Cost analysis of one-time intravenous antibiotic doses in the emergency department.

BACKGROUND: Research shows that one-time doses of intravenous (IV) antibiotics do not improve resolution of infection. Providers, however, continue to use them - especially in the emergency department. Very few studies have aimed to quantify the cost of this practice. OBJECTIVES: The primary objective was to evaluate the difference in average total cost of emergency department (ED) stay between patients who received a one-time dose of intravenous antibiotics in the ED before discharging on oral antibiotics and patients who were just discharged on oral antibiotics. Secondary objectives were to evaluate the differences in durations of stay between the two groups, as well as the differences in adverse drug effects and need for healthcare contact after discharge. METHODS: Chart review was conducted to identify patients who received and did not receive a one-time dose of IV antibiotics in the ED between April 30, 2020, and April 30, 2022. A micro-costing approach was used to determine ED-associated costs per patient. Comparisons in primary and secondary outcomes were performed using statistical inferential tests. RESULTS: A total of 102 patients were analyzed in each group. Patients who received a one-time dose of intravenous antibiotics in the emergency department before being discharged on oral antibiotics had an average length of stay of 4.55 hours, as opposed to patients who did not receive a one-time dose of intravenous antibiotics before being discharged on oral antibiotics who had an average length of stay of 2.82 hours (absolute difference: 1.73 hours, p < 0.001). One-time dosing of intravenous antibiotics in the emergency department incurred an additional cost of approximately $556 per patient, totaling to over $56,000 in our study cohort. CONCLUSION: The use of one-time intravenous antibiotics in the emergency department did not confer any additional benefits to patients. Use of one-time doses resulted in significantly reduced throughput in the emergency department and significantly increased healthcare costs.

Adaptations of bone and bone vasculature to muscular stretch training.

The magnitude of bone formation and remodeling is linked to both the magnitude of strain placed on the bone and the perfusion of bone. It was previously reported that an increase in bone perfusion and bone density occurs in the femur of old rats with moderate aerobic exercise training. This study determined the acute and chronic effects of static muscle stretching on bone blood flow and remodeling. Old male Fischer 344 rats were randomized to either a naive or stretch-trained group. Static stretching of ankle flexor muscles was achieved by placement of a dorsiflexion splint on the left ankle for 30 min/d, 5d/wk for 4wk. The opposite hindlimb served as a contralateral control (nonstretched) limb. Bone blood flow was assessed during and after acute stretching in naive rats, and at rest and during exercise in stretch-trained rats. Vascular reactivity of the nutrient artery of the proximal tibia was also assessed in stretch-trained rats. MicroCT analysis was used to assess bone volume and micro-architecture of the trabecular bone of both tibias near that growth plate. In naive rats, static stretching increased blood flow to the proximal tibial metaphasis. Blood flow to the proximal tibial metaphysis during treadmill exercise was higher in the stretched limb after 4 wk of daily stretching. Daily stretching also increased tibial bone weight and increased total volume in both the proximal and distal tibial metaphyses. In the trabecular bone immediately below the proximal tibial growth plate, total volume and bone volume increased, but bone volume/total volume was unchanged and trabecular connectivity decreased. In contrast, intravascular volume increased in this region of the bone. These data suggest that blood flow to the tibia increases during bouts of static stretching of the hindlimb muscles, and that 4 wk of daily muscle stretching leads to bone remodeling and an increase in intravascular volume of the tibial bone.

Implementation of a Protocol for Management of Febrile Neutropenia in the Emergency Department at Veteran Health Indiana.

Background: Febrile neutropenia (FN) is a life-threatening oncologic emergency requiring timely evaluation and treatment. Unrecognized fever and infection can progress quickly and have been shown to increase morbidity and mortality in patients with malignancy. It is critical to identify patients with neutropenic fever on presentation to the emergency department (ED) and to initiate treatment immediately. Observations: This quality improvement initiative sought to optimize ED care of patients presenting with FN. Delays in antibiotic prescribing for patients with FN presenting to the ED were identified. A protocol was implemented to streamline clinical decision making and decrease the time from triage to the first dose of antibiotics in the ED. Key interventions included obtaining ED staff support, developing a standard empiric therapy protocol, increasing prescriber awareness of the neutropenic fever protocol and integrating it into the electronic health record. Before the protocol, the mean time from triage to the first dose of antibiotics was 3.3 hours with only 6% of patients receiving appropriate empiric therapy within 1 hour. Postimplementation, the average time to antibiotics decreased to 2.3 hours. In the postimplementation group, 17% of patients within 1 hour. Conclusions: Early identification and timely empiric antibiotic therapy are critical to improving outcomes for patients presenting to the ED with FN. Additional optimization of the order sets along with increased protocol comfort and staff education will help to further reduce the time to antibiotic administration in alignment with guideline recommendations.

HIV-1 Resistance to Islatravir/Tenofovir Combination Therapy in Wild-Type or NRTI-Resistant Strains of Diverse HIV-1 Subtypes.

Tenofovir disoproxil fumarate (TDF) and islatravir (ISL, 4'-ethynyl-2-fluoro-2'-deoxyadensine, or MK-8591) are highly potent nucleoside reverse transcriptase inhibitors. Resistance to TDF and ISL is conferred by K65R and M184V, respectively. Furthermore, K65R and M184V increase sensitivity to ISL and TDF, respectively. Therefore, these two nucleoside analogs have opposing resistance profiles and could present a high genetic barrier to resistance. To explore resistance to TDF and ISL in combination, we performed passaging experiments with HIV-1 WT, K65R, or M184V in the presence of ISL and TDF. We identified K65R, M184V, and S68G/N mutations. The mutant most resistant to ISL was S68N/M184V, yet it remained susceptible to TDF. To further confirm our cellular findings, we implemented an endogenous reverse transcriptase assay to verify in vitro potency. To better understand the impact of these resistance mutations in the context of global infection, we determined potency of ISL and TDF against HIV subtypes A, B, C, D, and circulating recombinant forms (CRF) 01_AE and 02_AG with and without resistance mutations. In all isolates studied, we found K65R imparted hypersensitivity to ISL whereas M184V conferred resistance. We demonstrated that the S68G polymorphism can enhance fitness of drug-resistant mutants in some genetic backgrounds. Collectively, the data suggest that the opposing resistance profiles of ISL and TDF suggest that a combination of the two drugs could be a promising drug regimen for the treatment of patients infected with any HIV-1 subtype, including those who have failed 3TC/FTC-based therapies.

Implementation of a compulsory clinical pharmacist-led medication deprescribing intervention in high-risk seniors in the emergency department.

OBJECTIVES: The objective of this study was to assess the impact of an emergency department (ED) deprescribing intervention for geriatric adults. We hypothesized that pharmacist-led medication reconciliation for at-risk aging patients would increase the 60-day case rate of primary care provider (PCP) deprescribing of potentially inappropriate medications (PIMs). METHODS: This was a retrospective, before-and-after intervention pilot study conducted at an urban Veterans Affairs ED. In November 2020, a protocol utilizing pharmacists to perform medication reconciliations for patients 75 years or older who screened positive using an Identification of Seniors at Risk tool at triage was implemented. Reconciliations focused on identifying PIMs and providing deprescribing recommendations to patients' PCPs. A preintervention group was collected between October 2019 and October 2020, and a postintervention group was collected between February 2021 to February 2022. The primary outcome compared case rates of PIM deprescribing in the preintervention group to the postintervention group. Secondary outcomes include per-medication PIM deprescribing rate, 30-day PCP follow-up visits, 7- and 30-day ED visits, 7- and 30-day hospitalizations, and 60-day mortality. RESULTS: A total of 149 patients were analyzed in each group. Both groups were similar in age and sex, with an average age of 82 years and 98% male. The case rate of PIM deprescribing at 60 days was 11.1% preintervention compared to 57.1% postintervention (p < 0.001). Preintervention, 91% of PIMs remained unchanged at 60 days compared to 49% (p < 0.05) postintervention. Regardless of PIM identification, the 30-day primary care follow-up rate increased postintervention: 31.5% and 55.7% (p < 0.0001), respectively. There was no improvement in 7- or 30-day subsequent ED visits, hospitalization, or mortality. CONCLUSIONS: Pharmacist-led medication reconciliation in high-risk geriatric patients was associated with an increase both in the rate of PIM deprescribing and in post-ED primary care engagement.

Safety and Effectiveness of the Use of an Electronic Glucose Monitoring System Versus Weight-Based Dosing Nomogram for Treatment of Diabetic Ketoacidosis and Hyperglycemic Hyperosmolar Syndrome in a VA Hospital.

OBJECTIVE: The objective of this study is to assess the safety and effectiveness of an electronic glucose monitoring system (eGMS) versus paper-based protocols (PBPs) to manage diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) within the VA setting. METHODS: This study is a retrospective chart review of patients on an insulin drip, treated in the emergency department (ED) or intensive care unit (ICU) at Veteran Health Indiana for DKA or HHS. The primary outcome was evaluating the percentage of patients with hypoglycemia (blood glucose [BG] level <70 mg/dL) in patients admitted with DKA and HHS comparing an eGMS versus a PBP. A total of 168 patients were included in the analysis, with 84 patients in each group. RESULTS: The primary outcome comparing rates of hypoglycemia in the eGMS group versus the PBP group showed a lower rate of hypoglycemia in the eGMS group (0.024%) compared with the PBP group (0.060%); however, this difference was not found to be statistically significant (P = .90). Statistically significant secondary outcomes include the percentage of glucose checks drawn within the protocol recommendation (80.7% vs 52.6%, P = .02). CONCLUSIONS: While the primary endpoint of decreased hypoglycemia was not found to be statistically significant, it did reduce the overall number of hypoglycemia events in the eGMS group compared with the PBP group which may be clinically significant. This demonstrates that eGMS use has the potential to minimize hypoglycemia and glycemic variability in a critically-ill Veteran population by individualizing insulin drip titration based on a variety of patient-specific factors and providing reminders for staff to obtain BG checks in a timely manner.

Growth hormone receptor antagonism downregulates ATP-binding cassette transporters contributing to improved drug efficacy against melanoma and hepatocarcinoma in vivo.

Knockdown of GH receptor (GHR) in melanoma cells in vitro downregulates ATP-binding cassette-containing (ABC) transporters and sensitizes them to anti-cancer drug treatments. Here we aimed to determine whether a GHR antagonist (GHRA) could control cancer growth by sensitizing tumors to therapy through downregulation of ABC transporters in vivo. We intradermally inoculated Fluc-B16-F10 mouse melanoma cells into GHA mice, transgenic for a GHR antagonist (GHRA), and observed a marked reduction in tumor size, mass and tumoral GH signaling. Moreover, constitutive GHRA production in the transgenic mice significantly improved the response to cisplatin treatment by suppressing expression of multiple ABC transporters and sensitizing the tumors to the drug. We confirmed that presence of a GHRA and not a mere absence of GH is essential for this chemo-sensitizing effect using Fluc-B16-F10 allografts in GH knockout (GHKO) mice, where tumor growth was reduced relative to that in GH-sufficient controls but did not sensitize the tumor to cisplatin. We extended our investigation to hepatocellular carcinoma (HCC) using human HCC cells in vitro and a syngeneic mouse model of HCC with Hepa1-6 allografts in GHA mice. Gene expression analyses and drug-efflux assays confirm that blocking GH significantly suppresses the levels of ABC transporters and improves the efficacy of sorafenib towards almost complete tumor clearance. Human patient data for melanoma and HCC show that GHR RNA levels correlate with ABC transporter expression. Collectively, our results validate in vivo that combination of a GHRA with currently available anti-cancer therapies can be effective in attacking cancer drug resistance.

Leveraging Partnerships to Reduce Insulin Needlestick Injuries: Nurse-Led System-Wide Quality Improvement Project.

BACKGROUND: Percutaneous injuries from needlesticks are a major occupational hazard for nurses. LOCAL PROBLEM: Reducing subcutaneous insulin-related needlestick injuries was part of a nurse-led comprehensive sharps injury-reduction program at an integrated, not-for-profit health system. METHODS: The incident rate of needlestick injuries was compared between 1 year before and 1 year after introducing this quality improvement project. INTERVENTIONS: A system-wide educational program instituting changes in subcutaneous insulin administration practices was combined with supply chain standardization using a single type of safety-engineered insulin syringe. RESULTS: The average monthly incidence of needlestick injuries per 10 000 subcutaneous insulin injections fell significantly from year to year (incidence rate ratio, 0.49; 95% CI, 0.30-0.80; Poisson regression P = .004). One-year cost savings for supplies totaled $3500; additional annual median savings were $24 875 (2019 US dollars) in estimated costs of needlestick injuries averted. CONCLUSIONS: The effectiveness of this multifaceted project provides a practical template to reduce subcutaneous insulin-related needlestick injuries.

Transparent Conductive Two-Dimensional Titanium Carbide Epitaxial Thin Films.

Since the discovery of graphene, the quest for two-dimensional (2D) materials has intensified greatly. Recently, a new family of 2D transition metal carbides and carbonitrides (MXenes) was discovered that is both conducting and hydrophilic, an uncommon combination. To date MXenes have been produced as powders, flakes, and colloidal solutions. Herein, we report on the fabrication of ∼1 × 1 cm2 Ti3C2 films by selective etching of Al, from sputter-deposited epitaxial Ti3AlC2 films, in aqueous HF or NH4HF2. Films that were about 19 nm thick, etched with NH4HF2, transmit ∼90% of the light in the visible-to-infrared range and exhibit metallic conductivity down to ∼100 K. Below 100 K, the films' resistivity increases with decreasing temperature and they exhibit negative magnetoresistance-both observations consistent with a weak localization phenomenon characteristic of many 2D defective solids. This advance opens the door for the use of MXenes in electronic, photonic, and sensing applications.

Santal monohydrate, an isoflavone isolated from Wye-thia mollis.

THE TITLE COMPOUND [SYSTEMATIC NAME: 3-(3,4-di-hydroxy-phen-yl)-5-hy-droxy-7-meth-oxy-4H-chromen-4-one monohydrate], C16H12O6·H2O, is a monohydrate of a natural product santal isolated from Wye-thia mollis. In the santal mol-ecule, the dihedral angle between the benzo-quinone and di-hydroxy-phenyl fragments is 53.9 (1)° and an intra-molecular O-H⋯O hydrogen bond occurs. In the crystal, O-H⋯O hydrogen bonds link the components into corrugated layers parallel to the ac plane. The short distance of 3.474 (5) Šbetween the centroids of the benzene rings in neighbouring santal mol-ecules reveals then existence of π-π inter-actions within the layers.

Tenulin 0.25-hydrate, a sesquiterpene lactone isolated from Helenium amarum.

The asymmetric unit of the title compound, C17H22O5·0.25H2O [systematic name: 2-hy-droxy-2,2a,6,9a-tetra-methyl-2a,4a,5,6,6a,9a,9b,9c-octa-hydro-2H-1,4-dioxadi-cyclo-pent[cd,f]azulene-3,9-dione 0.25-hydrate], a natural product isolated from Helenium amarum, contains two independent tenulin mol-ecules and half a water mol-ecule of crystallization situated on a twofold rotation axis. The hy-droxy group of the hemiketal moiety is in a ß-position. In the crystal, each water mol-ecule inter-acts with four tenulin mol-ecules via O-H⋯O hydrogen bonds. The two independent tenulin mol-ecules (A and B) differ only in the character of their participation in hydrogen bonding. Specifically, while A is an acceptor of Owater-H⋯O A and a donor of O A -H⋯O B hydrogen bonds, mol-ecule B is an acceptor of the latter hydrogen bond and the donor of an O B -H⋯Owater hydrogen bond. In the crystal, these O-H⋯O hydrogen bonds link the tenulin and water mol-ecules into layers parallel to the ac plane.

Isotenulin.

Isotenulin, C17H22O5, is a sesquiterpene lactone isolated from sneezeweed Helenium amarum. It crystallizes with two independent mol-ecules in the asymmetric unit. In each mol-ecule, two five-membered rings (cyclo-pentenone and lactone) are trans-fused to the central seven-membered ring. The five-membered rings each adopt envelope conformations. The seven-membered ring adopts a twist-chair conformation. In the crystal, the molecules are linked by C-H⋯O interactions, which generate a three-dimensional network.

The true identity of the triterpene component of Wyethia mollis, a lanosta-diene containing a tetrahydropyran E-ring.

The crystal structure of a triterpene component of Wyethia mollis has been obtained and compared with the previously reported structure of the compound. The compound in the crystal structure, lanosta-8,24-dien-3-one, 16,23-epoxy-(161beta, 23R), (1), is different from the previously reported compound, but has identical NMR and mass spectrometric data. The revised structure contains a tetrahydropyran E ring, a structural moiety rare in steroid triterpenes.

Energy expenditure of below-knee amputees during harness-supported treadmill ambulation.

Traditional rehabilitation of amputees is primarily aimed at strengthening remaining musculature necessary for prosthetic use and gait training. Available gait training time, however, is often limited by pain, residual limb skin tolerance, and the patient's cardiovascular endurance. Harness-supported treadmill ambulation is a rehabilitation technique being used by physical therapists to decrease an individual's body weight by a given percentage during exercise. This, theoretically, allows an amputee to ambulate on a prosthesis at a lower energy cost. The purpose of this study was to compare the energy expenditure of healthy below-knee amputee volunteers with healthy able-bodied volunteers during harness-supported treadmill ambulation in order to determine if energy conservation is achieved. Subjects were tested on a treadmill, walking at .67 m/sec (1.5 mph) and 1.34 m/sec (3.0 mph) during each of the following randomized harness-supported treadmill ambulation situations: full body weight, 20% body weight supported, and 40% body weight supported. During the last minute of each trial, rate of perceived exertion, heart rate, and standardized indirect calorimetry oxygen consumption (VO2, ml/kg/min) measures were collected. Caloric expenditure (kl/min) was calculated using metabolic conversion equations. Peak heart rate, peak VO2, and peak kl/min were measured after the conclusion of the last walking trial by taking each subject to volitional fatigue. Data were analyzed for each harness-supported treadmill ambulation situation and group using analysis of variance (ANOVA). The researchers identified significantly lower ratings of perceived exertion, heart rates, and VO2s for able-bodied subjects vs. below-knee amputees for all trials. Both groups demonstrated significantly lower heart rates, VO2s, and kl/min at 1.34 m/sec with 40% body weight supported.(ABSTRACT TRUNCATED AT 250 WORDS)