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  • 1
    In: Antimicrobial Agents and Chemotherapy, American Society for Microbiology, Vol. 65, No. 8 ( 2021-07-16)
    Abstract: Isavuconazole, administered as the water-soluble prodrug isavuconazonium sulfate, is a new triazole agent used to treat invasive fungal infections. This phase 1 study evaluated the pharmacokinetics (PK), safety, and tolerability of isavuconazole in 46 immunocompromised pediatric patients, stratified by age (1 to 〈 6 [intravenous (i.v.) only], 6 to 〈 12, and 12 to 〈 18 years), receiving 10 mg/kg body weight (maximum, 372 mg) isavuconazonium sulfate either i.v. or orally. A population PK model using weight-based allometric scaling was constructed with the pediatric i.v. and oral data plus i.v. data from a phase 1 study in adults. The best model was a 3-compartment model with combined zero-order and first-order input, with linear elimination. Stepwise covariate modeling was performed in Perl-speaks-NONMEM version 4.7.0. None of the covariates examined, including age, sex, race, and body mass index, were statistically significant for any of the PK parameters. The area under the concentration–time curve at steady state (AUC SS ) was predicted for pediatric patients using 1,000 Monte Carlo simulations per age cohort for each administration route. The probability of target attainment (AUC SS range, 60 to 233 μg · h/ml) was estimated; this target range was derived from plasma drug exposures in adults receiving the recommended clinical dose. Predicted plasma drug exposures were within the target range for 〉 80% and 〉 76% of simulated pediatric patients following i.v. or oral administration, respectively. Intravenous and oral administration of isavuconazonium sulfate at the studied dosage of 10 mg/kg was well tolerated and resulted in exposure in pediatric patients similar to that in adults. (This study has been registered at ClinicalTrials.gov under identifier NCT03241550).
    Type of Medium: Online Resource
    ISSN: 0066-4804 , 1098-6596
    RVK:
    Language: English
    Publisher: American Society for Microbiology
    Publication Date: 2021
    detail.hit.zdb_id: 1496156-8
    SSG: 12
    SSG: 15,3
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2020
    In:  Open Forum Infectious Diseases Vol. 7, No. Supplement_1 ( 2020-12-31), p. S588-S589
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 7, No. Supplement_1 ( 2020-12-31), p. S588-S589
    Abstract: Vaccine hesitancy (VH) is one of the top 10 threats to global public health. While VH is common among parents, there are no accepted best practices for counseling, and training in this area is not required in residency. Strategies are needed to help providers address VH in practice. Methods The AIMS (Announce, Inquire, Mirror, Secure) Method for Healthy Conversations is a structured communication strategy that attempts to build trust between provider and patient (or parent), inviting receptivity to healthcare recommendations. To assess whether relatively inexperienced providers exhibit AIMS behaviors after training, blinded pediatric residents were pseudo-randomized to receive either AIMS or control training. Subjects underwent pre- and post-training clinical encounters with blinded standardized patients (SPs) portraying vaccine-hesitant parents; encounters were video-recorded and assessed by 3 blinded raters using the Vaccine Hesitancy Communication Assessment (VHCA) tool, which was developed by an iterative process and validated in pilot testing. Subject confidence was assessed pre- and post-training. Results Overall VHCA intraclass correlation was 0.273 for pre and 0.681 for post encounters (2-way mixed averages); reliability varied with AIMS phases. Fifty-eight subjects completed the protocol, and VHCA ratings for 29 subjects were available for this analysis. AIMS behaviors were more commonly detected among AIMS-trained subjects than control (median change in score [scale 0–30]=4.5 versus 0 for control) (Figure 1). Confidence improved in both groups (Figure 2). SPs perceived no differences between groups, nor between pre and post within groups, in aspects of subject performance such as respect, empathy, and promotion of trust (P=0.936 [ANCOVA] ; partial eta-squared 0.0). Figure 1 Figure 2 Conclusion Pediatric residents can be trained in AIMS behaviors, and an SP model of VH can be used to assess performance. AIMS training results in similar gains in self-confidence compared to control training. SP perceptions may be colored by their script, which in this case was to exhibit adamant vaccine refusal. Testing of AIMS training in longitudinal experimental scenarios and in real-world settings is warranted. Disclosures Kristina A. Bryant, MD, Pfizer (Research Grant or Support, Investigator on multi-center clinical trials) Gary S. Marshall, MD, GlaxoSmithKline (Consultant, Scientific Research Study Investigator)Merck (Consultant, Scientific Research Study Investigator)Pfizer (Consultant, Scientific Research Study Investigator)Sanofi Pasteur (Consultant, Grant/Research Support, Scientific Research Study Investigator, Honorarium for conference lecture)Seqirus (Consultant, Scientific Research Study Investigator)
    Type of Medium: Online Resource
    ISSN: 2328-8957
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2757767-3
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  • 3
    In: The Journal of Pediatrics, Elsevier BV, Vol. 241 ( 2022-02), p. 203-211.e1
    Type of Medium: Online Resource
    ISSN: 0022-3476
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2022
    detail.hit.zdb_id: 2005245-5
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  • 4
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: There are no accepted best practices for counseling vaccine-hesitant parents, and training in this area is not required in residency. In a prior study (J Pediatr 2022;241:203-11), we demonstrated that in-person training in a structured communication strategy called AIMS (Announce, Inquire, Mirror, Secure) resulted in behaviors of interest during live encounters with standardized patients (SPs) portraying vaccine-hesitant parents. We investigated whether similar effects would be seen if training and SP encounters occurred in a virtual environment. Methods Pediatrics and Medicine-Pediatrics residents were randomized to receive either AIMS or control training. Subjects underwent pre- and post-training SP encounters simulating an immunization visit for a 4-month-old. SP case materials were modified to more closely approximate well-intentioned reluctance to vaccinate and allow for more authentic interaction. Encounters were video-recorded and assessed by 3 raters using the Vaccine Hesitancy Communication Assessment (VHCA), developed and characterized in the initial study but modified based on factor analysis to improve reliability and validity. Subject confidence and SP evaluations of the encounter were assessed pre- and post-training. Investigators, subjects, SPs, and video raters were blinded to treatment allocation. Results Fifty-three subjects completed the protocol and 47 had complete video files. Subject confidence improved in both groups (Panel A). No differences in SP evaluations were detected between groups (B). Preliminary analysis demonstrated that AIMS behaviors were more commonly detected among AIMS-trained subjects than control, as evidenced by an increase in VHCA score (C). Conclusion Communication training and assessment using SPs were both successfully transitioned to a virtual environment; this opens the possibility of efficient training and assessment of residents who are not located on site. Training increased confidence non-specifically. Encounters with SPs can serve as a model to detect learned vaccine-specific communication behaviors among resident providers, but post-encounter assessments by SPs remained insensitive to differences in those behaviors despite modification of the case materials. Disclosures Shanna M. Barton, MD, M.Sc., Sanofi Pasteur: Grant/Research Support Aaron W. Calhoun, MD, FSSH, Sanofi-Pasteur: Grant/Research Support|Society for Simulation in Healthcare: Board Member|Society for Simulation in Healthcare: Honoraria Victoria A. Statler, M.D., M.Sc., Astellas: University Research Support|Gilead: University Research Support|Pfizer: Advisor/Consultant|Sanofi: University Research Support|Seqirus: Advisor/Consultant Gary S. Marshall, MD, GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|GlaxoSmithKline: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|Sanofi: Honoraria|Seqirus: Advisor/Consultant|Seqirus: Grant/Research Support|Seqirus: Honoraria.
    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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  • 5
    In: Journal of the Pediatric Infectious Diseases Society, Oxford University Press (OUP), Vol. 11, No. 2 ( 2022-02-23), p. 43-54
    Abstract: The COVID-19 pandemic continues to generate challenges for pediatric solid organ transplant (SOT) recipients and their families. As rates of COVID-19 fluctuate, new SARS-CoV-2 variants emerge, and adherence to and implementation of mitigation strategies vary from community to community, questions remain about the best and safest practices to prevent COVID-19 in vulnerable patients. Notably, decisions about returning to school remain difficult. We assembled a team of specialists in pediatric infectious diseases, transplant infectious diseases, public health, transplant psychology, and infection prevention and control to re-address concerns about school re-entry, as well as COVID-19 vaccines, for pediatric SOT recipients in the United States in 2021. Based on available literature and guidance from national organizations, we generated expert statements specific to pediatric SOT recipients focused on school attendance in 2021.
    Type of Medium: Online Resource
    ISSN: 2048-7207
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2668791-4
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  • 6
    In: Journal of the Pediatric Infectious Diseases Society, Oxford University Press (OUP), Vol. 9, No. 5 ( 2020-11-10), p. 551-563
    Abstract: The coronavirus disease 2019 (COVID-19) pandemic has created many challenges for pediatric solid organ transplant (SOT) recipients and their families. As the pandemic persists, patients and their families struggle to identify the best and safest practices for resuming activities as areas reopen. Notably, decisions about returning to school remain difficult. We assembled a team of pediatric infectious diseases (ID), transplant ID, public health, transplant psychology, and infection prevention and control specialists to address the primary concerns about school reentry for pediatric SOT recipients in the United States. Based on available literature and guidance from national organizations, we generated consensus statements pertaining to school reentry specific to pediatric SOT recipients. Although data are limited and the COVID-19 pandemic is highly dynamic, our goal was to create a framework from which providers and caregivers can identify the most important considerations for each pediatric SOT recipient to promote a safe return to school.
    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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  • 7
    Online Resource
    Online Resource
    SLACK, Inc. ; 2018
    In:  Pediatric Annals Vol. 47, No. 9 ( 2018-09)
    In: Pediatric Annals, SLACK, Inc., Vol. 47, No. 9 ( 2018-09)
    Abstract: Fever is a common symptom in children. Some children may present to their primary care physician with undifferentiated fever; that is, fever for which there is no obvious source from the history or physical examination. Undifferentiated fevers may be prolonged or recurrent. Distinguishing between the two is helpful for narrowing the differential diagnosis, which can be broad and include infections and inflammatory diseases and, rarely, malignancies and autoinflammatory disorders. The evaluation of such children requires a step-wise approach. Taking a detailed history, performing a thorough physical examination, and reviewing a fever and symptom diary is crucial in recognizing clues that may ultimately lead to a diagnosis. Some children who look good and whose fever disappears may never have a diagnosis, whereas referral to a specialist may be prudent for others. [ Pediatr Ann. 2018;47(9):e347–e353.]
    Type of Medium: Online Resource
    ISSN: 0090-4481 , 1938-2359
    Language: English
    Publisher: SLACK, Inc.
    Publication Date: 2018
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  • 8
    In: Open Forum Infectious Diseases, Oxford University Press (OUP), Vol. 9, No. Supplement_2 ( 2022-12-15)
    Abstract: Few data exist on the clinical features and outcome of pediatric patients with persistent unwellness following acute COVID. Methods Norton Children’s and the University of Louisville School of Medicine opened a Post-COVID Clinic (PCC) in Oct 2020. The study cohort included all 104 patients referred to the PCC through Dec 2021. Clinical data were collected using a standardized template during routine care. Diagnostic tests and subspecialty referrals were ordered at the discretion of clinic physicians. A telephone interview in 2022 assessed long-term outcomes. Results The median age at first visit was 14 y (IQR=12,16); the age distribution of PCC patients was different from that of Pediatric Infectious Diseases Clinic (PIDC) patients in that there were few patients under 10 y. Males and females were equally represented. The racial distribution was similar to that of PIDC, but patients were more often from mid/upper socioeconomic status (using commercial insurance as a surrogate; p=0.001). The median interval from onset of COVID to the first PCC visit was 2 mo (IQR=1.5,4.4), and an increase in referrals was seen 2 mo after each COVID wave in the community (Figure 1). Most PCC patients reported good health prior to COVID. Fifty-four percent of patients experienced moderate or severe disability according to Modified Functional Disability Inventory scores at the first PCC visit (Figure 2; median score 14, IQR=6,19). Common symptoms were fatigue or lethargy (73%), headache (60%), shortness of breath or difficulty breathing (48%), exercise intolerance (47%), and chest pain (39%). Few abnormalities were found on routine diagnostic tests. Common subspecialty referrals were to Neurology, Cardiology, Pulmonology, Physical Therapy, and Psychiatry; the total number and types of referrals varied widely among patients. Most patients did not receive a specific diagnosis other than post-COVID syndrome. Sixty-three follow-up interviews were completed a median of 6 mo after the initial PCC visit; 79% of patients were improved or back to normal. Figure 1Reported COVID-19 cases in persons & lt;20 years of age in Jefferson County, KY and number of new patients seen in Norton Children’s Infectious Diseases Post-COVID Clinic, by 2-week intervals. Figure 2 Box and whisker plot of Modified Functional Disability Inventory scores at first visit to Post-COVID Clinic. Upper and lower quartiles are marked by the top and bottom of the boxes. The median is marked by a horizontal line inside the box and the mean is shown by the “x.” Top whiskers indicate the largest value ≤ the 3rd quartile plus 1.5 times the interquartile range; bottom whiskers indicate the smallest value ≥ the 1st quartile minus 1.5 times the interquartile range. Open circles extending beyond the whiskers represent outliers. Disability categories are from Kashikar-Zuck S, et al. Pain 2011;152:1600-1607. Conclusion This large experience with a PCC established early in the pandemic demonstrates that symptoms of post-COVID unwellness are non-specific and varied, routine tests are seldom diagnostic, and the natural history is one of gradual recovery. Disclosures Shanna M. Barton, M.D., M.Sc., Sanofi Pasteur: Grant/Research Support Victoria A. Statler, M.D., M.Sc., Astellas: University Research Support|Gilead: University Research Support|Pfizer: Advisor/Consultant|Sanofi: University Research Support|Seqirus: Advisor/Consultant Gary S. Marshall, MD, GlaxoSmithKline: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|GlaxoSmithKline: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|Sanofi: Honoraria|Seqirus: Advisor/Consultant|Seqirus: Grant/Research Support|Seqirus: Honoraria.
    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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  • 9
    Online Resource
    Online Resource
    Wiley ; 2023
    In:  Pediatric Transplantation Vol. 27, No. 4 ( 2023-06)
    In: Pediatric Transplantation, Wiley, Vol. 27, No. 4 ( 2023-06)
    Abstract: Low‐vaccination rates worldwide have led to the re‐emergence of vaccine‐preventable infections, including measles. Immunocompromised patients, including pediatric solid organ transplant (SOT) recipients, are at risk for measles because of suboptimal vaccination, reduced or waning vaccine immunity, lifelong immunosuppression, and global re‐emergence of measles. Objectives To review published cases of measles in pediatric SOT recipients to heighten awareness of its clinical manifestations, summarize diagnostic and treatment strategies, and identify opportunities to optimize prevention. Methods We conducted a literature review of published natural measles infections in SOT recipients ≤21 years of age, summarizing management and outcomes. We describe measles epidemiology, recommended diagnostics, treatment, and highlight prevention strategies. Results There are seven published reports of measles infection in 12 pediatric SOT recipients, the majority of whom were unvaccinated or incompletely vaccinated. Subjects had atypical or severe clinical presentations, including lack of rash and complications, most frequently with encephalitis and pneumonitis, resulting in 33% mortality. Updated recommendations on testing and vaccination are provided. Treatment options beyond supportive care and vitamin A are limited, with no approved antivirals. Conclusion While measles is infrequently reported in pediatric SOT recipients, morbidity and mortality remain significant. A high index of suspicion is warranted in susceptible SOT recipients with clinically compatible illness or exposure. Providers must recognize this risk, educate families, and be aware of both classic and atypical presentations of measles to rapidly identify, isolate, and diagnose measles in pediatric SOT recipients. Continued efforts to optimize measles vaccination both pre‐ and post‐SOT are warranted.
    Type of Medium: Online Resource
    ISSN: 1397-3142 , 1399-3046
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2008614-3
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  • 10
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2016
    In:  Journal of the Pediatric Infectious Diseases Society Vol. 5, No. 3 ( 2016-09), p. 249-256
    In: Journal of the Pediatric Infectious Diseases Society, Oxford University Press (OUP), Vol. 5, No. 3 ( 2016-09), p. 249-256
    Type of Medium: Online Resource
    ISSN: 2048-7193 , 2048-7207
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2016
    detail.hit.zdb_id: 2668791-4
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