Compensation for Board of Pharmacy members in the United States.

BACKGROUND: No published data exist regarding per diem pay differences between the 50 United States Boards of Pharmacy. OBJECTIVES: The purpose of this study was to quantify and compare the per diem pay rate of Board of Pharmacy members for each state in the U.S. Compensation for mileage and meals, as well as demographic information regarding U.S. Board of Pharmacy members, was also evaluated. METHODS: In June 2022, each state Board of Pharmacy was contacted to gather data including per diem pay, mileage and meal compensation, number of meetings per year, number and gender of Board members, length of appointment, and regulatory statutes. RESULTS: The average per diem pay for Board members was $75.86 (median = $50.00, range = $0.00-$250.00, n = 48 states). Most states report paying Board members for mileage (95.1%, n = 39 of 41) and meals (80.0%, n = 28 of 35). On average, Boards are composed of 8.3 members (median = 7.5, range = 5-17, n = 50), meet 8.3 times annually (median = 8, range = 3-16, n = 47), and have a 4.5-year length of appointment (median = 4, range = 3-6, n = 47). Men represented 61.2% of occupied Board positions, and pharmacists accounted for 74.2% of all positions. The average year for per diem pay statute update was 2002. CONCLUSION: The per diem pay for U.S. Board of Pharmacy members varies from state to state, ranging from unpaid (n = 8 states) up to $250.00 per diem. Fair compensation, increased pharmacy technician and women representation, and more timely pharmacy statute updates are necessary in order to achieve inclusion, diversity, and equity across state Boards of Pharmacy.

Writing Multiple Choice Questions-Has the Student Become the Master?

CONSTRUCT: We compared the quality of clinician-authored and student-authored multiple choice questions (MCQs) using a formative, mock examination of clinical knowledge for medical students. BACKGROUND: Multiple choice questions are a popular format used in medical programs of assessment. A challenge for educators is creating high-quality items efficiently. For expediency's sake, a standard practice is for faculties to repeat items in examinations from year to year. This study aims to compare the quality of student-authored with clinician-authored items as a potential source of new items to include in faculty item banks. APPROACH: We invited Year IV and V medical students at the University of Adelaide to participate in a mock examination. The participants first completed an online instructional module on strategies for answering and writing MCQs, then submitted one original MCQ each for potential inclusion in the mock examination. Two 180-item mock examinations, one for each year level, were constructed. Each consisted of 90 student-authored items and 90 clinician-authored items. Participants were blinded to the author of each item. Each item was analyzed for item difficulty and discrimination, number of item-writing flaws (IWFs) and non-functioning distractors (NFDs), and cognitive skill level (using a modified version of Bloom's taxonomy). FINDINGS: Eighty-nine and 91 students completed the Year IV and V examinations, respectively. Student-authored items, compared with clinician-authored items, tended to be written at both a lower cognitive skill and difficulty level. They contained a significantly higher rate of IWFs (2-3.5 times) and NFDs (1.18 times). However, they were equally or better discriminating items than clinician-authored items. CONCLUSIONS: Students can author MCQ items with comparable discrimination to clinician-authored items, despite being inferior in other parameters. Student-authored items may be considered a potential source of material for faculty item banks; however, several barriers exist to their use in a summative setting. The overall quality of items remains suboptimal, regardless of author. This highlights the need for ongoing faculty training in item writing.

CaliPopGen: A genetic and life history database for the fauna and flora of California.

CaliPopGen is a database of population genetic data for native and naturalized eukaryotic species in California, USA. It summarizes the published literature (1985-2020) for 5,453 unique populations with genetic data from more than 187,394 individuals and 448 species (513 species plus subspecies) across molecular markers including allozymes, RFLPs, mtDNA, microsatellites, nDNA, and SNPs. Terrestrial habitats accounted for the majority (46.4%) of the genetic data. Taxonomic groups with the greatest representation were Magnoliophyta (20.31%), Insecta (13.4%), and Actinopterygii (12.85%). CaliPopGen also reports life-history data for most included species to enable analyses of the drivers of genetic diversity across the state. The large number of populations and wide taxonomic breadth will facilitate explorations of ecological patterns and processes across the varied geography of California. CaliPopGen covers all terrestrial and marine ecoregions of California and has a greater density of species and georeferenced populations than any previously published population genetic database. It is thus uniquely suited to inform conservation management at the regional and state levels across taxonomic groups.

Deflux Calcification Leading to Delayed Obstruction and Loss of Renal Function: A Case Report.

Dextranomer/hyaluronic acid (Deflux) has been widely used in the treatment of vesicoureteral reflux in the pediatric population. It has demonstrated acceptable early efficacy with minimal morbidity. Early complications from Deflux have been reported to occur in approximately 1% of cases. However, late complications from Deflux use, including calcification and delayed ureteral obstruction, are less well understood. We present the case of an asymptomatic 11 year old girl with severe ipsilateral hydroureteronephrosis, identified nearly 8 years after treatment. This case details a rare instance of loss of renal function after Deflux use in a patient with no apparent risk factors.

Helicopter versus ground ambulance: review of national database for outcomes in survival in transferred trauma patients in the USA.

BACKGROUND: Trauma care has improved substantially in the last decade. The emphasis of the Golden Hour in trauma care has encouraged the creation of faster transport and earlier prehospital intervention. Despite the clear time-saving advantage helicopter emergency medical services (HEMS) held over ground ambulances (GAs) in the past, advances in prehospital care over the last decade have created uncertainty as to whether HEMS transport is still associated with improved patient outcomes. We aimed to determine whether air transportation was associated with better outcomes compared with ground transportation. We hypothesized that air transportation is associated with better patient outcomes. METHODS: A retrospective review was performed on the National Trauma Data Bank in 2014 on patients transferred either by helicopter or ground ambulance. Demographic information, mean length of stay, mean ventilator days, and mortality rate was abstracted. All transferred patients and patients with missing information were excluded. χ2 test was performed to analyze categorical variables and independent t-test was performed to analyze continuous variables. A logistic regression was performed to ascertain the effects of Glasgow Coma Scale score, mechanism of injury (blunt vs penetrating), age, gender, Injury Severity Score (ISS), and method of transportation (HEMS vs GA) on the likelihood of mortality. RESULTS: A total of 469 407 transferred trauma patients were analyzed. Mortality appeared to be increased in trauma patients transported by helicopter ambulance (6.0%) versus GA (2.9%) (p<0.001). However, after adjusting for age, ISS, and gender, trauma patients who were transferred by helicopter were 57.0% less likely to die than those transferred by GA (95% CI 0.41 to 0.44, p<0.0001). CONCLUSION: The results of this study demonstrate that despite improvements in trauma care, patients have improved survival if transported by helicopter ambulance. LEVEL OF EVIDENCE AND STUDY TYPE: Level IV; Therapeutic/Care Management.

Mental health implications in bladder cancer patients: A review.

Although the majority of bladder cancer literature has been dedicated to optimizing oncological outcomes and focuses on physical prognostic criteria such as nutritional and performance status, emerging data has suggested that both pre- and post-treatment mental health may play as important a role in patient outcomes as physical health. In this review, we summarize the literature regarding the prognostic implications of mental illness on bladder cancer patients and review how both the diagnosis and treatment of bladder cancer can affect mental health across various disease states. Literature review via a modified, nonsystematic analysis was performed from 2000 to 2018 in PubMed, Web of Science, EMBASE, SCOPUS, and OVID. Search terms included "bladder cancer," "non-muscle-invasive bladder cancer," "muscle-invasive bladder cancer," "mental health," "psychological distress," "depression," and "suicide." Articles were limited to English-language, peer-reviewed, original research. A total of 87 publications were reviewed that met our initial inclusion criteria, and 19 relevant publications were incorporated in our review. Eleven studies were prospective and 8 were retrospective. Two articles included non-muscle-invasive bladder cancer patients, 11 included muscle-invasive bladder cancer patients, and 6 incorporated bladder cancer patients across all disease stages. Mental health issues, such as depression and anxiety, often coexist with a diagnosis of bladder cancer with a worse prognosis associated with greater psychological burden. Bladder cancer patients also have an increased risk of suicide especially in older, unmarried, male patients with more advanced disease states. Poor mental health can impact treatment outcomes such as postsurgical complication rates as well as survival-related outcomes similar to physical health. While awareness of the importance of mental health in bladder cancer patients is growing, further studies are needed to assess the role of interventions such as cognitive behavioral therapy or pharmacotherapy in order to optimize treatment.

Narcotic Pain Control for Ureterolithiasis Is Associated With Unnecessary Repeat Imaging in the Emergency Department.

A subset of patients with ureteral stones who present to the emergency department (ED) will return with recurring symptoms and will receive unnecessary repeat imaging. We retrospectively identified 112 patients from 2012 to 2016 diagnosed with at least one ureteral stone on computerized tomography (CT) at our institution who returned to the ED within 30 days. Patients were stratified based on the presence or absence of repeat CT scan imaging. Mean values were compared with independent t-test and proportions with chi-square analysis. Multivariate logistic regression was performed to determine independent predictors of repeat imaging. Sixty-eight patients (60.7%) underwent repeat CT scan imaging upon representation to the ED within 30 days of being diagnosed with ureterolithiasis. Ureteral stone position changed in 34 patients (30.4%) who underwent repeat imaging. On univariate analysis, younger age, nondiabetics, narcotics prescribed on discharge from first ED visit, and longer mean time between ED visits were associated with repeat CT scan imaging being performed (p < .05). Only prescription of narcotic pain medications was an independent predictor of repeat CT scan imaging (odds ratio: 3.18, 95% confidence interval: 1.22-8.28; p = .018). Nonsteroidal anti-inflammatory drugs or nonnarcotic pain medications, therefore, should primarily be used for pain control in these patients to avoid unnecessary testing.

Choosing medical assessments: Does the multiple-choice question make the grade?

Background: The multiple-choice question (MCQ) has been shown to measure the same constructs as the short-answer question (SAQ), yet the use of the latter persists. The study aims to evaluate whether assessment using the MCQ alone provides the same outcomes as testing with the SAQ. Methods: A prospective study design was used. A total of 276 medical students participated in a mock examination consisting of forty MCQs paired to forty SAQs, each pair matched in cognitive skill level and content. Each SAQ was marked by three independent markers. The impact of item-writing flaws (IWFs) on examination outcome was also evaluated. Results: The intraclass correlation coefficient (ICC) was 0.75 for the year IV examinations and 0.68 for the year V examinations. MCQs were more prone to IWFs than SAQs, but the effect when present in the latter was greater. Removal of questions containing IWFs from the year V SAQ allowed 39% of students who would otherwise have failed to pass. Discussion: The MCQ can test higher order skills as effectively as the SAQ and can be used as a single format in written assessment provided quality items testing higher order cognitive skills are used. IWFs can have a critical role in determining pass/fail results.

Emerging, newly-approved treatments for lower urinary tract symptoms secondary to benign prostatic hypertrophy.

INTRODUCTION: Oral therapy with alpha-blockers or 5-alpha reductase inhibitors remains the most common treatment in men with lower urinary tract symptoms (LUTS) secondary to benign prostatic hypertrophy (BPH). For patients who progress or fail medical therapy, the standard of care surgical treatment continues to be transurethral resection of the prostate (TURP), which has long-studied and durable outcomes. Emerging, minimally invasive options for LUTS secondary to the BPH, however, have been developed over the last decade with promising results and minimal side effects typically associated with TURP, such as retrograde ejaculation and erectile dysfunction. MATERIALS AND METHODS: We performed a literature review on PubMed over the last 10 years using keywords such as 'lower urinary tract symptoms,' 'benign prostatic hypertrophy,' 'minimally invasive,' and 'outpatient.' All relevant studies that reported on important urinary endpoints were included for each newly-approved treatment option. Available literature across varying prostate volumes was presented. RESULTS: Newly-approved therapies for BPH include new thermal energy sources (Rezum, aquablation), mechanical stenting (UroLift), prostate artery embolization, and injectable agents. These emerging techniques could be considered in patients where preservation of sexual function is a priority since they have demonstrated comparable urinary outcomes to medical therapy while causing no significant sexual dysfunction. Only prostate artery embolization has been extensively analyzed and proven efficacious in patients with > 80 g prostates who cannot undergo surgery. CONCLUSION: We have summarized the newly-approved treatment options for men with LUTS secondary to BPH as an alternative to traditional medical or surgical therapy. As more minimally invasive, office-based technologies emerge, physician and patients will have the ability to choose a treatment that is more catered to patient expectations.

Examining the impact of specific types of item-writing flaws on student performance and psychometric properties of the multiple choice question.

This article was migrated. The article was marked as recommended. Background: Item-writing flaws (IWFs) are common in multiple choice questions (MCQs) despite item-writing guidelines. Previous studies have shown that IWFs impact validity as observed through student performance, item difficulty, and discrimination. Most previous studies have examined IWFs collectively and have shown that they have a diverse impact. The aim of the study was to determine if the effects of individual types of IWFs are systematic and predictable. Method: A cross-over study design was used. 100 pairs of MCQ items (with and without an IWF) were constructed to test 10 types of IWFs. Medical students were invited to participate in a mock examination. Paper A consisted of 50 flawed followed by 50 unflawed items. Paper B consisted of 50 unflawed followed by 50 flawed items. The effect of each of the IWFs on mean item scores, item difficulty and discrimination were examined. Results: The hypothesised effect of IWFs on mean item scores was confirmed in only 4 out of 10 cases. ' Longest choice is correct', 'Clues to the right answer (Eponymous terms)' and ' Implausible distractors' positively impacted, while 'Central idea in choices rather than stem' negatively impacted mean item scores. Other flaws had either the opposite or no statistically significant effect. IWFs did not impact item difficulty or discrimination. Conclusion: The effect of IWFs is neither systematic nor predictable. Unpredictability in assessment produces error and thus loss of validity. Therefore, IWFs should be avoided. Faculties should be encouraged to invest in item-writing workshops in order to improve MCQs. However, the cost of doing so should be carefully weighed against the benefits of developing programmes of assessment.

Faster on-scene times associated with decreased mortality in Helicopter Emergency Medical Services (HEMS) transported trauma patients.

BACKGROUND: The 'Golden Hour' emphasizes the importance of rapidly providing definitive care to trauma patients. Dispatch time, defined as the time it takes the Helicopter Emergency Medical Service (HEMS) to dispatch from their base and reach the patient, and on-scene time, defined as the time spent with the patient prior to departure to a trauma center, can impact how quickly the patient will reach definitive care. We evaluated HEMS dispatch and on-scene times by investigating the survival rates among patients transported by air to a level 1 trauma center. We hypothesize that longer HEMS dispatch and on-scene times are associated with worse patient outcomes. METHODS: A retrospective, single institution analysis was performed on patients transported by HEMS. Inclusion criteria were air transported patients aged 18 years and above admitted to a level 1 trauma center from January 1, 2005 to January 1, 2015. Total dispatch time and on-scene times were divided into five incremental groups and mortality data were analyzed. Mortality was defined as death during initial hospital admission. A Pearson's correlation was used to analyze relationship between dispatch times, on-scene times, and mortality. Simple binary logistic regression was used to run a multivariate analysis on confounding variables of Injury Severity Score (ISS), gender, age, and Glasgow Coma Scale. RESULTS: There was a strong positive linear correlation between HEMS on-scene time and mortality, R=0.962, p=0.038. Additionally, there was a positive trend between HEMS dispatch time and mortality. ISS was found to be a significant confounder of mortality in our cohort with on-scene times >20 min, with mortality increasing by 7.5% for every 0.1 increase in ISS score (p=0.01). CONCLUSION: Longer HEMS on-scene and dispatch times appeared to be associated with increased mortality in trauma patients. However, those with higher ISS require longer on-scene times, increasing mortality. Regardless, efforts should focus on reducing on-scene and dispatch times. LEVEL OF EVIDENCE AND STUDY TYPE: Level III; Therapeutic/Care Management.

Transcriptional Regulation with CRISPR/Cas9 Effectors in Mammalian Cells.

CRISPR/Cas9-based regulation of gene expression provides the scientific community with a new high-throughput tool to dissect the role of genes in molecular processes and cellular functions. Single-guide RNAs allow for recruitment of a nuclease-dead Cas9 protein and transcriptional Cas9-effector fusion proteins to specific genomic loci, thereby modulating gene expression. We describe the application of a CRISPR-Cas9 effector system from Streptococcus pyogenes for transcriptional regulation in mammalian cells resulting in activation or repression of transcription. We present methods for appropriate target site selection, sgRNA design, and delivery of dCas9 and dCas9-effector system components into cells through lentiviral transgenesis to modulate transcription.

Functional annotation of native enhancers with a Cas9-histone demethylase fusion.

Understanding of mammalian enhancers is limited by the lack of a technology to rapidly and thoroughly test the cell type-specific function. Here, we use a nuclease-deficient Cas9 (dCas9)-histone demethylase fusion to functionally characterize previously described and new enhancer elements for their roles in the embryonic stem cell state. Further, we distinguish the mechanism of action of dCas9-LSD1 at enhancers from previous dCas9-effectors.

Simulations of enhancer evolution provide mechanistic insights into gene regulation.

There is growing interest in models of regulatory sequence evolution. However, existing models specifically designed for regulatory sequences consider the independent evolution of individual transcription factor (TF)-binding sites, ignoring that the function and evolution of a binding site depends on its context, typically the cis-regulatory module (CRM) in which the site is located. Moreover, existing models do not account for the gene-specific roles of TF-binding sites, primarily because their roles often are not well understood. We introduce two models of regulatory sequence evolution that address some of the shortcomings of existing models and implement simulation frameworks based on them. One model simulates the evolution of an individual binding site in the context of a CRM, while the other evolves an entire CRM. Both models use a state-of-the art sequence-to-expression model to predict the effects of mutations on the regulatory output of the CRM and determine the strength of selection. We use the new framework to simulate the evolution of TF-binding sites in 37 well-studied CRMs belonging to the anterior-posterior patterning system in Drosophila embryos. We show that these simulations provide accurate fits to evolutionary data from 12 Drosophila genomes, which includes statistics of binding site conservation on relatively short evolutionary scales and site loss across larger divergence times. The new framework allows us, for the first time, to test hypotheses regarding the underlying cis-regulatory code by directly comparing the evolutionary implications of the hypothesis with the observed evolutionary dynamics of binding sites. Using this capability, we find that explicitly modeling self-cooperative DNA binding by the TF Caudal (CAD) provides significantly better fits than an otherwise identical evolutionary simulation that lacks this mechanistic aspect. This hypothesis is further supported by a statistical analysis of the distribution of intersite spacing between adjacent CAD sites. Experimental tests confirm direct homodimeric interaction between CAD molecules as well as self-cooperative DNA binding by CAD. We note that computational modeling of the D. melanogaster CRMs alone did not yield significant evidence to support CAD self-cooperativity. We thus demonstrate how specific mechanistic details encoded in CRMs can be revealed by modeling their evolution and fitting such models to multispecies data.

Patients with polycythemia vera and essential thrombocythemia with prior malignancy do not have significantly worse outcome.

The clinical relevance of prior malignancy (PM) in patients with essential thrombocythemia (ET) and polycythemia vera (PV) is largely unknown. We retrospectively evaluated 437 patients (ET, n=263; PV, n=174) treated at MD Anderson between 1960 and 2010. Forty-four patients had PM (ET, 10%; PV, 11%), with median time to diagnosis of 66 months. PM was not associated with abnormal cytogenetics, JAK2-mutation frequency, blood-cell counts or progression to acute leukemia or myelofibrosis. In multivariate analysis, only older age and high LDH levels were associated with worse OS. In conclusion, PM does not predict worse outcomes for patients with ET and PV.

Computational identification of diverse mechanisms underlying transcription factor-DNA occupancy.

ChIP-based genome-wide assays of transcription factor (TF) occupancy have emerged as a powerful, high-throughput method to understand transcriptional regulation, especially on a global scale. This has led to great interest in the underlying biochemical mechanisms that direct TF-DNA binding, with the ultimate goal of computationally predicting a TF's occupancy profile in any cellular condition. In this study, we examined the influence of various potential determinants of TF-DNA binding on a much larger scale than previously undertaken. We used a thermodynamics-based model of TF-DNA binding, called "STAP," to analyze 45 TF-ChIP data sets from Drosophila embryonic development. We built a cross-validation framework that compares a baseline model, based on the ChIP'ed ("primary") TF's motif, to more complex models where binding by secondary TFs is hypothesized to influence the primary TF's occupancy. Candidates interacting TFs were chosen based on RNA-SEQ expression data from the time point of the ChIP experiment. We found widespread evidence of both cooperative and antagonistic effects by secondary TFs, and explicitly quantified these effects. We were able to identify multiple classes of interactions, including (1) long-range interactions between primary and secondary motifs (separated by ≤150 bp), suggestive of indirect effects such as chromatin remodeling, (2) short-range interactions with specific inter-site spacing biases, suggestive of direct physical interactions, and (3) overlapping binding sites suggesting competitive binding. Furthermore, by factoring out the previously reported strong correlation between TF occupancy and DNA accessibility, we were able to categorize the effects into those that are likely to be mediated by the secondary TF's effect on local accessibility and those that utilize accessibility-independent mechanisms. Finally, we conducted in vitro pull-down assays to test model-based predictions of short-range cooperative interactions, and found that seven of the eight TF pairs tested physically interact and that some of these interactions mediate cooperative binding to DNA.

Widespread evidence of cooperative DNA binding by transcription factors in Drosophila development.

Regulation of eukaryotic gene transcription is often combinatorial in nature, with multiple transcription factors (TFs) regulating common target genes, often through direct or indirect mutual interactions. Many individual examples of cooperative binding by directly interacting TFs have been identified, but it remains unclear how pervasive this mechanism is during animal development. Cooperative TF binding should be manifest in genomic sequences as biased arrangements of TF-binding sites. Here, we explore the extent and diversity of such arrangements related to gene regulation during Drosophila embryogenesis. We used the DNA-binding specificities of 322 TFs along with chromatin accessibility information to identify enriched spacing and orientation patterns of TF-binding site pairs. We developed a new statistical approach for this task, specifically designed to accurately assess inter-site spacing biases while accounting for the phenomenon of homotypic site clustering commonly observed in developmental regulatory regions. We observed a large number of short-range distance preferences between TF-binding site pairs, including examples where the preference depends on the relative orientation of the binding sites. To test whether these binding site patterns reflect physical interactions between the corresponding TFs, we analyzed 27 TF pairs whose binding sites exhibited short distance preferences. In vitro protein-protein binding experiments revealed that >65% of these TF pairs can directly interact with each other. For five pairs, we further demonstrate that they bind cooperatively to DNA if both sites are present with the preferred spacing. This study demonstrates how DNA-binding motifs can be used to produce a comprehensive map of sequence signatures for different mechanisms of combinatorial TF action.

Global analysis of Drosophila Cys2-His2 zinc finger proteins reveals a multitude of novel recognition motifs and binding determinants.

Cys2-His2 zinc finger proteins (ZFPs) are the largest group of transcription factors in higher metazoans. A complete characterization of these ZFPs and their associated target sequences is pivotal to fully annotate transcriptional regulatory networks in metazoan genomes. As a first step in this process, we have characterized the DNA-binding specificities of 129 zinc finger sets from Drosophila using a bacterial one-hybrid system. This data set contains the DNA-binding specificities for at least one encoded ZFP from 70 unique genes and 23 alternate splice isoforms representing the largest set of characterized ZFPs from any organism described to date. These recognition motifs can be used to predict genomic binding sites for these factors within the fruit fly genome. Subsets of fingers from these ZFPs were characterized to define their orientation and register on their recognition sequences, thereby allowing us to define the recognition diversity within this finger set. We find that the characterized fingers can specify 47 of the 64 possible DNA triplets. To confirm the utility of our finger recognition models, we employed subsets of Drosophila fingers in combination with an existing archive of artificial zinc finger modules to create ZFPs with novel DNA-binding specificity. These hybrids of natural and artificial fingers can be used to create functional zinc finger nucleases for editing vertebrate genomes.

Ligand-gated diffusion across the bacterial outer membrane.

Ligand-gated channels, in which a substrate transport pathway is formed as a result of the binding of a small-molecule chemical messenger, constitute a diverse class of membrane proteins with important functions in prokaryotic and eukaryotic organisms. Despite their widespread nature, no ligand-gated channels have yet been found within the outer membrane (OM) of Gram-negative bacteria. Here we show, using in vivo transport assays, intrinsic tryptophan fluorescence and X-ray crystallography, that high-affinity (submicromolar) substrate binding to the OM long-chain fatty acid transporter FadL from Escherichia coli causes conformational changes in the N terminus that open up a channel for substrate diffusion. The OM long-chain fatty acid transporter FadL from E. coli is a unique paradigm for OM diffusion-driven transport, in which ligand gating within a ß-barrel membrane protein is a prerequisite for channel formation.