Prevented harm and cost avoidance with pharmacist intervention while utilizing a discharge medication reconciliation tool.

PURPOSE: The aim of this study was to determine prevented harm and cost avoidance following pharmacist intervention utilizing a discharge medication reconciliation tool. METHODS: A retrospective chart review was conducted to identify patients with pharmacist-initiated, provider-accepted discharge medication reconciliation interventions completed at a community teaching hospital in January 2021. Investigators assigned the discrepancies targeted for intervention a National Coordinating Council for Medication Error Reporting and Prevention (NCC MERP) category, probability of harm, and calculated cost avoidance. The primary endpoint was the total cost avoidance associated with discharge medication reconciliation. RESULTS: Pharmacists intervened 190 times in January 2021, avoiding an estimated $46,958 to $231,032 in cost. High-risk medications were associated with $33,920 to $147,203 in cost avoidance. The 3 high-risk therapeutic classes associated with the highest cost avoidance were insulin ($16,738-$70,793), antithrombotics ($13,884-$60,016), and opioids ($2,638-$11,834). CONCLUSION: Targeted pharmacist discharge medication reconciliation and related interventions avoid significant cost and patient harm.

Optical attenuation coefficient in individual ZnO nanowires.

Attenuation coefficient measurements for the propagation of bandedge luminescence are made on individual ZnO nanowires by combining the localized excitation capability of a scanning electron microscope (SEM) with near-field scanning optical microscopy (NSOM) to record the distribution and intensity of wave-guided emission. Measurements were made for individual nanostructures with triangular cross-sections ranging in diameter from 680 to 2300 nm. The effective attenuation coefficient shows an inverse dependence on nanowire diameter (d(-1)), indicating scattering losses due to non-ideal waveguiding behavior.

Pilot and feasibility study: prospective proteomic profiling of mammary epithelial cells from high-risk women provides evidence of activation of pro-survival pathways.

Normal mammary gland homeostasis requires the coordinated regulation of protein signaling networks. However, we have little prospective information on whether activation of protein signaling occurs in premalignant mammary epithelial cells, as represented by cells with cytological atypia from women who are at high risk for breast cancer. This information is critical for understanding the role of deregulated signaling pathways in the initiation of breast cancer and for developing targeted prevention and/or treatment strategies for breast cancer in the future. In this pilot and feasibility study, we examined the expression of 52 phosphorylated, total, and cleaved proteins in 31 microdissected Random Periareolar Fine Needle Aspiration (RPFNA) samples by high-throughput Reverse Phase Protein Microarray. Unsupervised hierarchical clustering analysis indicated the presence of four clusters of proteins that represent the following signaling pathways: (1) receptor tyrosine kinase/Akt/mammalian target of rapamycin (RTK/Akt/mTOR), (2) RTK/Akt/extracellular signal-regulated kinase (RTK/Akt/ERK), (3) mitochondrial apoptosis, and (4) indeterminate. Clusters 1 through 3 comprised moderately to highly expressed proteins, while Cluster 4 comprised proteins that are lowly expressed in a majority of RPFNA samples. Our exploratory study showed that the interlinked components of mitochondrial apoptosis pathway are highly expressed in all mammary epithelial cells obtained from high-risk women. In particular, the expression levels of anti-apoptotic Bcl-xL and pro-apoptotic Bad are positively correlated in both non-atypical and atypical samples (unadjusted P < 0.0001), suggesting a delicate balance between the pro-apoptotic and anti-apoptotic regulation of cell proliferation during the early steps of mammary carcinogenesis. Our feasibility study suggests that the activation of key proteins along the RTK/Akt pathway may tip this balance to cell survival. Taken together, our results demonstrate the feasibility of mapping proteomic signaling networks in limited RPFNA samples obtained from high-risk women and the promise of developing rational drug targets or preventative strategies for breast cancer in future proteomic studies with a larger cohort of high-risk women.

Nitrogen deposition sources and patterns in the Greater Yellowstone Ecosystem determined from ion exchange resin collectors, lichens, and isotopes.

Over the past century, atmospheric nitrogen deposition (Ndep) has increased across the western United States due to agricultural and urban development, resulting in degraded ecosystem quality. Regional patterns of Ndep are often estimated by coupling direct measurements from large-scale monitoring networks and atmospheric chemistry models, but such efforts can be problematic in the western US because of complex terrain and sparse sampling. This study aimed not only to understand Ndep patterns in mountainous ecosystems but also to investigate whether isotope values of lichens and throughfall deposition can be used to determine Ndep sources, and serve as an additional tool in ecosystem health assessments. We measured Ndep amounts and δ15N in montane conifer forests of the Greater Yellowstone Ecosystem using canopy throughfall and bulk monitors and lichens. In addition, we examined patterns of C:N ratios in lichens as a possible indicator of lichen physiological condition. The isotopic signature of δ15N of Ndep helps to discern emission sources, because δ15N of NOx from combustion tends to be high (-5 to +25‰) while NHx from agricultural sources tends to be comparatively low (-40 to -10‰). Summertime Ndep increased with elevation and ranged from 0.26 to 1.66 kg ha-1. Ndep was higher than expected in remote areas. The δ15N values of lichens were typically -15.3 to -10‰ suggesting agriculture as a primary emission source of deposition. Lichen %N, δ15N and C:N ratios can provide important information about Ndep sources and patterns over small spatial scales in complex terrain.

Fluoxetine induces cytotoxic endoplasmic reticulum stress and autophagy in triple negative breast cancer.

AIM: To investigate the mechanism of action of lipophilic antidepressant fluoxetine (FLX) in representative molecular subtypes of breast cancer. METHODS: The anti-proliferative effects and mechanistic action of FLX in triple-negative (SUM149PT) and luminal (T47D and Au565) cancer cells and non-transformed MCF10A were investigated. Reverse phase protein microarray (RPPM) was performed with and without 10 µmol/L FLX for 24 and 48 h to determine which proteins are significantly changed. Viability and cell cycle analysis were also performed to determine drug effects on cell growth. Western blotting was used to confirm the change in protein expression examined by RPPM or pursue other signaling proteins. RESULTS: The FLX-induced cell growth inhibition in all cell lines was concentration- and time-dependent but less pronounced in early passage MCF10A. In comparison to the other lines, cell growth reduction in SUM149PT coincided with significant induction of endoplasmic reticulum (ER) stress and autophagy after 24 and 48 h of 10 µmol/L FLX, resulting in decreased translation of proteins along the receptor tyrosine kinase/Akt/mammalian target of rapamycin pathways. The increase in autophagy marker, cleaved microtubule-associated protein 1 light chain 3, in SUM149PT after 24 h of FLX was likely due to increased metabolic demands of rapidly dividing cells and ER stress. Consequently, the unfolded protein response mediated by double-stranded RNA-dependent protein kinase-like ER kinase resulted in inhibition of protein synthesis, growth arrest at the G1 phase, autophagy, and caspase-7-mediated cell death. CONCLUSION: Our study suggests a new role for FLX as an inducer of ER stress and autophagy, resulting in death of aggressive triple negative breast cancer SUM149PT.

Comparison of Random Periareolar Fine Needle Aspirate versus Ductal Lavage for Risk Assessment and Prevention of Breast Cancer.

Random periareolar fine needle aspiration (RPFNA) and ductal lavage (DL) are research techniques developed to (1) assess short-term breast cancer risk in asymptomatic women who are at increased risk for breast cancer and (2) track cytological response to risk reduction strategies. RPFNA and DL provide minimally invasive methods to repeatedly sample epithelial cells and research tools to investigate the biological origins of breast cancer in high-risk women. This review gives an overview of the strengths and limitations of both RPFNA and DL for risk assessment and breast cancer prevention in asymptomatic high-risk women.

Ductal carcinoma in situ: challenges, opportunities, and uncharted waters.

Ductal carcinoma in situ (DCIS) is a heterogeneous group of diseases that differ in biology and clinical behavior. Until 1980, DCIS represented less than 1% of all breast cancer cases. With the increased utilization of mammography, DCIS now accounts for 15% to 25% of newly diagnosed breast cancer cases in the United States. Although our ability to detect DCIS has radically improved, our understanding of the pathophysiology and factors involved in its progression to invasive carcinoma is still poorly defined. In many patients, DCIS will never progress to invasive breast cancer and these women are overtreated. In contrast, some DCIS cases are clinically aggressive and the women may be undertreated. We are able to define some of the predictors of aggressive DCIS compared with DCIS of low malignant potential. However, our ability to risk-stratify DCIS is still in its infancy. Clinical risk factors that predict aggressive disease and increased risk of local recurrence include young age at diagnosis, large lesion size, high nuclear grade, comedo necrosis, and involved margins. Treatment factors such as wider surgical margins and radiation therapy reduce the risk of local recurrence. DCIS represents a key intermediate in the stepwise progression to malignancy, but not all aggressive breast cancers appear to have a DCIS intermediate, notably within triple-negative breast cancer. Ongoing studies of the genetic and epigenetic alterations in precancerous breast lesions (atypia and DCIS) as well as the breast microenvironment are important for developing effective early detection and individualized targeted prevention.

Accuracy of ultrasonography and mammography in predicting pathologic response after neoadjuvant chemotherapy for breast cancer.

BACKGROUND: Neoadjuvant chemotherapy reduces tumor size before surgery in women with breast cancer. The aim of this study was to assess the ability of mammography and ultrasound to predict residual tumor size following neoadjuvant chemotherapy. METHODS: In a retrospective review of consecutive breast cancer patients treated with neoadjuvant chemotherapy, residual tumor size estimated by diagnostic imaging was compared with residual tumor size determined by surgical pathology. RESULTS: One hundred ninety-two patients with 196 primary breast cancers were studied. Of 104 tumors evaluated by both imaging modalities, ultrasound was able to size 91.3%, and mammography was able to size only 51.9% (chi(2)P < .001). Ultrasound also was more accurate than mammography in estimating residual tumor size (62 of 104 [59.6%] vs 33 of 104 [31.7%], P < .001). There was little difference in the ability of mammography and ultrasound to predict pathologic complete response (receiver operating characteristic, 0.741 vs 0.784). CONCLUSIONS: Breast ultrasound was more accurate than mammography in predicting residual tumor size following neoadjuvant chemotherapy. The likelihood of a complete pathologic response was 80% when both imaging modalities demonstrated no residual disease.