Impact of a Bronchiolitis Clinical Pathway on Management Decisions by Preferred Language.

Background: Clinical pathways standardize healthcare utilization, but their impact on healthcare equity is poorly understood. This study aims to measure the effect of a bronchiolitis pathway on management decisions by preferred language for care. Methods: We included all emergency department encounters for patients aged 1-12 months with bronchiolitis from 1/1/2010 to 10/31/2020. The prepathway period ended 10/31/2011, and the postpathway period was 1/1/2012-10/31/2020. We performed retrospective interrupted time series analyses to assess the impact of the clinical pathway by English versus non-English preferred language on the following outcomes: chest radiography (CXR), albuterol use, 7-day return visit, 72-hour return to admission, antibiotic use, and corticosteroid use. Analyses were adjusted for presence of a complex chronic condition. Results: There were 1485 encounters in the preperiod (77% English, 14% non-English, 8% missing) and 7840 encounters in the postperiod (79% English, 15% non-English, 6% missing). CXR, antibiotic, and albuterol utilization exhibited sustained decreases over the study period. Pathway impact did not differ by preferred language for any outcome except albuterol utilization. The prepost slope effect of albuterol utilization was 10% greater in the non-English versus the English group (p for the difference by language = 0.022). Conclusions: A clinical pathway was associated with improvements in care regardless of preferred language. More extensive studies involving multiple pathways and care settings are needed to assess the impact of clinical pathways on health equity.

Direct oral anticoagulants in skin surgery: a systematic review of their complications and recommendations for perioperative management.

INTRODUCTION: Many patients undergoing cutaneous surgery are prescribed at least one anticoagulant or antiplatelet agent. With the recent emergence of direct oral anticoagulants (DOACs), there is a deficit of knowledge regarding optimal perioperative management. This review aims to evaluate the evidence and risk surrounding management of DOACs in patients undergoing skin surgeries. METHODS: Systematic review of EMBASE, Scopus, and PubMed, with inclusion of studies that detailed perioperative management of DOACs in those undergoing skin surgery. Primary outcome measures were perioperative hemorrhagic and thromboembolic complications. RESULTS: Seven thousand seven hundred and forty-one abstracts were identified, with 13 articles meeting inclusion criteria. Two studies investigated complication risk associated with DOAC continuation in skin surgery and found an average rate of hemorrhagic complications of 1.74%. Two studies evaluated complications associated with DOAC cessation prior to skin surgery, with a pooled thromboembolic complication rate of 0.15%. Articles comparing continuation and cessation discovered no decreased risk of bleeding with DOAC cessation prior to surgery (P = 0.93). Seven of the 13 articles compared complications in a control vs a DOAC group undergoing cutaneous procedures. Evidence was conflicting but may have suggested a small increase in bleeding risk in those on DOAC therapy. CONCLUSION: Optimal management of anticoagulants perioperatively is difficult because of conflicting information, complicated by advent of novel agents. Risk of hemorrhagic complications with both continuation and interruption of DOAC therapy was low. Perioperative DOAC management can be guided by procedural bleeding and patient clotting risk and can often be continued in minor dermatologic procedures.

Race, Ethnicity, and Ancestry in Clinical Pathways: A Framework for Evaluation.

Clinical algorithms, or "pathways," promote the delivery of medical care that is consistent and equitable. Race, ethnicity, and/or ancestry terms are sometimes included in these types of guidelines, but it is unclear if this is appropriate for clinical decision-making. At our institution, we developed and applied a structured framework to determine whether race, ethnicity, or ancestry terms identified in our clinical pathways library should be retained, modified, or removed. First, we reviewed all text and associated reference documents for 132 institutionally-developed clinical pathways and identified 8 pathways that included race, ethnicity, or ancestry terms. Five pathways had clear evidence or a change in institutional policy that supported removal of the term. Multispecialty teams conducted additional in-depth evaluation of the 3 remaining pathways (Acute Viral Illness, Hyperbilirubinemia, and Weight Management) by applying the framework. In total, based on these reviews, race, ethnicity, or ancestry terms were removed (n = 6) or modified (n = 2) in all 8 pathways. Application of the framework established several recommended practices, including: (1) define race, ethnicity, and ancestry rigorously; (2) assess the most likely mechanisms underlying epidemiologic associations; (3) consider whether inclusion of the term is likely to mitigate or exacerbate existing inequities; and (4) exercise caution when applying population-level data to individual patient encounters. This process and framework may be useful to other institutional programs and national organizations in evaluating the inclusion of race, ethnicity, and ancestry in clinical guidelines.

An in vitro model of the macrophage-endothelial interface to characterize CAR T-cell induced cytokine storm.

Chimeric Antigen Receptor (CAR) T-cell therapy is a highly effective treatment for B-cell malignancies but limited in use due to clinically significant hyperinflammatory toxicities. Understanding the pathophysiologic mechanisms which mediate these toxicities can help identify novel management strategies. Here we report a novel in vitro model of the macrophage-endothelial interface to study the effects of CAR T-cell-induced cytokine storm. Using this model, we demonstrate that macrophage-mediated inflammation is regulated by endothelial cell activity. Furthermore, endothelial inflammation occurs independently of macrophages following exposure to CAR T-cell products and the induced endothelial inflammation potentiates macrophage-mediated inflammatory signaling, leading to a hyperinflammatory environment. While corticosteroids, the current gold standard of care, attenuate the resulting macrophage inflammatory signaling, the endothelial activity remains refractory to this treatment strategy. Utilizing a network model, coupled to in vitro secretion profiling, we identified STAT3 programming as critical in regulating this endothelial behavior. Lastly, we demonstrate how targeting STAT3 activity can abrogate endothelial inflammation and attenuate this otherwise hyperinflammatory environment. Our results demonstrate that endothelial cells play a central role in the pathophysiology of CAR T-cell toxicities and targeting the mechanisms driving the endothelial response can guide future clinical management.

Current Trends in Anti-Aging Strategies.

The process of aging manifests from a highly interconnected network of biological cascades resulting in the degradation and breakdown of every living organism over time. This natural development increases risk for numerous diseases and can be debilitating. Academic and industrial investigators have long sought to impede, or potentially reverse, aging in the hopes of alleviating clinical burden, restoring functionality, and promoting longevity. Despite widespread investigation, identifying impactful therapeutics has been hindered by narrow experimental validation and the lack of rigorous study design. In this review, we explore the current understanding of the biological mechanisms of aging and how this understanding both informs and limits interpreting data from experimental models based on these mechanisms. We also discuss select therapeutic strategies that have yielded promising data in these model systems with potential clinical translation. Lastly, we propose a unifying approach needed to rigorously vet current and future therapeutics and guide evaluation toward efficacious therapies.

Evaluating dermatology education in Australia: Medical students' and junior doctors' perceptions.

BACKGROUND: Despite a high frequency of dermatological general practice and emergency department presentations, including serious and potentially fatal skin conditions, evidence suggests that undergraduate dermatological education remains sparse. Given this, there exists a need to gauge dermatology-relevant knowledge and skill in our new doctors. METHODS: An online survey was completed by final-phase medical students and junior doctors from Australian medical schools. The survey appraised self-perceived confidence of dermatology knowledge and skills, in addition to 5 knowledge-based multiple-choice questions. RESULTS: Nine hundred and forty-two eligible responses were completed. Respondents reported low confidence in identifying dermatological conditions in people with skin of colour (µ = 1.69), handing over to dermatology colleagues (µ = 2.00) and in diagnosing and managing acute/emergency dermatology conditions (µ = 1.84). In contrast, participants felt most confident in counselling sun-protective behaviours (µ = 3.95) and suturing small wounds (µ = 3.43). 76.4% of respondents had not undertaken any dermatology placement, and 70.9% had never been formally assessed in dermatology. Those who received dermatology placement had a significantly higher aggregated self-reported confidence (p < 0.0001) and answered significantly more MCQs correctly (p = 0.0419). Those who had been formally assessed had a significantly higher self-reported confidence (p < 0.001) and answered significantly more MCQs correctly (p = 0.007). CONCLUSION: Final-phase medical students and junior doctors exhibit low confidence across many dermatology competencies. Participants believed they need more dermatology education, and seldom feel prepared when exposed to dermatologic pathologies. Introduction of a standardised curriculum, formal assessments and increased clinical exposure are possible solutions.

Defocused contrast sensitivity function in peripheral vision.

PURPOSE: Human peripheral detection performance is affected by optical factors such as defocus and higher order aberrations. From optical theory, we would expect defocus to produce local depressions (notches) in the contrast sensitivity function (CSF). However, such notches have not been observed in peripheral vision, and it is unknown whether human peripheral vision can detect local depressions (notches) in the CSF, such as those produced by monochromatic defocus when all monochromatic ocular aberrations are corrected. The purpose of the study was to identify such notches. METHODS: Participants were three adult emmetropes. Following full adaptive optics correction, on-axis and 20° nasal visual field detection CSFs in monochromatic light were measured for the right eye with a 7 mm diameter pupil, both without and with ±2 D defocus, and with separate determinations for horizontal and vertical gratings. Defocused CSFs were compared with predictions based on theoretical modulation transfer functions. RESULTS: Notches in the monochromatic defocused CSFs were identified for peripheral vision at optically predicted spatial frequencies with other monochromatic ocular aberrations corrected, provided that there was adequate spatial frequency sampling. The spatial frequencies of notches were similar to those predicted from optical theory, but their depths (0.3 to 0.9 log unit) were smaller than predicted. CONCLUSION: With fine spatial frequency sampling, notches were identified in defocused monochromatic CSFs when all other monochromatic ocular aberrations were corrected, both on-axis and at 20° eccentricity. Unless recognised as such, notches may contribute to noise in through-focus detection measurements of peripheral visual performance.

Peripheral detection acuity for interference fringes and screen-based Gabor gratings.

This study compared on-axis and peripheral detection acuities measured with interference fringes, that bypass eye optics, and with screen-based Gabor gratings combined with an adaptive optics system. Gabor gratings are sinusoidal gratings incorporated with a Gaussian envelope that attenuate spatial frequency broadening that occur at the window edge. The magnitude of the attenuation was varied. Peripheral detection acuities were always higher for interference fringes than for Gabor gratings. Less attenuated Gabors (with sharper edges) had higher acuities than more attenuated Gabors (with less sharp edges). Theoretical investigations indicated that the spatial frequency broadening occurring due to the sharp edge of the less attenuated Gabors contribute little to high detection grating acuity in the periphery, but that the lower attenuation provides a greater number of visible cycles which is of more benefit to detection than is the case on-axis.

Dominant outflow vein occlusion in the management of naturally occurring peripheral arteriovenous anomalies in cats and dogs.

Two dogs and 1 cat were referred to a tertiary veterinary center for the consultation and treatment of limb edema, variable dermal sanguineous crusting lesions, and intermittent lameness. A peripheral arteriovenous anomaly (PAA) was diagnosed via computed tomographic angiography (CTA) in each case. Arteriography enabled further evaluation of the PAA with confirmation of a dominant outflow vein. Dominant outflow vein occlusion was achieved by direct ligation in 1 dog and retrograde transvenous glue embolization in the cat and other dog. Repeat arteriography demonstrated resolution of arteriovenous shunting. Presenting clinical signs resolved in all animals. The previously identified aberrant vessels in 1 dog were not identified after CTA 40 days postoperatively. No postoperative complications or recurrence was identified in any case during the 6- to 55-month follow-up period.

Autofluorescence of blood and its application in biomedical and clinical research.

Autofluorescence of blood has been explored as a label free approach for detection of cell types, as well as for diagnosis and detection of infection, cancer, and other diseases. Although blood autofluorescence is used to indicate the presence of several physiological abnormalities with high sensitivity, it often lacks disease specificity due to use of a limited number of fluorophores in the detection of several abnormal conditions. In addition, the measurement of autofluorescence is sensitive to the type of sample, sample preparation, and spectroscopy method used for the measurement. Therefore, while current blood autofluorescence detection approaches may not be suitable for primary clinical diagnosis, it certainly has tremendous potential in developing methods for large scale screening that can identify high risk groups for further diagnosis using highly specific diagnostic tests. This review discusses the source of blood autofluorescence, the role of spectroscopy methods, and various applications that have used autofluorescence of blood, to explore the potential of blood autofluorescence in biomedical research and clinical applications.

Retrospective analysis of the efficacy and duration of botulinum toxin A injections in 30 patients with palmar hyperhidrosis.

Palmar hyperhidrosis is a common disorder characterised by excessive sweating due to hyperfunction of the sweat glands. It can be classified as primary disease, or secondary to other causes. It has a high morbidity, and a range of treatment options. Botulinum toxin injections inhibit the release of acetylcholine from the presynaptic receptors. It is an effective treatment; however, it is infrequently selected as only axillary hyperhidrosis currently attracts a Medicare subsidy. We conducted a retrospective review of 30 patients at a Sydney dermatology clinic who received botulinum toxin injections for palmar hyperhidrosis within the past 5 years. This study has the largest patient cohort with this condition in Australia. There was evidence for a median reduction in the Hyperhidrosis Disease Severity Scale, a qualitative self-reported score, as well as an increasing duration of efficacy with repeated injections. There were minimal side-effects of weakness and numbness. There is also an association between treatment of palmar disease and improvement in plantar disease, which suggests that treatment of palmar hyperhidrosis should be considered earlier and more frequently.

Peripheral vision and hazard detection with average phakic and pseudophakic optical errors.

The impact of peripheral optical errors induced by intraocular lenses was evaluated by simulating the average phakic and pseudophakic image qualities. An adaptive optics system was used to simulate the optical errors in 20° nasal and inferior visual field in phakic subjects. Peripheral resolution acuity, contrast sensitivity and hazard detection were evaluated. Pseudophakic errors typical for monofocal designs had a negative effect on resolution acuity and contrast sensitivity and the hazard detection task also showed increased false positive and misses and a longer reaction time compared to phakic optical errors. The induced peripheral pseudophakic optical errors affect the peripheral visual performance and thereby impact functional vision.

A Rapid, High-Sensitivity SARS-CoV-2 Nucleocapsid Immunoassay to Aid Diagnosis of Acute COVID-19 at the Point of Care: A Clinical Performance Study.

INTRODUCTION: The LumiraDx severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen test, which uses a high-sensitivity, microfluidic immunoassay to detect the nucleocapsid protein of SARS-CoV-2, was evaluated for diagnosing acute coronavirus disease 2019 (COVID-19) in adults and children across point-of-care settings (NCT04557046). METHODS: Two paired anterior nasal swabs or two paired nasopharyngeal swabs were collected from each participant. Swabs were tested by the LumiraDx SARS-CoV-2 antigen test and compared with real-time polymerase chain reaction (rt-PCR; Roche cobas 6800 platform). Sensitivity, specificity and likelihood ratios were calculated. Results were stratified on the basis of gender, age, duration of symptoms, and rt-PCR cycle threshold. RESULTS: Out of the 512 participants, aged 0-90 years, of this prospective validation study, 414 (81%) were symptomatic for COVID-19 and 123 (24%) swabs were positive for SARS-CoV-2 based on rt-PCR testing. Compared with rt-PCR, the 12-min nasal swab test had 97.6% sensitivity and 96.6% specificity, and nasopharyngeal swab had 97.5% sensitivity and 97.7% specificity, within 12 days of symptom onset, representing the period of infectivity. All (100%) samples detected within 33 rt-PCR cycles were also identified using the antigen test. Results were consistent across age and gender. The user error rate of the test system when used by minimally trained operators was 0.7% (95% confidence interval [CI] 0.1-3.7%). CONCLUSION: The rapid, high-sensitivity assay using nasopharyngeal or anterior nasal sampling may offer significant improvements for diagnosing acute SARS-CoV-2 infection in clinic- and community-based settings.

Factors associated with health-related quality of life in patients with cirrhosis: a systematic review.

BACKGROUND: Patients with cirrhosis have a poor health-related quality of life (HRQoL). Recognizing factors that affect HRQoL is key in delivering patient-centred care. AIM: To identify factors most commonly associated with a poor HRQoL in adults with cirrhosis in a systematic review of the literature. METHODS: Four databases (MEDLINE, EMBASE, CENTRAL and PsycINFO) were searched from inception to March 2020, using terms related to patient-reported outcomes plus cirrhosis. Studies that analysed an association between at least one factor and HRQoL in adult patients with cirrhosis were included. Abstract and full-text screening was performed by two reviewers. Data were collected on factors evaluated in each study and the significance of their association with HRQoL. RESULTS: A total of 10647 citations were reviewed, of which 109 met eligibility criteria. 76% of the studies used a generic instrument while only 45% used liver-specific instruments. Among identified factors, demographic factors and cirrhosis aetiology were not generally associated with poor HRQoL except for poor social support. Depression, poor sleep and muscle cramps affected HRQoL in all the studies that evaluated them. Among comorbidities, frailty, falls, malnutrition and cognitive impairment were also associated with poor HRQoL in the majority of studies. Among cirrhosis-specific decompensating events, only hepatic encephalopathy (HE) was consistently associated with impairment in HRQoL (75% of studies). CONCLUSION: Many factors impact poor HRQoL in patients with cirrhosis such as depression, muscle cramps, poor sleep, falls, frailty and malnutrition. Among cirrhosis decompensating events, HE was the complication most commonly associated with a poor HRQoL.

Leading synchronous virtual teaching sessions.

While there has been increasing demand for online education over the past decade, social distancing recommendations during the COVID-19 pandemic have accelerated the transition from the physical to the virtual classroom. Staples of clinical education, such as grand rounds, noon conferences, case conferences and chalk talks, have been abruptly forced to shift into the digital world. There is an immediate need for guidance on synchronous virtual teaching, especially since health professional educators may lack familiarity with the technologies available and theories that guide their use. The following framework can help educators plan, develop and deliver their virtual teaching sessions to optimize student engagement and produce meaningful learning outcomes.

Transcatheter Bariatric Embolotherapy for Weight Reduction in Obesity.

BACKGROUND: Obesity is well-appreciated to result in poor cardiovascular and metabolic outcomes. Dietary and medical weight loss strategies are frequently unsuccessful and unsustainable. Bariatric surgery is quite effective, but is reserved for the most obese patients because of the associated intraoperative/post-operative risks. In preclinical and early clinical case series, a novel therapy, transcatheter bariatric embolotherapy (TBE) of the left gastric artery, has been reported to promote weight loss by reducing ghrelin, an appetite-stimulating hormone secreted from the gastric fundus. OBJECTIVES: The purpose of this study was to examine TBE in a single-blind, sham procedure randomized trial. METHODS: Obese subjects (body mass index 35 to 55 kg/m2) were randomized 1:1 to either sham or TBE targeting the left gastric artery using an occlusion balloon microcatheter to administer 300- to 500-µm embolic beads. All patients entered a lifestyle counseling program. Patients and physicians performing follow-up were blind to the allocated therapy. Endoscopy was performed at baseline and 1-week post-procedure. The primary endpoint was 6-month total body weight loss (TBWL). RESULTS: Eligible subjects (n = 44; age 45.5 ± 9.4 years; 8 men/36 women; body mass index 39.6 ± 3.8 kg/m2) were randomized to undergo the sham or TBE procedure with no device-related complications and 1 vascular complication. Patients reported mild nausea and vomiting, and endoscopy revealed only minor self-limiting ulcers in 5 patients. At 6 months, in both the intention-to-treat and per-protocol populations, the TBWL was greater with TBE (7.4 kg/6.4% and 9.4 kg/8.3% loss, respectively) than sham (3.0 kg/2.8% and 1.9 kg/1.8%, respectively; p = 0.034/0.052 and p = 0.0002/0.0011, respectively). The TBWL was maintained with TBE at 12 months (intention-to-treat 7.8 kg/6.5% loss, per-protocol 9.3 kg/9.3% loss; p = 0.0011/0.0008, p = 0.0005/0.0005, respectively). CONCLUSIONS: In this randomized pilot trial, we have established the proof-of-principle that transcatheter bariatric embolotherapy of the left gastric artery is well-tolerated and promotes clinically significant weight loss over a sham procedure.(The Lowering Weight in Severe Obesity by Embolization of the Gastric Artery Trial [LOSEIT]; NCT03185949).