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  • 1
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 44, No. suppl_1 ( 2013-02)
    Abstract: Malignant infarction is characterized by the formation of cerebral edema, and decompressive craniectomy (DC) is the only proven therapy. The NC (Ca-ATP) channel, regulated by the SUR1 receptor, is blocked by the sulfonylurea drug glyburide, which attenuates brain water content in preclinical models of large stroke. A phase I study has been safely completed. We assessed the hypothesis that a pilot study of RP-1127 (Glyburide for Injection) in patients at high risk for malignant infarction was safe and feasible. Methods: The objective of this four-center prospective, open label, phase IIa trial was to assess the safety and feasibility of treating severe anterior circulation ischemic stroke patients with RP-1127, whether or not treated with IV rtPA. The study enrolled patients with a baseline MRI DWI lesion between 82 cm3 and 210 cm3, age 18-80 years, and time from symptom onset to drug infusion of ≤ 10 hours. Patients received a RP-1127 bolus followed by continuous infusion for 72 hours. Results: Recruitment of 10 patients was completed within 9.6 months. The mean initial DWI lesion volume was 102 ± 23 cm3. There were no serious adverse events related to the drug. The incidence of malignant edema was 20%, compared to 88% in a prospective observational study with DWI ≥82 cm3. Further, 8/10 patients did not require any bolus osmotherapy or DC. The mean increase in ipsilateral hemisphere volume was 50±33 cm3 compared to historical controls of 71.5±27 cm3. The proportion of 30 day mRS ≤ 4 was 90% compared to 23.8% (at 12 months) in control patients from a pooled analysis of DC trials. Conclusions: These findings suggest that a Phase II trial for patients at risk of malignant infarction is feasible and will provide important insights into the safety and potential efficacy of RP-1127.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2013
    detail.hit.zdb_id: 1467823-8
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  • 2
    In: Journal of the Pediatric Infectious Diseases Society, Oxford University Press (OUP), Vol. 9, No. 6 ( 2020-12-31), p. 716-737
    Abstract: Immune-mediated lung injury and systemic hyperinflammation are characteristic of severe and critical coronavirus disease 2019 (COVID-19) in adults. Although the majority of severe acute respiratory syndrome coronavirus 2 infections in pediatric populations result in minimal or mild COVID-19 in the acute phase of infection, a small subset of children develop severe and even critical disease in this phase with concomitant inflammation that may benefit from immunomodulation. Therefore, guidance is needed regarding immunomodulatory therapies in the setting of acute pediatric COVID-19. This document does not provide guidance regarding the recently emergent multisystem inflammatory syndrome in children (MIS-C). Methods A multidisciplinary panel of pediatric subspecialty physicians and pharmacists with expertise in infectious diseases, rheumatology, hematology/oncology, and critical care medicine was convened. Guidance statements were developed based on best available evidence and expert opinion. Results The panel devised a framework for considering the use of immunomodulatory therapy based on an assessment of clinical disease severity and degree of multiorgan involvement combined with evidence of hyperinflammation. Additionally, the known rationale for consideration of each immunomodulatory approach and the associated risks and benefits was summarized. Conclusions Immunomodulatory therapy is not recommended for the majority of pediatric patients, who typically develop mild or moderate COVID-19. For children with severe or critical illness, the use of immunomodulatory agents may be beneficial. The risks and benefits of such therapies are variable and should be evaluated on a case-by-case basis with input from appropriate specialty services. When available, the panel strongly favors immunomodulatory agent use within the context of clinical trials. The framework presented herein offers an approach to decision-making regarding immunomodulatory therapy for severe or critical pediatric COVID-19 and is informed by currently available data, while awaiting results of placebo-controlled randomized clinical trials.
    Type of Medium: Online Resource
    ISSN: 2048-7207
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2668791-4
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  • 3
    Online Resource
    Online Resource
    Pediatric Pharmacy Advocacy Group ; 2020
    In:  The Journal of Pediatric Pharmacology and Therapeutics Vol. 25, No. 8 ( 2020-11-01), p. 730-734
    In: The Journal of Pediatric Pharmacology and Therapeutics, Pediatric Pharmacy Advocacy Group, Vol. 25, No. 8 ( 2020-11-01), p. 730-734
    Abstract: Burkholderia cepacia complex (Bcc) is an opportunistic pathogen, posing little risk to healthy individuals. The presentation of Bcc can vary from a virtually asymptomatic chronic infection, to an acute, life-threatening necrotizing pneumonia, acute respiratory distress syndrome, and bacteremia (cepacia syndrome) associated with a mortality rate up to 75%. We present the successful treatment of a 17-year-old male with chronic granulomatous disorder who presented with cepacia syndrome and confirmed Bcc pneumonia using a novel antimicrobial approach. Despite initial IV antimicrobial therapy, our patient continued to decline, developing hypotension requiring pressor support and eventually extracorporeal membrane oxygenation. An aggressive, multimechanistic approach including the combination of nebulized tobramycin, IV sulfamethoxazole-trimethoprim, ceftazidime, enteral minocycline, and corticosteroids was implemented. This multimechanistic antimicrobial approach in combination with systemic corticosteroids led to the successful treatment of cepacia syndrome in the setting of necrotizing pneumonia due to B cepacia with full respiratory recovery. We suggest that in patients with cepacia syndrome who continue to decline despite IV antimicrobial therapy, using multiple antimicrobial mechanisms of action may improve clinical outcomes.
    Type of Medium: Online Resource
    ISSN: 1551-6776
    Language: English
    Publisher: Pediatric Pharmacy Advocacy Group
    Publication Date: 2020
    detail.hit.zdb_id: 3028543-4
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  • 4
    Online Resource
    Online Resource
    Pediatric Pharmacy Advocacy Group ; 2021
    In:  The Journal of Pediatric Pharmacology and Therapeutics Vol. 26, No. 7 ( 2021-11-01), p. 659-668
    In: The Journal of Pediatric Pharmacology and Therapeutics, Pediatric Pharmacy Advocacy Group, Vol. 26, No. 7 ( 2021-11-01), p. 659-668
    Abstract: The goals of antimicrobial stewardship programs (ASPs) are to optimize antimicrobial prescribing habits in order to improve patient outcomes, reduce antimicrobial resistance, and reduce hospital costs. Multiple society-endorsed guidelines and government policies reinforce the importance of ASP implementation. Effective antimicrobial stewardship can impact unique patients, hospitals, and societal antibiotic-resistance burden. The role and subsequent success of these programs has largely been reported in the adult population. Pediatric and neonatal intensive care units present unique challenges for traditional antimicrobial stewardship approaches. The purpose of this review article is to explore the challenges of appropriate antibiotic use in the pediatric and neonatal intensive care units and to summarize strategies ASPs can use to overcome these challenges. These problems include non-specific disease presentations, limited evidence for definitive treatment durations in many pediatric infections, fewer pediatric-trained infectious disease physicians, and applicability of intensive laboratory obtainment, collection, and interpretation. Additionally, many ASP implementation studies evaluating the efficacy of ASPs exclude the PICU and NICU. Areas of focus for pediatric ASPs should likely include appropriate antibiotic initiation, appropriate antibiotic duration, and appropriate antibiotic de-escalation.
    Type of Medium: Online Resource
    ISSN: 1551-6776
    Language: English
    Publisher: Pediatric Pharmacy Advocacy Group
    Publication Date: 2021
    detail.hit.zdb_id: 3028543-4
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  • 5
    Online Resource
    Online Resource
    Elsevier BV ; 2021
    In:  Journal of Clinical & Translational Endocrinology Vol. 26 ( 2021-12), p. 100271-
    In: Journal of Clinical & Translational Endocrinology, Elsevier BV, Vol. 26 ( 2021-12), p. 100271-
    Type of Medium: Online Resource
    ISSN: 2214-6237
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2834222-7
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  • 6
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: MIS-C is a hyper inflammatory condition following SARS-CoV-2 infection. Although COVID-19 infection rates and severity have varied based on circulating SARS-CoV-2 variants, it is unclear if cardiac involvement in MIS-C varies following infection with different SARS-CoV-2 variants. The objective of this study is to describe the severity of cardiac involvement in children with MIS-C following three different waves of SARS-CoV-2 infections. Methods Children hospitalized with a diagnosis of MIS-C were enrolled in a prospective observational study. Demographic, clinical, laboratory (troponin I and B-type natriuretic peptide (BNP)), electrocardiogram (EKG) and echocardiogram (ECHO) data for children diagnosed between 4/20 and 12/21 and followed at 1- and 6-months was analyzed. The cohort was divided into 3 groups to represent cases that followed infection with the Wuhan (4/20-10/20, group 1), Alpha (B.1.1.7, 11/20-7/21, group 2) and Delta (B.1. 617.2, 8/21-12/21, group 3) variants. Cardiac involvement during hospitalization and follow-up was compared between the groups. Results The cohort includes 131 children with MIS-C (32, 61 and 38 in groups 1, 2 and 3, respectively) with a median age of 10 years. Two-thirds were male (66.4%) and 49.6% were Black. Elevated BNP and troponin I levels were seen in 82% and 52.7% of children at initial diagnosis. A third of the cohort had at least one abnormal EKG finding. The proportion of children with abnormal laboratory and EKG findings was not different between the groups. Decreased left ventricular function on ECHO was seen in 25% (33/131) of the cohort with similar distribution among the three groups (p = 0.79). Trivial-small pericardial effusions were detected in 22% (29/131). Coronary artery abnormalities were detected in 11.45% (15/131), a majority in group 1 (25%; 8/32). At 1- and 6-monthfollow-up visits, BNP and Troponin I were normal in all children. At the 6-month follow-up visit, EKG was normal in all and ECHO was normal in 37/41 children with trivial to mild valvular regurgitation in four children. Conclusion In this single center prospective study, while a significant proportion of children with MIS-C had evidence of cardiac involvement at diagnosis, most resolved on follow-up demonstrating good outcomes. Disclosures Claudette Poole, MD, Therapy Brands: Stocks/Bonds Scott H. James, MD, Bayer: Advisor/Consultant|Pantheon Biosciences: Grant/Research Support Suresh Boppana, MD, Merck, Inc: Advisor/Consultant|Merck, Inc: Grant/Research Support|Pfizer: Grant/Research Support.
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2757767-3
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  • 7
    Online Resource
    Online Resource
    American Physiological Society ; 2019
    In:  American Journal of Physiology-Lung Cellular and Molecular Physiology Vol. 316, No. 4 ( 2019-04-01), p. L691-L700
    In: American Journal of Physiology-Lung Cellular and Molecular Physiology, American Physiological Society, Vol. 316, No. 4 ( 2019-04-01), p. L691-L700
    Abstract: The second messenger, cAMP, is highly compartmentalized to facilitate signaling specificity. Extracellular vesicles (EVs) are submicron, intact vesicles released from many cell types that can act as biomarkers or be involved in cell-to-cell communication. Although it is well recognized that EVs encapsulate functional proteins and RNAs/miRNAs, currently it is unclear whether cyclic nucleotides are encapsulated within EVs to provide an additional second messenger compartment. Using ultracentrifugation, EVs were isolated from the culture medium of unstimulated systemic and pulmonary endothelial cells. EVs were also isolated from pulmonary microvascular endothelial cells (PMVECs) following stimulation of transmembrane adenylyl cyclase (AC) in the presence or absence of the phosphodiesterase 4 inhibitor rolipram over time. Whereas cAMP was detected in EVs isolated from endothelial cells derived from different vascular beds, it was highest in EVs isolated from PMVECs. Treatment of PMVECs with agents that increase near-membrane cAMP led to an increase in cAMP within corresponding EVs, yet there was no increase in EV number. Elevated cell cAMP, measured by whole cell measurements, peaked 15 min after treatment, yet in EVs the peak increase in cAMP was delayed until 60 min after cell stimulation. Cyclic AMP was also increased in EVs collected from the perfusate of isolated rat lungs stimulated with isoproterenol and rolipram, thus corroborating cell culture findings. When added to unperturbed confluent PMVECs, EVs containing elevated cAMP were not barrier disruptive like cytosolic cAMP but maintained monolayer resistance. In conclusion, PMVECs release EVs containing cAMP, providing an additional compartment to cAMP signaling.
    Type of Medium: Online Resource
    ISSN: 1040-0605 , 1522-1504
    Language: English
    Publisher: American Physiological Society
    Publication Date: 2019
    detail.hit.zdb_id: 1477300-4
    SSG: 12
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  • 8
    Online Resource
    Online Resource
    Ovid Technologies (Wolters Kluwer Health) ; 2023
    In:  Pediatric Infectious Disease Journal Vol. 42, No. 2 ( 2023-02), p. 106-109
    In: Pediatric Infectious Disease Journal, Ovid Technologies (Wolters Kluwer Health), Vol. 42, No. 2 ( 2023-02), p. 106-109
    Abstract: Antimicrobial resistance and emerging spectrum-β-lactamase (ESBL) infections are a rising concern in public health. Despite the increasing prevalence of community-acquired (CA) ESBL- E. coli UTIs, there is little data on the antibiotic resistance profiles of this bacterial strain in the pediatric population. We review antibiotic resistance profile and rising trend in pediatric ESBL- E. coli UTI presentation at our pediatric hospital. Methods: This retrospective study reviewed data drawn from the infectious disease database at our pediatric hospital for all patients whose urine culture grew ESBL- E. coli from 01/2015 to 01/2021. Demographic information and antimicrobial susceptibility test results for ESBL- E. coli isolates from CA-UTIs were collected. Annual changes in resistance to antimicrobial agents and average annual percent change in ESBL- E. coli UTI presentation over the study period are reported. Results: From 01/2015 to 01/2021, 6403 urine cultures at our hospital grew E. coli . Of these, 169 urine cultures from 135 children grew ESBL- E. coli . The study population was 57% male (77) with a mean age of 6.9 ± 6.2 years and multiethnic. CA-UTI by ESBL-producing E. coli accounted for 2.62% of total E. coli UTIs within the study period and increased from 0.97% in 2015 to 3.54% in 2020 by an average of 0.51% each year. Conclusions: These findings demonstrate an increase in CA-ESBL E. coli UTIs in children. We observed most isolates demonstrated multidrug resistance. As CA-ESBL E. coli UTIs are associated with prolonged hospitalization and increased morbidity, our findings highlight the rising trend in pediatric CA-ESBL E. coli UTI.
    Type of Medium: Online Resource
    ISSN: 0891-3668
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
    detail.hit.zdb_id: 2020216-7
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  • 9
    In: Circulation: Heart Failure, Ovid Technologies (Wolters Kluwer Health), Vol. 12, No. 11 ( 2019-11)
    Abstract: Racial inequities for patients with heart failure (HF) have been widely documented. HF patients who receive cardiology care during a hospital admission have better outcomes. It is unknown whether there are differences in admission to a cardiology or general medicine service by race. This study examined the relationship between race and admission service, and its effect on 30-day readmission and mortality Methods: We performed a retrospective cohort study from September 2008 to November 2017 at a single large urban academic referral center of all patients self-referred to the emergency department and admitted to either the cardiology or general medicine service with a principal diagnosis of HF, who self-identified as white, black, or Latinx. We used multivariable generalized estimating equation models to assess the relationship between race and admission to the cardiology service. We used Cox regression to assess the association between race, admission service, and 30-day readmission and mortality. Results: Among 1967 unique patients (66.7% white, 23.6% black, and 9.7% Latinx), black and Latinx patients had lower rates of admission to the cardiology service than white patients (adjusted rate ratio, 0.91; 95% CI, 0.84–0.98, for black; adjusted rate ratio, 0.83; 95% CI, 0.72–0.97 for Latinx). Female sex and age 〉 75 years were also independently associated with lower rates of admission to the cardiology service. Admission to the cardiology service was independently associated with decreased readmission within 30 days, independent of race. Conclusions: Black and Latinx patients were less likely to be admitted to cardiology for HF care. This inequity may, in part, drive racial inequities in HF outcomes.
    Type of Medium: Online Resource
    ISSN: 1941-3289 , 1941-3297
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2019
    detail.hit.zdb_id: 2428100-1
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  • 10
    In: JAMA, American Medical Association (AMA), Vol. 328, No. 3 ( 2022-07-19), p. 270-
    Type of Medium: Online Resource
    ISSN: 0098-7484
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
    detail.hit.zdb_id: 2958-0
    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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