Evaluation of a Pharmacy Summer Camp to Recruit Students to the Field of Pharmacy.

OBJECTIVE: A 3-day pharmacy summer camp for high school and college students was implemented, which included active learning and information on the pharmacy curriculum, preparatory coursework, and the university community. The program served as a recruitment tool for participants to enter the pharmacy profession and our Doctor of Pharmacy program. Enrollment data from 4 cohorts (2016-2019) were examined, along with assessment data collected from 1 cohort (summer 2022). METHODS: Enrollment data were collected for the 194 participants from 2016 to 2019 to examine the number that applied to the university and to a pharmacy program. All participants from the summer 2022 cohort (n = 55) were asked to complete a knowledge assessment and survey after camp completion. The knowledge assessment contained items related to content covered in the camp. The survey used a self-report retrospective pre-and-post format to assess self-efficacy, and career and degree intentions. In addition, there were items asking participants to evaluate the camp, including 2 open-ended items. RESULTS: Data show that overall, 33% of past participants enrolled at the University at Buffalo, and 15% enrolled or intended to enroll in the School of Pharmacy and Pharmaceutical Sciences. There were 50 respondents to the evaluation survey (91% response rate). Scores on the knowledge assessment suggested participants understood the content. There were statistically significant increases from pre to post on the self-efficacy and intentions scales with the largest change in intentions to pursue a career in pharmacy and to pursue a degree in pharmacy at this university. On the evaluation, 90% agreed that they would recommend the camp to other students interested in pharmacy. Of the 30 comments regarding changes to improve the camp, 17 (57%) were related to including more interactive activities. CONCLUSION: Students who participated in a pharmacy hands-on educational camp demonstrated knowledge of and increased interest in the pharmacy profession.

Long-Term Risk of Death From Heart Disease Among Breast Cancer Patients.

Background: Most breast cancer patients die of non-cancer causes. The risk of death from heart disease, a leading cause of death, is unknown. The aim of this study is to characterize the long-term risk of fatal heart disease in breast cancer patients. Methods: This retrospective study used the Surveillance, Epidemiology, and End Results (SEER) database. Standard mortality ratios (SMR) were calculated for breast cancer patients diagnosed from 1992 to 2014. Patients were stratified by receipt of radiotherapy and/or chemotherapy, disease laterality, and diagnosis era. Hazard ratios (HRs) and odds ratios (ORs) were calculated to compare the risk of death from heart disease among other breast cancer patients. Results: There were 1,059,048 patients diagnosed with breast cancer from 1992 to 2014, of which 47,872 (4.6%) died from heart disease. The SMR for death from heart disease at 10+ years for patients who received only radiotherapy was 2.92 (95% CI 2.81-3.04, p < 0.001) and in patients who received only chemotherapy was 5.05 (95% CI 4.57-5.55, p < 0.001). There was no statistically significant difference in SMR for death from heart disease for left-sided vs. right-sided disease. At 10+ years, heart disease made up 28% of deaths from non-primary cancer. HRs and ORs showed that the risk of death from heart disease was highest in patients older than 70 years of age and with longer follow-up. Conclusion: The risk of fatal heart disease was highest in older breast cancer patients with longer follow-up (i.e., >5-10 years) and who received chemotherapy. These patients should be referred to cardio-oncology clinics to mitigate this risk.

Are Prerequisite Courses Barriers to Pharmacy Admission or the Keys to Student Success?

The variability and complexity of course prerequisites across colleges and schools of pharmacy can result in barriers to admission. While prerequisites play an important role in the admissions process and assuring student preparation, requiring excessive prerequisites can create unnecessary challenges for applicants. Prospective students may choose not to apply to a particular pharmacy school or even enter the profession because they cannot complete all course prerequisites in time to apply. Extraneous prerequisites can also contribute to the cost of education and educational indebtedness, which can more adversely affect minority and disadvantaged students. Pharmacy programs should carefully examine their course prerequisite requirements and consider new ways to measure preparedness to attract a diverse and competent pool of applicants to the profession while also being more competitive with other health professions programs.

Pregnancy screening practices and treatment of pregnant patients among radiation oncologists: results of an international survey.

BACKGROUND: The human embryo or foetus is susceptible to harmful effects of radiation, which include growth delay, malformations, impaired cognitive function, cancer and foetal demise. The purpose of this study is to describe pregnancy screening practices in radiation oncology, so that potential health effects may be avoided and areas of prevention may be identified. METHODS: An electronic survey was delivered to 6,304 members of the American Society for Radiation Oncology. The survey subjects were radiation oncologists who are currently practicing in the world. Chi-square tests and a multiple logistic regression model were used to analyse the data. All tests were two-sided and the statistical significance level used was 0.05. This study (STUDY00009765) was approved by an Institutional Review Board. RESULTS: A total of 434 responses from practicing radiation oncologists were received. Of these respondents, 69.1% were practicing in the United States. Of all respondents, 19.8% reported treating paediatric patients and 93.6% reported treating premenopausal patients. Despite 84.8% of radiation oncologists saying they would 'strongly agree' or 'agree' that one should screen for pregnancy prior to radiation therapy, 29.7% of respondents reported their department has no screening policy and 7.1% of respondents reported they do not screen for pregnancy. Having a departmental policy was associated with screening for pregnancy (p-value = 0.0005).Of all respondents, 93 reported treating a known pregnant patient. Of these 93 respondents, 76 reported intentionally treating and 17 reported accidentally treating a pregnant patient. Respondents who did not screen at time of simulation were significantly more likely to treat a pregnant patient than those who screened at time of simulation (p-value = 0.0459). CONCLUSIONS: Heterogeneity exists among practicing radiation oncologists regarding pregnancy screening. Institutional policies should be clear and consistent. All members of the radiation oncology team should make every effort to minimise unintended radiation exposure to the embryo or foetus.

Exercise Therapy and Radiation Therapy for Cancer: A Systematic Review.

PURPOSE: Exercise therapy (ET) is shown to improve toxicity and surrogates of survival for patients receiving chemotherapy. Current National Comprehensive Cancer Network (NCCN) guidelines lack recommendations for concurrent radiation therapy (RT) and ET. The main objective was to determine the impact of concurrent ET + RT with respect to (1) acceptability, feasibility, safety; and (2) to demonstrate how incorporating ET in cancer treatment can enhance patient-reported outcomes (PROs) and physical function-defined as strength or exercise capacity. METHODS AND MATERIALS: A PICOS/PRISMA selection protocol was used to search PubMed, Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Review for prospective randomized controlled trials evaluating concurrent ET + RT, including >10 patients and with 1 or more study arms. Acceptability, feasibility, and safety rates were calculated. PROs were assessed with study-specific metrics. Physical function was defined as improvements in strength or range of motion. Statistically significant improvement was defined by P <.05. RESULTS: Twenty-six of 693 screened studies including 1563 patients (831 receiving exercise, 732 controls) with localized breast cancer (67.1% of patients), prostate cancer (27.4%), head and neck cancers (2.8%), and spinal metastases (2.8%) were assessed. Objective 1: Among 3385 patients approached for ET, 1864 (55.1%) accepted the treatment; of those, 1563 patients (83.9%) completed the trials. Objective 2: Statistical improvements were noted in these PROs: quality of life (14 of 15 studies), fatigue (12 of 16 studies), mood/depression (9 of 13), and anxiety (6 of 7). Physical function improved statically in 16 of 16 studies. CONCLUSIONS: Combination ET + RT is safe and well-tolerated with improvements in PROs and physical function. Additional studies are needed in patients with metastatic cancers to assess survival and to compare effectiveness of different exercise regimens.

Implementation and evaluation of an advisement program focused on academic and career development.

INTRODUCTION: This research evaluated a formal academic and career advisement program implemented in a doctor of pharmacy program, which included a "Meet Your Advisor" luncheon and required faculty advisement sessions with an assigned faculty member. METHODS: The advising experience of students from two cohorts of first-year pharmacy students who received the formal advisement program (referred to as advisement cohort 1 and advisement cohort 2) were compared to the experience of a cohort of second-year students who entered prior to the formal advisement program (referred to as the pre-advisement cohort). All students completed a survey with both quantitative and qualitative questions regarding the advisement program. RESULTS: Our research demonstrates that the formal advisement program was successful at ensuring that nearly all students receive personalized advisement. In the pre-advisement cohort 65% of students reported receiving individual advisement, while 94% of students in advisement cohort 1 reported individual advisement and 95% in advisement cohort 2. Advisement cohort 2 responded similarly to the pre-advisement cohort on many of the advisement scales, especially the developing understanding scales, which provided evidence that two years after making the advisement program mandatory, students were having similar experiences to the smaller group of students who self-selected to receive advisement. CONCLUSIONS: A formal advisement program can be developed to include all students. Our research provides evidence that it may take time for the changes to be impactful and suggests the importance of faculty development.

Mutational profile of endometrial hyperplasia and risk of progression to endometrioid adenocarcinoma.

BACKGROUND: Endometrial hyperplasia is a precursor to endometrioid adenocarcinoma (EMC), the most common uterine cancer. The likelihood of progression to carcinoma may be evaluated by histologic subclassification of endometrial hyperplasia, although these subclasses are subjective and only modestly reproducible among pathologists. Patient care would be improved by a more objective test to predict the risk of cancer progression. METHODS: Next-generation sequencing was performed on archived endometrial biopsy specimens from a retrospective cohort of women with endometrial hyperplasia. Cases were considered to be either progressing if the patient subsequently developed EMC or resolving if the patient had a subsequent negative tissue sampling or no cancer during medium-term follow-up (32 patients: 15 progressing and 17 resolving). Somatic mutations in endometrial hyperplasia were assessed for enrichment in progressing cases versus resolving cases, with an emphasis on genes commonly mutated in EMC. RESULTS: Several mutations were more common in progressing hyperplasia than resolving hyperplasia, although significant overlap was observed between progressing and resolving cases. Mutations included those in PTEN, PIK3CA, and FGFR2, genes commonly mutated in EMC. Mutations in ARID1A and MYC were seen only in progressing hyperplasia, although these were uncommon; this limited diagnostic sensitivity. Progressing hyperplasia demonstrated an accumulation of mutations in oncogenic signaling pathways similarly to endometrial carcinoma. CONCLUSIONS: Because of mutational differences between progressing and nonprogressing hyperplasia, mutational analysis may predict the risk of progression from endometrial hyperplasia to EMC.

Reducing the Toxicity of Radiotherapy for Pancreatic Cancer With Magnetic Resonance-guided Radiotherapy.

Pancreatic cancer is a highly fatal malignancy for which surgery is currently considered to be the only curative treatment. However, less than a quarter of patients have disease amenable to definitive surgical resection. Local treatment with radiation therapy is a promising alternative to surgery for those patients with unresectable disease. However, conventional radiation techniques with computed tomography (CT)-guided therapy have yielded disappointing results due to the inability to deliver ablative doses of ionizing radiation, while sparing the radiosensitive adjacent organs at risk. Magnetic resonance-guided radiotherapy (MRgRT) has emerged as an alternative to CT-guided radiation treatment which allows for the delivery of higher doses of radiation with low toxicity to surrounding structures. Further study into the use of MRgRT and dose escalation for locally advanced unresectable pancreatic cancer is needed.

Toxicity after radiotherapy in patients with historically accepted contraindications to treatment (CONTRAD): An international systematic review and meta-analysis.

BACKGROUND AND PURPOSE: To investigate the incidence of radiotherapy-related acute and late toxicities among patients with pro-inflammatory comorbidities. MATERIAL AND METHODS: PICOS/PRISMA/MOOSE methods were used to identify studies on PubMed and MEDLINE, 1970-2018. The following were extracted: location, cancer, sample size, age, follow-up duration, medical contraindication, treatment, and toxicity. A weighted random effects model with the DerSimonian and Laird method was used in the meta-analysis. The primary endpoint was the grade ≥ 3 acute toxicity, and the secondary endpoint was late toxicity. RESULTS: There were 1137 articles screened and 18 included, assessing 621 patients. Among the 18 articles, 10 had collagen vascular disease (n = 417) and 8 had inflammatory bowel disease (n = 204). Median follow-up was 52.8 months. 457 patients received radiotherapy alone, and 153 received concurrent chemo-radiotherapy. The random effects estimate for incidence of grade ≥ 3 toxicity in collagen vascular disease patients (95% confidence interval) was 11.7% (5.4-19.6%) and 6.1% (1.4-12.6%) for acute and late toxicities, respectively. Incidence of grade ≥ 3 toxicity in inflammatory bowel disease patients was 14.0% (7.1-22.4%) and 10.2% (3.2-19.7%) for acute and late toxicities, respectively. Average grade 4 toxicity across both diseases was 1.5% and 4.5% for acute and late toxicities, respectively. Average grade 5 toxicity across both diseases was negligible (<1%). CONCLUSIONS: Patients with historically accepted contraindications to radiation therapy have a 10-15% risk of any grade ≥ 3 toxicity, <5% risk of grade 4 toxicity, and <1% risk for grade 5 toxicity, suggesting that collagen vascular disease and inflammatory bowel disease are not absolute contraindications to radiotherapy.

Let's talk about sex work in humanitarian settings: piloting a rights-based approach to working with refugee women selling sex in Kampala.

Although it is well known that refugees engage in sex work as a form of livelihood, stigma and silence around this issue persist within humanitarian circles. As a result, these refugees' sexual and reproductive health and rights, and related vulnerabilities, remain overlooked. Their protection and health needs, which are significant, often go unmet at the field level. In 2016, the Women's Refugee Commission and Reproductive Health Uganda partnered to pilot a peer-education intervention tailored to meet the needs of refugee women engaged in sex work in Kampala. Findings from the pilot project suggest the feasibility of adapting existing rights-based and evidence-informed interventions with sex workers to humanitarian contexts. Findings further demonstrate how taking a community empowerment approach can facilitate these refugees' access to a range of critical information, services and support options - from information on how to use contraceptives, to referrals for friendly HIV testing and treatment, to peer counselling and protective peer networks.

Feasibility and safety of cavity-directed stereotactic radiosurgery for brain metastases at a high-volume medical center.

OBJECTIVE: Our objective was to report safety and efficacy of stereotactic radiosurgery (SRS) to the surgical bed following resection of brain metastases. METHODS: Eighty-seven consecutive patients who underwent cavity-directed SRS to the operative bed for the treatment of brain metastases between 2002 and 2010 were evaluated. SRS required a gadolinium-enhanced, high-resolution, T1-weighted magnetic resonance imaging for tumor targeting and delivered a median dose of 18 Gy (14-22 Gy) prescribed to encompass the entire resection cavity. Whole brain irradiation was reserved for salvage. Patients were followed every 3 months with clinical examination and magnetic resonance imaging. Overall survival, local and regional recurrence, and factors affecting these outcomes were evaluated using Kaplan-Meier and log-rank analyses. RESULTS: The median imaging follow-up was 7.1 months, with >40% of patients having imaging for ≥1 year. Local control at 1 and 2 years was 82% and 75%, respectively. Cavity recurrence was more common with a tumor diameter >3 cm (P < .020) or resection cavity volume >14 mL (P < .050). One-year local control for tumors <2 cm, 2 cm to 3 cm, and >3 cm were 100%, 86%, and 72%, respectively. Neither subtotal resection nor target margins >2 mm to 3 mm affected local control. The median overall survival was 14.3 months with actuarial 5-year survival of 20%. Actuarial regional central nervous system recurrence was 44% at 1 year. On univariate analysis, only the presence of extracranial disease was associated with survival (P < .001) and central nervous system failure (P < .030). CONCLUSIONS: Excellent local control is achievable with cavity-directed SRS in well-selected patients, particularly for lesions with diameter <3 cm and resection cavity volumes <14 mL. Long-term survival is possible for select patients.

Individual prediction of dyslexia by single versus multiple deficit models.

The overall goals of this study were to test single versus multiple cognitive deficit models of dyslexia (reading disability) at the level of individual cases and to determine the clinical utility of these models for prediction and diagnosis of dyslexia. To accomplish these goals, we tested five cognitive models of dyslexia--two single-deficit models, two multiple-deficit models, and one hybrid model--in two large population-based samples, one cross-sectional (Colorado Learning Disability Research Center) and one longitudinal (International longitudinal Twin Study). The cognitive deficits included in these cognitive models were in phonological awareness, language skill, and processing speed and/or naming speed. To determine whether an individual case fit one of these models, we used two methods: 1) the presence or absence of the predicted cognitive deficits, and 2) whether the individual's level of reading skill best fit the regression equation with the relevant cognitive predictors (i.e., whether their reading skill was proportional to those cognitive predictors.) We found that roughly equal proportions of cases met both tests of model fit for the multiple deficit models (30-36%) and single deficit models (24-28%); hence, the hybrid model provided the best overall fit to the data. The remaining roughly 40% of cases in each sample lacked the deficit or deficits that corresponded with their best-fitting regression model. We discuss the clinical implications of these results for both diagnosis of school-age children and preschool prediction of children at risk for dyslexia.

Biochemical characterization of L-DOPA 2,3-dioxygenase, a single-domain type I extradiol dioxygenase from lincomycin biosynthesis.

L-DOPA-2,3-dioxygenase from Streptomyces lincolnensis is a single-domain type I extradiol dioxygenase of the vicinal oxygen chelate superfamily and catalyzes the second step in the metabolism of tyrosine to the propylhygric acid moiety of the antibiotic, lincomycin. S. lincolnensis L-DOPA-2,3-dioxygenase was overexpressed, purified and reconstituted with Fe(II). The activity of L-DOPA-2,3-dioxygenase was kinetically characterized with L-DOPA (K(M)=38 microM, k(cat)=4.2 min(-1)) and additional catecholic substrates including dopamine, 3,4-dihydroxyhydrocinnamic acid, catechol and D-DOPA. 3,4-Dihydroxyphenylacetic acid was characterized as a competitive inhibitor of the enzyme (K(i) =2.2 mM). Site-directed mutagenesis and its effects on enzymatic activity were used to identify His14 and His70 as iron ligands.

Update: new uses for lithium and anticonvulsants.

Anticonvulsants are being used clinically as monotherapy and adjuncts in mental illnesses other than affective disorders. This review focuses on the literature for anticonvulsants and lithium in substance use disorders, anxiety disorders, and schizophrenia. Given the abuse potential and other difficulties with prescribing benzodiazepines for alcohol and benzodiazepine withdrawal, anticonvulsants have been considered as an alternative. Promising therapeutic effects have been demonstrated in many of the anxiety disorders, with the greatest number of trials and positive results in posttraumatic stress disorder. Although anticonvulsant and lithium augmentation for schizophrenia is common in practice and has been studied in double-blind, randomized, controlled trials, the sum of the evidence has been inconclusive.

Genome-scale analysis of in vivo spatiotemporal promoter activity in Caenorhabditis elegans.

Differential regulation of gene expression is essential for cell fate specification in metazoans. Characterizing the transcriptional activity of gene promoters, in time and in space, is therefore a critical step toward understanding complex biological systems. Here we present an in vivo spatiotemporal analysis for approximately 900 predicted C. elegans promoters (approximately 5% of the predicted protein-coding genes), each driving the expression of green fluorescent protein (GFP). Using a flow-cytometer adapted for nematode profiling, we generated 'chronograms', two-dimensional representations of fluorescence intensity along the body axis and throughout development from early larvae to adults. Automated comparison and clustering of the obtained in vivo expression patterns show that genes coexpressed in space and time tend to belong to common functional categories. Moreover, integration of this data set with C. elegans protein-protein interactome data sets enables prediction of anatomical and temporal interaction territories between protein partners.

Colorectal cancer screening using stool DNA analysis in clinical practice: early clinical experience with respect to patient acceptance and colonoscopic follow-up of abnormal tests.

BACKGROUND: Stool-based DNA screening for colorectal cancer (CRC) was recently made available for use in daily clinical practice (PreGen-Plus). The main objectives of this study were to examine patients' screening experiences with stool DNA testing in routine clinical practice and the results of diagnostic colonoscopy in patients with an antecedent abnormal stool DNA test. PATIENTS AND METHODS: Patients undergoing stool-based DNA testing were asked to complete and return via mail an anonymous 10-item questionnaire inquiring about their test-related experiences. Colonoscopy findings for all abnormal stool-based DNA tests were ascertained via a telephone survey of the ordering primary care clinicians' offices. RESULTS: Patient survey responses were collected between August 2003 and July 2005 and reflect an 18% (1211 of 6730) response rate. The majority reported that the specimen collection process was very easy/easy to perform (87%), that they were very likely/likely to use the test again (91%), and that they had never been screened for CRC previously by any method (52%). Tests were ordered predominantly by the patient's primary care clinician (90%), including obstetrician/gynecologist providers. Colonoscopy findings from 69 of 159 patients with an antecedent abnormal stool DNA test screened with PreGen-Plus between August 2003 and July 2004 were available for review. An abnormal stool DNA test correlated with a colonoscopically demonstrable abnormality in 49% of cases (34 of 69). Abnormal findings, including CRC in 3 patients (4%; 1 with Dukes A and 2 with Dukes B disease), single or multiple adenomatous polyps in 23 patients (33%), hyperplastic polyps in 3 patients (4%), and colitis in 5 patients (7%). Colonoscopy was reported as negative in 51% of patients (35 of 69), including 2 cases (3%) with an altered BAT-26 microsatellite caused by a normal polymorphism. CONCLUSION: Stool DNA testing provides an acceptable noninvasive alternative for CRC screening that can identify early-stage CRCs and adenomatous polyps in routine clinical practice. Ongoing and broader surveys are indicated to support these early findings.

Towards a proteome-scale map of the human protein-protein interaction network.

Systematic mapping of protein-protein interactions, or 'interactome' mapping, was initiated in model organisms, starting with defined biological processes and then expanding to the scale of the proteome. Although far from complete, such maps have revealed global topological and dynamic features of interactome networks that relate to known biological properties, suggesting that a human interactome map will provide insight into development and disease mechanisms at a systems level. Here we describe an initial version of a proteome-scale map of human binary protein-protein interactions. Using a stringent, high-throughput yeast two-hybrid system, we tested pairwise interactions among the products of approximately 8,100 currently available Gateway-cloned open reading frames and detected approximately 2,800 interactions. This data set, called CCSB-HI1, has a verification rate of approximately 78% as revealed by an independent co-affinity purification assay, and correlates significantly with other biological attributes. The CCSB-HI1 data set increases by approximately 70% the set of available binary interactions within the tested space and reveals more than 300 new connections to over 100 disease-associated proteins. This work represents an important step towards a systematic and comprehensive human interactome project.