Comparison of the impact of a system tele-antimicrobial stewardship program on the conversion of intravenous-to-oral antimicrobials in community hospitals.

Objectives: Evaluate system-wide antimicrobial stewardship program (ASP) update impact on intravenous (IV)-to-oral (PO) antimicrobial conversion in select community hospitals through pre- and postimplementation trend analysis. Methods: Retrospective study across seven hospitals: region one (four hospitals, 827 beds) with tele-ASP managed by infectious diseases (ID)-trained pharmacists and region two (three hospitals, 498 beds) without. Data were collected pre- (April 2022-September 2022) and postimplementation (April 2023-September 2023) on nine antimicrobials for the IV to PO days of therapy (DOTs). Antimicrobial administration route and (DOTs)/1,000 patient days were extracted from the electronical medical record (EMR). Primary outcome: reduction in IV DOTs/1,000 patient days. Secondary outcomes: decrease in IV usage via PO:total antimicrobial ratios and cost reduction. Results: In region one, IV usage decreased from 461 to 209/1,000 patient days (P = < .001), while PO usage increased from 289 to 412/1,000 patient days (P = < .001). Total antimicrobial use decreased from 750 to 621/1,000 patient days (P = < .001). In region two, IV usage decreased from 300 to 243/1,000 patient days (P = .005), and PO usage rose from 154 to 198/1,000 patient days (P = .031). The PO:total antimicrobial ratios increased in both regions, from .42-.52 to .60-.70 in region one and from .36-.55 to .46-.55 in region two. IV cost savings amounted to $19,359.77 in region one and $4,038.51 in region two. Conclusion: The ASP intervention improved IV-to-PO conversion rates in both regions, highlighting the contribution of ID-trained pharmacists in enhancing ASP initiatives in region one and suggesting tele-ASP expansion may be beneficial in resource-constrained settings.

Bioinductive Collagen Implant Has Potential To Improve Rotator Cuff Healing - A Systematic Review.

PURPOSE: The purpose of this study was to systematically review the literature to evaluate the clinical studies on bioinductive collagen implant (BCI) for the treatment of rotator cuff tears. METHODS: A literature search of MEDLINE, Embase, and the Cochrane Library was performed based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Clinical studies reporting following BCI for rotator cuff tears were included. Quantitive and qualitative data was evaluated. RESULTS: A total of 21 studies were included. In patients with full thickness tears, 7 of the 8 studies with pre- to postoperative ASES scores demonstrated statistically significant improvements in mean pre- to postoperative ASES scores, with 75%-100% of patients meeting the MCID. In those with partial thickness tears, 7 of the 8 studies with pre- to postoperative ASES scores demonstrated statistically significant improvements in mean pre- to postoperative ASES scores, with 54.4%-100% of patients meeting the MCID. For studies that quantified percent increases in tendon thickness, the reported increases ranged from 13% in 44% full thickness tears, and 14% to 60% in partial thickness tears. There were 6 studies that evaluated rotator cuff re-tears after BCI treatment in the full thickness cohort, with rates reported ranging from 0-9%. There were 5 studies that evaluated rotator cuff re-tears after BCI treatment in the partial thickness cohort, with rates reported ranging from 0-18%. Two of the included studies found that BCI was cost-effective due to the increased tendon healing with cost savings of $5,338-$13,061 per healed rotator cuff tendon. CONCLUSION: The literature on rotator cuff tear augmentation with BCI has shown consistently reported good results. Additionally, there was evidence of low retear rates and consistently improved tendon thickness with BCI, with two randomized controlled trials showing improved tendon healing with BCI. However, there appears to be a higher rate of adhesive capsulitis reported. LEVEL OF EVIDENCE: Level IV, Systematic review of Level I, III and IV studies.

The International Consensus for Early TB framework (ICE-TB): Implications from a low-incidence setting.

In recent years, there has been increasing recognition of the public health significance of the spectrum of TB disease presentation, and the existing classification systems of asymptomatic infection and symptomatic TB have been limited in terms of explanatory power. Accordingly, in 2022-2023, a new International Consensus framework for Early TB (ICE-TB) was developed, categorising the spectrum of TB infection and disease into five states based on the presence or absence of macroscopic pathology, host infectiousness, and symptoms and signs.We used the ICE-TB framework to re-analyse existing notification data for 2022 within a low-incidence setting to explore the potential utility and future challenges for its public health application.Existing notification data were sufficient to allow substantial reclassification of currently recognised active disease states, but did not systematically capture Mycobacterium tuberculosis infection or subclinical TB. Fifty percent of existing TB notifications would be classified as 'Clinical, infectious', with the potential need to consider further subclassification.Our exploration highlighted limitations in existing classification systems and diagnostic approaches and should encourage researchers and programmatic implementers to emphasise person-centred and programmatic needs in the development of new tools for TB management..

Zirconium Hydride Catalysis Initiated by Tetrabutylammonium Fluoride.

In our drug discovery campaigns to target the oncogenic drivers of cancers, the demand for a chemoselective, stereoselective and economical synthesis of chiral benzylamines drove the development of a catalytic zirconium hydride reduction. This methodology uses the inexpensive, bench stable zirconocene dichloride, and a novel tetrabutylammonium fluoride activation tactic to catalytically generate a metal hydride under ambient conditions. The diastereo- and chemoselectivity of this reaction was tested with the preparation of key intermediates from our discovery programs and in the scope of sulfinyl ketimines and carbonyls relevant to medicinal chemistry and natural product synthesis. A preliminary mechanistic investigation conducted into the role of tetrabutylammonium fluoride indicates that formation of a zirconocene fluoride occurs to initiate catalysis. The implications of this convenient activation approach may provide expanded roles for zirconium hydrides in catalytic transformations.

An active site mutation induces oxygen reactivity in D-arginine dehydrogenase: A case of superoxide diverting protons.

Enzymes are potent catalysts that increase biochemical reaction rates by several orders of magnitude. Flavoproteins are a class of enzymes whose classification relies on their ability to react with molecular oxygen (O2) during catalysis using ionizable active site residues. Pseudomonas aeruginosa D-arginine dehydrogenase (PaDADH) is a flavoprotein that oxidizes D-arginine for P. aeruginosa survival and biofilm formation. The crystal structure of PaDADH reveals the interaction of the glutamate 246 (E246) side chain with the substrate and at least three other active site residues, establishing a hydrogen bond network in the active site. Additionally, E246 likely ionizes to facilitate substrate binding during PaDADH catalysis. This study aimed to investigate how replacing the E246 residue with leucine affects PaDADH catalysis and its ability to react with O2 using steady-state kinetics coupled with pH profile studies. The data reveal a gain of O2 reactivity in the E246L variant, resulting in a reduced flavin semiquinone species and superoxide (O2•-) during substrate oxidation. The O2•- reacts with active site protons, resulting in an observed nonstoichiometric slope of 1.5 in the enzyme's log (kcat/Km) pH profile with D-arginine. Adding superoxide dismutase results in an observed correction of the slope to 1.0. This study demonstrates how O2•- can alter the slopes of limbs in the pH profiles of flavin-dependent enzymes and serves as a model for correcting nonstoichiometric slopes in elucidating reaction mechanisms of flavoproteins.

Sucralose (C12H19Cl3O8) impact on microbial activity in estuarine and freshwater marsh soils.

As the general population's diet has shifted to reflect current weight-loss trends, there has been an increase in zero-calorie artificial sweetener usage. Sucralose (C12H19Cl3O8), commonly known as Splenda® in the USA, is a primary example of these sweeteners. In recent years, sucralose has been identified as an environmental contaminant that cannot easily be broken down via bacterial decomposition. This study focuses on the impact of sucralose presence on microbial communities in brackish and freshwater systems. Microbial respiration and fluorescence were measured as indicators of microbial activity in sucralose-dosed samples taken from both freshwater and estuarine marsh environments. Results showed a significant difference between microbial concentration and respiration when dosed with varying levels of sucralose. Diatom respiration implied a negative correlation of community abundance with sucralose concentration. The freshwater cyanobacterial respiration increased in the presence of sucralose, implying a positive correlation of community abundance with sucralose concentration. This was in direct contrast to its brackish water counterpart. However, further investigation is necessary to confirm any potential utility of these communities in the breakdown of sucralose in the marsh environment.

Descemet Membrane Endothelial Keratoplasty as Treatment for Late-Onset Interface Fluid Syndrome After Laser In Situ Keratomileusis.

PURPOSE: We herein present Descemet membrane endothelial keratoplasty (DMEK) as an effective surgical means of treatment for the management of interface fluid syndrome (IFS) in a series of cases with distant history of laser in situ keratomileusis (LASIK). METHODS: Three cases from a single institution were included. All patients had documented IFS in the setting of history of LASIK. All 3 patients underwent DMEK for the treatment of IFS. Visual acuity, clinical findings, pachymetry, endothelial cell count, and anterior segment optical coherence tomography were recorded. RESULTS: We describe 3 cases of late-onset IFS that developed in eyes many years after LASIK (ranging from 15 to 31 years). All 3 patients had clinically significant corneal edema and evidence of poor endothelial function at the time of IFS diagnosis. DMEK was subsequently performed in each case. All 3 eyes showed resolution of corneal edema and improvement in best-corrected visual acuity after DMEK. CONCLUSIONS: DMEK can provide successful visual and anatomical recovery in patients who have had previous LASIK and experience late-onset IFS due to endothelial cell dysfunction.

Water birth: a systematic review and meta-analysis of maternal and neonatal outcomes.

OBJECTIVE: This systematic review and meta-analysis aimed to conduct a thorough and contemporary assessment of maternal and neonatal outcomes associated with water birth in comparison with land-based birth. DATA SOURCES: We conducted a comprehensive search of PubMed, EMBASE, CINAHL, and gray literature sources, from inception to February 28, 2023. STUDY ELIGIBILITY CRITERIA: We included randomized and nonrandomized studies that assessed maternal and neonatal outcomes in patients who delivered either conventionally or while submerged in water. METHODS: Pooled unadjusted odds ratios with 95% confidence intervals were calculated using a random-effects model (restricted maximum likelihood method). We assessed the 95% prediction intervals to estimate the likely range of future study results. To evaluate the robustness of the results, we calculated fragility indices. Maternal infection was designated as the primary outcome, whereas postpartum hemorrhage, perineal lacerations, obstetrical anal sphincter injury, umbilical cord avulsion, low Apgar scores, neonatal aspiration requiring resuscitation, neonatal infection, neonatal mortality within 30 days of birth, and neonatal intensive care unit admission were considered secondary outcomes. RESULTS: Of the 20,642 articles identified, 52 were included in the meta-analyses. Based on data from observational studies, water birth was not associated with increased probability of maternal infection compared with land birth (10 articles, 113,395 pregnancies; odds ratio, 0.93; 95% confidence interval, 0.76-1.14). Patients undergoing water birth had decreased odds of postpartum hemorrhage (21 articles, 149,732 pregnancies; odds ratio, 0.80; 95% confidence interval, 0.68-0.94). Neonates delivered while submerged in water had increased odds of cord avulsion (10 articles, 91,504 pregnancies; odds ratio, 1.75; 95% confidence interval, 1.38-2.24) and decreased odds of low Apgar scores (21 articles, 165,917 pregnancies; odds ratio, 0.69; 95% confidence interval, 0.58-0.82), neonatal infection (15 articles, 53,635 pregnancies; odds ratio, 0.64; 95% confidence interval, 0.42-0.97), neonatal aspiration requiring resuscitation (19 articles, 181,001 pregnancies; odds ratio, 0.60; 95% confidence interval, 0.43-0.84), and neonatal intensive care unit admission (30 articles, 287,698 pregnancies; odds ratio, 0.56; 95% confidence interval, 0.45-0.70). CONCLUSION: When compared with land birth, water birth does not appear to increase the risk of most maternal and neonatal complications. Like any other delivery method, water birth has its unique considerations and potential risks, which health care providers and expectant parents should evaluate thoroughly. However, with proper precautions in place, water birth can be a reasonable choice for mothers and newborns, in facilities equipped to conduct water births safely.

Towards co-design of rehabilitation technologies: a collaborative approach to prioritize usability issues.

Introduction: Early stakeholder engagement is critical to the successful development and translation of rehabilitation technologies, a pivotal step of which is usability testing with intended end-users. To this end, several methods employ end-user feedback to identify usability and implementation issues. However, the process of prioritizing identified issues seldom leverages the knowledge and expertise of the range of stakeholders who will ultimately affect the demand and supply of a device. This paper describes a novel method to prioritize end-user feedback using transdisciplinary stakeholder consultation and address it in subsequent product development. The proposed approach was demonstrated using a case study relating to the development of a novel technology for neural recovery after spinal cord injury. Method: Feedback from five individuals with chronic spinal cord injury was collected during two-hour usability evaluation sessions with a fully functional high-fidelity system prototype. A think-aloud and semi-structured interview protocol was used with each participant to identify usability and acceptability issues relating to the system in a 3-phase approach. Phase 1 involved extracting usability issues from think-aloud and semi-structured interview data. Phase 2 involved rating the usability issues based on their significance, technical feasibility, and implementation priority by relevant internal and external stakeholders. Finally, Phase 3 involved aggregating the usability issues according to design and implementation elements to facilitate solution generation, and these solutions were then raised as action tasks for future design iterations. Results: Sixty usability issues representing nine facets of usability were rated. Eighty percent of issues were rated to be of moderate to high significance, 83% were rated as being feasible to address, and 75% were rated as addressable using existing project resources. Fifty percent of the issues were rated to be a high priority for implementation. Evaluation of the grouped issues identified 21 tasks which were mapped to the product roadmap for integration into future design iterations. Discussion: This paper presents a method for meaningful transdisciplinary stakeholder engagement in rehabilitation technology development that can extended to other projects. Alongside a worked example, we offer practical considerations for others seeking to co-develop rehabilitation technologies.

Complete genome sequences of Gordonia rubripertincta phages OtterstedtS21 and Patos.

We report the genomes of two viruses with siphovirus morphology, OtterstedtS21 and Patos, from Albany, New York, using Gordonia rubripertincta. The genomes of OtterstedtS21 and Patos are ~68 kbp long with 58% GC content. Both phages group with cluster DV based on gene content similarity to phages in the Actinobacteriophage database.

Pharmacokinetics of mebendazole in plasma and cerebrospinal fluid following a single oral dose in healthy dogs.

Novel therapies are needed for treatment of gliomas. Mebendazole previously demonstrated anti-neoplastic effects on canine glioma cell lines at in vitro mean inhibitory concentrations (IC50) of 10 ng/mL. Our study aimed to titrate the oral dose of mebendazole necessary to achieve concentrations ≥10 ng/mL in cerebrospinal fluid (CSF) of healthy dogs. We hypothesized that an oral dose up to 200 mg/kg would be necessary. Phase one was a dose titration study using a total of 6 mixed breed dogs that described dose vs. plasma concentrations for 72 h after single oral dosing of either 50 mg/kg (n = 2), 100 mg/kg (n = 2), or 200 mg/kg (n = 2). Based on phase one, phase two dogs (total of 9) received 100 mg/kg (n = 4) or 200 mg/kg (n = 5) orally and blood samples were collected intermittently for 60 h with CSF samples collected intermittently for 24 h. Mebendazole was quantitated in plasma and CSF using high performance liquid chromatography. Median peak plasma concentrations (Cmax) were reached at 7 ± 2 h (100 mg/kg) of 220 ng/mL (81, 283) and at 15 ± 4 h (200 mg/kg) of 147 ng/ml (112, 298). The respective area under the curve (AUC: ng/ml/h) reported as a median was 2,119 (1,876, 3,288) vs. 3,115 (1,559, 4,972). Median plasma concentrations (ng/ml) for 100 vs. 200 mg/kg were 47 (32, 52) vs. 65 (35, 104), respectively. For CSF, the median value for Cmax (at 100 mg/kg vs. 200 mg/kg) was 8 (2, 28) vs. 21 (12, 27) and AUC was 87 (22, 157) vs. 345 (92, 372), respectively. Relative bioavailability in CSF vs. plasma was 4 to 10%. Although several animals demonstrated clinical signs indicative of gastrointestinal upset [i.e., vomiting (n = 2), diarrhea (n = 2), or both (n = 1)], these events were not considered serious. The in vitro IC50 for gliomas can be reached in CSF at 100 mg/kg (n = 1), however a 200 mg/kg dose yielded more consistent concentrations.

Separation of cyclotron-produced cobalt-55/58m from iron targets using cation exchange chromatography with non-aqueous solvents and extraction chromatography.

Cobalt-55 and -58m form a theranostic pair that has relevant properties for cancer research. We report a cation exchange chromatography/extraction chromatography method that separates cyclotron-produced 55/58mCo from 54/57Fe in <1.5 h, recovers >85% Co and achieves [55Co]Co-NOTA and -DOTA AMA 89 ± 48 and 35 ± 7 MBq/nmol (EOB), respectively. Cobalt-55 and -58m were quantitatively labeled to functionalized NOTA at 106 and 50 MBq/nmol (EOB), respectively, corroborating measured AMA. This method is faster than previously published methods and achieves better [55/58mCo]Co-NOTA and -DOTA AMA.

Nipple properties affect sensorimotor integration during bottle feeding in an infant pig model.

Infant feeding is a critical neurological milestone in development defined by the coordination of muscles, peripheral nerves, and brainstem nuclei. In infants, milk flow rate is often limited to improve feeding performance without treating the underlying deficiencies in the sucking and swallowing processes. Modification of the neuromotor response via sensory information from the nipple during bottle feeding is an unexplored avenue for physiology-based interventions. In this study, we assessed how differences in nipple hole size and nipple stiffness affect sucking muscle activation and subsequent movement. We fabricated four bottle nipples of varying hole size and stiffness to determine how variation in nipple properties affects the sucking behavior of infant pigs. Our results demonstrate that sensory information from the nipple affects sucking motor output. Nipple hole sizes and stiffnesses with a larger milk flow rate resulted in greater muscle activity and kinematic movement. Additionally, our results suggest that sensorimotor interventions are better directed toward modulating tongue function rather than the mandible movements due to a greater response to sensory information. Understanding how sensory information influences infant feeding is instrumental in promoting effective infant feeding.

Recycling of 52Cr electroplated targets for 52gMn production.

52gMn is a promising radionuclide for positron emission tomography (PET). Enriched 52Cr targets are required to minimize formation of 54Mn radioisotopic impurities during production with proton beams. The need for radioisotopically pure 52gMn, accessibility and cost of 52Cr, sustainability of the radiochemical process, and potential for iterative purification of target materials motivate this development of recyclable, electroplated 52Cr metal targets and radiochemical isolation and labeling with resulting >99.89% radionuclidically pure 52gMn. The run-to-run replating efficiency is 60 ± 20%, and unplated chromium from this method is recovered with 94% efficiency as 52CrCl3 hexahydrate. The decay-corrected molar activity of chemically isolated 52gMn for common chelating ligands was 376 MBq/µmol.

Work Intensity of Postoperative Care Following Implantation of Presbyopia-Correcting versus Monofocal Intraocular Lenses.

Purpose: To compare the work intensity of postoperative care following implantation of presbyopia-correcting intraocular lenses (IOLs) to that of standard monofocal IOLs. Patients and Methods: This open-label, multicenter, comparative study retrospectively reviewed the case records of cataract surgery patients who underwent bilateral implantation of either presbyopia-correcting IOLs (presby-IOL group; N=177) or standard monofocal IOLs (monofocal group; N=177). Outcome measures included the total time the patient spent in the office, number of visits, mean duration of visits, and the number of procedures and diagnostic tests during the first postoperative year. Outcome measures were compared between the first 90 days and days 91-365 after surgery. Results: Mean (±SD) time spent in the office during the first postoperative year was 5:50 ± 3:35 hours (H:MM) over 6.6 ± 2.9 visits in the presby-IOL group, compared to 3:38 ± 1:36 hours over 4.9 ± 1.6 visits in the monofocal IOL group (p <0.001). During the first 90 days, a presby-IOL patient spent 40 minutes longer in the office than a monofocal IOL patient (3:39 ± 1:38 hours vs 2.59 ± 1:13 hours) (p <0.001). During days 91-365, time in the office was 1:32 hours longer (p <0.001), and the mean visit duration was 8 minutes longer for the presby-IOL patients (p=0.002) than those with monofocal IOL. In addition, the presby-IOL patients underwent more procedures and diagnostic tests (p ≤0.001) as compared with standard monofocal cataract surgery patients. Conclusion: Patients implanted with presbyopia-correcting IOLs require significantly more clinic time, diagnostic testing, and procedures postoperatively as compared with standard monofocal cataract surgery patients.

Cyclotron production of 43Sc and 44gSc from enriched 42CaO, 43CaO, and 44CaO targets.

Introduction: 43Sc and 44gSc are both positron-emitting radioisotopes of scandium with suitable half-lives and favorable positron energies for clinical positron emission tomography (PET) imaging. Irradiation of isotopically enriched calcium targets has higher cross sections compared to titanium targets and higher radionuclidic purity and cross sections than natural calcium targets for reaction routes possible on small cyclotrons capable of accelerating protons and deuterons. Methods: In this work, we investigate the following production routes via proton and deuteron bombardment on CaCO3 and CaO target materials: 42Ca(d,n)43Sc, 43Ca(p,n)43Sc, 43Ca(d,n)44gSc, 44Ca(p,n)44gSc, and 44Ca(p,2n)43Sc. Radiochemical isolation of the produced radioscandium was performed with extraction chromatography using branched DGA resin and apparent molar activity was measured with the chelator DOTA. The imaging performance of 43Sc and 44gSc was compared with 18F, 68Ga, and 64Cu on two clinical PET/CT scanners. Discussion: The results of this work demonstrate that proton and deuteron bombardment of isotopically enriched CaO targets produce high yield and high radionuclidic purity 43Sc and 44gSc. Laboratory capabilities, circumstances, and budgets are likely to dictate which reaction route and radioisotope of scandium is chosen.

Interface fluid syndrome after LASIK surgery: retrospective pooled analysis and systematic review.

Interface fluid syndrome (IFS) is a complication associated with laser in situ keratomileusis (LASIK) surgery where a fluid pocket in the corneal stroma decreases visual acuity. A systematic review of IFS cases using PRISMA guidelines was performed yielding a total of 33 patients. 2 outcomes were selected for logistic regression analysis: final corrected distance visual acuity (CDVA) and need for surgical management. Results showed 33.3% of patients required surgery, 51.5% had their IFS resolve within 1 month or sooner, and 51.5% had final CDVA 20/25 or better. Higher presenting intraocular pressure (IOP) and duration of IFS ≤1 month was associated with higher odds of final CDVA 20/25 or better (adjusted odds ratio [aOR] 1.12, P = .04; aOR 7.71, P = .02, respectively). Endothelial cell dysfunction led to 17.55 greater odds for requiring surgical compared to medical management (aOR 0.36, P = .04). Presenting IOP and duration of IFS predicted final CDVA, while prior endothelial cell dysfunction predicted need for surgery.

Nr2f1a maintains atrial nkx2.5 expression to repress pacemaker identity within venous atrial cardiomyocytes of zebrafish.

Maintenance of cardiomyocyte identity is vital for normal heart development and function. However, our understanding of cardiomyocyte plasticity remains incomplete. Here, we show that sustained expression of the zebrafish transcription factor Nr2f1a prevents the progressive acquisition of ventricular cardiomyocyte (VC) and pacemaker cardiomyocyte (PC) identities within distinct regions of the atrium. Transcriptomic analysis of flow-sorted atrial cardiomyocytes (ACs) from nr2f1a mutant zebrafish embryos showed increased VC marker gene expression and altered expression of core PC regulatory genes, including decreased expression of nkx2.5, a critical repressor of PC differentiation. At the arterial (outflow) pole of the atrium in nr2f1a mutants, cardiomyocytes resolve to VC identity within the expanded atrioventricular canal. However, at the venous (inflow) pole of the atrium, there is a progressive wave of AC transdifferentiation into PCs across the atrium toward the arterial pole. Restoring Nkx2.5 is sufficient to repress PC marker identity in nr2f1a mutant atria and analysis of chromatin accessibility identified an Nr2f1a-dependent nkx2.5 enhancer expressed in the atrial myocardium directly adjacent to PCs. CRISPR/Cas9-mediated deletion of the putative nkx2.5 enhancer leads to a loss of Nkx2.5-expressing ACs and expansion of a PC reporter, supporting that Nr2f1a limits PC differentiation within venous ACs via maintaining nkx2.5 expression. The Nr2f-dependent maintenance of AC identity within discrete atrial compartments may provide insights into the molecular etiology of concurrent structural congenital heart defects and associated arrhythmias.