The development of a visual dashboard report to assess physician assistant and nurse practitioner financial and clinical productivity.

The evolving COVID-19 pandemic has unevenly affected academic medical centers (AMCs), which are experiencing resource-constraints and liquidity challenges while at the same time facing high pressures to improve patient access and clinical outcomes. Technological advancements in the field of data analytics can enable AMCs to achieve operational efficiencies and improve bottom-line expectations. While there are vetted analytical tools available to track physician productivity, there is a significant paucity of analytical instruments described in the literature to adequately track clinical and financial productivity of physician assistants (PAs) and nurse practitioners (NPs) employed at AMCs. Moreover, there is no general guidance on the development of a dashboard to track PA/NP clinical and financial productivity at the individual, department, or enterprise level. At our institution, there was insufficient tracking of PA/NP productivity across many clinical areas within the enterprise. Thus, the aim of the project is to leverage our institution's existing visualization tools coupled with the right analytics to track PA/NP productivity trends using a dashboard report.MethodsWe created an intuitive and customizable highly visual clinical/financial analytical dashboard to track productivity of PAs/NPs employed at our AMC.ResultsThe APP financial and clinical dashboard is organized into two main components. The volume-based key performance indicators (KPIs) included work relative value units (wRVUs), gross charges, collections (payments), and payer-mix. The session utilization (KPIs) included (e.g., new versus return patient ratios, encounter type, visit volume, and visits per session by provider). After successful piloting, the dashboard was deployed across multiple specialty areas and results showed improved data transparency and reliable tracking of PAs/NPs productivity across the enterprise. The dashboard analytics were also helpful in assessing PA/NP recruitment requests, independent practice sessions, and performance expectations.ConclusionTo our knowledge, this is the first paper to highlight steps AMCs can take in developing, validating, and deploying a financial/clinical dashboard specific to PAs/NPs. However, empirical research is needed to assess the impact of qualitative and quantitative dashboards on provider engagement, revenue, and quality of care.

Comparison of Diagnostic Tools for the Detection of Dirofilaria immitis Infection in Dogs.

In the last two decades, reports of canine heartworm (HW) infection have increased even in non-endemic areas, with a large variability in prevalence data due to the diagnostic strategy employed. This study evaluated the relative performance of two microtiter plate ELISA methods for the detection of HW antigen in determining the occurrence of Dirofilaria immitis in a dog population previously tested by the modified Knott's test and SNAP 4Dx Plus test. The prevalence of this infection in the sheltered dog population (n = 363) from a high-risk area for HW infection was 44.4% according to the modified Knott's test and 58.1% according to a point-of-care antigen ELISA. All serum samples were then evaluated by a microtiter plate ELISA test performed with and without immune complex dissociation (ICD). The prevalence increased from 56.5% to 79.6% following ICD, indicating a high proportion of samples with immune complexing. Comparing these results to that of the modified Knott's test, the samples negative for microfilariae (mfs) and those positive only for D. repens mfs demonstrated the greatest increase in the proportion of positive results for D. immitis by ELISA following ICD. While the ICD method is not recommended for routine screening, it may be a valuable secondary strategy for identifying HW infections in dogs.

Whole-Cell Screen of Fragment Library Identifies Gut Microbiota Metabolite Indole Propionic Acid as Antitubercular.

Several key antituberculosis drugs, including pyrazinamide, with a molecular mass of 123.1 g/mol, are smaller than the usual drug-like molecules. Current drug discovery efforts focus on the screening of larger compounds with molecular masses centered around 400 to 500 g/mol. Fragment (molecular mass < 300 g/mol) libraries have not been systematically explored for antitubercular activity. Here we screened a collection of 1,000 fragments, present in the Maybridge Ro3 library, for whole-cell activity against Mycobacterium tuberculosis Twenty-nine primary hits showed dose-dependent growth inhibition equal to or better than that of pyrazinamide. The most potent hit, indole propionic acid [IPA; 3-(1H-indol-3-yl)propanoic acid], a metabolite produced by the gut microbiota, was profiled in vivo The molecule was well tolerated in mice and showed adequate pharmacokinetic properties. In a mouse model of acute M. tuberculosis infection, IPA reduced the bacterial load in the spleen 7-fold. Our results suggest that IPA should be evaluated as an add-on to current regimens and that fragment libraries should be further explored to identify antimycobacterial lead candidates.

Influence of Men's Personality and Social Support on Treatment Decision-Making for Localized Prostate Cancer.

BACKGROUND: Optimal treatment for localized prostate cancer (LPC) is controversial. We assessed the effects of personality, specialists seen, and involvement of spouse, family, or friends on treatment decision/decision-making qualities. METHODS: We surveyed a population-based sample of men ≤ 75 years with newly diagnosed LPC about treatment choice, reasons for the choice, decision-making difficulty, satisfaction, and regret. RESULTS: Of 160 men (71 black, 89 white), with a mean age of 61 (±7.3) years, 59% chose surgery, 31% chose radiation, and 10% chose active surveillance (AS)/watchful waiting (WW). Adjusting for age, race, comorbidity, tumor risk level, and treatment status, men who consulted friends during decision-making were more likely to choose curative treatment (radiation or surgery) than WW/AS (OR = 11.1, p < 0.01; 8.7, p < 0.01). Men who saw a radiation oncologist in addition to a urologist were more likely to choose radiation than surgery (OR = 6.0, p = 0.04). Men who consulted family or friends (OR = 2.6, p < 0.01; 3.7, p < 0.01) experienced greater decision-making difficulty. No personality traits (pessimism, optimism, or faith) were associated with treatment choice/decision-making quality measures. CONCLUSIONS: In addition to specialist seen, consulting friends increased men's likelihood of choosing curative treatment. Consulting family or friends increased decision-making difficulty.

Patient Knowledge and Qualities of Treatment Decisions for Localized Prostate Cancer.

BACKGROUND: Controversy surrounds treatment for localized prostate cancer (LPC). OBJECTIVES: To assess men's localized prostate cancer (LPC) knowledge and its association with decision-making difficulty, satisfaction and regret. METHODS: Population-based sample of 201 men (104 white, 97 black), ≤ 75 years with newly diagnosed LPC completed a self-administered survey. RESULTS: Mean age was 61(±7.6) years; two-thirds had less than a Bachelor's degree. Mean LPC knowledge was low, 5.87 (±2.53, maximum score 11). More than a third of men who received surgery or radiation did not know about serious long-term treatment side effects. Fewer than half of the men correctly answered comparative side effect and survival benefit questions between surgery and radiation. Knowledge gaps were greatest among black men, men with lower education, single men. Tumor aggressiveness (i.e. PSA level, Gleason score) and treatment choice were not associated with knowledge. Knowledge was not associated with decisional satisfaction or regret. However, greater knowledge was associated with greater decision-making difficulty (P = .018). CONCLUSIONS: Significant LPC knowledge gaps existed across groups, with greater knowledge gaps among black men. The association of decision-making difficulty with knowledge was independent of race. Better patient education is needed, but may not alleviate men's decision-making difficulty due to inherent scientific uncertainty.

Patients' Survival Expectations With and Without Their Chosen Treatment for Prostate Cancer.

PURPOSE: Overtreatment of screen-detected localized prostate cancer (LPC) is an important public health concern, since the survival benefit of aggressive treatment (surgery or radiation) has not been well established. We investigated the survival expectations of patients who had LPC with and without their chosen treatment. METHODS: A population-based sample of 260 men (132 black, 128 white) 75 years old or younger with newly diagnosed LPC completed a self-administered survey. How long the patients expected to live with their chosen treatment, how long they would expect to live with no treatment, and factors associated with the difference in perceived life expectancy were assessed using multivariable analysis. RESULTS: Without any treatment, 33% of patients expected that they would live less than 5 years, 41% 5 to 10 years, 21% 10 to 20 years, and 5% more than 20 years. With their chosen treatment, 3% of patients expected to live less than 5 years, 9% 5 to 10 years, 33% 10 to 20 years, and 55% more than 20 years. Treatment chosen, age, general health perception, and perceived cancer seriousness predicted the differences in perceived life expectancy, while race and actual tumor risk did not. After adjustment for other covariates, men who choose surgery or radiation expected greater gain in survival than men who chose watchful waiting or active surveillance. CONCLUSIONS: Most patients with LPC underestimated their life expectancy without treatment and overestimated the gain in life expectancy with surgery or radiation. These unrealistic expectations may compromise patients' ability to make informed treatment decisions and may contribute to overtreatment of LPC. Primary care physicians, when included in the decision process, should focus on helping patients develop realistic expectations and choices that support their treatment goals.

The role of SOX11 immunostaining in confirming the diagnosis of mantle cell lymphoma on fine-needle aspiration samples.

BACKGROUND: Mantle cell lymphoma (MCL) demonstrates cytologic features that overlap with those of other types of B-cell non-Hodgkin lymphomas (B-cell NHLs) containing small to medium-sized cells. The accurate diagnosis of MCL is important because MCL has relatively more aggressive biologic behavior and thus requires specific treatment regimens. Fine-needle aspiration (FNA) is used for diagnosing or staging lymphoma, often with the help of immunophenotyping by flow cytometry. However, the cellularity of an FNA sample may not be high enough for flow cytometry, leading to diagnostic difficulty. SOX11 immunostaining is helpful in the diagnosis of MCL in histologic sections. However, to the authors' knowledge, its diagnostic value for FNA samples has not been studied to date. METHODS: Immunostains for SOX11 were performed on 69 FNA cases with final diagnoses of MCL (13 cases, including 10 classic type and 3 blastoid variant), marginal zone lymphoma (8 cases), follicular lymphoma (10 cases), small lymphocytic lymphoma (12 cases), Burkitt lymphoma (9 cases), plasma cell myeloma (7 cases), and benign lymph nodes (10 cases). Preparation types included cytospin slides (65 cases), direct smears (2 cases), and cell block sections (2 cases). The percentage of positive cells (defined as nuclear staining) and staining intensity were recorded. RESULTS: All 13 cases of MCL were positive for SOX11 staining, with 12 cases demonstrating diffuse positivity. All other types of B-cell NHL cases, plasma cell myelomas, and benign lymph nodes were found to have negative results. Weak staining was found in 1 MCL case of blastoid variant. CONCLUSIONS: SOX11 immunostaining on FNA samples is highly sensitive and specific for MCL and can be used as a reliable adjunct to confirm MCL, especially in a recurrent setting.

Intrathecal infusion of BMAA induces selective motor neuron damage and astrogliosis in the ventral horn of the spinal cord.

The neurotoxin beta-N-methylamino-l-alanine (BMAA) was first identified as a "toxin of interest" in regard to the amyotrophic lateral sclerosis-Parkinsonism Dementia Complex of Guam (ALS/PDC); studies in recent years highlighting widespread environmental sources of BMAA exposure and providing new clues to toxic mechanisms have suggested possible relevance to sporadic ALS as well. However, despite clear evidence of uptake into tissues and a range of toxic effects in cells and animals, an animal model in which BMAA induces a neurodegenerative picture resembling ALS is lacking, possibly in part reflecting limited understanding of critical factors pertaining to its absorption, biodistribution and metabolism. To bypass some of these issues and ensure delivery to a key site of disease pathology, we examined effects of prolonged (30day) intrathecal infusion in wild type (WT) rats, and rats harboring the familial ALS associated G93A SOD1 mutation, over an age range (80±2 to 110±2days) during which the G93A rats are developing disease pathology yet remain asymptomatic. The BMAA exposures induced changes that in many ways resemble those seen in the G93A rats, with degenerative changes in ventral horn motor neurons (MNs) with relatively little dorsal horn pathology, marked ventral horn astrogliosis and increased 3-nitrotyrosine labeling in and surrounding MNs, a loss of labeling for the astrocytic glutamate transporter, GLT-1, surrounding MNs, and mild accumulation and aggregation of TDP-43 in the cytosol of some injured and degenerating MNs. Thus, prolonged intrathecal infusion of BMAA can reproduce a picture in spinal cord incorporating many of the pathological hallmarks of diverse forms of human ALS, including substantial restriction of overt pathological changes to the ventral horn, consistent with the possibility that environmental BMAA exposure could be a risk factor and/or contributor to some human disease.

Lipophilic adamantyl- or deferasirox-based conjugates of desferrioxamine B have enhanced neuroprotective capacity: implications for Parkinson disease.

Parkinson disease (PD) is a neurodegenerative disease characterized by death of dopaminergic neurons in the substantia nigra region of the brain. Iron content is also elevated in this region in PD and is implicated in the pathobiology of the disease. Desferrioxamine B (DFOB) is a high-affinity iron chelator and has shown efficacy in animal models of Parkinson disease. The high water solubility of DFOB, however, attenuates its ability to enter the brain. In this study, we have conjugated DFOB to derivatives of adamantane or the clinical iron chelator deferasirox to produce lipophilic compounds designed to increase the bioavailability of DFOB to brain cells. We found that the novel compounds are highly effective in preventing iron-mediated paraquat and hydrogen peroxide toxicity in neuronal-like BE2-M17 dopaminergic cells, primary neurons, and iron-loaded or glutathione-depleted primary astrocytes. The compounds also alleviated paraquat toxicity in BE2-M17 cells that express the PD-causing A30P mutation of α-synuclein. This protection was ∼66-fold more potent than DFOB alone and also more effective than other cell-permeative metal chelators, clioquinol and phenanthroline. These results demonstrate that increasing the bioavailability of DFOB through the conjugation of lipophilic fragments greatly enhances its protective capacity. These novel compounds have potential as therapeutics for the treatment of PD and other conditions of Fe dyshomeostasis.

The many faces of the adamantyl group in drug design.

Adamantyl-based compounds are used clinically for the treatment of neurological conditions, as anti-viral agents and as agents against type 2 diabetes. The value of the adamantyl group in drug design is multidimensional. The hydrophobic substituent constant for the adamantyl group has been estimated from the calculated partition coefficients (clogP values) of 31 adamantyl-bearing compounds in the clinic or in development as πadamantyl=3.1, which indicates that the logP value of a compound with high water solubility (logP<<0) could be moved with an adamantyl-based modification to a region that is more clinically useful. The steric bulk of the adamantyl group can: (i) restrict or modulate intramolecular reactivity; and (ii) impede the access of hydrolytic enzymes, thereby increasing drug stability and plasma half life. The value of the adamantyl group in drug design has been recognized most recently in the design of agents to treat iron overload disease (in development), malaria (in clinical trials) and type 2 diabetes (in the clinic).

Comparing the potential renal protective activity of desferrioxamine B and the novel chelator desferrioxamine B-N-(3-hydroxyadamant-1-yl)carboxamide in a cell model of myoglobinuria.

Accumulating Mb (myoglobin) in the kidney following severe burns promotes oxidative damage and inflammation, which leads to acute renal failure. The potential for haem-iron to induce oxidative damage has prompted testing of iron chelators [e.g. DFOB (desferrioxamine B)] as renal protective agents. We compared the ability of DFOB and a DFOB-derivative {DFOB-AdAOH [DFOB-N-(3-hydroxyadamant-1-yl)carboxamide]} to protect renal epithelial cells from Mb insult. Loading kidney-tubule epithelial cells with dihydrorhodamine-123 before exposure to 100 µM Mb increased rhodamine-123 fluorescence relative to controls (absence of Mb), indicating increased oxidative stress. Extracellular Mb elicited a reorganization of the transferrin receptor as assessed by monitoring labelled transferrin uptake with flow cytometry and inverted fluorescence microscopy. Mb stimulated HO-1 (haem oxygenase-1), TNFα (tumour necrosis factor α), and both ICAM (intercellular adhesion molecule) and VCAM (vascular cell adhesion molecule) gene expression and inhibited epithelial monolayer permeability. Pre-treatment with DFOB or DFOB-AdAOH decreased Mb-mediated rhodamine-123 fluorescence, HO-1, ICAM and TNFα gene expression and restored monolayer permeability. MCP-1 (monocyte chemotactic protein 1) secretion increased in cells exposed to Mb-insult and this was abrogated by DFOB or DFOB-AdAOH. Cells treated with DFOB or DFOB-AdAOH alone showed no change in permeability, MCP-1 secretion or HO-1, TNFα, ICAM or VCAM gene expression. Similarly to DFOB, incubation of DFOB-AdAOH with Mb plus H2O2 yielded nitroxide radicals as detected by EPR spectroscopy, indicating a potential antioxidant activity in addition to metal chelation; Fe(III)-loaded DFOB-AdAOH showed no nitroxide radical formation. Overall, the chelators inhibited Mb-induced oxidative stress and inflammation and improved epithelial cell function. DFOB-AdAOH showed similar activity to DFOB, indicating that this novel low-toxicity chelator may protect the kidney after severe burns.

Conjugates of desferrioxamine B (DFOB) with derivatives of adamantane or with orally available chelators as potential agents for treating iron overload.

Desferrioxamine B (DFOB) conjugates with adamantane-1-carboxylic acid, 3-hydroxyadamantane-1-carboxylic acid, 3,5-dimethyladamantane-1-carboxylic acid, adamantane-1-acetic acid, 4-methylphenoxyacetic acid, 3-hydroxy-2-methyl-4-oxo-1-pyridineacetic acid (N-acetic acid derivative of deferiprone), or 4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]benzoic acid (deferasirox) were prepared and the integrity of Fe(III) binding of the compounds was established from electrospray ionization mass spectrometry and RP-HPLC measurements. The extent of intracellular (59)Fe mobilized by the DFOB-3,5-dimethyladamantane-1-carboxylic acid adduct was 3-fold greater than DFOB alone, and the IC(50) value of this adduct was 6- or 15-fold greater than DFOB in two different cell types. The relationship between logP and (59)Fe mobilization for the DFOB conjugates showed that maximal mobilization of intracellular (59)Fe occurred at a logP value approximately 2.3. This parameter, rather than the affinity for Fe(III), appears to influence the extent of intracellular (59)Fe mobilization. The low toxicity-high Fe mobilization efficacy of selected adamantane-based DFOB conjugates underscores the potential of these compounds to treat iron overload disease in patients with transfusional-dependent disorders such as beta-thalassemia.

Zn(II)-dependent histone deacetylase inhibitors: suberoylanilide hydroxamic acid and trichostatin A.

Suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza) and trichostatin A (TSA) are inhibitors of the Zn(II)-dependent class I and class II histone deacetylases (HDACs), which are enzymes that operate in concert with histone acetyltransferases (HATs) to regulate the acetylation status of the epsilon-amino group of lysine residues of nucleosomal histones in chromatin. An increased level of histone acetylation resulting from the SAHA or TSA inhibition of Zn(II)-dependent HDACs relaxes the chromatin structure and upregulates transcription. The links made in the 1990s between the inhibition of HDAC activity and the suppression of tumor growth have brought the design of HDAC inhibitors (HDACi) to the forefront of oncology research. SAHA has anticancer activity against hematologic and solid tumors and has been approved by the FDA for the treatment of cutaneous T-cell lymphoma. The increased molecular-level understanding of class I and class IIa HDACs from X-ray crystallography highlights differences in the residues distal to the active site and in the cavity size, which has implications for HDACi substrate specificity and enzyme mechanism. Results from HDAC-focussed activity-based protein profiling experiments may lead to the design of molecules that are class-specific HDACi.

2,5-Dioxopyrrolidin-1-yl adamantane-1-carboxyl-ate.

The title compound, C(15)H(19)NO(4), contains one crystallographically independent mol-ecule in the asymmetric unit. The N-O-C-O torsion angle is 1.97 (9)°. The two pairs of vicinal H atoms that lie above or below the plane defined by the five-membered pyrrolidine-2,5-dione ring are an average of 6.57 (5)° from being eclipsed. The average absolute C-C-C-C torsion angle in the adamantane skeleton, in which each fused cyclo-hexane ring is in a chair configuration, is 59.99 (5)°. The crystal packing is unremarkable.

Methyl 3-[(1-adamantylcarbon-yloxy)amino-carbon-yl]propanoate.

In the title compound, C(16)H(23)NO(5), the H-N-O-C torsion angle is 98.6 (1)°, which is of a similar magnitude to other N,O-diacyl-hydroxy-lamines. The N-O distance is 1.4029 (14) Å, which is similar to the N-O distance in other N,O-diacyl-hydroxy-lamines. In the crystal, intermolecular N-H⋯O hydrogen bonds generate chains of molecules.

Unilateral retrobulbar optic neuritis due to varicella zoster virus in a patient with AIDS: a case report and review of the literature.

Unilateral retrobulbar optic neuritis developed in a 43-year-old man with acquired immune deficiency syndrome (AIDS). This was secondary to varicella zoster virus (VZV) as confirmed by cerebrospinal fluid (CSF) polymerase chain reaction (PCR) detection of VZV in the cerebrospinal fluid. There was no typical cutaneous infection and no evidence of retinitis. The onset of unexplained visual loss due to optic neuritis in HIV positive individuals may be due to VZV infection. Prompt recognition, and early intervention with antiVZV therapy may preserve vision. Retrobulbar optic neuritis secondary to VZV infection should be considered in immunocompromised patients even in the absence of cutaneous or retinal lesions. Previous cases are reviewed and the varied nature of viral transport in the nervous system is noted.