Centralizing Telehealth Test-to-Treat Through a Regional Clinical Contact Center: A Veterans Health Administration Pilot.

Background: This project describes a Veterans Health Administration telehealth pilot to facilitate COVID-19 oral antiviral treatment as part of the national test-to-treat (T2T) strategy. The pilot was operationalized for two pilot VA medical centers by the regional clinical contact center (CCC) for a Veteran Integrated Service Network, which offers multiple services through several virtual modalities. Methods: Nurse triage and medical provider evaluation templates were developed for the CCC to standardize clinical interventions with veteran callers reporting positive home COVID-19 test results. When veterans were determined eligible and consented to treatment with an emergency use authorization (EUA) antiviral medication, CCC providers used secure direct messaging for synchronous communication with local pharmacy services to facilitate adjudication and dispensing. Templates for pharmacy documentation and primary care follow-up monitoring were also developed and disseminated. Results: In total, 198 veterans (mean age 65 years, 89% male, 88% non-Hispanic White) were evaluated through telehealth by regional CCC providers using the T2T process and 96% were prescribed an antiviral medication. Primary care follow-up occurred in 86% of cases, a median of 3 days after the telehealth evaluation. The 30-day all-cause hospitalization rate was 1.5% and there were no deaths within 30 days of treatment initiation. Conclusions: Veterans Integrated Service Network's CCC telehealth triage and evaluation processes enabled safe EUA-compliant care delivery, improved evaluator experience and efficiency, and augmented existing EUA processes in place by front-line pharmacy and primary care teams.

Artificial intelligence to diagnose meniscus tears on MRI.

PURPOSE: The purpose of this study was to build and evaluate a high-performance algorithm to detect and characterize the presence of a meniscus tear on magnetic resonance imaging examination (MRI) of the knee. MATERIAL AND METHODS: An algorithm was trained on a dataset of 1123 MR images of the knee. We separated the main task into three sub-tasks: first to detect the position of both horns, second to detect the presence of a tear, and last to determine the orientation of the tear. An algorithm based on fast-region convolutional neural network (CNN) and faster-region CNN, was developed to classify the tasks. The algorithm was thus used on a test dataset composed of 700 images for external validation. The performance metric was based on area under the curve (AUC) analysis for each task and a final weighted AUC encompassing the three tasks was calculated. RESULTS: The use of our algorithm yielded an AUC of 0.92 for the detection of the position of the two meniscal horns, of 0.94 for the presence of a meniscal tear and of 083 for determining the orientation of the tear, resulting in a final weighted AUC of 0.90. CONCLUSION: We demonstrate that our algorithm based on fast-region CNN is able to detect meniscal tears and is a first step towards developing more end-to-end artificial intelligence-powered diagnostic tools.

The Effects of Selective Muscle Weakness on Muscle Coordination in the Human Arm.

Despite the fundamental importance of muscle coordination in daily life, it is currently unclear how muscle coordination adapts when the musculoskeletal system is perturbed. In this study, we quantified the impact of selective muscle weakness on several metrics of muscle coordination. Seven healthy subjects performed 2D and 3D isometric force target matches, while electromyographic (EMG) signals were recorded from 13 elbow and shoulder muscles. Subsequently, muscle weakness was induced by a motor point block of brachialis muscle. Postblock subjects repeated the force generation tasks. We quantified muscle coordination pre- and postblock using three metrics: tuning curve preferred direction, tuning curve area, and motor modules analysis via nonnegative matrix factorization. For most muscles, the tuning direction for the 2D protocol was not substantially altered postblock, while tuning areas changed more drastically. Typically, five motor modules were identified from the 3D task, and four motor modules were identified in the 2D task; this result held across both pre- and postblock conditions. The composition of one or two motor modules, ones that involved mainly the activation of shoulder muscles, was altered postblock. Our results demonstrate that selective muscle weakness can induce nonintuitive alternations in muscle coordination in the mechanically redundant human arm.

Prevention of bone loss and vertebral fractures in patients with chronic epilepsy--antiepileptic drug and osteoporosis prevention trial.

PURPOSE: To evaluate whether use of a bisphosphonate (risedronate) in addition to calcium and vitamin D in male veterans with epilepsy who were taking antiepileptic drugs (AEDs) long term can prevent the loss of bone mass (BMD, bone mineral density) associated with AED use compared to patients who were treated with a placebo plus calcium and vitamin D. As a secondary end point we studied the incidence of new morphometric vertebral and nonvertebral fractures. METHODS: Antiepileptic drug and osteoporosis prevention trial (ADOPT) was designed as a prospective 2-year double-blind, randomized placebo controlled study involving 80 male veterans with epilepsy who were being treated with AEDs such as phenytoin, phenobarbital, sodium valproate, or carbamazepine for a minimum of 2 years. All enrolled participants received calcium and vitamin D supplementation, and were randomized to risedronate or matching placebo. Total body, bilateral proximal femora, and anteroposterior (AP) lumbar spine BMDs in addition to morphometric lateral vertebral assessments (LVAs) were evaluated by a dual energy x-ray absorptiometry (DXA) instrument. Comparisons of BMDs were made between baseline, 1 year, and after 2 years of enrollment in the study. The incidence of new vertebral and nonvertebral fractures was secondary end point. KEY FINDINGS: Of the 80 patients initially enrolled in the study, 53 patients completed the study. Baseline characteristics of the two groups were similar. At the end of the study, in the placebo plus calcium and vitamin D group, we observed a significant improvement in BMD at any of the evaluated sites when compared to their baseline scans in 69% (18/26) of the participants. In the risedronate plus calcium and vitamin D group, we observed significant improvement of BMDs in 70% (19/27) of the participants. At the end of the study, the risedronate group experienced a significant increase of BMD at the lumbar spine L1-4 (1.267-1.332 g/cm(2)), which was significantly larger than that seen in the placebo group) (1.229 g/cm(2) vs. 1.245 g/cm(2) ; p = 0.0066).There were nonsignificant differences between the two groups regarding changes of total body BMD or at the proximal bilateral femora. Five new vertebral fractures and one nonvertebral fracture were observed only in the placebo group. SIGNIFICANCE: Calcium and vitamin D supplementation or calcium and vitamin D supplementation in addition to risedronate improved BMD in more than 69% of male veterans with epilepsy who were taking AEDs. In the group receiving risedronate plus calcium and vitamin D there was a significant improvement of BMD at the lumbar spine as compared to the placebo group, which also received calcium and vitamin D. The use of risedronate plus calcium and vitamin D prevented the incidence of new vertebral fractures and one nonvertebral fracture in this cohort.

Evaluation of the flora of Puerto Rico for in vitro antiplasmodial and antimycobacterial activities.

The emergence of resistant strains of Plasmodium falciparum and Mycobacterium tuberculosis underscores the need for novel drugs that are effective against these microorganisms. As part of our screening programme of the flora of Puerto Rico, we tested a number of ethanol extracts of higher plants for antiplasmodial and antimycobacterial activities. A total of 40 extracts belonging to 23 plant families and 37 species were tested for antiplasmodial activity. Five extracts demonstrated activity against Plasmodium falciparum in vitro (50%-100% parasite suppression at 5 microg/mL). Another 63 extracts belonging to 30 plant families and 50 species were tested in vitro against Mycobacterium tuberculosis. Two extracts were found to be active, Ficus citrifolia and Pisonia borinquena (85% or more inhibition of microbial growth at 100 microg/mL of extract).

Behavior of triadimefon in two Lebanese soils.

The retention and fate of triadimefon fungicide were studied under two environmental conditions. Field studies were conducted on two soils, a sandy loam soil (Fanar) and a clay soil (Raouda). Fanar is a wet coastal area while Raouda is a dry agricultural area of the Bekaa plain located at an elevation of 870 m above sea level. Triadimefon was applied with a jet sprayer at 267 g a.i.ha(-1) and 200 g a.i.ha(-1) at Fanar and Raouda, respectively. Reconstituted soil columns (600 x 30 mm) glasses, were used to study the fungicide movement and metabolism in the two soils. Analyses of triadimefon and its metabolites were carried out using gas chromatography (GC) and high performance liquid chromatography (HPLC). The results indicated a weak reversibility of the adsorbed fraction in the clay soil. Clay is considered an important factor in triadimefon adsorption. Triadimefon mobility in the sandy-loam soil was relatively high in comparison with behavior in the clay soil where about half of the applied fungicide was detected in the upper 25 cm of soil, six days after treatment. Rapid degradation of triadimefon to triadimenol was observed in the two soils. The observed half-life was 8 days in sandy-loam and 13 days in clay soils.

Glucosidase inhibition assay as prescreen for natural products.

A glucosidase inhibition assay has been used to evaluate extracts from higher plants. An enzyme inhibition of fifty percent or more correlated with the observed cytotoxicity of the extracts.

Reverse transcriptase inhibition as prescreen for potential antiviral bioactives.

Extracts from higher plants were evaluated for inhibitory activity against avian myeloblastosis virus reverse transcriptase. The assay may serve as a useful prescreen for potential anti-HIV bioactives.

Cytotoxicity of Hymenocallis expansa alkaloids.

From the bulbs and leaves of Hymenocallis expansa (Amaryllidaceae), three alkaloid constituents were identified: (+)-tazettine, (+)-hippeastrine, and (-)-haemanthidine. These alkaloids demonstrated significant cytotoxicity when tested against a panel of human and murine tumor cell lines.

Effect of various microbial preparations on P-388 mouse lymphocytic leukemia.

Four bacteria-derived immunopotentiators were tested for their protective effect on a P-388 mouse lymphocytic leukemia model. The microbial test products were prepared from the following bacterial strains: ATCC 35983 Staphylococcus epidermidis isolated from a patient with IV catheter; ATCC 31874, a patented strain listed as Staphylococcus epidermidis isolated from the urine of a cancer patient; ATCC 25615 Staphylococcus hominis obtained from a child with lymphocytic leukemia, and ATCC 25614 Staphylococcus warneri, an isolate from a patient with adenocarcinoma of the breast. A limited degree of protection and prolongation in survival time was observed in the animal group treated with the bacterial strain ATCC 31874.

Increased kidney glucose utilization induced by cyclosporine: lack of relation to magnesium excretion.

Cyclosporine enhances D-[5-3H]glucose utilization in homogenates of rat kidney medulla but not kidney cortex or liver. This is true whether cyclosporine is added to fresh tissue homogenates or is given to rats prior to sacrifice. Through the use of isolated perfused rat kidneys, an attempt was made to relate increased glucose utilization by cyclosporine to a possible consequence of cyclosporine nephrotoxicity, viz., loss of magnesium in urine. Although an enhanced rate of glucose utilization by cyclosporine was evident in isolated kidneys, glucose consumption was not related to urinary magnesium loss. In fact, kidneys from cyclosporine-treated rats actually showed a normal or even diminished urinary magnesium loss. The data suggest that cyclosporine-induced magnesium imbalance may be extrarenal in origin and that the kidney medulla may be a primary site of the nephrotoxic action of cyclosporine since the drug increases glucose utilization at this site.

New cytotoxic aristolactams from Pararistolochia flos-avis.

Two new aristolactams, aristolactam-FI [1] and -FII [2], were isolated from active extracts of Pararistolochia flos-avis. Their structures were elucidated on the basis of nmr, ms, uv, and ir spectral data. Aristolactam-I [3] and -AII [4] were also isolated from this plant. Aristolactam-AII showed cytotoxicity against PS and KB cells in culture.

Stereochemistry of the kynureninase reaction.

The steric course of the replacement of the anthranilyl group of kynurenine by hydrogen was determined by conversion of (2S,3R)- and (2S,3S)-[3-3H]kynurenine into alanine with kynureninase in D2O, followed by chirality analysis of the alanine methyl group. To minimize enolization, the labeled substrates were generated in situ from the corresponding stereospecifically tritiated tryptophan species. The result, replacement in a retention mode, together with the finding that tritium from the alpha-position of the substrate is recycled and appears both at C alpha and C beta of the product suggests a single base mechanism and an active site geometry of the pyridoxal phosphate-substrate complex in which H alpha and the beta-substituent are syn oriented.

Studies on Sudanese medicinal plants III.

A prelimenary study was carried out to evaluate the potential of cultivating Hyoscyamus muticus L. as a source of hyoscyamine. The alkaloid yield was found to be quite favorable for the commercial utilization of this plant.

Potential antitumor agents. XVII. physalin B and 25,26-epidihydrophysalin C from Witheringia coccoloboides.

An investigation of Witheringia coccoloboides (Dammer) A. T. Hunziker [Capsicum fuscoviolaceum (Cufodontis) Mort. And Standl.] roots has resulted in the isolation of two cytotoxic compounds: physalin B (1) and a novel physalin, which was characterized by spectral analysis as 25,26-epidihydrophysalin C (2). Both compounds have demonstrated cytotoxic activity in 9KB and 9PS tumor cells (in vitro). Physalin B (1) has demonstrated moderate activity against the 3PS mouse leukemia (in vivo).

Studies on Sudanese medicinal plants. II. Evaluation of an extract of Lupinus termis seeds in chronic eczema.

A double-blind clinical trial comparing a 10% ointment prepared from a 95% ethanol extract of Lupinus termis seeds with a 0.02% flumethasone pivalate ointment and a placebo showed that the Lupinus termis extractive was effective in the treatment of chronic eczema. The results obtained with the extract were statistically comparable to those obtained with the corticoid therapy.