Preoperative management and postoperative complications in 9 dogs undergoing surgical treatment of thymic-associated myasthenia gravis.

Objective: Thymoma-associated paraneoplastic syndromes in dogs and cats include myasthenia gravis, hypercalcemia, exfoliative dermatitis, erythema multiforme, T-cell lymphocytosis, myocarditis, anemia, and polymyositis. Paraneoplastic myasthenia gravis (MG) is the most commonly reported paraneoplastic syndrome in dogs with thymic epithelial tumors. The objective of this study was to examine cases of canine thymic-associated MG treated surgically, with the specific objective of providing an updated clinical picture of the preoperative management, postoperative complications, and outcomes of these cases. Animals: Nine dogs with paraneoplastic MG underwent surgical removal of a thymic epithelial tumor. Procedure: Medical records of dogs with MG that received surgical treatment of a thymic epithelial tumor between January 1, 2012 and October 1, 2022 were obtained from 4 veterinary teaching hospitals. Descriptions of perioperative MG management, complications, and outcomes were reported. Results: Six of the 9 dogs received medical therapy for MG, with either a cholinesterase inhibitor (4 dogs) or a cholinesterase inhibitor and immunosuppressive agent (2 dogs), before surgery. The median duration of medical therapy for MG before surgery was 7.5 d (range: 2 to 60 d). Three of 9 dogs experienced immediate postoperative complications and were euthanized. Six of 9 dogs (66.6%) survived to discharge and 3 of 6 dogs that survived to discharge were alive at the time of writing. At the time of writing, 3 of 6 dogs had complete resolution of clinical signs attributable to MG and 2 of 6 had partial resolution. The median time from surgery to resolution of clinical signs of MG in these dogs was 63 d (range: 2 to 515 d). Conclusion: Dogs with thymic epithelial tumors and paraneoplastic MG are at a high risk for perioperative complications. Clinical relevance: The findings of this study corroborate previous literature stating that paraneoplastic MG is a poor prognostic indicator for dogs with thymic epithelial tumors, while also highlighting the variation in approaches to clinical management of thymic-associated MG in veterinary medicine and the lack of established protocols guiding perioperative management.

Prise en charge préopératoire et complications postopératoires chez 9 chiens subissant un traitement chirurgical de la myasthénie grave associée au thymus. Objectif: Les syndromes paranéoplasiques associés au thymome chez le chien et le chat comprennent la myasthénie grave, l'hypercalcémie, la dermatite exfoliative, l'érythème polymorphe, la lymphocytose à cellules T, la myocardite, l'anémie et la polymyosite. La myasthénie paranéoplasique (MG) est le syndrome paranéoplasique le plus fréquemment rapporté chez les chiens atteints de tumeurs épithéliales thymiques. L'objectif de cette étude était d'examiner les cas de MG canine associée au thymus traités chirurgicalement, dans le but spécifique de fournir un tableau clinique actualisé de la prise en charge préopératoire, des complications postopératoires et des résultats de ces cas. Animaux: Neuf chiens atteints de MG paranéoplasique ont subi l'ablation chirurgicale d'une tumeur épithéliale thymique. Procédure: Les dossiers médicaux des chiens atteints de MG ayant reçu un traitement chirurgical d'une tumeur épithéliale thymique entre le 1er janvier 2012 et le 1er octobre 2022 ont été obtenues auprès de 4 hôpitaux universitaires vétérinaires. Des descriptions de la prise en charge péri-opératoire de la MG, des complications et des résultats ont été rapportées. Résultats: Six des 9 chiens ont reçu un traitement médical pour la MG, avec soit un inhibiteur de la cholinestérase (4 chiens), soit un inhibiteur de la cholinestérase et un agent immunosuppresseur (2 chiens), avant la chirurgie. La durée médiane du traitement médical de la MG avant la chirurgie était de 7,5 jours (plage : 2 à 60 jours). Trois des neuf chiens ont présenté des complications postopératoires immédiates et ont été euthanasiés. Six des 9 chiens (66,6 %) ont survécu jusqu'à leur sortie et 3 des 6 chiens qui ont survécu jusqu'à leur sortie étaient en vie au moment de la rédaction. Au moment de la rédaction de cet article, 3 chiens sur 6 présentaient une résolution complète des signes cliniques attribuables à la MG et 2 chiens sur 6 présentaient une résolution partielle. Le délai médian entre l'intervention chirurgicale et la résolution des signes cliniques de MG chez ces chiens était de 63 jours (plage : 2 à 515 jours). Conclusion: Les chiens atteints de tumeurs épithéliales thymiques et de MG paranéoplasique présentent un risque élevé de complications périopératoires. Pertinence clinique: Les résultats de cette étude corroborent la littérature antérieure indiquant que la MG paranéoplasique est un indicateur de mauvais pronostic pour les chiens atteints de tumeurs épithéliales thymiques, tout en soulignant également la variation des approches de prise en charge clinique de la MG associée au thymus en médecine vétérinaire et le manque de protocoles établis de gestion guidant les interventions périopératoires.(Traduit par Dr Serge Messier).

Protocol for a pragmatic trial of Cannabidiol (CBD) to improve chronic pain symptoms among United States Veterans.

BACKGROUND: Chronic pain affects over 100 million Americans, with a disproportionately high number being Veterans. Chronic pain is often difficult to treat and responds variably to medications, with many providing minimal relief or having adverse side effects that preclude use. Cannabidiol (CBD) has emerged as a potential treatment for chronic pain, yet research in this area remains limited, with few studies examining CBD's analgesic potential. Because Veterans have a high need for improved pain care, we designed a clinical trial to investigate CBD's effectiveness in managing chronic pain symptoms among Veterans. We aim to determine whether CBD oral solution compared to placebo study medication is associated with greater improvement in the Patient Global Impression of Change (PGIC). METHODS: We designed a randomized, double-blind, placebo-controlled, pragmatic clinical trial with 468 participants. Participants will be randomly assigned in a 1:1 ratio to receive either placebo or a CBD oral solution over a 4-week period. The trial is remote via a smartphone app and by shipping study materials, including study medication, to participants. We will compare the difference in PGIC between the CBD and placebo group after four weeks and impacts on secondary outcomes (e.g., pain severity, pain interference, anxiety, suicide ideation, and sleep disturbance). DISCUSSION: Once complete, this trial will be among the largest to date investigating the efficacy of CBD for chronic pain. Findings from this clinical trial will contribute to a greater knowledge of CBD's analgesic potential and guide further research. Given the relative availability of CBD, our findings will help elucidate the potential of an accessible option for helping to manage chronic pain among Veterans. TRIAL REGISTRATION: This protocol is registered at clinicaltrials.gov under study number NCT06213233.

Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement.

Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions.

Feasibility and acceptability of patient- and clinician-level antithrombotic stewardship interventions to reduce gastrointestinal bleeding risk in patients using warfarin (Anticoagulation with Enhanced Gastrointestinal Safety): a factorial randomized controlled pilot trial.

Background: Overuse of antiplatelet therapy and underuse of gastroprotection contribute to preventable bleeding in patients taking anticoagulants. Objectives: (1) Determine the feasibility of a factorial trial testing patient activation and clinician outreach to reduce gastrointestinal (GI) bleeding risk in patients prescribed warfarin-antiplatelet therapy without proton pump inhibitor gastroprotection and (2) assess intervention acceptability. Methods: Pragmatic 2 × 2 factorial cluster-randomized controlled pilot comparing (1) a patient activation booklet vs usual care and (2) clinician notification vs clinician notification plus nurse facilitation was performed. The primary feasibility outcome was percentage of patients completing a structured telephone assessment after 5 weeks. Exploratory outcomes, including effectiveness, were evaluated using chart review, surveys, and semistructured interviews. Results: Among 47 eligible patients, 35/47 (74.5%; 95% CI, 58.6%-85.7%) met the feasibility outcome. In the subset confirmed to be high risk for upper GI bleeding, 11/29 (37.9%; 95% CI, 16.9%-64.7%) made a medication change, without differences between intervention arms. In interviews, few patients reported reviewing the activation booklet; barriers included underestimating GI bleeding risk, misunderstanding the booklet's purpose, and receiving excessive health communication materials. Clinicians responded to notification messages for 24/47 patients (51.1%; 95% CI, 26.4%-75.4%), which was lower for surgeons than nonsurgeons (22.7% vs 76.0%). Medical specialists but not surgeons viewed clinician notification as acceptable. Conclusion: The proposed trial design and outcome ascertainment strategy were feasible, but the patient activation intervention is unlikely to be effective as designed. While clinician notification appears promising, it may not be acceptable to surgeons, findings which support further refinement and testing of a clinician notification intervention.

Focused Ultrasound Neuromodulation of Human In Vitro Neural Cultures in Multi-Well Microelectrode Arrays.

The neuromodulatory effects of focused ultrasound (FUS) have been demonstrated in animal models, and FUS has been used successfully to treat movement and psychiatric disorders in humans. However, despite the success of FUS, the mechanism underlying its effects on neurons remains poorly understood, making treatment optimization by tuning FUS parameters difficult. To address this gap in knowledge, we studied human neurons in vitro using neurons cultured from human-induced pluripotent stem cells (HiPSCs). Using HiPSCs allows for the study of human-specific neuronal behaviors in both physiologic and pathologic states. This report presents a protocol for using a high-throughput system that enables the monitoring and quantification of the neuromodulatory effects of FUS on HiPSC neurons. By varying the FUS parameters and manipulating the HiPSC neurons through pharmaceutical and genetic modifications, researchers can evaluate the neural responses and elucidate the neuro-modulatory effects of FUS on HiPSC neurons. This research could have significant implications for the development of safe and effective FUS-based therapies for a range of neurological and psychiatric disorders.

Prognostic Implications of Delirium After Left Ventricular Assist Device Implantation: A Retrospective Study.

BACKGROUND: In critically ill patients, delirium is a prognostic indicator of morbidity and mortality. OBJECTIVE: This study investigates the impact of a delirium diagnosis on outcomes after left ventricular assist device (LVAD) implantation. METHODS: This retrospective study included all adult patients who received LVADs at our institution between January 2016 and December 2020. We compared preimplantation characteristics between the two groups, with and without a diagnosis of delirium, and compared their outcomes, including 1-month, 6-month, and in-hospital mortality, as well as reintubation rate, length of stay, discharge disposition, and readmission rates. RESULTS: In total, 361 patients (26.7% women and 75.8% African American) received durable LVADs. Ninety-four patients (26.1%) were diagnosed with delirium during the index admission. Preimplantation demographic characteristics, past medical and psychiatric conditions, Interagency Registry for Mechanically Assisted Circulatory Support Profile, and laboratory values did not differ between the two groups with and without a diagnosis of delirium; older age (59 vs 56; P = 0.03) was associated with delirium. Delirium diagnosis was associated with higher 1-month (P = 0.007), 6-month (P = 0.004), and in-hospital mortality (P < 0.001), unplanned reintubations (P < 0.001), and a lower likelihood of discharge home (P = 0.03). Total hospital and intensive care unit length of stay were higher in patients with a diagnosis of delirium, though these results were not statistically significant. Readmission to the hospital after index admission was quicker in patients with a diagnosis of delirium, but this result was not statistically significant. CONCLUSIONS: In this study, a diagnosis of delirium during the LVAD implantation admission was associated with higher mortality, adverse postsurgical outcomes, and unfavorable discharge dispositions. Future prospective research is needed to validate the prognostic implications of delirium in both the short and long term. Additionally, there is a need to identify modifiable risk factors associated with delirium to promote early diagnosis and implement evidence-based management strategies to enhance outcomes within this population.

Trauma-Informed Healthcare Leadership? Evidence and opportunities from interviews with leaders during COVID-19.

BACKGROUND: COVID-19 impacted the mental health of healthcare workers, who endured pressures as they provided care during a prolonged crisis. We aimed to explore whether and how a Trauma-Informed Care (TIC) approach was reflected in qualitative perspectives from healthcare leaders of their experience during COVID-19 (2020-2021). METHODS: Semi-structured interviews with healthcare leaders from four institutions were conducted. Data analysis consisted of four stages informed by interpretative phenomenological analysis: 1) deductive coding using TIC assumptions, 2) inductive thematic analysis of coded excerpts, 3) keyword-in-context coding of full transcripts for 6 TIC principles with integration into prior inductive themes, and 4) interpretation of themes through 6 TIC principles (safety; trustworthiness and transparency; peer support; collaboration and mutuality; empowerment, voice, and choice; and awareness of cultural, historical, and gender issues). RESULTS: The actions of leaders (n = 28) that were reported as successful and supportive responses to the COVID-19 pandemic or else missed opportunities reflected core principles of Trauma-Informed Care. To promote safety, leaders reported affirmative efforts to protect staff by providing appropriate physical protection, and enhanced psychological safety by providing channels for communication about emotional well-being. To promote trustworthiness and transparency, leaders listened to their staff, shared current COVID-19 information, and increased frequency of meetings to disseminate accurate information. To promote mutual support, strategies included wellness check-ins, sharing uplifting stories, affirming common goals, articulating fears, and leading by example. Examples of empowerment included: making time and adjusting modalities for flexible communication; naming challenges outside of the hospital; and functioning as a channel for complaints. Reported missed opportunities included needing more dedicated time and space for healthcare employees to process emotions, failures in leadership managing their own anxiety, and needing better support for middle managers. Awareness of the TIC principle of cultural, historical, and gender issues was largely absent. Results informed the nascent Trauma-Informed Healthcare Leadership (TIHL) framework. CONCLUSIONS: We propose the Trauma-Informed Healthcare Leadership framework as a useful schema for action and analysis. This approach yields recommendations for healthcare leaders including creating designated spaces for emotional processing, and establishing consistent check-ins that reference personal and professional well-being.

The experiences among bereaved family members after a left ventricular assist device (LVAD) deactivation.

BACKGROUND: The use of left ventricular assist devices (LVADs) is increasing with an estimated 2500 devices implanted each year. When burdens of the LVAD outweigh benefits, most individuals with LVADs will undergo deactivation in the hospital setting. While the decision to deactivate an LVAD is considered an ethical practice, little is known about the experience and needs of bereaved family members. OBJECTIVE: To investigate the experiences of bereaved family members of patients who died following LVAD deactivation. METHODS: In this qualitative study, 11 family members of patients who underwent LVAD deactivation were interviewed. The semi-structured interviews were conducted until data saturation was reached and relevant themes emerged. RESULTS: This qualitative study was conducted to understand the experience of family members before, during and after the patient underwent LVAD deactivation, including their perceptions of engagement with the healthcare team. Analysis revealed six overarching themes from the experience, including 1) hope for survival, 2) communication, 3) spirituality and faith, 4) absence of physical suffering, 5) positive relationships with staff, 6) post-death care needs. CONCLUSION: Bereaved family members of patients undergoing LVAD deactivation have unique lived experiences and concerns. This study highlights the importance of effective communication not only near end-of-life but throughout the LVAD experience. While the positive relationships with staff and the absence of physical suffering were strengths identified by bereaved caregivers, there is an opportunity for improvement, particularly during the decision-making and post-death periods.

Disease-State Understanding and Experience of Patients Receiving Continuous Intravenous Inotropic Support as Palliative Therapy: A Multicenter Survey.

Background: The use of continuous intravenous inotropic support (CIIS) as palliative therapy in patients with advanced heart failure (HF) has increased over the past decade. CIIS improves New York Heart Association (NYHA) functional class but does not impact survival. Objective: The objective of this study was to examine patients' understanding of the therapeutic intent of CIIS, prognostic awareness, and quality of life with CIIS. Design: We conducted a prospective, cross-sectional, multicenter study of patients with advanced HF receiving CIIS as palliative therapy between 2020 and 2022. Settings/Subjects: An investigator-developed survey instrument was administered to outpatients on CIIS in the United States via telephone. Measurements: Survey data were analyzed using descriptive and inferential statistics. Results: Forty-eight patients, 63% male, 81% African American/Black, with a mean age of 68.9 (standard deviation 12.3) years, participated in this study. The majority of patients responded that they expected CIIS to make them feel better (79%) and increase longevity (75%), but few expected that CIIS would cure their HF (19%). Patients described their overall quality of life on CIIS as not better/worse (19%), somewhat better (46%), and significantly better (35%) and reported high treatment satisfaction (87% were at least somewhat satisfied). Conclusions: In this study, patients report improved quality of life with CIIS as palliative therapy. Patients on CIIS as palliative therapy expected increased survival on CIIS, which is incongruent with current evidence. Further studies on how we can improve care processes so that patients have accurate prognostic and disease-state awareness, and receive goal concordant care, are warranted.

Small animal patient preoperative preparation: a review of common antiseptics, comparison studies, and resistance.

This review aims to describe commonly used antiseptics in veterinary medicine including their mechanism of action, spectrum of activity, potential adverse effects, and application techniques. Additionally, it provides a review of the veterinary literature comparing antiseptics, a discussion of effectiveness and efficacy studies, and the potential for increased resistance to biocides and antimicrobials. This review concludes that appropriate selection and use is necessary to prevent the occurrence of surgical site infections, adverse effects, and potential for increasing resistance to antimicrobials. Continued research is needed to fill gaps in the current knowledge such as optimal preparation procedures for various surgical sites, standardization of efficacy and effectiveness testing, and the clinical impact of decreased susceptibility to chlorhexidine and other antiseptics.

The role of palliative care for patients with left ventricular assist devices: a narrative review.

BACKGROUND AND OBJECTIVE: Left ventricular assist devices (LVADs) have revolutionized the care of patients with advanced heart failure (HF). Compared to guideline-directed medical and device therapies, LVAD technology improves quality of life and reduces mortality. Palliative care specialists have an important role to play in the pre-LVAD evaluation phase, in the post-operative longitudinal care phase, and at the end-of-life in patients with LVADs. The objective of this narrative review is to describe the evidence regarding the role of palliative care for patients with LVAD across the care continuum: pre-implantation, post-implantation, and at the end-of-life. METHODS: Clinical trials relevant to care of patients with HF, LVADs, and the role of palliative care were analyzed for this narrative review. KEY CONTENT AND FINDINGS: Palliative care involvement in 'preparedness planning' has been described in the literature, though no standardized protocol for preparedness planning exists, to date. In the longitudinal care phase after LVAD implantation, the role of palliative care is less defined; depending on institutional culture and availability of palliative care, patients may be referred based on symptom-management needs or for advance care planning (ACP). At the end-of-life, either due to an acute event or a gradually worsening condition, palliative care is often engaged to participate in discussions regarding treatment preferences and to consider transitions in care from disease-directed treatments to comfort-focused treatments. Given the medical complexity of dying with LVADs, most patients with an LVAD die in hospital with support from palliative care teams for the physical, existential, and psychosocial distress that accompanies end-of-life and LVAD deactivation. CONCLUSIONS: In this narrative review, we describe the integral role of palliative care throughout the care continuum of patients living with LVADs and suggest opportunities for further research.

Subtypes of Alcohol Expectancies Are Differentially Associated With Alcohol Use for Bisexual and Heterosexual Women.

Background: Bisexual women, compared to heterosexual women, report greater amounts of alcohol use and heavy drinking. Alcohol expectancies (i.e., beliefs about alcohol outcomes) are a strong predictor of alcohol use, but few studies have examined the importance of alcohol expectancies in relation to alcohol use among bisexual women specifically or in comparison to heterosexual women. Objectives: The current study examined 262 heterosexual and 225 bisexual women using an online survey about alcohol use, sexual risk-taking, and alcohol expectancy subtypes (sexuality, tension reduction, and aggression). Results: Compared to heterosexual women, bisexual women reported greater sexuality and tension reduction expectancies after accounting for their level of drinking, but groups did not differ on aggression expectancies. Moreover, sexual identity status moderated the associations between sexuality and tension reduction expectancies and alcohol use, respectively. Specifically, our study findings suggested that sexuality and tension reduction alcohol expectancies were more strongly tied to alcohol use among bisexual women than heterosexual women. Conclusions: Taken together, in our study, bisexual women held stronger sexuality and tension reduction expectancies, as compared to heterosexual women. Interventions targeting alcohol expectancies may be considered when tailoring intervention content for this population.

5G2 mutant mice model loss of a commonly deleted segment of chromosome 7q22 in myeloid malignancies.

Monosomy 7 and del(7q) are among the most common and poorly understood genetic alterations in myelodysplastic neoplasms and acute myeloid leukemia. Chromosome band 7q22 is a minimally deleted segment in myeloid malignancies with a del(7q). However, the rarity of "second hit" mutations supports the idea that del(7q22) represents a contiguous gene syndrome. We generated mice harboring a 1.5 Mb germline deletion of chromosome band 5G2 syntenic to human 7q22 that removes Cux1 and 27 additional genes. Hematopoiesis is perturbed in 5G2+/del mice but they do not spontaneously develop hematologic disease. Whereas alkylator exposure modestly accelerated tumor development, the 5G2 deletion did not cooperate with KrasG12D, NrasG12D, or the MOL4070LTR retrovirus in leukemogenesis. 5G2+/del mice are a novel platform for interrogating the role of hemopoietic stem cell attrition/stress, cooperating mutations, genotoxins, and inflammation in myeloid malignancies characterized by monosomy 7/del(7q).

Differences in testing for drugs of abuse amongst racial and ethnic groups at children's hospitals.

OBJECTIVES: Racial and ethnic differences in drug testing have been described among adults and newborns. Less is known regarding testing patterns among children and adolescents. We sought to describe the association between race and ethnicity and drug testing at US children's hospitals. We hypothesized that non-Hispanic White children undergo drug testing less often than children from other groups. METHODS: We conducted a retrospective cohort study of emergency department (ED)-only encounters and hospitalizations for children diagnosed with a condition for which drug testing may be indicated (abuse or neglect, burns, malnutrition, head injury, vomiting, altered mental status or syncope, psychiatric, self-harm, and seizure) at 41 children's hospitals participating in the Pediatric Health Information System during 2018 and 2021. We compared drug testing rates among (non-Hispanic) Asian, (non-Hispanic) Black, Hispanic, and (non-Hispanic) White children overall, by condition and patient cohort (ED-only vs. hospitalized) and across hospitals. RESULTS: Among 920,755 encounters, 13.6% underwent drug testing. Black children were tested at significantly higher rates overall (adjusted odds ratio [aOR]: 1.18; 1.05-1.33) than White children. Black-White testing differences were observed in the hospitalized cohort (aOR: 1.42; 1.18-1.69) but not among ED-only encounters (aOR: 1.07; 0.92-1.26). Asian, Hispanic, and White children underwent testing at similar rates. Testing varied by diagnosis and across hospitals. CONCLUSIONS: Hospitalized Black children were more likely than White children to undergo drug testing at US children's hospitals, though this varied by diagnosis and hospital. Our results support efforts to better understand and address healthcare disparities, including the contributions of implicit bias and structural racism.

Effects of large-scale gold mining on habitat use and selection by American pronghorn.

Anthropogenic disturbances, including extraction of natural resources and development of alternative energy, are reducing and fragmenting habitat for wildlife across the globe. Effects of those disturbances have been explored by studying populations that migrate through oil and gas fields or alternative energy facilities. Extraction of minerals, including precious metals and lithium, is increasing rapidly in remote areas, which results in dramatically altered landscapes in areas of resident populations of wildlife. Our goal was to examine how a resident population of American pronghorn (Antilocapra americana) in the Great Basin ecosystem selected resources near a large-scale disturbance year around. We investigated how individuals selected resources around a large, open-pit gold mine. We classified levels of disturbance associated with the mine, and used a random forest model to select ecological covariates associated with habitat selection by pronghorn. We used resource selection functions to examine how disturbances affected habitat selection by pronghorn both annually and seasonally. Pronghorn strongly avoided areas of high disturbance, which included open pits, heap leach fields, rock disposal areas, and a tram. Pronghorn selected areas near roads, although selection was strongest about 2 km away. We observed relatively broad variation among individuals in selection of resources, and how they responded to the mine. The Great Basin is a mineral-rich area that continues to be exploited for natural resources, especially minerals. Sagebrush-dependent species, including pronghorn, that rely on this critical habitat were directly affected by that transformation of the landscape, which is likely to increase with expansion of the mine. As extraction of minerals from remote landscapes around the world continues to fragment habitats for wildlife, increasing our understanding of impacts of those changes on behaviors of wildlife before populations decline, may assist in the mitigation and minimization of negative impacts on mineral-rich landscapes and on wildlife populations.

Polypharmacy, over-the-counter medications, and aromatase inhibitor adherence in early-stage breast cancer.

PURPOSE: Polypharmacy is associated with negative health outcomes and decreased medication adherence. Polypharmacy is common in cancer populations, but few studies have evaluated the relationship between polypharmacy and aromatase inhibitor (AI) adherence. No studies have evaluated the relationship between over-the-counter (OTC) supplements and AI adherence. Our primary hypothesis was that polypharmacy would be associated with increased risk of premature AI discontinuation. METHODS: This exploratory analysis used data from the Exemestane and Letrozole Pharmacogenetics (ELPh) trial, a prospective, multicenter, randomized controlled trial that enrolled participants from 2005 to 2009. Included patients were female, postmenopausal, with stage 0-III breast cancer, who had completed indicated chemotherapy, surgery, and radiation. Participants were randomized to adjuvant exemestane or letrozole and completed serial clinical examinations and questionnaires for two years. Concomitant medication data were collected prospectively. Cox proportion models were used for statistical analysis of the relationship between polypharmacy, OTCs, medication class, and AI adherence. RESULTS: In the 490 analyzed participants, use of any prescription medications at baseline was associated with decreased risk of premature AI discontinuation (HR 0.56, p = 0.02). Use of selective serotonin reuptake inhibitors (SSRIs) or selective serotonin and norepinephrine reuptake inhibitors (SNRIs) at baseline was associated with decreased risk of premature AI discontinuation (HR 0.67, p = 0.04). Use of any OTCs was not associated with AI discontinuation. CONCLUSION: Baseline use of prescription medications but not OTCs was associated with increased AI persistence. Future research is needed to understand how this can be utilized to promote AI adherence.

Tethered spinal cord tension assessed via ultrasound elastography in computational and intraoperative human studies.

BACKGROUND: Tension in the spinal cord is a trademark of tethered cord syndrome. Unfortunately, existing tests cannot quantify tension across the bulk of the cord, making the diagnostic evaluation of stretch ambiguous. A potential non-destructive metric for spinal cord tension is ultrasound-derived shear wave velocity (SWV). The velocity is sensitive to tissue elasticity and boundary conditions including strain. We use the term Ultrasound Tensography to describe the acoustic evaluation of tension with SWV. METHODS: Our solution Tethered cord Assessment with Ultrasound Tensography (TAUT) was utilized in three sub-studies: finite element simulations, a cadaveric benchtop validation, and a neurosurgical case series. The simulation computed SWV for given tensile forces. The cadaveric model with induced tension validated the SWV-tension relationship. Lastly, SWV was measured intraoperatively in patients diagnosed with tethered cords who underwent treatment (spinal column shortening). The surgery alleviates tension by decreasing the vertebral column length. RESULTS: Here we observe a strong linear relationship between tension and squared SWV across the preclinical sub-studies. Higher tension induces faster shear waves in the simulation (R2 = 0.984) and cadaveric (R2 = 0.951) models. The SWV decreases in all neurosurgical procedures (p < 0.001). Moreover, TAUT has a c-statistic of 0.962 (0.92-1.00), detecting all tethered cords. CONCLUSIONS: This study presents a physical, clinical metric of spinal cord tension. Strong agreement among computational, cadaveric, and clinical studies demonstrates the utility of ultrasound-induced SWV for quantitative intraoperative feedback. This technology is positioned to enhance tethered cord diagnosis, treatment, and postoperative monitoring as it differentiates stretched from healthy cords.

Tethered spinal cord syndrome occurs when surrounding tissue attaches to and causes stretching across the spinal cord. People with a tethered cord can experience weakness, pain, and loss of bladder control. Although increased tension in the spinal cord is known to cause these symptoms, evaluating the amount of stretching remains challenging. We investigated the ability of an ultrasound imaging approach to measure spinal cord tension. We studied our method in a computer simulation, a benchtop validation model, and in six people with tethered cords during surgery that they were undergoing to reduce tension. In each phase, the approach could detect differences between stretched spinal cords and spinal cords in a healthy state. Our method could potentially be used in the future to improve the care of people with a tethered cord.