Retrospective Review for Medication Dose Errors in Pediatric Emergency Department Medication Orders That Bypassed Pharmacist Review.

OBJECTIVE: To identify and evaluate dose errors on medication orders that bypassed pharmacist verification in a pediatric emergency department (PED). METHODS: Descriptive, retrospective study about dose errors in an academic PED over 1 year. A report of automatically verified orders (those that bypassed pharmacist verification) was obtained from the electronic medical record. Potential medication dose errors were defined as those greater than 20% above or below standard dose ranges by age or weight. A retrospective chart review was performed for all identified dose errors. For orders deemed erroneous, additional metrics collected included order time of day and day of week and provider training level. RESULTS: A total of 46,185 medication orders were placed; 32,928 (71%) bypassed pharmacist review. Altogether, 676 orders (2%) were outside standard dose ranges. Ondansetron represented 569 of the 676 orders; most were doses rounded down to 4 mg and technically qualifying as underdoses, but were attributed to practice variance and not further analyzed. The number of orders deemed potentially erroneous was 107: most were wrong dose (75 overdose and 21 underdose), 5 were wrong patient, and 6 were wrong formulation. Ibuprofen, benzodiazepine, and corticosteroid orders had the most errors. No errors resulted in identifiable harm to the patient: 49 were near misses, and 47 reached the patient with no evident harm. CONCLUSIONS: The overall number of dose errors in autoverified orders was low. Certain medications or ordering modalities may be targeted to enhance patient safety and satisfaction.

Mitigating the impact of COVID-19 on oncology: Clinical and operational lessons from a prospective radiation oncology cohort tested for COVID-19.

BACKGROUND AND PURPOSE: The COVID-19 pandemic warrants operational initiatives to minimize transmission, particularly among cancer patients who are thought to be at high-risk. Within our department, a multidisciplinary tracer team prospectively monitored all patients under investigation, tracking their test status, treatment delays, clinical outcomes, employee exposures, and quarantines. MATERIALS AND METHODS: Prospective cohort tested for SARS-COV-2 infection over 35 consecutive days of the early pandemic (03/19/2020-04/22/2020). RESULTS: A total of 121 Radiation Oncology patients underwent RT-PCR testing during this timeframe. Of the 7 (6%) confirmed-positive cases, 6 patients were admitted (4 warranting intensive care), and 2 died from acute respiratory distress syndrome. Radiotherapy was deferred or interrupted for 40 patients awaiting testing. As the median turnaround time for RT-PCR testing decreased from 1.5 (IQR: 1-4) to ≤1-day (P < 0.001), the median treatment delay also decreased from 3.5 (IQR: 1.75-5) to 1 business day (IQR: 1-2) [P < 0.001]. Each patient was an exposure risk to a median of 5 employees (IQR: 3-6.5) through prolonged close contact. During this timeframe, 39 care-team members were quarantined for a median of 3 days (IQR: 2-11), with a peak of 17 employees simultaneously quarantined. Following implementation of a "dual PPE policy," newly quarantined employees decreased from 2.9 to 0.5 per day. CONCLUSION: The severe adverse events noted among these confirmed-positive cases support the notion that cancer patients are vulnerable to COVID-19. Active tracking, rapid diagnosis, and aggressive source control can mitigate the adverse effects on treatment delays, workforce incapacitation, and ideally outcomes.

Periconceptional undernutrition of ewes impairs glucose tolerance in their adult offspring.

Maternal undernutrition throughout pregnancy can have long-term effects on the health of adult offspring. Undernutrition around the time of conception alters growth, metabolism, and endocrinology of the sheep fetus, but the impact on offspring after birth is largely unknown. We determined the effect of maternal periconceptional undernutrition in sheep on glucose tolerance in the offspring before and after puberty. Undernourished (UN) ewes were fed individually to maintain weight loss of 10-15% bodyweight from 61 d before until 30 d after mating. Offspring (24 UN, 30 control) underwent an i.v. glucose tolerance test at 4 and 10 mo of age. Glucose tolerance was similar in both groups at 4 mo. Insulin area under the curve increased by 33% between 4 and 10 mo (101 +/- 8 versus 154 +/- 12 ng x min x mL(-1), p < 0.0001). At 10 mo, UN offspring had a 10% greater glucose area under the curve than controls (809 +/- 22 versus 712 +/- 20 mM x min, p < 0.01), a reduced first phase insulin response (p = 0.003) which was particularly apparent in females and in singletons, and a decreased insulin:glucose ratio (p = 0.01). We conclude that maternal undernutrition around the time of conception results in impaired glucose tolerance in postpubertal offspring.

Flow does not alter eNOS phosphoryation at Ser1179 or Thr495 in preconstricted mouse mesenteric arteries.

In arteries, endothelium-dependent vasodilatory agonists and flow-induced shear stress cause vasodilation largely by activation of the endothelial enzyme eNOS, which generates nitric oxide that relaxes vascular smooth muscle. Agonists activate eNOS in part through increased phosphorylation at Ser1179 and decreased phosphorylation at Thr495. We previously found that preconstriction of intact, isolated mouse mesenteric arteries with phenylephrine also caused increased Ser1179 and decreased Thr495 eNOS phosphorylation, and sequential treatment with the vasodilatory agonist acetylcholine did not cause any further change in phosphorylation at these sites, despite producing vasodilation. The present study tests the hypothesis that luminal flow in these arteries preconstricted with phenylephrine also produces vasodilation without phosphorylation changes at these sites. First-order mesenteric arteries, isolated from male C57/BL6 mice (7-20 weeks of age) anesthetized with pentobarbital (50 mg/kg, i.p.), were cannulated, pressurized, and treated with stepped increases in luminal flow (15-120 µL/min). Flow resulted in dilation that plateaued at ~60 µL/min (31.3 ± 3.0% dilation) and was significantly (P < 0.001) NOS-dependent at all flow rates (determined by 10-4 mol/L L-NAME treatment). In separate arteries, preconstriction with phenylephrine (10-5 mol/L) resulted in increased eNOS phosphorylation at Ser1179 (P < 0.05) and decreased phosphorylation at Thr495, but subsequent flow at 60 µL/min for 5 or 15 min did not cause further changes in phosphorylation, despite causing dilation. Thus, flow-induced dilation does not require changes in these eNOS phosphorylation sites beyond those induced by alpha1-adrenergic stimulation with phenylephrine, indicating that eNOS is activated by other mechanisms during acute flow-induced dilation of preconstricted arteries.

Alpha(1)-adrenergic-mediated eNOS phosphorylation in intact arteries.

Activation of arterial smooth muscle alpha(1)-adrenergic receptors results in vasoconstriction, as well as a secondary release of nitric oxide and slow vasodilation, presumably through gap junction communication from smooth muscle to endothelium. We hypothesized that this slow vasodilation is due to activation of eNOS through phosphorylation at Ser1179 and dephosphorylation at Thr495. Phosphorylation was measured by western blot using mouse mesenteric arteries that were cannulated and pressurized (75 mm Hg) and treated either by 1) 5 min of phenylephrine superfusion (10(-5)M) (PE5), 2) 15 min of phenylephrine (PE15), 3) 15 min phenylephrine followed by acetylcholine (10(-4)M) (PE+ACh), or 4) 20 min time control with no treatment (NT) [4-5 arteries pooled per treatment per blot; 5 blots performed]. These treatments allowed correlation between vasomotor changes, namely maximal constriction (PE5), slow vasodilation (PE15), and maximal dilation (PE+ACh), and relative phosphorylation changes. Phosphorylation of eNOS at Ser1179 was increased relative to NT by more than 2-fold at PE5 and remained similarly increased at PE15 and PE+ACh. Phosphorylation of eNOS at Thr495 was less in all treatments relative to NT, but not significantly. Treatment with L-NAME (10(-4)M) or endothelial denudation indicated that the slow dilation in response to phenylephrine was completely due to nitric oxide synthase and was endothelial dependent. These results indicate that eNOS phosphorylation at Ser1179 occurs before the slow dilation and is not actively involved in this vasodilation or dilation to acetylcholine, but may play a permissive role in eNOS activation by other mechanisms. It is not yet known what mechanism is responsible for Ser1179 phosphorylation with phenylephrine stimulation.

Pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a devastating disease with significant disability and mortality, and it has much higher prevalence than previously thought. During the past 15 years, we have witnessed remarkable advances in our understanding of pathogenesis, in diagnostic process and in the development of disease-specific treatments for PAH. Nowadays, the diagnosis is more clearly defined, non-invasive markers of disease severity can be widely applied, and finally we can adopt evidence-based treatment. Newer drugs availability has resulted in radical change in the management of this disease. The article reviews established approaches to evaluation and treatment of this disorder.