients with epithelial ovarian cancer (EOC) on responses to first and subsequent lines of chemotherapy, treatment-free interval ...(TFI) between each line of therapy, and overall survival (OS).
Twenty-two EOC patients with germ-line BRCA1 or BRCA2 mutations (BRCA-positive) were selected from our database and matched (1:2) with 44 nonhereditary EOC controls (defined by no associated personal history of breast cancer and no family history of breast and ovarian cancer or an uninformative BRCA mutation test) for stage, histologic subtype, age, and year of diagnosis. All patients received primary platinum-based chemotherapy. Statistical comparisons included responses after first-, second-, and third-line treatment (chi(2)/Fisher's exact test) and median OS (Kaplan-Meier method/log-rank test).
Compared with controls, BRCA-positive patients had higher overall (95.5% v 59.1%; P = .002) and complete response rates (81.8% v 43.2%; P = .004) to first line treatment, higher responses to second and third line platinum-based chemotherapy (second line, 91.7% v 40.9% P = .004; third line, 100% v 14.3% P = .005) and longer TFIs. A significant improvement in median OS in BRCA-positive patients compared with controls was observed from both time of diagnosis (8.4 v 2.9 years; P < .002) and time of first relapse (5 v 1.6 years; P < .001). BRCA status, stage, and length of first response were independent prognostic factors from time of first relapse.
BRCA-positive EOC patients have better outcomes than nonhereditary EOC patients. There exists a clinical syndrome of BRCAness that includes serous histology, high response rates to first and subsequent lines of platinum-based treatment, longer TFIs between relapses, and improved OS.
Computed tomography (CT) imaging of children is increasing in emergent settings without an understanding of parental knowledge of potential cancer risks. In children with head injuries, our primary ...objective was to determine the proportion of parents who were aware of the potential of CT to increase a child's lifetime risk of malignancy. We also examined willingness to proceed with recommended CT after risk disclosure and preference to be informed of potential risks.
This was a prospective cross-sectional survey of parents whose children presented to a tertiary care pediatric emergency department with a head injury. Survey questions were derived and validated by using expert opinion, available literature, and pre- and pilot testing of questions with the target audience.
Of the 742 enrolled parents, 454 (61.2%) were female and 594 (80.0%) were aged 31 to 50 years. Importantly, 357 (46.8%) were aware of the potential for an increased lifetime malignancy risk from CT. Before risk estimate provision, the proportion of parents "very willing/willing" to proceed with head CT was 90.4%; after disclosure, willingness decreased to 69.6% (P < .0001), and 42 (5.6%) would refuse the CT. Of note, 673 (90.3%) wished to be informed of potential malignancy risks.
Approximately half of the participating parents were aware of the potential increased lifetime malignancy risk associated with head CT imaging. Willingness to proceed with CT testing was reduced after risk disclosure but was a significant barrier for a small minority of parents. Most parents wanted to be informed of potential malignancy risks before proceeding with imaging.
This retrospective cohort study aims to determine the epidemiology of iron deficiency among extreme preterm neonates and the association of iron-deficient status during the NICU stay with ...neurodevelopmental outcomes at 18−24 months. Neonates ≤29 weeks gestational age (GA) born between June 2016 and December 2019, who received routine iron supplementation were enrolled. Iron deficiency was defined as reticulocyte−hemoglobin (Ret-Hb) levels ≤ 29 pg at 36 weeks corrected age. A subcohort of neonates completed standardized developmental assessment at 18−24 months corrected age. Significant neurodevelopmental impairment (sNDI) was defined as either Bayley Scales of Infant Development score < 70 or cerebral palsy or blindness or hearing aided. Among a cohort of 215 neonates GA 25.8 (1.7) weeks, birthweight 885 (232) g, prevalence of iron deficiency was 55%, 21%, 26%, and 13%, in neonates <24 weeks, 24−25 + 6 weeks, 26−27 + 6 weeks, and ≥ 28 weeks GA, respectively. Male sex and receipt of corticosteroid therapy were associated with iron-deficiency. In the subcohort analysis (n = 69), there was no statistically significant association between Ret-Hb levels at 36 weeks corrected age and the risk of sNDI OR 0.99 (95% CI 0.85−1.2). Male infants and those who received postnatal corticosteroids are likely to have iron-limited erythropoiesis at corrected term despite routine iron-supplementation; however, low Ret-Hb levels during the neonatal period were not associated with significant neurological disability in early childhood.
Summary
Nest boxes are commonly installed to support hollow‐using species where the abundance of hollow‐bearing trees is deficient. Recent studies have provided equivocal evidence about the ...effectiveness of nest box projects and have highlighted significant management costs associated with some projects. We document the functionality of 303 nest boxes installed across five different community‐led projects in southern Australia for periods of 10–25 years. As expected, we found that nest boxes lost functionality over time. However, 60% remained functional to support the Brush‐tailed Phascogale (Phascogale tapoatafa) and the Sugar Glider (Petaurus breviceps) after almost 20 years. Years installed, method of nest box attachment and tree species influenced whether boxes remained functional. Nest box construction material changed over time so could not be assessed specifically. When inspected in a single year, the Brush‐tailed Phascogale occupied 9% of functional boxes and another 48% contained their nests. The Sugar Glider occupied 15% of functional boxes and another 22% contained their nests. These values suggest the nest box installations were highly effective for these species, although more detailed study is needed to understand what contribution these installations have made to support the local populations. Maintenance of most nest boxes occurred twice a year in the first five years after installation, but many received no maintenance for periods of three years, and some 10–15 years, before our census. Our findings suggest that infrequent maintenance by community groups can sustain nest box projects over periods of several decades. Research into employing nest boxes as a management tool in Australia is still in its infancy. Further studies are needed to resolve factors that limit their effectiveness.
Falls are a major health concern for older adults with Parkinson’s disease (PD). This study was designed to examine differences in falls risk and its relation to changes in the average and ...variability (i.e. intra-individual variability) of reaction time (RT), finger tapping, standing balance and walking between healthy older adults and persons with PD. Thirty-nine adults with PD (70.0 ± 8.1 years) and 29 healthy older adults (66.8 ± 10.4 years) participated in this study. Falls risk (using the physiological profile assessment), gait, RT, balance and tapping responses were assessed for all persons. Results demonstrated that individuals with PD exhibited a greater risk of falling coupled with a general slowing of motor function covering declines in walking, RT and finger tapping. In addition, the movement responses of the PD group were more variable than the healthy older adults. Correlation results revealed group differences with regards to the neuromotor measures which were significantly correlated with falls risk. For the PD group, gait measures were highly correlated with their falls risk while, for the healthy older adults, falls risk was linked to balance measures even though PD persons had increased sway. Overall, persons with PD were at greater falls risk, moved slower and with increased variability compared to the healthy older adults. Further, while there are some similarities between the two groups in terms of those measures related to falls risk, there were also several differences which highlight that persons with PD can have different risk factors for falling compared to healthy adults of similar age.
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