Choosing Wisely and reducing the simultaneous ordering of erythrocyte sedimentation rate and C-reactive protein testing in a large safety net system.

OBJECTIVES: C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) are commonly used inflammatory markers. C-reactive protein is more sensitive and specific for monitoring acute inflammation. However, it is commonly co-ordered with ESR despite recommendations against this. Our objective was to reduce unnecessary ESR orders and ESR/CRP co-ordering rates across a large safety net health system. METHODS: This was a quality improvement project that used a quasi-experimental pre- and postintervention interrupted time-series regression analysis. Patients with a positive COVID-19 test were excluded. We designed a nonintrusive, normative nudge within the ESR order that recommended against co-ordering ESR and CRP. In addition, a best practice advisory triggered when ESR and CRP were simultaneously ordered. The outcome measures were ESR order rates per 1000 patient days in the inpatient setting and per 1000 patient encounters in the outpatient setting, as well as ESR/CRP co-ordering rates. RESULTS: Inpatient ESR orders decreased from 12.02 preintervention to 5.61 per 1000 patient days (-53.3%, P < .001). Outpatient ESR orders decreased from 6.09 to 4.07 per 1000 patient encounters (-33.2%, P < .001). Relative co-ordering rates decreased by 50%. CONCLUSIONS: This electronic health record initiative successfully reduced ESR testing across 11 hospitals and 70 ambulatory centers in a safety net setting.

Reducing 25-Hydroxyvitamin D Testing in a Large, Urban Safety Net System.

BACKGROUND: 25-Hydroxyvitamin D testing is increasing despite national guidelines and Choosing Wisely recommendations against routine screening. Overuse can lead to misdiagnosis and unnecessary downstream testing and treatment. Repeat testing within 3 months is a unique area of overuse. OBJECTIVE: To reduce 25-hydroxyvitamin D testing in a large safety net system comprising 11 hospitals and 70 ambulatory centers. DESIGN: This was a quality improvement initiative with a quasi-experimental interrupted time series design with segmented regression. PARTICIPANTS: All patients in the inpatient and outpatient settings with at least one order for 25-hydroxyvitamin D were included in the analysis. INTERVENTIONS: An electronic health record clinical decision support tool was designed for inpatient and outpatient orders and involved two components: a mandatory prompt requiring appropriate indications and a best practice advisory (BPA) focused on repeat testing within 3 months. MAIN MEASURES: The pre-intervention period (6/17/2020-6/13/2021) was compared to the post-intervention period (6/14/2021-8/28/2022) for total 25-hydroxyvitamin D testing, as well as 3-month repeat testing. Hospital and clinic variation in testing was assessed. Additionally, best practice advisory action rates were analyzed, separated by clinician type and specialty. KEY RESULTS: There were 44% and 46% reductions in inpatient and outpatient orders, respectively (p < 0.001). Inpatient and outpatient 3-month repeat testing decreased by 61% and 48%, respectively (p < 0.001). The best practice advisory true accept rate was 13%. CONCLUSION: This initiative successfully reduced 25-hydroxyvitamin D testing through the use of mandatory appropriate indications and a best practice advisory focusing on a unique area of overuse: the repeat testing within a 3-month interval. There was wide variation among hospitals and clinics and variation among clinician types and specialties regarding actions to the best practice advisory.

Choosing wisely initiative for reducing urine cultures for asymptomatic bacteriuria and catheter-associated asymptomatic bacteriuria in an 11-hospital safety net system.

BACKGROUND: Treatment of asymptomatic bacteriuria (ASB) is common. Overtreatment of ASB leads to harm, including adverse effects from antibiotics, antibiotic resistance, and increased length of stay. METHODS: This quality improvement initiative targeted inappropriate urine cultures across 11 hospitals in a safety-net setting. A mandatory prompt for appropriate indications for urine culture orders and a best practice advisory (BPA) for urine culture on patients with urinary catheters were created. Urine culture ordering was compared pre-intervention (6/2020 to 10/2021) to post-intervention (12/2021 to 8/2022). Catheter associated urinary tract infections (CAUTI) was compared pre- and post-intervention. Variation in urine culture ordering and CAUTI rates in hospitals were assessed. RESULTS: Inpatient urine cultures decreased by 20.9% (p<0.001). Inpatient urine cultures on patients with urinary catheters decreased by 21.6% (p<0.001). CAUTI rates remained unchanged post-intervention. High variation in urine culture ordering and CAUTI rates was seen among hospitals. CONCLUSIONS: This initiative successfully decreased urine cultures in a large, safety-net system. Further study is needed in assessing variation among hospitals.

Acupuncture for Pediatrics: An Educational Initiative.

Objective: With the ongoing opioid crisis, the Centers for Disease Control and Prevention recommends nonpharmacologic therapies (e.g., acupuncture) for treating pain. Multiple agencies, such as the National Institutes of Health and World Health Organization, recognize acupuncture's effectiveness for treating pain, but acupuncture education for providers is scarce. A Workshop to Introduce Acupuncture for Pediatrics (AcuPeds-Workshop) was developed with support from American Academy of Pediatrics to educate providers. Additional funding was given by the Virginia Apgar Academy to evaluate the effects of attending this workshop. Materials and Methods: This prospective study used Immediate and 1-Month Post-Workshop (PWS) surveys. The AcuPeds-Workshop components included: history; a literature review; videos of patients receiving acupuncture; and hands-on experience. The workshop was presented at numerous conferences. Attendee survey completion was voluntary. Results: Of 327 attendees, the majority were female, non-Hispanic, and were physicians. At baseline, attendees had: heard of acupuncture, 96%; used it, 28%; and/or had a prior lecture, 13%. In the Immediate-PWS: 97% reported an increase in their knowledge and understanding of the indications for acupuncture; majority correctly addressed 3 clinical application scenarios and contraindications. With respect to attitude: 85% would use acupuncture for themselves and 88% would use it for patients. More than 80% rated the workshop components as useful or very useful. In the One-Month-PWS: majority addressed the same 3 clinical scenarios and contraindications correctly, and 11% considered referring patients for acupuncture. Conclusions: Attendance at this AcuPeds-Workshop had a positive impact on attendees' knowledge, application of, and attitude about acupuncture. This workshop supports efforts to educate medical providers on this nonpharmacologic pain therapy.

The relationship between INTEM/HEPTEM coagulation time ratio and heparin plasma concentration in obstetric patients: an exploratory in vitro investigation.

PURPOSE: Unfractionated heparin continues to be one of the main agents used for thromboprophylaxis in obstetrics, which can complicate the placement of neuraxial anesthetics. In this study, we explored the relationship between a point-of-care coagulation test (thromboelastometry) and plasma heparin concentrations in vitro. METHODS: We obtained blood from consenting obstetric patients with uncomplicated pregnancies in their third trimester who were not in labour and had a specific hematocrit range. Blood was processed and analyzed. We added increasing amounts of unfractionated heparin to samples from 0 to 0.3 U·mL-1 in 0.05 U·mL-1 increments to simulate increasing doses of unfractionated heparin. We performed INTEM and HEPTEM testing in parallel with activated partial thromboplastin time (aPTT) testing. We created a model of the relationship between heparin concentration and the INTEM/HEPTEM coagulation time (IH CT) ratio using nonlinear regression. A similar model for aPTT was also created. RESULTS: Seventy-seven patients were included in the study. Only one concentration of heparin was added to blood samples of each patient. At a concentration of 0.05 U·mL-1, the IH CT ratio was less than or equal to 1.1 in 9/11 (82%) samples. Activated partial thromboplastin time was not prolonged (> 35 sec) until a concentration of 0.1 U·mL-1 heparin was added. In all samples, the IH CT ratio was prolonged at a concentration ≥ 0.2 U·mL-1 as measured by thromboelastometry; however, at no concentration of heparin was aPTT prolonged in all samples. CONCLUSION: The point-of-care IH CT ratio may be useful in identifying the presence of little to no heparin activity. Further research is needed to determine if this ratio can predict heparin activity in vivo.

RéSUMé: OBJECTIF: L'héparine non fractionnée demeure l'un des principaux agents utilisés pour la thromboprophylaxie en obstétrique, ce qui peut compliquer la mise en place d'anesthésiques neuraxiaux. Dans cette étude, nous avons exploré la relation entre un test de coagulation au chevet de la patiente (thromboélastométrie) et les concentrations plasmatiques d'héparine in vitro. MéTHODE: Nous avons obtenu du sang de patientes obstétricales consentantes ayant des grossesses non compliquées au cours de leur troisième trimestre qui n'étaient pas en travail et dont l'hématocrite était dans une plage spécifique. Le sang a été traité et analysé. Des quantités croissantes d'héparine non fractionnée ont été ajoutées à des échantillons de 0 à 0,3 U·mL−1 en incréments de 0,05 U·mL−1 pour simuler des doses croissantes d'héparine non fractionnée. Des tests INTEM et HEPTEM ont été réalisés en parallèle avec des tests de temps de thromboplastine partielle activée (aPTT). Un modèle de la relation entre la concentration d'héparine et le ratio temps de coagulation INTEM/HEPTEM (IH CT) a été créé en utilisant une régression non linéaire. Un modèle similaire pour l'aPTT a également été créé. RéSULTATS: Soixante-dix-sept patientes ont été incluses dans l'étude. Une seule concentration d'héparine a été ajoutée aux échantillons de sang de chaque patiente. À une concentration de 0,05 U·mL−1, le ratio IH CT était inférieur ou égal à 1,1 dans 9/11 échantillons (82 %). L'aPTT n'a pas été prolongé (> 35 sec) jusqu'à ce qu'une concentration d'héparine de 0,1 U·mL−1 soit ajoutée. Dans tous les échantillons, le ratio IH CT a été prolongé à une concentration ≥ 0,2 U·mL−1 telle que mesurée par thromboélastométrie; cependant, dans tous les échantillons, aucune concentration d'héparine n'a prolongé l'aPTT. CONCLUSION: Le ratio IH CT au chevet de la patiente peut être utile pour identifier la présence d'une activité d'héparine faible ou nulle. D'autres recherches sont nécessaires pour déterminer si ce ratio peut prédire l'activité héparinique in vivo.

Alcohol-associated capillarization of sinusoids: A critique since the discovery by Schaffner and Popper in 1963.

This article reviews the literature on capillarization of hepatic sinusoids since its discovery in 1963. Liver sinusoidal endothelial cells are uniquely fenestrated and lack an underlying basement membrane. In chronic liver disease, the sinusoids capillarize and transform into systemic capillaries, a process termed capillarization of sinusoids. The histopathology is marked by defenestration, basement membrane formation, and space of Disse fibrogenesis. Capillarized sinusoids compromise the bidirectional exchange of materials between sinusoids and hepatocytes, leading to hepatocellular dysfunction. Sinusoidal capillarization was first described in active cirrhosis of alcoholics in 1963. Since then, it has been found in early and progressive stages of alcoholic hepatic fibrosis before the onset of cirrhosis. The sinusoidal structure is not altered in alcoholic steatosis without fibrosis. Defenestration impairs the ability of the endothelium to filter chylomicron remnants from sinusoids into the Disse's space, contributing to alcohol-induced postprandial hyperlipidemia and possibly atherosclerosis. Ethanol also modulates the fenestration dynamics in animals. In baboons, chronic alcohol consumption diminishes endothelial porosity in concomitance with hepatic fibrogenesis and in rats defenestrates the endothelium in the absence of fibrosis, and sometimes capillarizes the sinusoids. Acute ethanol ingestion enlarges fenestrations in rats and contracts fenestrations in rabbits. In sinusoidal endothelial cell culture, ethanol elicits fenestration dilation, which is likely related to its interaction with fenestration-associated cytoskeleton. Ethanol potentiates sinusoidal injury caused by cocaine, acetaminophen or lipopolysaccharide in mice and rats. Understanding ethanol's mechanisms on pathogenesis of sinusoidal capillarization and fenestration dynamics will lead to development of methods to prevent risks for atherosclerosis in alcoholism.

Baseline parameters for non-activated rotational thromboelastometry tests with and without heparinase in healthy pregnant women at term gestation.

OBJECTIVE: To determine the normal values for non-activated thromboelastometry parameters among pregnant women. DESIGN: Prospective, observational study. SETTING: Tertiary care hospital. PATIENTS: Non-laboring women at term gestation without history of bleeding or clotting disorder or anticoagulation use. INTERVENTIONS: Venous blood samples were collected and ROTEM® was performed using NATEM and NaHEPTEM assays. MEASUREMENTS: Reference ranges were derived by calculating 2.5 and 97.5 percentiles for the following parameters: clotting time (CT), clot formation time (CFT), amplitude at 10 (A10) and 20 min (A20), alpha angle, maximum clot firmness (MCF), and lysis index at 30 (LI30) and 60 min (LI60). The NATEM/NaHEPTEM CT ratio was calculated to determine the baseline ratio in term pregnant women. MAIN RESULTS: 146 women were screened and 120 were enrolled. The median age was 34 years [31-36], median gestational age was 39.1 weeks [38.3-39.3], and median parity was 1 [0-2]. Median pre-delivery platelet and hematocrit levels were within the normal ranges. The reference ranges for NATEM parameters were: CT (232-759 (s)), CFT (69-243 (s)), alpha angle (50-77 (°)), A10 (44-69 (mm)), A20 (54-75 (mm)), MCF (57-77 (mm)), LI30 (100-100 (%)), LI60 (90-100 (%)). The reference ranges for NaHEPTEM parameters were: CT (224-717 (s)), CFT (66-210 (s)), alpha angle (53-77 (°)), A10 (44-67 (mm)), A20 (55-73 (mm)), MCF (58-74 (mm)), LI30 (99-100 (%)), LI60 (90-100 (%)). The NATEM to NaHEPTEM CT ratio reference range was 0.73-1.3. CONCLUSIONS: This study is the first to our knowledge to report reference ranges for non-activated ROTEM® tests with and without heparinase in non-laboring term pregnant women. These reference ranges may serve as a baseline comparison and may be useful for future research on anticoagulation management in pregnancy.

Barrier Devices, Intubation, and Aerosol Mitigation Strategies: Personal Protective Equipment in the Time of Coronavirus Disease 2019.

BACKGROUND: Numerous barrier devices have recently been developed and rapidly deployed worldwide in an effort to protect health care workers (HCWs) from exposure to coronavirus disease 2019 (COVID-19) during high-risk procedures. However, only a few studies have examined their impact on the dispersion of droplets and aerosols, which are both thought to be significant contributors to the spread of COVID-19. METHODS: Two commonly used barrier devices, an intubation box and a clear plastic intubation sheet, were evaluated using a physiologically accurate cough simulator. Aerosols were modeled using a commercially available fog machine, and droplets were modeled with fluorescein dye. Both particles were propelled by the cough simulator in a simulated intubation environment. Data were captured by high-speed flash photography, and aerosol and droplet dispersion were assessed qualitatively with and without a barrier in place. RESULTS: Droplet contamination after a simulated cough was seemingly contained by both barrier devices. Simulated aerosol escaped the barriers and flowed toward the head of the bed. During barrier removal, simulated aerosol trapped underneath was released and propelled toward the HCW at the head of the bed. Usage of the intubation sheet concentrated droplets onto a smaller area. If no barrier was used, positioning the patient in slight reverse Trendelenburg directed aerosols away from the HCW located at the head of the bed. CONCLUSIONS: Our observations imply that intubation boxes and sheets may reduce HCW exposure to droplets, but they both may merely redirect aerosolized particles, potentially resulting in increased exposure to aerosols in certain circumstances. Aerosols may remain within the barrier device after a cough, and manipulation of the box may release them. Patients should be positioned to facilitate intubation, but slight reverse Trendelenburg may direct infectious aerosols away from the HCW. Novel barrier devices should be used with caution, and further validation studies are necessary.

Hepatic sinusoids versus central veins: Structures, markers, angiocrines, and roles in liver regeneration and homeostasis.

The blood circulates through the hepatic sinusoids delivering nutrients and oxygen to the liver parenchyma and drains into the hepatic central vein, yet the structures and phenotypes of these vessels are distinctively different. Sinusoidal endothelial cells are uniquely fenestrated, lack basal lamina and possess organelles involved in endocytosis, pinocytosis, degradation, synthesis and secretion. Hepatic central veins are nonfenestrated but are also active in synthesis and secretion. Endothelial cells of sinusoids and central veins secrete angiocrines that play respective roles in hepatic regeneration and metabolic homeostasis. The list of markers for identifying sinusoidal endothelial cells is long and their terminologies are complex. Further, their uses vary in different investigations and, in some instances, could be confusing. Central vein markers are fewer but more distinctive. Here we analyze and categorize the molecular pathways/modules associated with the sinusoid-mediated liver regeneration in response to partial hepatectomy and chemical-induced acute or chronic injury. Similarly, we highlight the findings that central vein-derived angiocrines interact with Wnt/ß-catenin in perivenous hepatocytes to direct gene expression and maintain pericentral metabolic zonation. The proposal that perivenous hepatocytes behave as stem/progenitor cells to provoke hepatic homeostatic cell renewal is reevaluated and newer concepts of broad zonal distribution of hepatocyte proliferation in liver homeostasis and regeneration are updated. Thus, this review integrates the structures, biology and physiology of liver sinusoids and central veins in mediating hepatic regeneration and metabolic homeostasis.

Acupuncture as a Nonpharmacologic Treatment for Pain in a Pediatric Emergency Department.

OBJECTIVES: With epidemic opioid deaths and abuse in the United States, government agencies recommend nonpharmacological treatments for pain. However nonopioid treatment options for moderate to severe pain in the pediatric emergency department (PED) are limited. Acupuncture has been shown to be effective for pain. The objective of this study was to evaluate the feasibility of using traditional acupuncture (TA) and battlefield acupuncture (BFA) in the treatment of pain in the PED. METHODS: A pediatric cohort treated with acupuncture for pain in an urban PED was assessed. All subjects received TA or BFA as treatment, and pre/postacupuncture pain scores, feedback, and adverse events were assessed. The primary outcome was a change in pain score. RESULTS: Twelve patients received BFA, and 13 received TA for these pain conditions: headaches, sciatica, paraphimosis, torticollis, joint pains (knee, shoulder, jaw), sprains (foot, wrist, thumb), dysmenorrhea, otitis externa, sickle cell, and muscle knot. The mean ± SD pain score change, 5.8 ± 2.5 (P < 0.05; 95% confidence interval, 4.9-7.0), was clinically and statistically significant. Over 90% of subjects reported significant improvement or resolution of pain; 96% were satisfied with pain relief and would receive acupuncture again. Two adverse events were noted: one patient reported dizziness, and another, a tinge of blood at 1 of 90 needled points. CONCLUSIONS: This study suggests that acupuncture is a potential nonpharmacologic therapeutic option for acute pain management in the PED.

In Vivo Modulation of the Blood-Brain Barrier Permeability by Transcranial Direct Current Stimulation (tDCS).

tDCS has been used to treat various brain disorders and its mechanism of action (MoA) was found to be neuronal polarization. Since the blood-brain barrier (BBB) tightly regulates the neuronal microenvironment, we hypothesized that another MoA of tDCS is direct vascular activation by modulating the BBB structures to increase its permeability (P). To test this hypothesis, we used high resolution multiphoton microscopy to determine P of the cerebral microvessels in rat brain. We found that 20 min 0.1-1 mA tDCS transiently increases P to a small solute, sodium fluorescein (MW 376) and to a large solute, Dextran-70k, with a much higher increase in P to the large solute. By pretreating the vessel with a nitric oxide synthase inhibitor, we revealed that the tDCS-induced increase in P is NO dependent. A transport model for the BBB was further employed to predict the structural changes by the tDCS. Comparing model predictions with the measured data suggests that tDCS increases P by temporarily disrupting the structural components forming the paracellular pathway of the BBB. That the transient and reversible increase in the BBB permeability also suggests new applications of tDCS such as a non-invasive approach for brain drug delivery through the BBB.

Quantification of transient increase of the blood-brain barrier permeability to macromolecules by optimized focused ultrasound combined with microbubbles.

Radioimmunotherapy using a radiolabeled monoclonal antibody that targets tumor cells has been shown to be efficient for the treatment of many malignant cancers, with reduced side effects. However, the blood-brain barrier (BBB) inhibits the transport of intravenous antibodies to tumors in the brain. Recent studies have demonstrated that focused ultrasound (FUS) combined with microbubbles (MBs) is a promising method to transiently disrupt the BBB for the drug delivery to the central nervous system. To find the optimal FUS and MBs that can induce reversible increase in the BBB permeability, we employed minimally invasive multiphoton microscopy to quantify the BBB permeability to dextran-155 kDa with similar molecular weight to an antibody by applying different doses of FUS in the presence of MBs with an optimal size and concentration. The cerebral microcirculation was observed through a section of frontoparietal bone thinned with a micro-grinder. About 5 minutes after applying the FUS on the thinned skull in the presence of MBs for 1 minute, TRITC (tetramethylrhodamine isothiocyanate)-dextran-155 kDa in 1% bovine serum albumin in mammalian Ringer's solution was injected into the cerebral circulation via the ipsilateral carotid artery by a syringe pump. Simultaneously, the temporal images were collected from the brain parenchyma ~100-200 µm below the pia mater. Permeability was determined from the rate of tissue solute accumulation around individual microvessels. After several trials, we found the optimal dose of FUS. At the optimal dose, permeability increased by ~14-fold after 5 minutes post-FUS, and permeability returned to the control level after 25 minutes. FUS without MBs or MBs injected without FUS did not change the permeability. Our method provides an accurate in vivo assessment for the transient BBB permeability change under the treatment of FUS. The optimal FUS dose found for the reversible BBB permeability increase without BBB disruption is reliable and can be applied to future clinical trials.