Outcomes From Referrals and Unscheduled Visits From Community Emergency Departments to a Regional Pediatric Emergency Department in Canada.

OBJECTIVES: Existing pediatric literature describing repeat visits to the emergency department (ED) for the same medical complaint has yet to report on patient flow patterns from general EDs (GEDs) to a pediatric ED (PED). We sought to characterize the population of patients who are treated in a GED and subsequently present to a PED for further care. METHODS: We conducted a retrospective cohort study reviewing all pediatric visits (age < 17 y) at 5 GEDs in Vancouver. Our primary outcome measure was the proportion of visits with a subsequent visit to a PED (<7 days) during the 2012 to 2013 fiscal year. Secondary outcomes included reasons for PED consultation, the clinical services accessed, and disposition at the PED. RESULTS: During the study period, 581 (3.3%) of the 17,824 children seen at GEDs subsequently presented to the PED within 7 days. The top 3 diagnoses among these were fracture, viral infection, and musculoskeletal complaints. Of the 581 children with a visit to the PED, 180 (31.0%) were referred to the PED for a consultation, whereas the rest were family initiated. Referred visits were more frequently associated with pediatric subspecialist consultation than family-initiated visits (45.0% vs 19.5%, P < 0.01). The referred group more frequently resulted in a surgical procedure (13.9% vs 2.5%, P < 0.01) or hospital admission (51.7% vs 8.7%, P < 0.01). CONCLUSIONS: Knowing the proportion, management, and outcomes of children who are treated in a GED and subsequently at a PED may provide an important quality measure and opportunities to improve the management of common pediatric emergencies in the community.

Targeting tumor hypoxia: suppression of breast tumor growth and metastasis by novel carbonic anhydrase IX inhibitors.

Carbonic anhydrase IX (CAIX) is a hypoxia and HIF-1-inducible protein that regulates intra- and extracellular pH under hypoxic conditions and promotes tumor cell survival and invasion in hypoxic microenvironments. Interrogation of 3,630 human breast cancers provided definitive evidence of CAIX as an independent poor prognostic biomarker for distant metastases and survival. shRNA-mediated depletion of CAIX expression in 4T1 mouse metastatic breast cancer cells capable of inducing CAIX in hypoxia resulted in regression of orthotopic mammary tumors and inhibition of spontaneous lung metastasis formation. Stable depletion of CAIX in MDA-MB-231 human breast cancer xenografts also resulted in attenuation of primary tumor growth. CAIX depletion in the 4T1 cells led to caspase-independent cell death and reversal of extracellular acidosis under hypoxic conditions in vitro. Treatment of mice harboring CAIX-positive 4T1 mammary tumors with novel CAIX-specific small molecule inhibitors that mimicked the effects of CAIX depletion in vitro resulted in significant inhibition of tumor growth and metastasis formation in both spontaneous and experimental models of metastasis, without inhibitory effects on CAIX-negative tumors. Similar inhibitory effects on primary tumor growth were observed in mice harboring orthotopic tumors comprised of lung metatstatic MDA-MB-231 LM2-4(Luc+) cells. Our findings show that CAIX is vital for growth and metastasis of hypoxic breast tumors and is a specific, targetable biomarker for breast cancer metastasis.