Development and evaluation of best practice advisory alert for patient eligibility in a hospital-at-home program: A multicenter retrospective study.

BACKGROUND: Hospital-at-home (HaH) is a growing model of care that has been shown to improve patient outcomes, satisfaction, and cost-effectiveness. However, selecting appropriate patients for HaH is challenging, often requiring burdensome manual screening by clinicians. To facilitate HaH enrollment, electronic health record (EHR) tools such as best practice advisories (BPAs) can be used to alert providers of potential HaH candidates. OBJECTIVE: To describe the development and implementation of a BPA for identifying HaH eligible patients in Mayo Clinic's Advanced Care at Home (ACH) program, and to evaluate the provider response and the patient characteristics that triggered the BPA. DESIGN, SETTING, AND PARTICIPANTS: We conducted a retrospective multicenter study of hospitalized patients who triggered the BPA notification for ACH eligibility between March and December 2021 at Mayo Clinic in Jacksonville, FL and Mayo Clinic Health System in Eau Claire, WI. We extracted demographic and diagnosis data from the patients as well as characteristics of the providers who received the BPA notification. INTERVENTION: The BPA was developed based on the ACH inclusion and exclusion criteria, which were derived from clinical guidelines, literature review, and expert consensus. The BPA was integrated into the EHR and displayed a pop-up message to the provider when a patient met the criteria for ACH eligibility. The provider could choose to refer the patient to ACH, dismiss the notification, or defer the decision. MAIN OUTCOMES AND MEASURES: The main outcomes were the number and proportion of BPA notifications that resulted in a referral to ACH, and the number and proportion of referrals that were accepted by the ACH clinical team and transferred to ACH. We also analyzed the factors associated with the provider's decision to refer or not refer the patient to ACH, such as the provider's role, location, and specialty. RESULTS: During the study period, 8962 notifications were triggered for 2847 patients. Providers opted to refer 711 (11.4%) of the total notifications linked to 324 unique patients. After review by the ACH clinical team, 31 of the 324 referrals (9.6%) met clinical and social criteria and were transferred to ACH. In multivariable analysis, Wisconsin nurses, physician assistants, and in-training personnel had lower odds of referring the patients to ACH when compared to attending physicians.

Electronic Health Record Closed-Loop Communication Program for Unexpected Nonemergent Findings.

Background Reliance on examination reporting of unexpected imaging findings does not ensure receipt of findings or appropriate follow-up. A closed-loop communication system should include provider and patient notifications and be auditable through the electronic health record (EHR). Purpose To report the initial design of and results from using an EHR-integrated unexpected findings navigator (UFN) program that ensures closed-loop communication of unexpected nonemergent findings. Materials and Methods An EHR-integrated UFN program was designed to enable identification and communication of unexpected findings and aid in next steps in findings management. Three navigators (with prior training as radiologic technologists and sonographers) facilitated communication and documentation of results to providers and patients. Twelve months (October 2019 to October 2020) of results were retrospectively reviewed to evaluate patient demographics and program metrics. Descriptive statistics and correlation analysis were performed by using commercially available software. Results A total of 3542 examinations were reported within 12 months, representing 0.5% of all examinations performed (total of 749 649); the median patient age was 62 years (range, 1 day to 98 years; interquartile range, 23 years). Most patients were female (2029 of 3542 [57%]). Almost half of the examinations submitted were from chest radiography and CT (1618 of 3542 [46%]), followed by MRI and CT of the abdomen and pelvis (1123 of 3542 [32%]). The most common unexpected findings were potential neoplasms (391 of 3542 [11%]). The median time between examination performance and patient notification was 12 days (range, 0-136 days; interquartile range, 13 days). A total of 2127 additional imaging studies were performed, and 1078 patients were referred to primary care providers and specialists. Most radiologists (89%, 63 of 71 respondents) and providers (65%, 28 of 43 respondents) found the system useful and used it most frequently during regular business hours. Conclusion An electronic health record-integrated, navigator-facilitated, closed-loop communication program for unexpected radiologic findings led to near-complete success in notification of providers and patients and facilitated the next steps in findings management. © RSNA, 2021 See also the editorial by Safdar in this issue.

Fluorescent Light Energy (FLE) Acts on Mitochondrial Physiology Improving Wound Healing.

Fluorescent light energy (FLE) has been used to treat various injured tissues in a non-pharmacological and non-thermal fashion. It was applied to stimulate cell proliferation, accelerate healing in chronic and acute wounds, and reduce pain and inflammation. FLE has been shown to reduce pro-inflammatory cytokines while promoting an environment conducive to healing. A possible mechanism of action of FLE is linked to regulation of mitochondrial homeostasis. This work aims to investigate the effect of FLE on mitochondrial homeostasis in an in vitro model of inflammation. Confocal microscopy and gene expression profiling were performed on cultures of inflamed human dermal fibroblasts treated with either direct light from a multi-LED lamp, or FLE from either an amorphous gel or sheet hydrogel matrix. Assessment using confocal microscopy revealed mitochondrial fragmentation in inflamed cells, likely due to exposure to inflammatory cytokines, however, mitochondrial networks were restored to normal 24-h after treatment with FLE. Moreover, gene expression analysis found that treatment with FLE resulted in upregulation of uncoupling protein 1 (UCP1) and carnitine palmitoyltransferase 1B (CPT1B) genes, which encode proteins favoring mitochondrial ATP production through oxidative phosphorylation and lipid ß-oxidation, respectively. These observations demonstrate a beneficial effect of FLE on mitochondrial homeostasis in inflamed cells.

Neuropsychopharmacology of JNJ-55308942: evaluation of a clinical candidate targeting P2X7 ion channels in animal models of neuroinflammation and anhedonia.

Emerging data continues to point towards a relationship between neuroinflammation and neuropsychiatric disorders. ATP-induced activation of P2X7 results in IL-1ß release causing neuroinflammation and microglial activation. This study describes the in-vitro and in-vivo neuropharmacology of a novel brain-penetrant P2X7 antagonist, JNJ-55308942, currently in clinical development. JNJ-55308942 is a high-affinity, selective, brain-penetrant (brain/plasma of 1) P2X7 functional antagonist. In human blood and in mouse blood and microglia, JNJ-55308942 attenuated IL-1ß release in a potent and concentration-dependent manner. After oral dosing, the compound exhibited both dose and concentration-dependent occupancy of rat brain P2X7 with an ED50 of 0.07 mg/kg. The P2X7 antagonist (3 mg/kg, oral) blocked Bz-ATP-induced brain IL-1ß release in conscious rats, demonstrating functional effects of target engagement in the brain. JNJ-55308942 (30 mg/kg, oral) attenuated LPS-induced microglial activation in mice, assessed at day 2 after a single systemic LPS injection (0.8 mg/kg, i.p.), suggesting a role for P2X7 in microglial activation. In a model of BCG-induced depression, JNJ-55308942 dosed orally (30 mg/kg), reversed the BCG-induced deficits of sucrose preference and social interaction, indicating for the first time a role of P2X7 in the BCG model of depression, probably due to the neuroinflammatory component induced by BCG inoculation. Finally, in a rat model of chronic stress induced sucrose intake deficit, JNJ-55308942 reversed the deficit with concurrent high P2X7 brain occupancy as measured by autoradiography. This body of data demonstrates that JNJ-55308942 is a potent P2X7 antagonist, engages the target in brain, modulates IL-1ß release and microglial activation leading to efficacy in two models of anhedonia in rodents.

Photography in Telemedicine: Improving Diagnosis of Chronic Graft-Versus-Host Disease.

BACKGROUND: The long-term follow-up (LTFU) team at the Seattle Cancer Care Alliance uses telemedicine to diagnose and treat post-transplantation complications in hematopoietic cell transplantation (HCT) survivors. Photos are often requested via the telemedicine service to aid in diagnosis, but they are typically of poor quality, making them unusable. OBJECTIVES: This project offered bachelor of science in nursing students, partnered with a comprehensive cancer center, the opportunity to participate in an evidence-based practice project to improve detection and management of chronic graft-versus-host disease (cGVHD) in patients after HCT. METHODS: Students partnered with RNs to develop instructional tools using multiple evidence sources. A brochure and video were developed. FINDINGS: Providing these instructional tools to those in the LTFU program improved patient outcomes for managing cGVHD through telemedicine. This partnership provided an opportunity for mutual learning and improved clinical practice.

Corticotropin-releasing factor receptor-1 antagonism mitigates beta amyloid pathology and cognitive and synaptic deficits in a mouse model of Alzheimer's disease.

INTRODUCTION: Stress and corticotropin-releasing factor (CRF) have been implicated as mechanistically involved in Alzheimer's disease (AD), but agents that impact CRF signaling have not been carefully tested for therapeutic efficacy or long-term safety in animal models. METHODS: To test whether antagonism of the type-1 corticotropin-releasing factor receptor (CRFR1) could be used as a disease-modifying treatment for AD, we used a preclinical prevention paradigm and treated 30-day-old AD transgenic mice with the small-molecule, CRFR1-selective antagonist, R121919, for 5 months, and examined AD pathologic and behavioral end points. RESULTS: R121919 significantly prevented the onset of cognitive impairment in female mice and reduced cellular and synaptic deficits and beta amyloid and C-terminal fragment-ß levels in both genders. We observed no tolerability or toxicity issues in mice treated with R121919. DISCUSSION: CRFR1 antagonism presents a viable disease-modifying therapy for AD, recommending its advancement to early-phase human safety trials.

Reproductive Stage and Modulation of Stress-Induced Tau Phosphorylation in Female Rats.

Chronic stress is implicated as a risk factor for Alzheimer's disease (AD) and other neurodegenerative disorders. Although the specific mechanisms linking stress exposure and AD vulnerability have yet to be fully determined, our laboratory and others have shown that acute and repeated restraint stress in rodents leads to an increase in hippocampal tau phosphorylation (tau-P) and tau insolubility, a critical component of tau pathology in AD. Although tau phosphorylation induced by acute psychological stress is dependent on intact signaling through the type 1 corticotropin-releasing factor receptor, how sex steroids or other modulators contribute to this effect is unknown. A naturally occurring attenuation of the stress response is observed in female rats at the end of pregnancy and throughout lactation. To test the hypothesis that decreased sensitivity to stress during lactation modulates stress-induced tau-P, cohorts of virgin, lactating and weaned female rats were subjected to 30 min of restraint stress or no stress (control) and were killed 20 min or 24 h after the episode. Exposure to restraint stress induced a significant decrease in tau-P in the hippocampus of lactating rats killed 20 min after stress compared to lactating controls and virgins subjected to stress treatment. Lactating rats killed 24 hr after restraint stress exposure showed significant elevation in tau-P compared to lactating cohorts killed 20 min after stress. Levels of tau-P in these latter cohorts did not differ signficantly from control animals. Furthermore, glycogen synthase kinase (GSK)3-α levels were significantly decreased in stressed lactating animals at both timepoints. This suggests a steep, yet transient stress-induced dephosphorylation of tau, influenced by GSK3, in the hippocampus of lactating rats.

Impact of CRFR1 Ablation on Amyloid-ß Production and Accumulation in a Mouse Model of Alzheimer's Disease.

Stress exposure and the corticotropin-releasing factor (CRF) system have been implicated as mechanistically involved in both Alzheimer's disease (AD) and associated rodent models. In particular, the major stress receptor, CRF receptor type 1 (CRFR1), modulates cellular activity in many AD-relevant brain areas, and has been demonstrated to impact both tau phosphorylation and amyloid-ß (Aß) pathways. The overarching goal of our laboratory is to develop and characterize agents that impact the CRF signaling system as disease-modifying treatments for AD. In the present study, we developed a novel transgenic mouse to determine whether partial or complete ablation of CRFR1 was feasible in an AD transgenic model and whether this type of treatment could impact Aß pathology. Double transgenic AD mice (PSAPP) were crossed to mice null for CRFR1; resultant CRFR1 heterozygous (PSAPP-R1(+/-)) and homozygous (PSAPP-R1(-/-)) female offspring were used at 12 months of age to examine the impact of CRFR1 disruption on the severity of AD Aß levels and pathology. We found that both PSAPP-R1(+/-) and PSAPP-R1(-/-) had significantly reduced Aß burden in the hippocampus, insular, rhinal, and retrosplenial cortices. Accordingly, we observed dramatic reductions in Aß peptides and AßPP-CTFs, providing support for a direct relationship between CRFR1 and Aß production pathways. In summary, our results suggest that interference of CRFR1 in an AD model is tolerable and is efficacious in impacting Aß neuropathology.

Increased tau phosphorylation and aggregation in the hippocampus of mice overexpressing corticotropin-releasing factor.

Clinical and basic science research suggests that stress and/or changes in central stress signaling intermediates may be involved in Alzheimer's disease (AD) pathogenesis. Although the links between stress and AD remain unsettled, data from our group and others have established that stress exposure in rodents may confer susceptibility to AD pathology by inducing hippocampal tau phosphorylation (tau-P). Work in our laboratory has shown that stress-induced tau-P requires activation of the type-1 corticotropin-releasing factor receptor (CRFR1). CRF overexpressing (CRF-OE) mice are a model of chronic stress that display cognitive impairment at 9-10 month of age. In this study we used 6-7 month old CRF-OE mice to examine whether sustained exposure to CRF and stress steroids would impact hippocampal tau-P and kinase activity in the presence or absence of the CRFR1-specific antagonist, R121919, given daily for 30 days. CRF-OE mice had significantly elevated tau-P compared to wild type (WT) mice at the AT8 (S202/T204), PHF-1 (S396/404), S262, and S422 sites. Treating CRF-OE mice with R121919 blocked phosphorylation at the AT8 (S202/T204) and PHF-1 (S396/404) sites, but not at the S262 and S422 sites and reduced phosphorylation of c-Jun N Terminal Kinase (JNK). Examination of hippocampal extracts from CRF-OE mice at the ultrastructural level revealed negatively stained round/globular aggregates that were positively labeled by PHF-1. These data suggest critical roles for CRF and CRFR1 in tau-P and aggregation and may have implications for the development of AD cognitive decline.

Ocular melanoma and the BAP1 hereditary cancer syndrome: implications for the dermatologist.

Ocular melanoma is a rare subtype of melanoma, which includes uveal melanoma (UM) and conjunctival melanoma. UM is associated with an increased risk of cutaneous melanoma (CM) in addition to mesothelioma, skin lesions such as epithelioid atypical Spitz tumors, and other internal malignancies due to a germline mutation of the BRCA1-associated protein 1 (BAP1) gene. Such familial risks are important for dermatologists to recognize when screening patients with a history of UM for CM and other malignancies. Molecular genetics further help to elucidate the connections between UM and CM by revealing similarities and differences in important mutations among the melanoma subtypes. Both UM and CM have been shown to harbor germline mutation of BAP1. However, somatic mutations in either GNAQ or GNA11 are unique to UM tumors and could be used as potential markers to differentiate UM from metastatic CM and act as direct therapeutic targets. However, CM-associated BRAF and CDKN2A mutations are rare in UM. This review addresses the clinical features, pathogenesis, and current treatment options of UM, focusing on UM and the BAP1 cancer syndrome to raise awareness of ocular melanoma and its greater role in the predisposition to a hereditary cancer syndrome.

Pediatricians' perspectives on indoor tanning.

This report presents results from an online survey of New York State pediatricians regarding their counseling habits and attitudes toward indoor tanning among adolescents, as well as their awareness of current legislation that restricts youth access to tanning beds.

Erythema Induratum Caused by Mycobacterium chelonei in an Immunocompetent Patient.

Erythema induratum is a disease characterized by nodules on the flexural surface of the lower legs strongly associated with Mycobacterium tuberculosis infection. In the presented case, erythema induratum was found in a middle-aged woman caused by an atypical mycobacterium, Mycobacterium chelonei, identified via culture. Mycobacterium chelonei is best known for its pathogenicity in immunocompromised hosts and has been reported secondary to traumatic implantation. However, the patient described in this case did not have any comorbidities associated with erythema induratum, had a negative purified protein derivative skin test, and was immunocompetent. Disease resolution was achieved with clarithromycin and doxycycline therapy.

Skin cancer education among massage therapists: a survey at the 2010 meeting of the American Massage Therapy Association.

Massage therapists encounter skin on a daily basis and have a unique opportunity to recognize potential skin cancers. The purpose of this study was to describe the skin cancer education provided to massage therapists and to assess their comfort regarding identification and communication of suspicious lesions. An observational retrospective survey study was conducted at the 2010 American Massage Therapy Association Meeting. Sixty percent reported receiving skin cancer education during and 25% reported receiving skin cancer education after training. Massage therapists who examine their own skin are more likely to be comfortable with recognizing a suspicious lesion and are more likely to examine their client's skin. Greater number of clients treated per year and greater frequency of client skin examinations were predictors of increased comfort level with recognizing a suspicious lesion. Massage therapists are more comfortable discussing than identifying a potential skin cancer. Massage therapists may be able to serve an important role in the early detection of skin cancer.

Onycholemmal carcinoma: a morphologic comparison of 6 reported cases.

BACKGROUND: We report 6 new cases of onycholemmal carcinoma, a rare, often misdiagnosed, subcategory of squamous cell carcinoma. All reported cases to date have been treated with amputation of the affected digit. OBJECTIVE: The purpose of this study was to present the clinical and pathological features of each new case and to discuss treatment options that spare digit functionality. METHODS: Hematoxylin-eosin stains were performed on tumor sections and examined using light microscopy. In situ hybridization using probes against human papillomavirus were examined in 1 case. RESULTS: The female to male ratio was 1:1 with involvement of fingers in 3, thumb in 1, and toe in 1. Among the symptoms were onycholysis, periungual erythema, and pain; symptom duration ranged from 6 months to 2 years. Histologically, all cases showed a well-differentiated atypical infiltrative squamous proliferative lesion exhibiting a lobulated and cystic pattern of growth in the dermis. Abrupt keratinization reminiscent of trichilemmal keratinization was noted. Mohs micrographic surgery and radiation therapy were used as primary treatment modalities, maintaining digit functionality and achieving remission. LIMITATIONS: Limitations of this study included the small number of cases, the infrequency with which this tumor has been reported in the literature, and the inability to obtain follow-up on an older archival case. CONCLUSIONS: Onycholemmal carcinoma is a distinct type of squamous cell carcinoma arising from the nail isthmus; its natural clinical course is indolent. In this regard less aggressive digit-sparing treatment modalities such as radiation or Mohs micrographic surgery should be considered.

Osteopathic manipulative treatment: novel application to dermatological disease.

Dermatological diseases, such as dysesthesia syndromes, stasis dermatoses, and hyperhidrosis are difficult to treat due to their complex etiologies. Current theories suggest these diseases are caused by physiological imbalances, such as nerve impingement, localized tissue congestion, and impaired autonomic regulation. Osteopathic manipulative therapy targets these physiological dysfunctions and may serve as a beneficial therapeutic option. Osteopathic manipulative therapy techniques include high velocity low amplitude, muscle energy, counterstrain, myofascial release, craniosacral, and lymphatic drainage. An osteopathic manipulative therapy technique is chosen based on its physiological target for a particular disease. Osteopathic manipulative therapy may be useful alone or in combination with standard therapeutic options. However, due to the lack of standardized trials supporting the efficacy of osteopathic manipulative therapy treatment for dermatological disease, randomized, well-controlled studies are necessary to confirm its therapeutic value.

Fatal Henoch-Schonlein purpura in an adult related to bowel perforation: report and review of the literature.

BACKGROUND: Henoch-Schonlein purpura is an idiopathic, IgA associated, systemic small-vessel vasculitis characterized by the clinical tetrad of palpable purpura, arthralgias, renal dysfunction, and abdominal pain. Whereas Henoch-Schonlein is an overwhelmingly pediatric disease, its rare diagnosis in adults carries a much higher morbidity and mortality. OBSERVATIONS: We describe a 52-year-old man with biopsy proven Henoch-Schonlein who expired from bowel perforation. CONCLUSIONS: Severe gastrointestinal complications and death from gastrointestinal involvement by Henoch-Schonlein purpura is rare. The authors surmise that multiple co-morbidities may have contributed to our patient's demise.

CD4+ CD56+ hematodermic neoplasm and plasmacytoid dendritic cell tumor: case report and review of the literature.

CD4+ CD56+ hematodermic neoplasm (HN) is a rare and aggressive neoplasm that has raised controversy regarding its etiology. CD4+ CD56+ HN is thought to be derived from plasmacytoid dendritic cells (pDCs) and most commonly stains with CD4, CD56, CD123, and T-cell leukemia/lymphoma 1 (TCL1). Skin manifestations usually are the presenting signs and vary in appearance. Lymph node involvement also is common at the time of presentation, and the natural course of the disease is a progression to leukemia. Treatment of CD4+CD56+ HN focuses on multiple chemotherapeutic regimens but none have been proven to successfully impact overall survival.

Pemphigoid gestationis: a case report and review of the literature.

Pemphigoid gestationis (PG) is an uncommon autoimmune bullous disease that almost exclusively presents during pregnancy. Patients typically present with a diffuse blistering and intensely pruritic eruption that begins periumbilically and spreads to involve the rest of the body. Direct immunofluorescence demonstrating C3 in a linear pattern along the dermoepidermal junction confirms the diagnosis of PG. Corticosteroids remain the choice of therapy and early intervention is essential because of possible adverse effects of PG on the fetus. We report a case of PG and review the literature.

Dermatology: a specialty that exemplifies the osteopathic medical profession.

Even though the tradition of osteopathic medicine is based in primary care, more osteopathic graduates than in the past are pursuing subspecialties within medicine. Some claim that medical specialties, such as dermatology, compromise osteopathic principles and philosophy. However, the authors contend that dermatology exemplifies the ideals expressed by Andrew Taylor Still, MD, DO, and explain how osteopathic manipulative treatment and the principles of osteopathic medicine can be applied to dermatologic disease and patient care.