Immune Analysis Using Vitreous Optical Coherence Tomography Imaging in Rats with Steroid-Induced Glaucoma.

Glaucoma is a multifactorial pathology involving the immune system. The subclinical immune response plays a homeostatic role in healthy situations, but in pathological situations, it produces imbalances. Optical coherence tomography detects immune cells in the vitreous as hyperreflective opacities and these are subsequently characterised by computational analysis. This study monitors the changes in immunity in the vitreous in two steroid-induced glaucoma (SIG) animal models created with drug delivery systems (microspheres loaded with dexamethasone and dexamethasone/fibronectin), comparing both sexes and healthy controls over six months. SIG eyes tended to present greater intensity and a higher number of vitreous opacities (p < 0.05), with dynamic fluctuations in the percentage of isolated cells (10 µm2), non-activated cells (10-50 µm2), activated cells (50-250 µm2) and cell complexes (>250 µm2). Both SIG models presented an anti-inflammatory profile, with non-activated cells being the largest population in this study. However, smaller opacities (isolated cells) seemed to be the first responder to noxa since they were the most rounded (recruitment), coinciding with peak intraocular pressure increase, and showed the highest mean Intensity (intracellular machinery), even in the contralateral eye, and a major change in orientation (motility). Studying the features of hyperreflective opacities in the vitreous using OCT could be a useful biomarker of glaucoma.

Innovations in Tele-Critical Care Nursing During the COVID-19 Pandemic.

For decades, tele-critical care (TCC) programs have provided expert population surveillance with standardized clinical interventions for critically ill patients. The COVID-19 pandemic created massive strains on critical care resources. For this report, standard questions were used to solicit COVID-19 pandemic workflow and service modifications from a network of TCC leaders to describe the rapid expansion of TCC-supported services during the pandemic. In this article, leaders from 7 TCC programs report on the effective use of services to support changing hospital needs during the pandemic in areas such as clinical education, personal protective equipment stewardship, expansion of virtual care, and creative staffing models, among others.

Evaluation of evolving sepsis screening criteria in discriminating suspected sepsis and mortality among adult patients admitted to the intensive care unit.

BACKGROUND: Institutions struggle with successful use of sepsis alerts within electronic health records. OBJECTIVE: Test the association of sepsis screening measurement criteria in discrimination of mortality and detection of sepsis in a large dataset. DESIGN: Retrospective, cohort study using a large United States (U.S.) intensive care database. The Institutional Review Board exempt status was obtained from Kansas University Medical Center Human Research Protection Program (10-1-2015). SETTING: 334 U.S. hospitals participating in the eICU Research Institute. PARTICIPANTS: Nine hundred twelve thousand five hundred and nine adult intensive care admissions from 183 hospitals. METHODS: Exposures included: systemic inflammatory response syndrome criteria ≥ 2 (Sepsis-1); systemic inflammatory response syndrome criteria with organ failure criteria ≥ 3.5 points (Sepsis-2); and sepsis-related organ failure assessment score ≥ 2 and quick score ≥ 2 (Sepsis-3). Discrimination of outcomes was determined with/without (adjusted/unadjusted) baseline risk exposure to a model. The receiver operating characteristic curve (AUROC) and odds ratios (ORs) for each decile of baseline risk of sepsis or death were assessed. RESULTS: Within the eligible cohort of 912,509, a total of 86,219 (9.4 %) patients did not survive their hospital stay and 186,870 (20.5 %) met the definition of suspected sepsis. For suspected sepsis discrimination, Sepsis-2 (unadjusted AUROC 0.67, 99 % CI: 0.66-0.67 and adjusted AUROC 0.77, 99 % CI: 0.77-0.77) outperformed Sepsis-3 (SOFA unadjusted AUROC 0.61, 99 % CI: 0.61-0.61 and adjusted AUROC 0.74, 99 % CI: 0.74-0.74) (qSOFA unadjusted AUROC 0.59, 99 % CI: 0.59-0.60 and adjusted AUROC 0.73, 99 % CI: 0.73-0.73). Sepsis-2 also outperformed Sepsis-1 (unadjusted AUROC 0.58, 99 % CI: 0.58-0.58 and adjusted AUROC 0.73, 99 % CI: 0.73-0.73). In between differences of AUROCs were statistically significantly different. Sepsis-2 ORs were higher for the outcome of suspected sepsis when considering deciles of risk than the other measurement systems. CONCLUSIONS AND RELEVANCE: Sepsis-2 outperformed other systems in suspected sepsis detection and was comparable to SOFA in prognostic accuracy of mortality in adult intensive care patients.

Improving ICU Risk Predictive Models Through Automation Designed for Resiliency Against Documentation Bias.

OBJECTIVES: Electronic health records enable automated data capture for risk models but may introduce bias. We present the Philips Critical Care Outcome Prediction Model (CCOPM) focused on addressing model features sensitive to data drift to improve benchmarking ICUs on mortality performance. DESIGN: Retrospective, multicenter study of ICU patients randomized in 3:2 fashion into development and validation cohorts. Generalized additive models (GAM) with features designed to mitigate biases introduced from documentation of admission diagnosis, Glasgow Coma Scale (GCS), and extreme vital signs were developed using clinical features representing the first 24 hours of ICU admission. SETTING: eICU Research Institute database derived from ICUs participating in the Philips eICU telecritical care program. PATIENTS: A total of 572,985 adult ICU stays discharged from the hospital between January 1, 2017, and December 31, 2018, were included, yielding 509,586 stays in the final cohort; 305,590 and 203,996 in development and validation cohorts, respectively. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Model discrimination was compared against Acute Physiology and Chronic Health Evaluation (APACHE) IVa/IVb models on the validation cohort using the area under the receiver operating characteristic (AUROC) curve. Calibration assessed by actual/predicted ratios, calibration-in-the-large statistics, and visual analysis. Performance metrics were further stratified by subgroups of admission diagnosis and ICU characteristics. Historic data from two health systems with abrupt changes in Glasgow Coma Scale (GCS) documentation were assessed in the year prior to and after data shift. CCOPM outperformed APACHE IVa/IVb for ICU mortality (AUROC, 0.925 vs 0.88) and hospital mortality (AUROC, 0.90 vs 0.86). Better calibration performance was also attained among subgroups of different admission diagnoses, ICU types, and over unique ICU-years. The CCOPM provided more stable predictions compared with APACHE IVa within an external cohort of greater than 120,000 patients from two health systems with known changes in GCS documentation. CONCLUSIONS: These mortality risk models demonstrated excellent performance compared with APACHE while appearing to mitigate bias introduced through major shifts in GCS documentation at two large health systems. This provides evidence to support using automated capture rather than trained personnel for capture of GCS data used in benchmarking ICUs on mortality performance.

What the Joint Commission Medication Management Titration Standards Mean to Quality Care for Complex Patients.

ABSTRACT: The Joint Commission (TJC), the nation's largest healthcare accreditor, was founded in the 1950s. Its Standards for Medication Management (MM) of titratable medications focused on prescriptive ordering practices versus reliance on nurse clinical decision making. The use of measurable endpoints to guide nurse decision making regarding medication titration has been the standard of care since the inception of TJC. Evidence to support altering these practice patterns is lacking. Using the 6 aims for the healthcare system (safe, timely, effective, efficient, equitable, and patient-centered) from the National Academy of Medicine, formerly the Institute of Medicine, and the American Association of Critical-Care Nurses Healthy Work Environment essential standards (skilled communication, true collaboration, effective decision making, appropriate staffing, meaningful recognition, authentic leadership), this article examines the impact of TJC MM standards on system design in critical care environments.

Tunable degrees of neurodegeneration in rats based on microsphere-induced models of chronic glaucoma.

This study compares four different animal models of chronic glaucoma against normal aging over 6 months. Chronic glaucoma was induced in 138 Long-Evans rats and compared against 43 aged-matched healthy rats. Twenty-five rats received episcleral vein sclerosis injections (EPIm cohort) while the rest were injected in the eye anterior chamber with a suspension of biodegradable microspheres: 25 rats received non-loaded microspheres (N-L Ms cohort), 45 rats received microspheres loaded with dexamethasone (MsDexa cohort), and 43 rats received microspheres co-loaded with dexamethasone and fibronectin (MsDexaFibro cohort). Intraocular pressure, neuroretinal function, structure and vitreous interface were evaluated. Each model caused different trends in intraocular pressure, produced specific retinal damage and vitreous signals. The steepest and strongest increase in intraocular pressure was seen in the EPIm cohort and microspheres models were more progressive. The EPIm cohort presented the highest vitreous intensity and percentage loss in the ganglion cell layer, the MsDexa cohort presented the greatest loss in the retinal nerve fiber layer, and the MsDexaFibro cohort presented the greatest loss in total retinal thickness. Function decreased differently among cohorts. Using biodegradable microspheres models it is possible to generate tuned neurodegeneration. These results support the multifactorial nature of glaucoma based on several noxa.

Analysis of Parainflammation in Chronic Glaucoma Using Vitreous-OCT Imaging.

Glaucoma causes blindness due to the progressive death of retinal ganglion cells. The immune response chronically and subclinically mediates a homeostatic role. In current clinical practice, it is impossible to analyse neuroinflammation non-invasively. However, analysis of vitreous images using optical coherence tomography detects the immune response as hyperreflective opacities. This study monitors vitreous parainflammation in two animal models of glaucoma, comparing both healthy controls and sexes over six months. Computational analysis characterizes in vivo the hyperreflective opacities, identified histologically as hyalocyte-like Iba-1+ (microglial marker) cells. Glaucomatous eyes showed greater intensity and number of vitreous opacities as well as dynamic fluctuations in the percentage of activated cells (50-250 microns2) vs. non-activated cells (10-50 microns2), isolated cells (10 microns2) and complexes (>250 microns2). Smaller opacities (isolated cells) showed the highest mean intensity (intracellular machinery), were the most rounded at earlier stages (recruitment) and showed the greatest change in orientation (motility). Study of vitreous parainflammation could be a biomarker of glaucoma onset and progression.

TeleICU Interdisciplinary Care Teams.

Telehealth in intensive care units (TeleICU) is the provision of critical care using audio-visual communication and health information systems across varying clinical and geographically dispersed settings. The optimal structure of a TeleICU team is one that leverages expert clinical knowledge to address the needs of critical care patients, regardless of hospital location or availability of an onsite intensivist. Information related to the optimal TeleICU team structure is lacking. This article examines the optimal TeleICU team composition, which is one that incorporates the use of an interdisciplinary approach, leverages technology, and is cognizant of varying geographic locations.

Influence of Sex on Neuroretinal Degeneration: Six-Month Follow-Up in Rats With Chronic Glaucoma.

Purpose: To evaluate differences by sex in the neuroretina of rats with chronic glaucoma over 24 weeks of follow-up, and to assess by sex the influence on neurodegeneration of different methods of inducing ocular hypertension. Methods: Forty-six Long-Evans rats-18 males and 28 females-with induced chronic glaucoma were analyzed. Glaucoma was achieved via 2 models: repeatedly sclerosing the episcleral veins (9 male/14 female) or by injecting poly(lactic-co-glycolic acid) microspheres measuring 20 to 10 µm (Ms20/10) into the anterior chamber (9 male/14 female). The IOP was measured weekly by tonometer; neuroretinal function was recorded by dark/light-adapted electroretinography at baseline and weeks 12 and 24; and structure was analyzed by optical coherence tomography using the retina posterior pole, retinal nerve fiber layer and ganglion cell layer protocols at baseline and weeks 8, 12, 18, and 24. Results: Males showed statistically significant (P < 0.05) higher IOP in both chronic glaucoma models, and greater differences were found in the episcleral model at earlier stages. Males with episclerally induced glaucoma showed a statistically higher increase in retinal thickness in optical coherence tomography recordings than females and also when comparing Ms20/10 at 12 weeks. Males showed a higher percentage of retinal nerve fiber layer thickness loss in both models. Ganglion cell layer thickness loss was only detected in the Ms20/10 model. Males exhibited worse dark/light-adapted functionality in chronic glaucoma models, which worsened in the episcleral sclerosis model at 12 weeks, than females. Conclusions: Female rats with chronic glaucoma experienced lower IOP and structural loss and better neuroretinal functionality than males. Sex and the ocular hypertension-inducing method influenced neuroretinal degeneration.

Survey of Nurses' Experiences Applying The Joint Commission's Medication Management Titration Standards.

BACKGROUND: Critical care nurses titrate continuous infusions of medications to achieve clinical end points. In 2017, The Joint Commission (TJC) placed restrictions on titration practice, decreasing nurses' autonomous decision-making. OBJECTIVES: To describe the practice and perceptions of nurses regarding the 2017 TJC accreditation/regulatory standards for titration of continuous medication infusions. METHODS: A survey of nurses' experiences titrating continuous medication infusions was developed, validated, and distributed electronically to members of the American Association of Critical-Care Nurses. RESULTS: The content validity index for the survey was 1.0 for relevance and 0.95 for clarity. A total of 781 nurses completed the survey; 625 (80%) perceived titration standards to cause delays in patient care, and 726 (93%) experienced moral distress (mean [SD], 4.97 [2.67]; scale, 0-10). Among respondents, 33% could not comply with titration orders, 68% reported suboptimal care resulting from pressure to comply with orders, 70% deviated from orders to meet patient needs, and 84% requested revised orders to ensure compliance. Suboptimal care and delays in care significantly and strongly (regression coefficients ≥0.69) predicted moral distress. CONCLUSIONS: Critical care nurses perceive TJC medication titration standards to adversely impact patient care and contribute to moral distress. The improved 2020 updates to the standards do not address delays and inability to comply with orders, leading to moral distress. Advocacy is indicated in order to mitigate unintended consequences of TJC medication management titration standards.

Thematic Analysis of Nurses' Experiences With The Joint Commission's Medication Management Titration Standards.

BACKGROUND: For decades, medication titration has been within nurses' scope and practice. In 2017 The Joint Commission (TJC) revised elements for orders for the titration of continuous intravenous medications. OBJECTIVES: To explore the practice and perceptions of nurses regarding TJC standards for titration of continuous intravenous medications. METHODS: Nurses with experience titrating medications completed an investigator-designed, validated cross-sectional survey. Inductive thematic analysis was conducted in order to analyze the open-ended comments from that quantitative survey. RESULTS: From among 730 completed surveys, 159 comments were received. Analysis of the comments yielded 3 levels of abstraction. Two overarching themes were harm and professionalism. Additional abstraction for the harm theme revealed categories of erosion of workplace wellness, moral dilemma, and patient safety, which were coded as relating to workplace stress, workload, burnout/turnover, physical risk, inefficiency, demeaning/devalued, falsification of records, problematic orders, burden of documentation, suboptimal care, delay in care, individualized care, and provider availability. Within the professionalism theme, categories of autonomy and nurse proficiency were identified, with 7 associated codes: top of scope, critical thinking, overregulation, teamwork, education, registered nurse knowledge, and novice registered nurse guidance. CONCLUSIONS: The standards from TJC impose harm by eroding workplace wellness and introducing moral dilemmas and patient safety concerns. Professionalism is threatened through limits on scope and autonomy. Further advocacy is necessary in order to resolve unanticipated consequences related to the titration standards.

Influence of Chronic Ocular Hypertension on Emmetropia: Refractive, Structural and Functional Study in Two Rat Models.

Chronic ocular hypertension (OHT) influences on refraction in youth and causes glaucoma in adulthood. However, the origin of the responsible mechanism is unclear. This study analyzes the effect of mild-moderate chronic OHT on refraction and neuroretina (structure and function) in young-adult Long-Evans rats using optical coherence tomography and electroretinography over 24 weeks. Data from 260 eyes were retrospectively analyzed in two cohorts: an ocular normotension (ONT) cohort (<20 mmHg) and an OHT cohort (>20 mmHg), in which OHT was induced either by sclerosing the episcleral veins (ES group) or by injecting microspheres into the anterior chamber. A trend toward emmetropia was found in both cohorts over time, though it was more pronounced in the OHT cohort (p < 0.001), especially in the ES group (p = 0.001) and males. IOP and refraction were negatively correlated at week 24 (p = 0.010). The OHT cohort showed early thickening in outer retinal sectors (p < 0.050) and the retinal nerve fiber layer, which later thinned. Electroretinography demonstrated early supranormal amplitudes and faster latencies that later declined. Chronic OHT accelerates emmetropia in Long-Evans rat eyes towards slowly progressive myopia, with an initial increase in structure and function that reversed over time.

Chronic Glaucoma Using Biodegradable Microspheres to Induce Intraocular Pressure Elevation. Six-Month Follow-Up.

BACKGROUND: To compare two prolonged animal models of glaucoma over 24 weeks of follow-up. A novel pre-trabecular model of chronic glaucoma was achieved by injection of biodegradable poly lactic-co-glycolic acid (PLGA) microspheres (10-20 µm) (Ms20/10) into the ocular anterior chamber to progressively increase ocular hypertension (OHT). METHODS: Rat right eyes were injected to induce OHT: 50% received a suspension of Ms20/10 in the anterior chamber at 0, 2, 4, 8, 12, 16 and 20 weeks, and the other 50% received a sclerosing episcleral vein injection biweekly (EPIm). Ophthalmological clinical signs, intraocular pressure (IOP), neuroretinal functionality measured by electroretinography (ERG), and structural analysis of the retina, retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) protocols using optical coherence tomography (OCT) and histological exams were performed. RESULTS: Both models showed progressive neuroretinal degeneration (p < 0.05), and contralateral eye affectation. The Ms20/10 model showed a more progressive increase in IOP and better preservation of ocular surface. Although no statistical differences were found between models, the EPIm showed a tendency to produce thicker retinal and thinner GCL thicknesses, slower latency and smaller amplitude as measured using ERG, and more aggressive disturbances in retinal histology. In both models, while the GCL showed the greatest percentage loss of thickness, the RNFL showed the greatest and earliest rate of thickness loss. CONCLUSIONS: The intracameral model with biodegradable microspheres resulted more like the conditions observed in humans. It was obtained by a less-aggressive mechanism, which allows for adequate study of the pathology over longer periods.

Novel Use of PLGA Microspheres to Create an Animal Model of Glaucoma with Progressive Neuroretinal Degeneration.

Progressive degeneration of neuroretinal tissue with maintained elevated intraocular pressure (IOP) to simulate chronic glaucoma was produced by intracameral injections of poly (lactic-co-glycolic) acid (PLGA) microspheres (Ms) in rat eyes. The right eye of 39 rats received different sizes of PLGA-Ms (2 µL suspension; 10% w/v): 14 with 38-20 µm Ms (Ms38/20 model) and 25 with 20-10 µm particles (Ms20/10 model). This novel glaucoma animal model was compared to the episcleral vein sclerosis (EPI) model (25 eyes). Injections were performed at baseline, two, four and six weeks. Clinical signs, IOP, retina and optic nerve thicknesses (using in vivo optical coherence tomography; OCT), and histological studies were performed. An IOP increment was observed in all three groups, however, the values obtained from the PLGA-Ms injection resulted lower with a better preservation of the ocular surface. In fact, the injection of Ms20/10 created a gentler, more progressive, and more sustained increase in IOP. This IOP alteration was correlated with a significant decrease in most OCT parameters and in histological ganglion-cell count for the three conditions throughout the eight-week follow-up. In all cases, progressive degeneration of the retina, retinal ganglion cells and optic nerve, simulating chronic glaucoma, was detected by OCT and corroborated by histological study. Results showed an alternative glaucoma model to the well-known episcleral vein model, which was simpler to perform, more reproducible and easier to monitor in vivo.

Monitoring New Long-Lasting Intravitreal Formulation for Glaucoma with Vitreous Images Using Optical Coherence Tomography.

Intravitreal injection is the gold standard therapeutic option for posterior segment pathologies, and long-lasting release is necessary to avoid reinjections. There is no effective intravitreal treatment for glaucoma or other optic neuropathies in daily practice, nor is there a non-invasive method to monitor drug levels in the vitreous. Here we show that a glaucoma treatment combining a hypotensive and neuroprotective intravitreal formulation (IF) of brimonidine-Laponite (BRI/LAP) can be monitored non-invasively using vitreoretinal interface imaging captured with optical coherence tomography (OCT) over 24 weeks of follow-up. Qualitative and quantitative characterisation was achieved by analysing the changes in vitreous (VIT) signal intensity, expressed as a ratio of retinal pigment epithelium (RPE) intensity. Vitreous hyperreflective aggregates mixed in the vitreous and tended to settle on the retinal surface. Relative intensity and aggregate size progressively decreased over 24 weeks in treated rat eyes as the BRI/LAP IF degraded. VIT/RPE relative intensity and total aggregate area correlated with brimonidine levels measured in the eye. The OCT-derived VIT/RPE relative intensity may be a useful and objective marker for non-invasive monitoring of BRI/LAP IF.

Effect of age and sex on neurodevelopment and neurodegeneration in the healthy eye: Longitudinal functional and structural study in the Long-Evans rat.

The processes involved in neurodevelopment and aging have not yet been fully discovered. This is especially challenging in premorbid or borderline situations of neurodegenerative diseases such as Alzheimer's or glaucoma. The retina, as part of the central nervous system, can be considered the easiest and most accessible neural structure that can be analyzed using non-invasive methods. Animal studies of neuroretinal tissue in situations of health and under controlled conditions allow the earliest sex- and aging-induced changes to be analyzed so as to differentiate them from the first signs occurring in manifested disease. This study evaluates differences by age and sex based on intraocular pressure (IOP) and neuroretinal function and structure in healthy young and adult rats before decline due to senescence. For this purpose, eighty-five healthy Long-Evans rats (31 males and 54 females) were analyzed in this 6-month longitudinal study running from childhood to adulthood. IOP was measured by tonometer (Tonolab; Tiolat Oy Helsinki, Finland), neuroretinal function was recorded by flash scotopic and light-adapted photopic negative response electroretinography (ERG) (Roland consult® RETIanimal ERG, Germany) at 4, 16 and 28 weeks of age; and structure was evaluated by in vivo optical coherence tomography (OCT) (Spectralis, Heidelberg® Engineering, Germany). Analyzing both sexes together, IOP was below 20 mmHg throughout the study; retina (R), retinal nerve fiber layer (RNFL) and ganglion cell layer (GCL) thicknesses measured by OCT decreased over time; an increase in ERG signal was recorded at week 16; and no differences were found between right and left eyes. However, analyzing differences by sex revealed that males had higher IOP (even reaching ocular hypertension [>20 mmHg] by the end of the study [7 months of age]), exhibited greater neuroretinal thickness but higher structural percentage loss, and had worse dark- and light-adapted function as measured by ERG than females. This study concludes that age and sex influenced neurodevelopment and neurodegeneration. Different structural and functional degenerative patterns were observed by sex; these occurred earlier and more intensely in males than in age-matched females.

Describing advanced practice provider roles within critical care teams with Tele-ICUs: Exemplars from seven US health systems.

Telehealth is an acknowledged strategy to meet patient healthcare needs. In critical care settings, Tele-ICU's are expanding to deliver clinical services across a diverse spectrum of critically ill patients. The expansion of telehealth provides increased opportunities for advanced practice providers including advanced practice nurses and physician assistants; however, limited information on roles and models of care for advanced practice providers in telehealth exist. This article reviews current and evolving roles for advanced practice providers in telehealth in acute and critical care settings across 7 healthcare systems in the United States. The health system exemplars described in this article identify the important role of advanced practice providers in providing patient care oversight and in improving outcomes for acute and critically ill patients. As telehealth continues to expand, additional opportunities will lead to novel roles for advanced practice providers in the field of telehealth to assist with patient care management for subacute, acute, and critically ill patients.

How NPs can help expand telehealth services.

Consumers of healthcare services are demanding more convenient and accessible options to care. Technologic advancements can support this demand, but telehealth knowledge is lacking. This article will describe the current state of telehealth and examine the role that NPs can play in furthering its adoption.

TeleICU Interdisciplinary Care Teams.

Telehealth in intensive care units (TeleICU) is the provision of critical care using audio-visual communication and health information systems across varying clinical and geographically dispersed settings. The optimal structure of a TeleICU team is one that leverages expert clinical knowledge to address the needs of critical care patients, regardless of hospital location or availability of an onsite intensivist. Information related to the optimal TeleICU team structure is lacking. This article examines the optimal TeleICU team composition, which is one that incorporates the use of an interdisciplinary approach, leverages technology, and is cognizant of varying geographic locations.