A Quality Improvement Initiative for Detection of Attention-Deficit/Hyperactivity Disorder in an Urban, Academic Safety Net Hospital.

OBJECTIVE: Improve detection of Attention Deficit/Hyperactivity Disorder (ADHD) in a safety net, hospital-based, academic pediatric practice by optimizing screening with the Pediatric Symptom Checklist attention score (PSC-AS) and further evaluation with the Vanderbilt ADHD Diagnostic Rating Scale (VADRS). METHODS: We implemented a multi-component intervention by (1) optimizing electronic medical record (EMR) features; (2) adjusting clinic operational workflow; and (3) creating a decision-making algorithm for pediatric primary care clinicians (PPCCs). We extracted 4 outcomes manually from the EMR (pediatrician acknowledgment of a positive PSC-AS, documentation of a plan for further evaluation, distribution of VADRS, and completion of at least 1 VADRS). Outcomes were measured monthly in run charts compared to the pre-intervention control period, and implementation was optimized with Plan-Do-Study-Act cycles. RESULTS: PPCCs were significantly more likely to acknowledge a positive PSC-AS in the intervention versus control (65.3% vs 41.5%; p < 0.001), although this did not change documentation of a plan (70% vs 67.1%; p -value = 0.565). Significantly more children with a positive PSC-AS were distributed a parent or teacher VADRS in the intervention versus control (30.6% vs 17.7%; p -value = 0.0059), but the percentage of returned VADRS rating scales did not improve (12.9% vs 9.2%; p -value = 0.269). CONCLUSION: Our ADHD detection quality improvement initiative improved use of the PSC-AS to identify attention problems and distribution of VADRS diagnostic rating scales, but additional interventions are needed to improve the completion of ADHD evaluations in primary care to ensure that children are appropriately identified and offered evidence-based care.

One Year Outcomes Following Transplantation with COVID-19-Positive Donor Hearts: A National Database Cohort Study.

The current understanding of the safety of heart transplantation from COVID-19+ donors is uncertain. Preliminary studies suggest that heart transplants from these donors may be feasible. We analyzed 1-year outcomes in COVID-19+ donor heart recipients using 1:3 propensity matching. The OPTN database was queried for adult heart transplant recipients between 1 January 2020 and 30 September 2022. COVID-19+ donors were defined as those who tested positive on NATs or antigen tests within 21 days prior to procurement. Multiorgan transplants, retransplants, donors without COVID-19 testing, and recipients allocated under the old heart allocation system were excluded. A total of 7211 heart transplant recipients met the inclusion criteria, including 316 COVID-19+ donor heart recipients. Further, 290 COVID-19+ donor heart recipients were matched to 870 COVID-19- donor heart recipients. Survival was similar between the groups at 30 days (p = 0.46), 6 months (p = 0.17), and 1 year (p = 0.07). Recipients from COVID-19+ donors in the matched cohort were less likely to experience postoperative acute rejection prior to discharge (p = 0.01). National COVID-19+ donor heart usage varied by region: region 11 transplanted the most COVID-19+ hearts (15.8%), and region 6 transplanted the fewest (3.2%). Our findings indicate that COVID-19+ heart transplantation can be performed with safe early outcomes. Further analyses are needed to determine if long-term outcomes are equivalent between groups.

Does Failure to Rescue Drive Race/Ethnicity-based Disparities in Survival After Heart Transplantation?

OBJECTIVE: The objective was to assess whether race/ethnicity is an independent predictor of failure to rescue (FTR) after orthotopic heart transplantation (OHT). SUMMARY BACKGROUND DATA: Outcomes following OHT vary by patient level factors; for example, non-White patients have worse outcomes than White patients after OHT. Failure to rescue is an important factor associated with cardiac surgery outcomes, but its relationship to demographic factors is unknown. METHODS: Using the United Network for Organ Sharing database, we included all adult patients who underwent primary isolated OHT between 1/1/2006 snd 6/30/2021. FTR was defined as the inability to prevent mortality after at least one of the UNOS-designated postoperative complications. Donor, recipient, and transplant characteristics, including complications and FTR, were compared across race/ethnicity. Logistic regression models were created to identify factors associated with complications and FTR. Kaplan Meier and adjusted Cox proportional hazards models evaluated the association between race/ethnicity and posttransplant survival. RESULTS: There were 33,244 adult, isolated heart transplant recipients included: the distribution of race/ethnicity was 66% (n=21,937) White, 21.2% (7,062) Black, 8.3% (2,768) Hispanic, and 3.3% (1,096) Asian. The frequency of complications and FTR differed significantly by race/ethnicity. After adjustment, Hispanic recipients were more likely to experience FTR than White recipients (OR 1.327, 95% CI[1.075-1.639], P =0.02). Black recipients had lower 5-year survival compared with other races/ethnicities (HR 1.276, 95% CI[1.207-1.348], P <0.0001). CONCLUSIONS: In the US, Black recipients have an increased risk of mortality after OHT compared with White recipients, without associated differences in FTR. In contrast, Hispanic recipients have an increased likelihood of FTR, but no significant mortality difference compared with White recipients. These findings highlight the need for tailored approaches to addressing race/ethnicity-based health inequities in the practice of heart transplantation.

Acute rejection in donation after circulatory death (DCD) heart transplants.

BACKGROUND: Donation after circulatory death (DCD) heart transplantation has promising early survival, but the effects on rejection remain unclear. METHODS: The United Network for Organ Sharing database was queried for adult heart transplants from December 1, 2019, to December 31, 2021. Multiorgan transplants and loss to follow-up were excluded. The primary outcome was acute rejection, comparing DCD and donation after brain death (DBD) transplants. RESULTS: A total of 292 DCD and 5,582 DBD transplants met study criteria. Most DCD transplants were transplanted at status 3-4 (61.0%) compared to 58.6% of DBD recipients at status 1-2. DCD recipients were less likely to be hospitalized at transplant (26.7% vs 58.3%, p < 0.001) and to require intra-aortic balloon pumping (IABP; 9.6% vs 28.9%, p < 0.001), extracorporeal membrane oxygenation (ECMO; 0.3% vs 5.9%, p < 0.001) or temporary left ventricular assist device (LVAD; 1.0% vs 2.7%, p < 0.001). DCD recipients were more likely to have acute rejection prior to discharge (23.3% vs 18.4%, p = 0.044) and to be hospitalized for rejection (23.4% vs 11.4%, p = 0.003) at a median follow-up of 15 months; the latter remained significant after propensity matching. On multivariable logistic regression, DCD donation was an independent predictor of acute rejection (odds ratio [OR] 1.47, 95% confidence interval [CI] 1.00-2.15, p = 0.048) and hospitalization for rejection (OR 2.03, 95% CI 1.06-3.70, p = 0.026). On center-specific subgroup analysis, DCD recipients continued to have higher rates of hospitalization for rejection (23.4% vs 13.8%, p = 0.043). CONCLUSIONS: DCD recipients are more likely to experience acute rejection. Early survival is similar between DCD and DBD recipients, but long-term implications of increased early rejection in DCD recipients require further investigation.

Genomic analysis of azithromycin-resistant Salmonella from food animals at slaughter and processing, and retail meats, 2011-2021, United States.

IMPORTANCE: Macrolides of different ring sizes are critically important antimicrobials for human medicine and veterinary medicine, though the widely used 15-membered ring azithromycin in humans is not approved for use in veterinary medicine. We document here the emergence of azithromycin-resistant Salmonella among the NARMS culture collections between 2011 and 2021 in food animals and retail meats, some with co-resistance to ceftriaxone or decreased susceptibility to ciprofloxacin. We also provide insights into the underlying genetic mechanisms and genomic contexts, including the first report of a novel combination of azithromycin resistance determinants and the characterization of multidrug-resistant plasmids. Further, we highlight the emergence of a multidrug-resistant Salmonella Newport clone in food animals (mainly cattle) with both azithromycin resistance and decreased susceptibility to ciprofloxacin. These findings contribute to a better understating of azithromycin resistance mechanisms in Salmonella and warrant further investigations on the drivers behind the emergence of resistant clones.

Airbrushed nanofibers with bioactive core and antibacterial shell for wound healing application.

Acute and chronic wounds are vulnerable to infection and delayed healing and require critical care and advanced wound protection. To overcome the challenges, dual therapy of antibacterial and growth factors will be a novel wound care strategy. The present study explores airbrushed core-shell nanofiber for dual delivery of epidermal growth factor (EGF) and amoxicillin (AMOX) in a sustained manner. A blend of polycaprolactone (PCL)-polyethylene oxide (PEO) was used to prepare the shell compartment for amoxicillin loading and poly-DL-lactide (PDLLA) core for EGF loading by using a customized airbrush setup. Characterization result shows a uniform distribution of nanofibers ranging between 200 and 500 nm in diameter. Amoxicillin loading in the shell compartment offers an initial burst release followed by a sustained release for up to 14 days. Whereas EGF in the core part shows a continuous sustained release throughout the release study.In-vitrostudy indicates the biocompatibility of EGF-AMOX loaded core-shell nanofibers with human dermal fibroblast cell (HDF) cells and a higher cellular proliferation compared to control samples. Gene expression data show an increase in fold change of collagen I and tropoelastin expression, indicating the regenerative properties of EGF-AMOX encapsulated nanofiber. The combination of bioactive core (EGF) and antibiotic shell (amoxicillin) in an airbrushed nanofibrous scaffold is a novel approach, which is the first time explored to deliver sustainable therapy to treat skin wounds. Our results demonstrate that PCL-PEO-Amoxicillin/PDLLA-EGF-loaded core-shell nanofibers are promising dual therapy scaffolds to deliver effective skin wound care, with the possibility of direct deposition on the wound.

Neural cell membrane-coated DNA nanogels as a potential target-specific drug delivery tool for the central nervous system.

A major bottleneck in drug/gene delivery to enhance tissue regeneration after injuries is to achieve targeted delivery to the cells of interest. Unfortunately, we have not been able to attain effective targeted drug delivery in tissues due to the lack of efficient delivery platforms. Since specific cell-cell interactions exist to impart the unique structure and functionality of tissues and organs, we hypothesize that such specific cellular interactions may also be harnessed for drug delivery applications in the form of cell membrane coatings. Here, we employed neural cell-derived membrane coating technique on DNA nanogels to improve target specificity. The efficacy of neural cell membrane-coated DNA nanogels (NCM-nanogels) was demonstrated by using four types of cell membranes derived from the central nervous system (CNS), namely, astrocytes, microglia, cortical neurons, and oligodendrocyte progenitor cells (OPCs). A successful coating of NCMs over DNA nanogels was confirmed by dynamic light scattering, zeta potential measurements and transmission electron microscopy. Subsequently, an overall improvement in cellular uptake of NCM-nanogels over uncoated DNA nanogels (p < 0.005) was seen. Additionally, we observed a selective uptake of OPC membrane-coated DNA nanogels (NCM-O mem) by oligodendrocytes over other cell types both in vitro and in vivo. Our quantitative polymerase chain reaction (qPCR) results also showed selective and effective gene knockdown capacity of NCM-O mem for OPC transfection. The findings in this work may be beneficial for future drug delivery applications targeted at the CNS.

Is Transplantation With Coronavirus Disease 2019-Positive Donor Lungs Safe? A US Nationwide Analysis.

BACKGROUND: Since the beginning of the pandemic, coronavirus disease 2019 (COVID-19) has caused debilitating lung failure in many patients. Practitioners have understandably been hesitant to use lungs from donors with COVID-19 for transplantation. This study aimed to analyze the characteristics and short-term outcomes of lung transplantation from donors with recent positive COVID-19 testing results. METHODS: Lung transplantations performed between January 2020 and June 2022 were queried from the United Network for Organ Sharing database. Pediatric, multiorgan, and repeat lung transplantations were excluded. Propensity scoring matched recipients of lungs from donors with recent positive COVID-19 testing results to recipients of lungs from donors with negative COVID-19 testing results, and comparisons of 30-day mortality, 3-month mortality, and perioperative outcomes were performed. RESULTS: A total of 5270 patients underwent lung transplantation during the study dates, including 51 patients who received lungs from donors with recent positive COVID-19 testing results. Forty-five recipients of lungs from donors with recent positive COVID-19 testing results were matched with 135 recipients of lungs from donors with negative COVID-19 testing results. After matching, there was no difference in 30-day (log-rank P = .42) and 3-month (log-rank P = .42) mortality. The incidence of other perioperative complications was similar between the groups. CONCLUSIONS: The 30-day and 3-month survival outcomes were similar between recipients of lungs from donors with recent positive COVID-19 testing results and recipients of lungs from donors with negative COVID-19 testing results. This finding suggests that highly selected COVID-19-positive donors without evidence of active infection may be safely considered for lung transplantation. Further studies should explore long-term outcomes to provide reassurance about the safety of this practice.

An assessment of the physicochemical characteristics and essential oil composition of Mentha longifolia (L.) Huds. exposed to different salt stress conditions.

Salt stress adversely influences growth, development, and productivity in plants, resulting in a limitation on agriculture production worldwide. Therefore, this study aimed to investigate the effect of four different salts, i.e., NaCl, KCl, MgSO4, and CaCl2, applied at various concentrations of 0, 12.5, 25, 50, and 100 mM on the physico-chemical properties and essential oil composition of M. longifolia. After 45 days of transplantation, the plants were irrigated at different salinities at 4-day intervals for 60 days. The resulting data revealed a significant reduction in plant height, number of branches, biomass, chlorophyll content, and relative water content with rising concentrations of NaCl, KCl, and CaCl2. However, MgSO4 poses fewer toxic effects than other salts. Proline concentration, electrolyte leakage, and DPPH inhibition (%) increase with increasing salt concentrations. At lower-level salt conditions, we had a higher essential oil yield, and GC-MS analysis reported 36 compounds in which (-)-carvone and D-limonene covered the most area by 22%-50% and 45%-74%, respectively. The expression analyzed by qRT-PCR of synthetic Limonene (LS) and Carvone (ISPD) synthetic genes has synergistic and antagonistic relationships in response to salt treatments. To conclude, it can be said that lower levels of salt enhanced the production of essential oil in M. longifolia, which may provide future benefits commercially and medicinally. In addition to this, salt stress also resulted in the emergence of novel compounds in essential oils, for which future strategies are needed to identify the importance of these compounds in M. longifolia.

Public health supply chain for iron and folic acid supplementation in India: Status, bottlenecks and an agenda for corrective action under Anemia Mukt Bharat strategy.

PURPOSE: The IFA supplementation program under the Anemia Mukt Bharat (AMB) program is one of the most ambitious nutrient supplementation programs in India. The delivery of services often suffers due to frequent stock outs and shortages. It is critical to understand the bottleneck in the supply chain adversely affecting the performance and coverage of the program. The paper attempts to identify the bottlenecks of the IFA supply chain in key areas of supply chain i.e., forecasting, procurement, warehousing and inventory management, transportation, distribution, logistic information system and suggests a plan of action aimed at ensuring uninterrupted supplies to the end beneficiaries. DESIGN/METHODOLOGY/APPROACH: The data source for the present paper is the nationwide IFA Supply Chain Assessment (2018-19) conducted across 29 Indian states with a total of 58 districts, 116 blocks, 232 Sub-Centres, 232 Anganwadi centres and 232 schools covered under the assessment as a multi-partner collaborative initiative. Field insights from supply chain strengthening interventions under different public health programs in India and other developing countries were taken to arrive at corrective actions and recommendations. Findings were disseminated to government and an action plan was suggested for connecting service delivery points through an app-based system, developing a micro plan for ensuring fixed distribution schedule, followed by continuous monitoring and review meetings identified for follow up. FINDINGS: The average lead time across states was 35 weeks with top three performing states being Goa, Sikkim, and Telangana. The average per unit cost of procurement was Rs 0.35 for IFA Red, Rs 0.25 for IFA Blue, Rs 0.31 for IFA Pink and Rs 7.30 for IFA syrup. Out of the 704 districts in India, only 213 has IFA Red, only 140 had IFA Blue, 152 had IFA Pink and 163 had IFA Syrup available in four quarters of 2018-19. The key issues identified in the assessment were-a lack of standardized forecasting process, absence of inventory management techniques, no fixed distribution schedule, inadequate availability of transport vehicles and an absence of an integrated MIS. ORIGINALITY/VALUE: The identification of bottlenecks in the IFA supply chain and its impact on the performance of the supply chain would provide policy guidelines for the government as well as development partner agencies to design an effective and efficient supply chain. It would also enable the policy planners to understand the challenges associated with managing different components of a supply chain, their interrelation and impact on the overall performance of the supply chain. The suggested recommendations would equip program managers with the tool to devise and implement field level solutions.

A New Class of Cluster-Matrix Nanocomposite Made of Fully Miscible Components.

Nanocomposite materials, consisting of two or more phases, at least one of which has a nanoscale dimension, play a distinctive role in materials science because of the multiple possibilities for tailoring their structural properties and, consequently, their functionalities. In addition to the challenges of controlling the size, size distribution, and volume fraction of nanometer phases, thermodynamic stability conditions limit the choice of constituent materials. This study goes beyond this limitation by showing the possibility of achieving nanocomposites from a bimetallic system, which exhibits complete miscibility under equilibrium conditions. A series of nanocomposite samples with different compositions are synthesized by the co-deposition of 2000-atom Ni-clusters and a flux of Cu-atoms using a novel cluster ion beam deposition system. The retention of the metastable nanostructure is ascertained from atom probe tomography (APT), magnetometry, and magnetotransport studies. APT confirms the presence of nanoscale regions with ≈100 at% Ni. Magnetometry and magnetotransport studies reveal superparamagnetic behavior and magnetoresistance stemming from the single-domain ferromagnetic Ni-clusters embedded in the Cu-matrix. Essentially, the magnetic properties of the nanocomposites can be tailored by the precise control of the Ni concentration. The initial results offer a promising direction for future research on nanocomposites consisting of fully miscible elements.

An Evaluation of the Drug Permeability Properties of Human Cadaveric In Situ Tympanic and Round Window Membranes.

It is estimated that hearing loss currently affects more than 1.5 billion people, or approximately 20% of the global population; however, presently, there are no Food and Drug Administration-approved therapeutics or prophylactics for this condition. While continued research on the development of otoprotective drugs to target this clear unmet need is an obvious path, there are numerous challenges to translating promising therapeutic candidates into human clinical testing. The screening of promising drug candidates relies exclusively on preclinical models. Current models do not permit the rapid high-throughput screening of promising drug candidates, and their relevance to clinical scenarios is often ambiguous. With the current study, we seek to understand the drug permeability properties of the cadaveric tympanic and round window membranes with the goal of generating knowledge that could inform the design and/or evaluation of in vitro organotypic models. The development of such models could enable the early high-throughput screening of topical therapeutic candidates and should address some of the limitations of currently used animal models.

Development and Characterization of an In Vitro Round Window Membrane Model for Drug Permeability Evaluations.

Hearing loss and balance disorders are highly common disorders, and the development of effective oto-therapeutics remains an area of intense research. Drug development and screening in the hearing research field heavily rely on the use of preclinical models with often ambiguous translational relevance. This often leads to failed advancement in the market of effective therapeutics. In this context, especially for inner ear-specific pathologies, the availability of an in vitro, physiologically relevant, round window membrane (RWM) model could enable rapid, high-throughput screening of potential topical drugs for inner ear and cochlear dysfunctions and could help accelerate the advancement to clinic and market of more viable drug candidates. In this study, we report the development and evaluation of an in vitro model that mimics the native RWM tissue morphology and microenvironment as shown via immunostaining and histological analyses. The developed three-dimensional (3D) in vitro model was additionally assessed for barrier integrity by transepithelial electrical resistance, and the permeability of lipophilic and hydrophilic drugs was determined. Our collective findings suggest that this in vitro model could serve as a tool for rapid development and screening of topically deliverable oto-therapeutics.

An In Vitro Model for Characterization of Drug Permeability across the Tympanic Membrane.

Otic disorders, such as otitis media and hearing loss, affect a substantial portion of the global population. Despite this, oto-therapeutics, in particular those intended to treat hearing loss, have seen limited development and innovation. A significant factor to this is likely a result of the inherent costs and complexities of drug discovery and development. With in vitro 3D tissue models seeing increased utility for the rapid, high-throughput screening of drug candidates, it stands to reason that the field of otology could greatly benefit from such innovations. In this study, we propose and describe an in vitro 3D model, designed using a physiologically based approach, which we suggest can be used to estimate drug permeability across human tympanic membranes (TM). We characterize the permeability properties of several template drugs in this model under various growth and storage conditions. The availability of such cost-effective, rapid, high-throughput screening tools should allow for increased innovation and the discovery of novel drug candidates over the currently used animal models. In the context of this TM permeation model, it may promote the development of topical drugs and formulations that can non-invasively traverse the TM and provide tissue-targeted drug delivery as an alternative to systemic treatment, an objective which has seen limited study until present.

Silver sulfadiazine loaded core-shell airbrushed nanofibers for burn wound healing application.

Ideal dressing materials for complex and large asymmetric burns should have the dual properties of anti-bacterial and regenerative with advanced applicability of direct deposit on the wound at the patient bedside. In this study, core-shell nanofibers (polycaprolactone; PCL and polyethylene oxide; PEO) with different percent of silver sulfadiazine (SSD) loading (2-10%) were prepared by the airbrushing method using a custom build device. Results indicate a sustained release profile of silver sulfadiazine (SSD) up to 28 days and concentration-dependent anti-bacterial activity. The morphology and proliferation of human dermal fibroblast (HDF) cells and human dental follicle stem cells (HDFSC) on the silver sulfadiazine loaded nanofibers confirm the biocompatibility of airbrushed nanofibers. Moreover, upregulation of extracellular matrix (ECM) proteins (Col I, Col III, and elastin) support the differentiation and regenerative properties of silver sulfadiazine nanofiber mats. This was further confirmed by the complete recovery of rabbit burn wound models within 7 days of silver sulfadiazine loaded nanofiber dressing. Histopathology data show silver sulfadiazine loaded core-shell nanofibers' anti-inflammatory and proliferative activity without any adverse response on the tissue. Overall data display that the airbrushed silver sulfadiazine-loaded core-shell nanofibers are effective dressing material with the possibility of direct fiber deposition on the wound to cover, heal, and regenerate large asymmetric burn wounds.