Implementation of a Pharmacist-Driven Penicillin and Cephalosporin Allergy Assessment Tool: A Pilot Evaluation.

OBJECTIVE: Penicillin is the most commonly reported drug allergy despite the low incidence of true immune-mediated reactions. Penicillin allergy labels have been shown to lead to significant patient, institutional, and public health care consequences. This project's purpose was to improve quality of care for patients with penicillin and cephalosporin allergies, admitted to a pediatric institution, by implementation of a pharmacist-driven allergy assessment tool. METHODS: A group of physicians, pharmacists, and a nurse collaborated for process development. The process was standardized, and a tool was created to assist with assessments. Pharmacists were educated on the importance of this quality improvement project and trained on the process and tool used. Implementation occurred on March 2, 2020. RESULTS: During the 3-month implementation period, 40 patients were admitted with a documented penicillin or cephalosporin allergy. Of these, 11 patients (27.5%) received an allergy assessment. Most were identified as having low or moderate risk of recurrent reaction with future use of a penicillin or cephalosporin agent (81.8%), and 2 patients (18.2%) were de-labeled from their documented allergy. CONCLUSIONS: Penicillin and cephalosporin allergy assessment implementation at a pediatric hospital was successfully implemented and allowed for identification and initiation of future quality improvement projects including implementation of penicillin skin testing and direct oral amoxicillin challenges.

Improving Guideline-Based Streptococcal Pharyngitis Testing: A Quality Improvement Initiative.

BACKGROUND AND OBJECTIVES: Acute pharyngitis is a common diagnosis in ambulatory pediatrics. The Infectious Diseases Society of America (IDSA) clinical practice guideline for group A streptococcal (GAS) pharyngitis recommends strict criteria for GAS testing to avoid misdiagnosis and unnecessary treatment of children who are colonized with group A Streptococcus. We sought to improve adherence to the IDSA guideline for testing and treatment of GAS pharyngitis in a large community pediatrics practice. METHODS: The Model for Improvement was used, and iterative Plan-Do-Study-Act cycles were completed. The quality improvement project was approved for American Board of Pediatrics Part 4 Maintenance of Certification credit. Interventions included provider education, modification of existing office procedure, communication strategies, and patient and family education. Outcomes were assessed by using statistical process control charts. RESULTS: An absolute reduction in unnecessary GAS testing of 23.5% (from 64% to 40.5%) was observed during the project. Presence of viral symptoms was the primary reason for unnecessary testing. Appropriate antibiotic use for GAS pharyngitis did not significantly change during the project; although, inappropriate use was primarily related to unnecessary testing. At the end of the intervention period, the majority of providers perceived an improvement in their ability to communicate with families about the need for GAS pharyngitis testing and about antibiotic use. CONCLUSIONS: The majority of GAS pharyngitis testing in this practice before intervention was inconsistent with IDSA guideline recommendations. A quality improvement initiative, which was approved for Part 4 Maintenance of Certification credit, led to improvement in guideline-based testing for GAS pharyngitis.

Compliance differences between patients with breast cancer in university and county hospitals.

PURPOSE: Compliance with recommended breast cancer treatments outside the context of a clinical trial differs from that in study populations. The purpose of this study was to examine differences in compliance of breast cancer treatments. PATIENTS AND METHODS: We conducted a retrospective review of 529 patients treated at 2 teaching hospitals in the same city from 2003 to 2006. Compliance with adjuvant therapy recommendations and choice of breast-conserving operations were compared between a university hospital (UH) and a county hospital (CH). RESULTS: The 2 populations demonstrated similar rates of breast conservation (72% vs. 69%). Although use of radiation therapy at the CH was acceptable (82%), patients at the UH were more likely to undergo radiation therapy (95%). The use of hormone therapy was similar at the UH and the CH (> 93%). Patients were more likely to follow physician recommendations for adjuvant chemotherapy at the UH (89%) compared with the CH (70%; P = .0005). Univariate analysis revealed that patient age, tumor size, stage, grade, and estrogen receptor status were all significant predictors of patient compliance with chemotherapy. Preoperative chemotherapy was a strong predictor of patient compliance with chemotherapy (P < .0001). In multivariate analysis, all of the factors predictive of patient compliance in univariate analysis remained significant except tumor grade. CONCLUSION: Preoperative chemotherapy appeared to increase compliance compared with adjuvant chemotherapy in the CH population. Compared with national standards, breast-conserving operations and radiation therapy compliance can be accomplished in an acceptable percentage of underinsured patients.

The effect of dedicated breast surgeons on the short-term outcomes in breast cancer.

OBJECTIVE: The impact of breast surgeons on short-term outcomes in breast cancer care was compared at a single institution. SUMMARY BACKGROUND DATA: Many studies have demonstrated a correlation between high procedural volume and lower mortality in technically challenging procedures. Breast cancer treatment has significant impact on patient behavior, psychology, and appearance. Therefore, evaluation of outcomes cannot be limited to only operative mortality and morbidity. We sought to determine the effect of dedicated breast cancer surgeons on short-term outcomes at a single institution. METHODS: Wishard Memorial Hospital is the county hospital affiliated with the Indiana University School of Medicine. A retrospective review was performed of all patients from January 1, 1997, to February 28, 2006. On July 1, 2003, coverage for the Breast Clinic was changed from general surgeons (G) to breast surgeons (B). There were 596 patients included in the study period. RESULTS: There were no significant differences in patient demographics or disease characteristics between the 2 time periods. For early stage (stage I and II) breast cancer, a higher percentage of patients underwent breast conservation in the breast surgeon period than in the general surgeon period (P = 0.04). Lumpectomy margins in breast conserving operations during the G period were more often positive (P = 0.025) or close (<1 mm) (P = 0.01). Similarly, the rates of re-excision lumpectomy were also significantly lower during the B period (21% vs. 39%, respectively, P = 0.01). Breast surgeons were more likely to perform the sentinel node procedure (P = 0.001). There were no differences in the use of adjuvant chemotherapy and radiation therapy. The use of hormonal manipulation, however, was significantly higher in the B group than in the G group (P < 0.0002). CONCLUSIONS: Surgeons specialized in diseases of the breast demonstrate significant improvement in short-term outcomes associated with breast cancer treatment at a single institution. The differences identified cannot be attributed to differences in institutional function, patient population, surgeon case volume, or on the influence of nonsurgeon physicians.

Involvement of MMPs in the outward remodeling of collateral mesenteric arteries.

Persistent elevation in shear stress within conduit or resistance arteries causes structural luminal expansion, which serves to normalize shear stress while maintaining increased flow to the downstream vasculature. Although it is known that this adaptation involves cellular proliferation and remodeling of the extracellular matrix, the specific cellular events underlying these responses are poorly understood. Matrix metalloproteinases (MMPs) contribute to extensive remodeling of the extracellular matrix in conduit vessels and vein grafts exposed to high flow. However, involvement of MMPs in remodeling of small muscular collateral arteries, which are exposed to less severe increases in shear stress, has not been tested. We utilized an established model of outward remodeling in mesenteric collateral arteries to determine whether MMPs were upregulated during the remodeling response and to test whether MMP activity was required for luminal expansion. By 4 days, MMP-2 and membrane type 1 MMP (MT1-MMP), but not MMP-9, protein levels were significantly elevated in collateral arteries, as assessed by gelatin zymography and immunostaining. MMP-2 and MT1-MMP proteins, together with their respective transcriptional activators c-Jun and Egr-1 were localized predominantly to the smooth muscle layer of the collateral arteries. The general MMP inhibitor doxycycline prevented luminal expansion of collateral arteries but did not affect the endothelial cell proliferative or medial growth responses. In conclusion, this study provides evidence that MMP-2 and MT1-MMP are upregulated in collateral arteries exposed to elevated shear stress and that MMP activity is essential for the full remodeling response that leads to outward luminal expansion.

The role of the renin-angiotensin system and oxidative stress in spontaneously hypertensive rat mesenteric collateral growth impairment.

Recent clinical and animal studies have shown that collateral artery growth is impaired in the presence of vascular risk factors, including hypertension. Available evidence suggests that angiotensin-converting enzyme inhibitors (ACEI) promote collateral growth in both hypertensive humans and animals; however, the specific mechanisms are not established. This study evaluated the hypothesis that collateral growth impairment in hypertension is mediated by excess superoxide produced by NAD(P)H oxidase in response to stimulation of the ANG II type 1 receptor. After ileal artery ligation, mesenteric collateral growth did not occur in untreated, young, spontaneously hypertensive rats. Significant luminal expansion occurred in collaterals of spontaneously hypertensive rats treated with the superoxide dismutase mimetic tempol, the NAD(P)H oxidase inhibitor apocynin, and the ACEI captopril, but not ANG II type 1 (losartan) or type 2 (PD-123319) receptor blockers. The ACEI enalapril produced equivalent reduction of arterial pressure as captopril but did not promote luminal expansion. This suggests the effects of captopril on collateral growth might result from its antioxidant properties. RT-PCR demonstrated that ANG II type 1 receptor and angiotensinogen expression was reduced in collaterals of untreated rats. This local suppression of the renin angiotensin system provides a potential explanation for the lack of effect of enalapril and losartan on collateral growth. The results demonstrate the capability of antioxidant therapies, including captopril, to reverse impaired collateral artery growth and the novel finding that components of the local renin angiotensin system are naturally suppressed in collaterals.

Benign glandular inclusions a rare cause of a false positive sentinel node.

An 84-year-old female underwent a wire-guided lumpectomy and sentinel lymph node biopsy. Two sentinel nodes were identified and sent for immediate pathological evaluation. One of the nodes was reported as "glandular epithelium consistent with metastatic adenocarcinoma." Permanent sections of the sentinel node initially considered positive revealed glandular structures primarily within the fibrous capsule of the involved lymph node. These glands were lined by tall columnar epithelial cells, which had cilia on the luminal surface and did not show significant cytologic atypia. The limitations of intra-operative evaluation of sentinel nodes make differentiation of uncommon pathology difficult. A conservative approach should be taken with these lesions as permanent sections will often elucidate the diagnosis.

Role of calmodulin methionine residues in mediating productive association with cardiac ryanodine receptors.

Calmodulin (CaM) binds to the cardiac ryanodine receptor Ca2+ release channel (RyR2) with high affinity and may act as a regulatory channel subunit. Here we determine the role of CaM Met residues in the productive association of CaM with RyR2, as assessed via determinations of [3H]ryanodine and [35S]CaM binding to cardiac muscle sarcoplasmic reticulum (SR) vesicles. Oxidation of all nine CaM Met residues abolished the productive association of CaM with RyR2. Substitution of the COOH-terminal Mets of CaM with Leu decreased the extent of CaM inhibition of cardiac SR (CSR) vesicle [3H]ryanodine binding. In contrast, replacing the NH2-terminal Met of CaM with Leu increased the concentration of CaM required to inhibit CSR [3H]ryanodine binding but did not alter the extent of inhibition. Site-specific substitution of individual CaM Met residues with Gln demonstrated that Met124 was required for both high-affinity CaM binding to RyR2 and for maximal CaM inhibition. These results thus identify a Met residue critical for the productive association of CaM with RyR2 channels.

Calmodulin oxidation and methionine to glutamine substitutions reveal methionine residues critical for functional interaction with ryanodine receptor-1.

Calmodulin (CaM) binds to the skeletal muscle ryanodine receptor Ca(2+) release channel (RyR1) with high affinity, and it may act as a Ca(2+)-sensing subunit of the channel. Apo-CaM increases RyR1 channel activity, but Ca(2+)-CaM is inhibitory. Here we examine the functional effects of CaM oxidation on RyR1 regulation by both apo-CaM and Ca(2+)-CaM, as assessed via determinations of [(3)H]ryanodine and [(35)S]CaM binding to skeletal muscle sarcoplasmic reticulum vesicles. Oxidation of all nine CaM Met residues abolished functional interactions of CaM with RyR1. Incomplete CaM oxidation, affecting 5-8 Met residues, increased the CaM concentration required to modulate RyR1, having a greater effect on the apo-CaM species. Mutating individual CaM Met residues to Gln demonstrated that Met-109 was required for apo-CaM activation of RyR1 but not for Ca(2+)-CaM inhibition of the channel. Furthermore, substitution of Gln for Met-124 increased the apo- and Ca(2+)-CaM concentrations required to regulate RyR1. These results thus identify Met residues critical for the productive association of CaM with RyR1 channels and suggest that oxidation of CaM may contribute to altered regulation of sarcoplasmic reticulum Ca(2+) release during oxidative stress.