In June 2022, the mRNA COVID-19 vaccination was recommended for young children. We examined clinical characteristics and factors associated with vaccination status among vaccine-eligible young ...children hospitalized for acute COVID-19.
We enrolled inpatients 8 months to <5 years of age with acute community-acquired COVID-19 across 28 US pediatric hospitals from September 20, 2022 to May 31, 2023. We assessed demographic and clinical factors, including the highest level of respiratory support, and vaccination status defined as unvaccinated, incomplete, or complete primary series at least 2 (Moderna) or 3 (Pfizer-BioNTech) mRNA vaccine doses ≥14 days before hospitalization.
Among 597 children, 174 (29.1%) patients were admitted to the intensive care unit and 75 (12.6%) had a life-threatening illness, including 51 (8.5%) requiring invasive mechanical ventilation. Children with underlying respiratory and neurologic/neuromuscular conditions more frequently received higher respiratory support. Only 4.5% of children hospitalized for COVID-19 (n = 27) had completed their primary COVID-19 vaccination series and 7.0% (n = 42) of children initiated but did not complete their primary series. Among 528 unvaccinated children, nearly half (n = 251) were previously healthy, 3 of them required extracorporeal membrane oxygenation for acute COVID-19 and 1 died.
Most young children hospitalized for acute COVID-19, including most children admitted to the intensive care unit and with life-threatening illness, had not initiated COVID-19 vaccination despite being eligible. Nearly half of these children had no underlying conditions. Of the small percentage of children who initiated a COVID-19 primary series, most had not completed it before hospitalization.
OBJECTIVE To evaluate interventions to reduce avoidable antibiotic use on pediatric oncology and hematopoietic stem cell transplantation (HSCT) services. DESIGN Interrupted time series. SETTING ...Academic pediatric hospital with separate oncology and HSCT services. PARTICIPANTS Children admitted to the services during baseline (October 2011-August 2013) and 2 intervention periods, September 2013-June 2015 and July 2015-June 2016, including 1,525 oncology hospitalizations and 301 HSCT hospitalizations. INTERVENTION In phase 1, we completed an update of the institutional febrile neutropenia (FN) guideline for the pediatric oncology service, recommending first-line β-lactam monotherapy rather than routine use of 2 gram-negative agents. Phase 2 included updating the HSCT service FN guideline and engagement with a new pediatric antimicrobial stewardship program. The use of target antibiotics (tobramycin and ciprofloxacin) was measured in days of therapy per 1,000 patient days collected from administrative data. Intervention effects were evaluated using interrupted time series with segmented regression. RESULTS Phase 1 had mixed effects-long-term reduction in tobramycin use (97% below projected at 18 months) but rebound with increasing slope in ciprofloxacin use (+18% per month). Following phase 2, tobramycin and ciprofloxacin use on the oncology service were both 99% below projected levels at 12 months. On the HSCT service, tobramycin use was 99% below the projected level and ciprofloxacin use was 96% below the projected level at 12 months. CONCLUSIONS Locally adapted guidelines can facilitate practice changes in oncology and HSCT settings. More comprehensive and ongoing interventions, including follow-up education, feedback, and engagement of companion services may be needed to sustain changes. Infect Control Hosp Epidemiol 2017;38:1039-1047.
Background. Coccidioidomycosis is a spectrum of diseases caused by the dimorphic fungi Coccidioides. Current regimens for severe or disseminated disease include fluconazole, itraconazole, or ...amphotericin; newer triazoles (ie, voriconazole, posaconazole) have been demonstrated to be useful in refractory disease. Previous reported experience with combination triazole and caspofungin therapy has been very limited; however, the utility of this combination for treatment of other invasive fungal diseases suggests potential benefit in refractory coccidioidomycosis. Methods. We conducted a retrospective review of 9 pediatric patients treated with combination voriconazole and caspofungin (V/C) salvage therapy for refractory coccidioidomycosis at two children's hospitals between January 2000 and June 2012. Results. Nine children with refractory coccidioidomycosis were treated with V/C salvage therapy after failing conventional therapy consisting of a triazole, amphotericin B, or a combination of both. Eight of the 9 patients are currently in remission; 1 patient with central nervous system involvement continues to progress. Conclusions. We report our positive clinical experience treating medically refractory coccidioidomycosis in the pediatric population with concurrent voriconazole and caspofungin therapy. Additional in vitro and in vivo evaluations are warranted to support the role of V/C salvage therapy for refractory coccidioidomycosis.
NF-κB plays a variety of roles in oncogenesis and immunity that may be beneficial for therapeutic targeting, but strategies to selectively inhibit NF-κB to exert antitumor activity have been elusive. ...Here, we describe IT-901, a bioactive naphthalenethiobarbiturate derivative that potently inhibits the NF-κB subunit c-Rel. IT-901 suppressed graft-versus-host disease while preserving graft-versus-lymphoma activity during allogeneic transplantation. Further preclinical assessment of IT-901 for the treatment of human B-cell lymphoma revealed antitumor properties in vitro and in vivo without restriction to NF-κB-dependent lymphoma. This nondiscriminatory, antilymphoma effect was attributed to modulation of the redox homeostasis in lymphoma cells resulting in oxidative stress. Moreover, NF-κB inhibition by IT-901 resulted in reduced stimulation of the oxidative stress response gene heme oxygenase-1, and we demonstrated that NF-κB inhibition exacerbated oxidative stress induction to inhibit growth of lymphoma cells. Notably, IT-901 did not elicit increased levels of reactive oxygen species in normal leukocytes, illustrating its cancer selective properties. Taken together, our results provide mechanistic insight and preclinical proof of concept for IT-901 as a novel therapeutic agent to treat human lymphoid tumors and ameliorate graft-versus-host disease.
Acute hematogenous osteomyelitis (AHO) is a relatively infrequent but significant infection in pediatric patients. As
is the most common cause of AHO, intravenous and oral first-generation ...cephalosporins are common therapies. Cephalexin is a commonly prescribed oral therapy for pediatric AHO, although it requires frequent dosing that may affect adherence. Cefadroxil is a comparable oral first-generation cephalosporin with a more desirable dosing schedule.
We reviewed pediatric patients admitted to Mayo Clinic between March 2002 and September 2020 for management of AHO who received treatment with a first-generation cephalosporin. We reviewed timing of oral therapy transition, therapy-associated adverse effects, and recurrence of disease after completion of therapy.
There were 59 patients included in the study. There was similar occurrence of adverse effects in patients receiving cefadroxil and cephalexin, although use of cefadroxil coincided with more gastrointestinal adverse effects and leukopenia and use of cephalexin with more rash and neutropenia. One secondary treatment failure occurred in our study, in a patient receiving cephalexin for treatment of septic arthritis.
Cefadroxil may be a reasonable alternative oral therapy for methicillin-susceptible
or culture-negative AHO in pediatric patients, particularly when a less frequent dosing schedule is desired. Future study with a larger sample size is warranted.
The emergency use authorisation of BNT162b2 (tozinameran; Comirnaty, Pfizer–BioNTech) for children aged 5–17 years has resulted in rapid vaccination in the paediatric population. However, there are ...few studies of adverse events associated with vaccination in children. The aim of this study was to systematically assess the adverse events of two-dose BNT162b2 vaccination in the paediatric population.
We conducted a retrospective analysis of patient electronic health records (EHRs) of children aged 5–17 years who received the primary two-dose series of the BNT162b2 vaccine between Jan 5, 2021, and Aug 5, 2022, at the Mayo Clinic Health System (MN, FL, AZ, IA, and WI), USA. Using natural language processing, we automatically curated adverse events reported by physicians in EHR clinical notes before and after vaccination. To determine significant adverse events after BNT162b2 vaccination, we calculated risk differences, which was defined as the percentage difference between the rate of children with an adverse event after a vaccine dose and the baseline rate of children with an adverse event before vaccination. 95% CIs and p values were calculated using the Miettinen and Nurminen score method.
56 436 individuals aged 5–17 years (20 227 aged 5–11 years and 36 209 aged 12–17 years) with EHRs in the Mayo Clinic Health Systems were included in the study. Overall, the reporting of adverse events remained low in passive surveillance. Serious adverse events were rare after the first and second doses of BNT162b2, with rates of anaphylaxis (six 0·01% of 56 436), myocarditis (five 0·01%), and pericarditis (three 0·01%) consistent with previous studies. Among the 20 227 5–11-year-olds, there were increased risks of fatigue (58 after second dose vs 41 before first dose; risk difference RDdose2 0·08% 95% CI –0·01 to 0·18, p=0·044) and fever (104 after second dose vs 77 before first dose; RDdose2 0·13% 0·00 to 0·27, p=0·022) after the second dose. Among the 36 209 12–17-year-olds, there were increased risks of arthralgia (69 after second dose vs 48 before first dose; RDdose2 0·06% –0·00 to 0·12, p=0·026), chills (58 after second dose vs 40 before first dose; RDdose2 0·05% –0·00 to 0·11, p=0·034), and myalgia (96 after second dose vs 73 before first dose; RDdose2 0·06% –0·01 to 0·14, p=0·038) after the second dose. Although the overall incidence was low, there was an increased risk of myocarditis in males aged 12–17 years after the second dose (five after second dose vs zero before first dose; RDdose2 0·03% 0·01 to 0·07, p=0·013), with median age being 15 years (IQR 14 to 16).
Overall, this data suggests that vaccination with BNT162b2 in the paediatric population is generally safe and well-tolerated. Further research is warranted to investigate the basis for the increased risk of myocarditis in adolescent males. Additionally, further studies are needed to confirm whether the findings in our study population apply to the whole vaccinated paediatric population.
nference.
Polygenic risk scores (PRS) have potential to improve health care by identifying individuals that have elevated risk for common complex conditions. Use of PRS in clinical practice, however, requires ...careful assessment of the needs and capabilities of patients, providers, and health care systems. The electronic Medical Records and Genomics (eMERGE) network is conducting a collaborative study which will return PRS to 25,000 pediatric and adult participants. All participants will receive a risk report, potentially classifying them as high risk (∼2-10% per condition) for 1 or more of 10 conditions based on PRS. The study population is enriched by participants from racial and ethnic minority populations, underserved populations, and populations who experience poorer medical outcomes. All 10 eMERGE clinical sites conducted focus groups, interviews, and/or surveys to understand educational needs among key stakeholders-participants, providers, and/or study staff. Together, these studies highlighted the need for tools that address the perceived benefit/value of PRS, types of education/support needed, accessibility, and PRS-related knowledge and understanding. Based on findings from these preliminary studies, the network harmonized training initiatives and formal/informal educational resources. This paper summarizes eMERGE's collective approach to assessing educational needs and developing educational approaches for primary stakeholders. It discusses challenges encountered and solutions provided.
Without prophylaxis, Pneumocystis jiroveci pneumonia (PCP) develops in 5%-15% of pediatric hematopoietic stem cell transplant (HCT) patients with mortality above 50%. Trimethoprim-sulfamethoxazole is ...a standard PCP prophylaxis; pentamidine is frequently used as second-line prophylaxis because of trimethoprim-sulfamethoxazole's potential for cytopenias. Monthly intravenous (IV) pentamidine has variable efficacy with PCP infection rates of 0%-10% in pediatric patients, and higher breakthrough rates in those younger than 2 years. We hypothesized that bimonthly (twice monthly) pentamidine might have equivalent safety and improved efficacy; therefore, we conducted a retrospective analysis of bimonthly pentamidine PCP prophylaxis.
We retrospectively reviewed records of all pediatric HCT patients who received bimonthly IV pentamidine between December 2006 and June 2013, and collected data regarding demographics, clinical course, prophylaxis rationale, laboratory values and adverse events.
Between December 2006 and June 2013, 111 pediatric HCT patients received bimonthly IV pentamidine (574 doses, 8758 patient-days); 31 patients were younger than 2 years at initiation. In the majority (53% of courses), pentamidine was initiated because of cytopenias. Fourteen patients (12.6% of patients, 2.4% of doses) experienced a side-effect prompting discontinuation, including 3 patients with infusion-related hypotension/anaphylaxis and 3 with acute pancreatic dysfunction. No patients 0% (95% confidence interval: 0-3.2) developed PCP during or after bimonthly IV pentamidine prophylaxis.
Bimonthly IV pentamidine for PCP prophylaxis in the HCT pediatric population has comparable safety to monthly IV pentamidine and was highly effective, including in the very young. Bimonthly IV pentamidine should be considered in pediatric patients as second-line PCP prophylaxis.
Guidelines recommend cancer care clinicians offer smoking cessation treatment. Cost analyses will help stakeholders understand and plan for implementation of cessation programs.
To estimate the ...incremental cost per quit (ICQ) of adopting an intensive smoking cessation intervention among patients undergoing treatment at cancer care clinics, from a clinic perspective.
This economic evaluation, a secondary analysis of the Smokefree Support Study (conducted 2013-2018; completed 2021), used microcosting methods and sensitivity analyses to estimate the ICQ of the interventions. Participants included patients undergoing treatment for a broad range of solid tumors and lymphomas who reported current smoking and were receiving care at cancer care clinics within 2 academic medical centers.
Intensive smoking cessation treatment (up to 11 counseling sessions with free medications), standard of care (up to 4 counseling sessions with medication advice), or usual care (referral to the state quitline).
Total costs, component-specific costs, and the ICQ of the intensive smoking cessation treatment relative to both standard of care (comparator in the parent randomized trial) and usual care (a common comparator outside this trial) were calculated. Overall and post hoc site-specific estimates are provided. Because usual care was not included in the parent trial, sensitivity analyses were conducted to assess how assumptions about usual care quit rates affected study outcomes (ie, base case from a published smoking cessation trial among patients with thoracic cancer, best case, and conservative case scenarios).
The per-patient costs of offering intensive smoking cessation treatment, standard of care, and usual care were $1989, $1482, and $0, respectively. For intensive treatment, the dominant costs were treatment (35%), staff supervision (26%), and patient enrollment (24%). Relative to standard of care, intensive treatment had an overall ICQ of $3906, and one site had an ICQ of $2892. Relative to usual care, intensive treatment had an ICQ of $9866 overall (base case), although at one site, the ICQ was $5408 (base case) and $3786 (best case).
In this economic evaluation study, implementation of an intensive smoking cessation treatment intervention was moderately to highly cost-effective, depending on existing smoking cessation services in place.
Abstract Background Despite the well-established risks of persistent smoking, 10–30% of cancer patients continue to smoke after diagnosis. Evidence-based tobacco treatment has yet to be integrated ...into routine oncology care. This paper describes the protocol, manualized treatment, evaluation plan, and overall study design of comparing the effectiveness and cost of two treatments across two major cancer centers. Methods/design A two-arm, two-site randomized controlled comparative effectiveness trial is testing the hypothesis that an Intensive Treatment (IT) intervention is more effective than a Standard Treatment (ST) intervention in helping recently diagnosed cancer patients quit smoking. Both interventions include 4 weekly counseling sessions and FDA-approved smoking cessation medication advice. The IT includes an additional 4 biweekly and 3 monthly booster sessions as well as dispensal of the recommended FDA-approved smoking cessation medication at no cost. The trial is enrolling patients with suspected or newly diagnosed cancer who have smoked a cigarette in the past 30 days. Participants are randomly assigned to receive the ST or IT condition. Tobacco cessation outcomes are assessed at 3 and 6 months. The primary study outcome is 7-day point prevalence biochemically-validated tobacco abstinence. Secondary study outcomes include the incremental cost-effectiveness of the IT vs. ST. Discussion This trial will answer key questions about delivering tobacco treatment interventions to newly diagnosed cancer patients. If found to be efficacious and cost-effective, this treatment will serve as a model to be integrated into oncology care settings nation-wide, as we strive to improve treatment outcomes and quality of life for cancer patients.
PDF
