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.
Background Cardiac complications related to COVID‐19 in children and adolescents include ventricular dysfunction, myocarditis, coronary artery aneurysm, and bradyarrhythmias, but tachyarrhythmias are ...less understood. The goal of this study was to evaluate the frequency, characteristics, and outcomes of children and adolescents experiencing tachyarrhythmias while hospitalized for acute severe COVID‐19 or multisystem inflammatory syndrome in children. Methods and Results This study involved a case series of 63 patients with tachyarrhythmias reported in a public health surveillance registry of patients aged <21 years hospitalized from March 15, 2020, to December 31, 2021, at 63 US hospitals. Patients with tachyarrhythmias were compared with patients with severe COVID‐19–related complications without tachyarrhythmias. Tachyarrhythmias were reported in 22 of 1257 patients (1.8%) with acute COVID‐19 and 41 of 2343 (1.7%) patients with multisystem inflammatory syndrome in children. They included supraventricular tachycardia in 28 (44%), accelerated junctional rhythm in 9 (14%), and ventricular tachycardia in 38 (60%); >1 type was reported in 12 (19%). Registry patients with versus without tachyarrhythmia were older (median age, 15.4 range, 10.4–17.4 versus 10.0 range, 5.4–14.8 years) and had higher illness severity on hospital admission. Intervention for treatment of tachyarrhythmia was required in 37 (59%) patients and included antiarrhythmic medication (n=31, 49%), electrical cardioversion (n=11, 17%), cardiopulmonary resuscitation (n=8, 13%), and extracorporeal membrane oxygenation (n=9, 14%). Patients with tachyarrhythmias had longer hospital length of stay than those who did not, and 9 (14%) versus 77 (2%) died. Conclusions Tachyarrhythmias were a rare complication of acute severe COVID‐19 and multisystem inflammatory syndrome in children and adolescents and were associated with worse clinical outcomes, highlighting the importance of close monitoring, aggressive treatment, and postdischarge care.
Objectives: Comorbidity in diagnosis raises critical challenges for psychological assessment and treatment. The Research Domain Criteria (RDoC) Project, launched by the National Institutes of Mental ...Health, proposes domains of functioning as a way to conceptualize the overlap between comorbid conditions and inform treatment selection. However, further research is needed to understand common comorbidities (e.g., posttraumatic stress disorder PTSD and substance use disorder SUD) from an RDoC framework and how existing evidence-based treatments would be expected to promote change in the RDoC domains of functioning. To address these gaps, the current study examined change in 3 RDoC domains (Negative Valence Systems, Arousal/Regulatory Systems, and Cognitive Systems) during concurrent prolonged exposure (PE) and substance use treatment. Method: Participants were 85 individuals with co-occurring PTSD and SUD who received PE in a residential substance use treatment facility. They completed an experimental task to assess physiological reactivity to trauma and alcohol cues at pre- and posttreatment. Results: Results showed decreased severity in all 3 RDoC domains of interest across the study period. Pairwise comparisons between domains revealed that Arousal/Regulatory Systems had the lowest severity at posttreatment. Subsequent hierarchical linear regression analyses showed that posttreatment domain scores were associated with posttreatment cue reactivity for trauma and alcohol cues. Conclusions: The findings provide preliminary evidence of how the RDoC domains of functioning may change with evidence-based treatments and are discussed in terms of the assessment and treatment of mental health problems using the RDoC framework.
T-cell deficiency related to disease, medical treatment, or aging represents a major clinical challenge and is associated with significant morbidity and mortality in cancer and bone marrow ...transplantation recipients. This study describes several innovative and clinically relevant strategies to manipulate thymic function based on an interventional radiology technique for intrathymic injection of cells or drugs. We show that intrathymic injection of multipotent hematopoietic stem/progenitor cells into irradiated syngeneic or allogeneic young or aged recipients resulted in efficient and long-lasting generation of functional donor T cells. Persistence of intrathymic donor cells was associated with intrathymic presence of cells resembling long-term hematopoietic stem cells, suggesting a self-renewal capacity of the intrathymically injected cells. Furthermore, our approach enabled the induction of long-term antigen-specific T-cell–mediated antitumor immunity following intrathymic injection of progenitor cells harboring a transgenic T-cell receptor gene. The intrathymic injection of interleukin-7 prior to irradiation conferred radioprotection. In addition, thymopoiesis of aged mice improved with a single intrathymic administration of low-dose keratinocyte growth factor, an effect that was sustained even in the setting of radiation-induced injury. Taken together, we established a preclinical framework for the development of novel clinical protocols to establish lifelong antigen-specific T-cell immunity.
•Image-guided intrathymic injection of cells or drugs permits implementation of clinically relevant strategies to improve thymic function.•Intrathymic injection of hematopoietic stem cells generates long-lasting antigen-specific T-cell immunity.
Low mannose-binding lectin levels and haplotypes associated with low mannose-binding lectin production have been associated with infection and severe sepsis. We tested the hypothesis that ...mannose-binding lectin levels would be associated with severe infection in a large cohort of critically ill children.
Prospective cohort study.
Medical and Surgical PICUs, Boston Children's Hospital.
Children less than 21 years old admitted to the ICUs from November 2009 to November 2010.
None.
We measured mannose-binding lectin levels in 479 of 520 consecutively admitted children (92%) with severe or life-threatening illness. We genotyped 213 Caucasian children for mannose-binding lectin haplotype tagging variants and assigned haplotypes. In the univariate analyses of mannose-binding lectin levels with preadmission characteristics, levels were higher in patients with preexisting renal disease. Patients who received greater than 100 mL/kg of fluids in the first 24 hours after admission had markedly lower mannose-binding lectin, as did patients who underwent spinal fusion surgery. Mannose-binding lectin levels had no association with infection status at admission, or with progression from systemic inflammatory response syndrome to sepsis or septic shock. Although mannose-binding lectin haplotypes strongly influenced mannose-binding lectin levels in the predicted relationship, low mannose-binding lectin-producing haplotypes were not associated with increased risk of infection.
Mannose-binding lectin levels are largely genetically determined. This relationship was preserved in children during critical illness, despite the effect of large-volume fluid administration on mannose-binding lectin levels. Previous literature evaluating an association between mannose-binding lectin levels and severe infection is inconsistent; we found no relationship in our PICU cohort. We found that mannose-binding lectin levels were lower after aggressive fluid resuscitation and suggest that studies of mannose-binding lectin in critically ill patients should assess mannose-binding lectin haplotypes to reflect preillness levels.
Abstract
Background
Community-onset bacterial coinfection in adults hospitalized with coronavirus disease 2019 (COVID-19) is reportedly uncommon, though empiric antibiotic use has been high. However, ...data regarding empiric antibiotic use and bacterial coinfection in children with critical illness from COVID-19 are scarce.
Methods
We evaluated children and adolescents aged <19 years admitted to a pediatric intensive care or high-acuity unit for COVID-19 between March and December 2020. Based on qualifying microbiology results from the first 3 days of admission, we adjudicated whether patients had community-onset bacterial coinfection. We compared demographic and clinical characteristics of those who did and did not (1) receive antibiotics and (2) have bacterial coinfection early in admission. Using Poisson regression models, we assessed factors associated with these outcomes.
Results
Of the 532 patients, 63.3% received empiric antibiotics, but only 7.1% had bacterial coinfection, and only 3.0% had respiratory bacterial coinfection. In multivariable analyses, empiric antibiotics were more likely to be prescribed for immunocompromised patients (adjusted relative risk aRR, 1.34 95% confidence interval {CI}, 1.01–1.79), those requiring any respiratory support except mechanical ventilation (aRR, 1.41 95% CI, 1.05–1.90), or those requiring invasive mechanical ventilation (aRR, 1.83 95% CI, 1.36–2.47) (compared with no respiratory support). The presence of a pulmonary comorbidity other than asthma (aRR, 2.31 95% CI, 1.15–4.62) was associated with bacterial coinfection.
Conclusions
Community-onset bacterial coinfection in children with critical COVID-19 is infrequent, but empiric antibiotics are commonly prescribed. These findings inform antimicrobial use and support rapid de-escalation when evaluation shows coinfection is unlikely.
The majority of US children admitted to intensive care for COVID-19 received empiric antibiotics. Community-onset bacterial coinfection was infrequent but increased with the degree of organ dysfunction, and was more common in patients with underlying nonasthma lung disease.
Pfizer-BioNTech COVID-19 vaccine received emergency use authorization for persons ≥ 16 years in December 2020 and for adolescents 12-15 years in May 2021. Despite the clear benefits and favorable ...safety profile, vaccine uptake in adolescents has been suboptimal. We sought to assess factors associated with COVID-19 non-vaccination in adolescents 12-18 years of age.
Between June 1, 2021 and April 29, 2022, we assessed factors associated with COVID-19 non-vaccination in hospitalized adolescents ages 12-18 years enrolled in the Overcoming COVID-19 vaccine effectiveness network. Demographic characteristics and clinical information were captured through parent interviews and/or electronic medical record abstraction; COVID-19 vaccination was assessed through documented sources. We assessed associations between receipt of the COVID-19 vaccine and demographic and clinical factors using univariate and multivariable logistic regression and estimated adjusted odds ratios (aOR) for each factor associated with non-vaccination.
Among 1665 hospitalized adolescents without COVID-19, 56% were unvaccinated. Unvaccinated adolescents were younger (median age 15.1 years vs. 15.4 years, p < .01) and resided in areas with higher social vulnerability index (SVI) scores (median 0.6 vs 0.5, p < .001) than vaccinated adolescents. Residence in the Midwest aOR 2.60 (95% CI: 1.80, 3.79) or South aOR 2.49 (95% CI: 1.77, 3.54) US census regions, rarely or never receiving influenza vaccine aOR 5.31 (95% CI: 3.81, 7.47), and rarely or never taking precautions against COVID-19 aOR 3.17 (95% CI: 1.94, 5.31) were associated with non-vaccination against COVID-19.
Efforts to increase COVID-19 vaccination of adolescents should focus on persons with geographic, socioeconomic, and medical risk factors associated with non-vaccination.
To identify risk factors for persistent impairments after pediatric hospitalization for acute coronavirus disease 2019 (COVID-19) or multisystem inflammatory syndrome in children (MIS-C) during the ...SARS-CoV-2 pandemic.
Across 25 U.S.
Network hospitals, we conducted a prospective cohort study of patients <21-years-old hospitalized for acute COVID-19 or MIS-C (May 2020 to March 2022) surveyed 2- to 4-months post-admission. Multivariable regression was used to calculate adjusted risk ratios (aRR) and 95% confidence intervals (CI).
Of 232 children with acute COVID-19, 71 (30.6%) had persistent symptoms and 50 (21.6%) had activity impairments at follow-up; for MIS-C (
= 241), 56 (23.2%) had persistent symptoms and 58 (24.1%) had activity impairments. In adjusted analyses of patients with acute COVID-19, receipt of mechanical ventilation was associated with persistent symptoms aRR 1.83 (95% CI: 1.07, 3.13) whereas obesity aRR 2.18 (95% CI: 1.05, 4.51) and greater organ system involvement aRR 1.35 (95% CI: 1.13, 1.61) were associated with activity impairment. For patients with MIS-C, having a pre-existing respiratory condition was associated with persistent symptoms aRR 3.04 (95% CI: 1.70, 5.41) whereas obesity aRR 1.86 (95% CI: 1.09, 3.15) and greater organ system involvement aRR 1.26 (1.00, 1.58) were associated with activity impairments.
Among patients hospitalized, nearly one in three hospitalized with acute COVID-19 and one in four hospitalized with MIS-C had persistent impairments for ≥2 months post-hospitalization. Persistent impairments were associated with more severe illness and underlying health conditions, identifying populations to target for follow-up.
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