Initial Employment Plans of PharmD Graduates from Ten Public Colleges/Schools of Pharmacy, 2018-2022.

OBJECTIVE: Since 2009, the Big Ten Pharmacy Assessment Collaborative has surveyed their Doctor of Pharmacy (PharmD) graduates regarding their first employment plans. The current study updates the results from 2013-2017, since which the nationwide demand for pharmacists decreased, then increased again due to COVID-19. METHODS: Quantitative first-position employment data from 2018-2022 were tracked among 6687 Big Ten PharmD graduates. Outcomes included job/residency/fellowship placement; satisfaction with placement; salary; time spent searching; and perceived difficulty finding placement. RESULTS: Over the study period, 5276 usable surveys were received (survey participation rate 79%). Respondents who reported applying for employment (2699) spent nearly 3 months searching for a position, although 64% had received employment offers before graduation. Annual salaries in pharmacy positions of at least 32 h per week (excluding residencies or fellowships) trended downward from $113,754 in 2018 to $99,175 in 2021, rebounding to $114,097 in 2022. Approximately 42% of respondents who applied for jobs reported difficulty finding a position in 2018 and 2019, decreasing to 20% in 2022. In total, 73% of respondents were satisfied with the offers they received, with 72% finding positions in their preferred job setting. An average of 57% applied for residencies from 2018 to 2022, nearly 10% higher than 2013-2017, with 76% of applicants matching. An additional 19% planned to pursue additional academic degrees, fellowship training, or both. CONCLUSION: From 2018 to 2022, Big Ten PharmD graduates found pharmacy-related first positions to the same extent as did Big Ten PharmD graduates from 2013-2017, at similar salaries.

Moving AACP Curriculum Quality Survey Results from Good to Great.

Although the American Association of Colleges of Pharmacy (AACP) Curriculum Quality Surveys (CQS) are required for programs to distribute and utilize as part of accreditation standards, programs face challenges in survey administration and timing, interpreting data and results, and following up on action plans. Because the CQS surveys are standardized, they can allow for greater comparison among institutions, yet interpretation of the items can vary considerably. Programs have flexibility in determining samples for administration and timing of administration (ie, number of years), but some participants (such as preceptors) can suffer from survey overload if multiple institutions administer in the same year. Determining thresholds for action and providing feedback to stakeholders on improvements made based on data triangulations can be daunting. These are a few of the elements that programs must consider when determining their own approach to the AACP CQS. Thus, the purpose of this Commentary is to describe good practices for using the AACP CQS, discuss challenges associated with the surveys, and recommend how to move the utilization of the surveys from good to great.

Detection of Academic Early Warning Signs and Effective Intervention "Takes a Village".

Early intervention for students at risk of academic difficulty can be more effectively accomplished using a team-based approach that capitalizes on the expertise of many in a pharmacy education community. Authored by members of the Big Ten Alliance Pharmacy Assessment Collaborative, this commentary advocates for better integration of assessment professionals, pharmacy faculty, and student support services to capture academic, accountability, and behavior-related data that might signal student intellectual and/or behavioral challenges and manifest as marginal academic performance. Assessment professionals can assist with creating data dashboards/monitoring systems, recognizing trends within the data, refining formulas to identify at-risk students, and measuring the impact of interventions to determine which approaches positively and significantly influence outcomes. Effective early warning and intervention takes a village and should go beyond narrowly focused attempts that fail to account for the complexity of students as individuals or fail to acknowledge the multifaceted skill set students are expected to develop to become competent and responsible pharmacists.

Zn-based physiometacomposite nanoparticles: distribution, tolerance, imaging, and antiviral and anticancer activity.

The aim of this study was to investigate the distribution, tolerance, and anticancer and antiviral activity of Zn-based physiometacomposites (PMCs). Manganese, iron, nickel and cobalt-doped ZnO, ZnS or ZnSe were synthesized. Cell uptake, distribution into 3D culture and mice, and biochemical and chemotherapeutic activity were studied by fluorescence/bioluminescence, confocal microscopy, flow cytometry, viability, antitumor and virus titer assays. Luminescence and inductively coupled plasma mass spectrometry analysis showed that nanoparticle distribution was liver >spleen >kidney >lung >brain, without tissue or blood pathology. Photophysical characterization as ex vivo tissue probes and LL37 peptide, antisense oligomer or aptamer delivery targeting RAS/Ras binding domain (RBD) was investigated. Treatment at 25 µg/ml for 48 h showed ≥98-99% cell viability, 3D organoid uptake, 3-log inhibition of ß-Galactosidase and porcine reproductive respiratory virus infection. Data support the preclinical development of PMCs for imaging and delivery targeting cancer and infectious disease.

Preliminary evaluation of probiotic effects on gastrointestinal signs in dogs with multicentric lymphoma undergoing multi-agent chemotherapy: A randomised, placebo-controlled study.

BACKGROUND: Gastrointestinal (GI) toxicity is a major dose-limiting factor in dogs undergoing chemotherapy. A proposed mechanism of GI toxicity includes chemotherapy-driven GI dysbiosis. This study was designed to determine the effects of probiotic administration on GI side-effects in dogs receiving multi-agent chemotherapy. METHODS: Ten client-owned dogs with multicentric lymphoma were enrolled in a prospective, randomised, placebo-controlled single-blinded study. On the first day of the cyclophosphamide doxorubicin vincristine prednisone (CHOP)-based chemotherapy protocol, dogs were randomised to receive either daily oral probiotic at a dose of 200 × 109 cfu/10 kg (n = 5) or daily oral placebo (n = 5). Complete blood count, faecal score (FS), faecal microbiome analysis (qPCR) and adverse events scores were performed at baseline and on the day of each subsequent chemotherapy dose, as well as 3 days after doxorubicin (days 0, 7, 14, 21, 24 and 28). RESULTS: Overall, 40% of dogs had an abnormal GI microbiome at baseline, specifically decreased faecal C. hiranonis and Fusobacterium abundances. Dogs receiving probiotics had increased faecal Streptococcus (p = 0.02) and E. coli. (p = 0.01). No dogs receiving probiotics experienced diarrhoea (FS ≥ 3.5) compared to four of five receiving placebo. (F 2.895; p = 0.13). CONCLUSION: GI microbiome dysbiosis was common in this group of dogs with multicentric lymphoma. Probiotics were well-tolerated, with no negative side effects. Further studies are needed to explore broader microbiome and metabolome changes, as well as clinical benefit.

Adjuvant Sirolimus Does Not Improve Outcome in Pet Dogs Receiving Standard-of-Care Therapy for Appendicular Osteosarcoma: A Prospective, Randomized Trial of 324 Dogs.

PURPOSE: The mTOR pathway has been identified as a key nutrient signaling hub that participates in metastatic progression of high-grade osteosarcoma. Inhibition of mTOR signaling is biologically achievable with sirolimus, and might slow the outgrowth of distant metastases. In this study, pet dogs with appendicular osteosarcoma were leveraged as high-value biologic models for pediatric osteosarcoma, to assess mTOR inhibition as a therapeutic strategy for attenuating metastatic disease progression. PATIENTS AND METHODS: A total of 324 pet dogs diagnosed with treatment-naïve appendicular osteosarcoma were randomized into a two-arm, multicenter, parallel superiority trial whereby dogs received amputation of the affected limb, followed by adjuvant carboplatin chemotherapy ± oral sirolimus therapy. The primary outcome measure was disease-free interval (DFI), as assessed by serial physical and radiologic detection of emergent macroscopic metastases; secondary outcomes included overall 1- and 2-year survival rates, and sirolimus pharmacokinetic variables and their correlative relationship to adverse events and clinical outcomes. RESULTS: There was no significant difference in the median DFI or overall survival between the two arms of this trial; the median DFI and survival for standard-of-care (SOC; defined as amputation and carboplatin therapy) dogs was 180 days [95% confidence interval (CI), 144-237] and 282 days (95% CI, 224-383) and for SOC + sirolimus dogs, it was 204 days (95% CI, 157-217) and 280 days (95% CI, 252-332), respectively. CONCLUSIONS: In a population of pet dogs nongenomically segmented for predicted mTOR inhibition response, sequentially administered adjuvant sirolimus, although well tolerated when added to a backbone of therapy, did not extend DFI or survival in dogs with appendicular osteosarcoma.

CD4 and CD8 double-negative immunophenotype of thymoma-associated lymphocytes in a dog.

Persistent small-cell lymphocytosis in dogs with a concurrent mediastinal mass has been associated with both thymoma and small-cell lymphoma. In thymomas, neoplastic thymic epithelial cells induce overproduction and release of polyclonal lymphocytes, whereas thymic lymphoma results in thymic effacement by a clonal expansion of neoplastic lymphocytes and subsequent leukemic phase of lymphoma. Flow cytometry has been used to differentiate these 2 entities by immunophenotyping mediastinal mass aspirates. It has been reported that cases with mediastinal masses in which ≥ 10% of the associated small-cell lymphocytes were double positive for CD4 and CD8 were thymomas, whereas masses associated with < 10% were suggestive of lymphoma. We report a unique case of thymoma-associated lymphocytosis lacking the classic CD4+CD8+ immunophenotype. Our findings suggest that there may be more diversity in the thymoma-associated lymphocyte immunophenotype than has been identified previously; immunophenotyping alone might not be sufficient to differentiate thymic small-cell lymphoma from thymoma-associated lymphocytosis. In dogs with mediastinal masses and peripheral lymphocytosis, employing a variety of testing modalities to avoid misdiagnosis is prudent. These modalities include cytologic and/or histologic evaluation, immunophenotyping, and clonality assessment.

Carboplatin-induced myelosuppression as related to body weight in dogs.

Smaller dogs are known to have an increased risk of chemotherapy-induced myelosuppression for doxorubicin, mitoxantrone and melphalan. This retrospective study aimed to determine if dogs <15 kg and <10 kg experienced greater degrees of myelosuppression following treatment with carboplatin chemotherapy compared with dogs ≥15 kg. One hundred and one dogs treated with carboplatin for a variety of malignancies were retrospectively analysed. Eight dogs (61%) weighing <10 kg, three (38%) weighing 10 kg to <15 kg and 14 (17%) weighing ≥15 kg experienced a grade 3 or 4 neutropenia. Five dogs (38%) weighing <10 kg, two (25%) weighing 10 kg to <15 kg and 13 (16%) weighing ≥15 kg experienced a grade 3 or 4 thrombocytopenia. Dogs <10 kg were significantly more likely to develop a grade 3 or 4 neutropenia following carboplatin than dogs ≥10 kg (3.5 RR; 95% CI, 1.9-6.3; P < .001). Dogs <15 kg were also significantly more likely to develop a grade 3 or 4 neutropenia than dogs ≥15 kg (3 RR; 95% CI, 1.6-5.6; P = .004). Dogs <10 kg were significantly more likely to develop a grade 3 or 4 thrombocytopenia than those dogs ≥10 kg (2.5 RR; 95% CI, 1.1-5.6; P = .006). Hospitalization was significantly more likely for dogs <10 kg vs ≥10 kg (P = .014) as well as for dogs <15 kg vs ≥15 kg (P = .039). This study demonstrates an increased risk of carboplatin-induced myelosuppression in dogs <15 kg, and particularly those <10 kg. This information should be considered by clinicians when making decisions regarding the initial carboplatin dose for smaller canine patients, especially those <15 kg.

Translating Nanomedicine to Comparative Oncology-the Case for Combining Zinc Oxide Nanomaterials with Nucleic Acid Therapeutic and Protein Delivery for Treating Metastatic Cancer.

The unique anticancer, biochemical, and immunologic properties of nanomaterials are becoming a new tool in biomedical research. Their translation into the clinic promises a new wave of targeted therapies. One nanomaterial of particular interest are zinc oxide (ZnO) nanoparticles (NPs), which has distinct mechanisms of anticancer activity including unique surface, induction of reactive oxygen species, lipid oxidation, pH, and also ionic gradients within cancer cells and the tumor microenvironment. It is recognized that ZnO NPs can serve as a direct enzyme inhibitor. Significantly, ZnO NPs inhibit extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) associated with melanoma progression, drug resistance, and metastasis. Indeed, direct intratumoral injection of ZnO NPs or a complex of ZnO with RNA significantly suppresses ERK and AKT phosphorylation. These data suggest ZnO NPs and their complexes or conjugates with nucleic acid therapeutic or anticancer protein may represent a potential new strategy for the treatment of metastatic melanoma, and potentially other cancers. This review focuses on the anticancer mechanisms of ZnO NPs and what is currently known about its biochemical effects on melanoma, biologic activity, and pharmacokinetics in rodents and its potential for translation into large animal, spontaneously developing models of melanoma and other cancers, which represent models of comparative oncology.

Development and validation of a hemangiosarcoma likelihood prediction model in dogs presenting with spontaneous hemoabdomen: The HeLP score.

OBJECTIVE: To calculate a risk prediction model for hemangiosarcoma (HSA) diagnosis in dogs presenting with nontraumatic hemoabdomen. DESIGN: Retrospective multicenter observational cohort study enrolling dogs presented 2003-2016. SETTING: Five academic veterinary medical centers. ANIMALS: A total of 406 dogs with nontraumatic hemoabdomen as the presenting complaint that underwent surgical exploration or necropsy and received a histological diagnosis. Overall, 219 dogs from 3 centers provided the data for model construction, and 187 dogs from 2 centers provided the population for external validation. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: The risk score was modeled on 4 predictors: bodyweight (P = 0.01), total plasma protein (P < 0.01), platelet count (P < 0.01), and thoracic radiograph findings (P = 0.02). The incidence of HSA diagnosis was 36%, 76%, and 96% in the low risk (≤40), medium risk (41-55), and high risk (>55) score groups, respectively. The risk score AUROC was 0.85 (95% CI 0.79-0.90) on the construction population, and 0.77 (95% CI 0.70-0.84) on the validation population. CONCLUSIONS: The risk of HSA diagnosis in dogs presenting with nontraumatic hemoabdomen could be predicted using a simple risk score, which could aid in identification and treatment of dogs at lower risk for this diagnosis.

Receptor tyrosine kinase expression and phosphorylation in canine nasal carcinoma.

Preliminary studies have supported use of toceranib phosphate (Palladia®) in treatment of canine nasal carcinomas, though the mechanisms of its activity are unknown. This study evaluated sixteen canine nasal carcinoma and five normal nasal epithelium samples for expression and phosphorylation of known targets of toceranib [vascular endothelial growth factor receptor-2 (VEGR2), platelet derived growth factor alpha (PDGFR-α), platelet derived growth factor receptor beta (PDGFR-ß), and stem cell factor receptor (c-KIT)] and epidermal growth factor receptor 1 (EGFR1) using immunohistochemistry, RT-PCR and a receptor tyrosine kinase (RTK) phosphorylation panel. Protein for VEGFR2 was expressed in all carcinomas, PDGFR-α was noted in 15/16, whereas PDGFR-ß was detected in 3/16 samples, but showed significant stromal staining. Protein expression for c-KIT was present in 4/16 and EGFR1 was noted in 14/16 samples. Normal tissue showed variable protein expression of the RTKs. Messenger RNA for VEGFR2, PDGFR-ß, and c-KIT were noted in all samples. Messenger RNA for PDGFR-α and EGFR1 were detected in 15/16 samples. All normal nasal tissue detected messenger RNA. Phosphorylation of VEGFR2, PDGFR-α, PDGFR-ß and c-KIT was not observed in any carcinoma or normal nasal sample, but phosphorylation of EGFR1 was noted in 10/16 carcinoma and 3/5 normal samples. The absence of phosphorylated RTK targets of toceranib suggests any clinical effect of toceranib occurs through inhibition of alternative unidentified RTK pathways in canine nasal carcinomas. The observed protein and message expression and phosphorylation of EGFR1 in the nasal carcinoma samples merits further inquiry into EGFR1 as a therapeutic target for this cancer.

Metastatic intraocular hemangiopericytoma in a dog.

A 10-year-old Labrador Retriever who had been undergoing therapy for a recurrent hemangiopericytoma of the right flank presented to the Kansas State University Ophthalmology service for evaluation of a painful left eye. Examination revealed secondary glaucoma and irreversible blindness of the affected eye and multifocal chorioretinal lesions in the fellow eye. Therapeutic and diagnostic enucleation of the left eye was performed and histopathologic examination demonstrated the presence of a presumed metastatic spindle cell sarcoma. Further immunohistochemical staining confirmed the intraocular neoplasia to be metastatic spread from the previously removed flank mass. Rapid progression in size and number of chorioretinal lesions in the right eye was noted in the post-operative period until the patient was euthanized one month after surgery. This case report is the first to document intraocular metastasis of hemangiopericytoma in a veterinary patient.

Evaluation of Environmental Cytotoxic Drug Contamination in a Clinical Setting.

The use of cytotoxic drugs to treat neoplastic conditions is increasing in veterinary practices. Many agents have the potential to be genotoxic and evidence of exposure to cytotoxic drugs has been found in healthcare workers handling these pharmaceuticals. To date, limited contamination evaluations have been performed in veterinary practices. Evaluation for carboplatin contamination was performed at a veterinary teaching hospital involving twelve areas in the dispensary and treatment room. Detectable levels of platinum were found on the surface of the biological safety cabinet where drugs are transferred from vial to administration device. Results indicate contamination did occur and care must be taken during all phases of cytotoxic drug preparation and administration; precautionary procedures must be in place to limit the spread of surface contamination and personnel exposure.

Occurrence and Clinicopathologic Features of Splenic Neoplasia Based on Body Weight: 325 Dogs (2003-2013).

Medical records of 396 dogs undergoing splenectomy for treatment of a splenic mass or nodular disease were reviewed retrospectively. Overall distribution of histopathologic diagnosis and clinicopathologic features were evaluated for 325 dogs that met inclusion criteria. Dogs were dichotomized into two groups based on weight, with the statistically derived cutoff identified as 27.8 kg. Malignancy was diagnosed in 58% of dogs, with no difference between small (55%) and large (61%) dogs (P = .291). Overall, 32% of splenic masses were hemangiosarcoma (HSA), which comprised 25 and 39% of all masses in small and large dogs, respectively. The diagnosis of HSA, non-HSA malignancy, or benign splenic disease was significantly different between the groups (P = .019). Of malignant diagnoses, HSA comprised 46 and 65% of small and large dog splenic neoplasms, respectively (P = .009). In both groups, dogs with HSA were significantly more likely to have preoperative anemia, hemoabdomen, thrombocytopenia, and a blood transfusion, as compared to dogs with non-HSA malignancy or benign lesions. Overall, dogs had similar odds of having a malignant splenic lesion regardless of weight, but dogs ≤27.8 kg were significantly less likely to be diagnosed with HSA.

Regional Nodal Metastasis of Humeral Chondrosarcoma in a Dog.

A 6 yr old castrated male English springer spaniel was evaluated with a 1 mo history of progressive right forelimb lameness with recent swelling around the elbow joint. Physical examination findings included lameness of the right forelimb, muscle atrophy around the right shoulder, grade 2/6 heart murmur, and moderate dental disease. Results of a complete blood cell count and serum biochemical analysis were unremarkable with the exception of a mildly increased alkaline phosphatase (368 U/L; reference range, 128-328 U/L). Radiographs of the right elbow revealed a mixed lytic and proliferative osseous lesion most consistent with either neoplasia or infection. Thoracic radiographs and the echocardiogram were unremarkable. Fine-needle aspiration of the bone lesion was performed. The cytological diagnosis was chondrosarcoma. The right forelimb was amputated and the axillary lymph nodes were collected. Histopathological examination of the bone lesion and axillary lymph nodes revealed chondrosarcoma with metastasis to the lymph nodes. Lymph node metastasis of chondrosarcoma is rare and needs to be further evaluated as a prognostic indicator.

Treatment of a maxillary fibrosarcoma in an adult alpaca.

CASE DESCRIPTION: An approximately 5-year-old sexually intact male alpaca was evaluated because of a right-sided maxillary mass that had recurred after previous surgical debulking. CLINICAL FINDINGS: Clinical, radiographic, and CT examination revealed an approximately 1.5-cm-diameter soft tissue mass associated with expansile osteolysis of the maxillary alveolar bone, beginning at the level of the right maxillary third premolar tooth extending caudally to the level of the rostral roots of the second molar tooth. TREATMENT AND OUTCOME: Right partial maxillectomy was performed, and histologic examination revealed an incompletely excised fibrosarcoma with osseous metaplasia. External beam radiation therapy to the tumor bed was initiated 1 month after surgery. Computerized planning was performed, and a total radiation dose of 48 Gy was prescribed in eleven 4.4-Gy fractions. Follow-up CT evaluations 6 and 58 weeks after radiation therapy was completed revealed no evidence of tumor recurrence. No clinical evidence of tumor recurrence was detected through 110 weeks after radiation therapy. CLINICAL RELEVANCE: The oral fibrosarcoma in the alpaca described here was successfully treated with surgical excision and adjuvant radiation therapy, resulting in excellent quality of life of the treated animal.

Hospital hand hygiene compliance improves with increased monitoring and immediate feedback.

BACKGROUND: Health care-associated infections are serious complications impacting 2 million patients and accounting for approximately 100,000 deaths per year. In the present study, we evaluated the effectiveness of a new hand hygiene monitoring program (HHMP) and measured the sustainability of this effectiveness over a 1-year period. METHODS: The HHMP consisted of 4 key components: extensive education, conspicuous and visible monitors, immediate feedback concerning compliance to health care workers, and real-time data dissemination to leadership. The HHMP was implemented in 2 hospital care units. Two different, but similar, departments served as controls, and hand hygiene compliance was monitored via the "secret shopper" technique. All 4 departments were followed for 12 months. RESULTS: Both experimental departments showed statistically significant increases in hand hygiene compliance. Experimental department 1 increased compliance from 49% to an average of 90%, and experimental department 2 increased compliance from 60% to an average of 96%. Both experimental departments were able to sustain these results for at least 6 months. Compliance rates were significantly higher in the experimental departments compared with the control departments. No significant changes were seen in the control departments. CONCLUSIONS: These finding suggest that continuous monitoring by salient observers and immediate feedback are critical to the success of hand hygiene programs.

Intermittent single-agent doxorubicin for the treatment of canine B-cell lymphoma.

Canine B-cell lymphoma is a highly treatable disease, but cost and logistical factors may hamper an owner's ability to pursue treatment of their pet with this disease. The authors evaluated the use of single-agent doxorubicin in an intermittent fashion for efficacy in the treatment of this disease. Morphologic and clinical data were analyzed for prognostic significance. Eighteen dogs with B-cell lymphoma, all with multicentric disease, were enrolled. The overall complete response (CR) rate was 78%, median total doxorubicin remission time (TDR) was 80.5 days, and median overall survival (OS) was 169.5 days. The median number of doxorubicin doses administered was 4.5. First remission times were significantly affected by clinical stage and substage of disease. Outcome for the dogs in this study were similar to those previously reported for single-agent doxorubicin treatment. Additionally, the intermittent nature of the treatments made the described protocol more feasible for the owners who enrolled their pets in this study. Intermittent single-agent doxorubicin is not a substitute for multiagent chemotherapy protocols in the treatment of canine lymphoma; however, it is a reasonable alternative if the cost and time commitments are limiting factors for an owner.

Web-based documentation of clinical skills to assess the competency of veterinary students.

Kansas State University implemented a Web-based program to assess students' competency to perform technical skills during clinical rotations throughout the fourth year of the veterinary curriculum. The classes of 2009 and 2010 recorded a minimum number of procedures (104 and 103, respectively) from a menu of more than 220 recommended procedures. Procedures were categorized by species (small animal, equine, food animal) and disciplines (imaging, anesthesia, diagnostic medicine/necropsy). Ophthalmology was added as a fourth discipline for the class of 2010. Students recorded procedures into the Web-based system, including information about the patient, procedure performed, supervisor, and a self-assessment of performance. Faculty, staff, and house officers evaluated the procedures electronically by confirming that they witnessed the procedure and providing qualitative and written feedback. The class of 2009 recorded 18,492 procedures (M=171/student) and the class of 2010 recorded 16,935 procedures (M=158/student). Two students from each class (2009 and 2010) did not complete the minimum required skills during clinical rotations and returned to perform procedures immediately before (n=3) or immediately after (n=1) graduation to receive their diploma. The Web-based system captured a large number of assessments of technical competency performed in the clinical setting. The system provided students with formative feedback throughout the clinical year, ensured equitable distribution of procedural opportunities across the student body, and required minimal additional resources.