bluuebunny/crossref_metadata_2025 huggingface dataset:
Comprehensive mapping of SARS-CoV-2 peptide epitopes for development of a highly sensitive serological test for total and neutralizing antibodies
Authors: Kumar Garima , Sterrett Sarah , Hall Lucinda , Tabengwa Edlue , Honjo Kazuhito , Larimer Michael , Davis Randall S , Goepfert Paul A , Larimer Benjamin M
Published: January 2022

Quantification of the anti-SARS-CoV-2 antibody response has proven to be a prominent diagnostic tool during the COVID-19 pandemic. Antibody measurements have aided in the determination of humoral protection following infection or vaccination and will likely be essential for predicting the prevalence of population level immunity over the next several years. Despite widespread use, current tests remain limited in part, because antibody capture is accomplished through the use of complete spike and nucleocapsid proteins that contain significant regions of overlap with common circulating coronaviruses. To address this limitation, a unique epitope display platform utilizing monovalent display and protease-driven capture of peptide epitopes was used to select high affinity peptides. A single round of selection using this strategy with COVID-19 positive patient plasma samples revealed surprising differences and specific patterns in the antigenicity of SARS-CoV-2 proteins, especially the spike protein. Putative epitopes were assayed for specificity with convalescent and control samples, and the individual binding kinetics of peptides were also determined. A subset of prioritized peptides was used to develop an antibody diagnostic assay that showed low cross reactivity while detecting 37% more positive antibody cases than a gold standard FDA EUA test. Finally, a subset of peptides were compared with serum neutralization activity to establish a 2 peptide assay that strongly correlates with neutralization. Together, these data demonstrate a novel phage display method that is capable of comprehensively and rapidly mapping patient viral antibody responses and selecting high affinity public epitopes for the diagnosis of humoral immunity.
eHealth Interventions to Support Self-Management in People With Musculoskeletal Disorders, “eHealth: It’s TIME”—A Scoping Review
Authors: Kelly Marie , Fullen Brona , Martin Denis , McMahon Sinéad , McVeigh Joseph G
Published: January 2022

Objective

eHealth-mediated interventions have been proposed as one option to support self-management in those with musculoskeletal disorders (MSDs). This scoping review aimed to chart the evidence regarding eHealth modalities, musculoskeletal diagnosis, and outcomes of eHealth-mediated self-management support interventions in persons with MSDs and identify any gaps within the literature.

Methods

Six electronic databases (MEDLINE, CINAHL, PsycINFO, Embase, Scopus, and the Cochrane Database of Systematic Reviews), 7 grey literature sources (eg, OpenGrey), and reference and citation lists of included studies were searched from database inception to July 2020. Published studies of adult participants with a MSD utilizing an eHealth intervention to support self-management were included. Studies were limited to those published in English. Two reviewers independently screened all studies. Data were extracted by 1 reviewer and reviewed by another reviewer.

Results

After screening 3377 titles and abstracts followed by 176 full texts, 87 studies fulfilled the eligibility criteria. The majority were published in the last 5 years (n = 48; 55%), with almost one-third originating in the United States (n = 28; 32%). The most common eHealth modality type was internet based (n = 22; 35%), with almost one-half (n = 41; 47%) of the included studies involving participants with widespread musculoskeletal symptoms. The most commonly reported outcomes were related to body functions (ie, pain intensity) (n = 67; 45%), closely followed by activities and participation (ie, function) (n = 65; 44%), with environmental factors (ie, health care utilization) the least commonly reported (n = 17; 20%).

Conclusions

There is considerable variation within the eHealth-mediated self-management support intervention literature. Research is needed on the role of eHealth-mediated self-management support interventions across a broad range of MSDs to guide clinical practice.

Impact

This scoping review has identified gaps in the literature relating to specific eHealth modalities, musculoskeletal diagnoses, and health care utilization data, which should guide future research.
No evidence that genetic predictors of susceptibility predict changes in core outcomes in JIA
Authors: Yarwood Annie , Shoop-Worrall Stephanie , López-Isac Elena , Smith Samantha Louise , Morris Andrew P ,   Childhood Arthritis Prospective Study (CAPS) group, Baildam Eileen , Chieng Alice , Cleary Gavin , Ciurtin Coziana , Davidson Joyce E , Foster Helen E , Ioannou Yiannis , McErlane Flora , Wedderburn Lucy R , Hyrich Kimme , Thomson Wendy , Bowes John David , Tordoff Melissa , Hyrich Kimme L , Thomson Wendy , Eyre Stephen
Published: January 2022

Objectives

The clinical progression of JIA is unpredictable. Knowing who will develop severe disease could facilitate rapid intensification of therapies. We use genetic variants conferring susceptibility to JIA to predict disease outcome measures.

Methods

A total of 713 JIA patients with genotype data and core outcome variables (COVs) at diagnosis (baseline) and 1 year follow-up were identified from the Childhood Arthritis Prospective Study (CAPS). A weighted genetic risk score (GRS) was generated, including all single nucleotide polymorphisms (SNPs) previously associated with JIA susceptibility (P-value < 5×10−08). We used multivariable linear regression to test the GRS for association with COVS (limited joint count, active joint count, physician global assessment, parent/patient general evaluation, childhood HAQ and ESR) at baseline and change in COVS from baseline to 1 year, adjusting for baseline COV and International League of Associations of Rheumatology (ILAR) category. The GRS was split into quintiles to identify high (quintile 5) and low (quintile 1) risk groups.

Results

Patients in the high-risk group for the GRS had a younger age at presentation (median low risk 7.79, median high risk 3.51). No association was observed between the GRS and any outcome measures at 1 year follow-up or baseline.

Conclusion

For the first time we have used all known JIA genetic susceptibility loci (P=<5×10−08) in a GRS to predict changes in disease outcome measured over time. Genetic susceptibility variants are poor predictors of changes in core outcome measures, it is likely that genetic factors predicting disease outcome are independent to those predicting susceptibility. The next step will be to conduct a genome-wide association analysis of JIA outcome.
Hepatitis C Screening Among Medicaid Patients With Schizophrenia, 2002–2012
Authors: Thomas Marilyn D , Vittinghoff Eric , Crystal Stephen , Walkup James , Olfson Mark , Khalili Mandana , Dahiya Priya , Keenan Walker , Cournos Francine , Mangurian Christina
Published: January 2022

Objective

Although people with schizophrenia are disproportionately affected by Hepatitis C virus (HCV) compared to the general population, HCV screening among US Medicaid recipients with schizophrenia has not been characterized. Following 1998 CDC recommendations for screening in high-risk populations, we estimated the proportion of Medicaid recipients with and without schizophrenia screened for HCV across states and over time. Examining patterns of screening will inform the current public health imperative to test all adults for HCV now that safer and more effective treatments are available.

Methods

Data are drawn from 1 353 424 Medicaid recipients aged 15–64 years with schizophrenia and frequency-matched controls from 2002 to 2012. Participants with known HCV infection one year prior and those dual-eligible for Medicare were excluded. Multivariable logistic regression estimated associations between predictor variables and HCV screening.

Results

HCV screening was low (<4%) but increased over time. Individuals with schizophrenia consistently showed higher screening compared to controls across years and states. Several demographic and clinical characteristics predicted higher screening, especially comorbid HIV (OR = 6.5; 95% CI = 6.0–7.0). Outpatient medical care utilization increased screening by nearly double in 2002 (OR = 1.8; CI = 1.7–1.9) and almost triple in 2012 (OR = 2.7; CI = 2.6–2.9).

Conclusions

Low screening was a missed opportunity to improve HCV prevention efforts and reduce liver-related mortality among people with schizophrenia. Greater COVID-19 disease severity in HCV patients and the availability of effective HCV treatments increase the urgency to improve HCV screening. Eliminating Medicaid restrictions and expanding statewide HIV policies to include HCV would have multiple public health benefits, particularly for people with schizophrenia.
Too Much of a Good Thing? Testing the Curvilinear Relationship between Parental Involvement and Student Outcomes in Elementary School
Authors: Li Angran , Cheng Simon , Vachon Todd E
Published: January 2022

Most scholars, parents, and educators agree that parental involvement is beneficial for children’s academic and developmental outcomes. However, a small but growing body of scholarship suggests that intensive parental involvement may potentially hinder children’s development. In this study, we examine the “more is less” assumption in parental involvement research and formally test the argument of parental overinvolvement. Using nationally representative data from the Early Childhood Longitudinal Study, Kindergarten Class of 1998–1999 (ECLS-K), we examine whether high levels of involvement are associated with unintended negative child development in elementary school. Analyses based on curvilinear mixed effects models show that elevated parental expectations, intensive participation in extracurricular activities, and increased parental school involvement are associated with diminishing returns to children’s outcomes. The most meaningful parental overinvolvement pattern is found for internalizing problems. These patterns are generally consistent for children from all socioeconomic levels. We conclude with a discussion of the research and policy implications of these findings.
Phylogenetic Diversity and Mycotoxin Potential of Emergent Phytopathogens Within the Fusarium tricinctum Species Complex
Authors: Laraba Imane , Busman Mark , Geiser David M. , O’Donnell Kerry
Published: January 2022

Recent studies on multiple continents indicate members of the Fusarium tricinctum species complex (FTSC) are emerging as prevalent pathogens of small-grain cereals, pulses, and other economically important crops. These understudied fusaria produce structurally diverse mycotoxins, among which enniatins (ENNs) and moniliformin (MON) are the most frequent and of greatest concern to food and feed safety. Herein a large survey of fusaria in the Fusarium Research Center and Agricultural Research Service culture collections was undertaken to assess species diversity and mycotoxin potential within the FTSC. A 151-strain collection originating from diverse hosts and substrates from different agroclimatic regions throughout the world was selected from 460 FTSC strains to represent the breadth of FTSC phylogenetic diversity. Evolutionary relationships inferred from a five-locus dataset, using maximum likelihood and parsimony, resolved the 151 strains as 24 phylogenetically distinct species, including nine that are new to science. Of the five genes analyzed, nearly full-length phosphate permease sequences contained the most phylogenetically informative characters, establishing its suitability for species-level phylogenetics within the FTSC. Fifteen of the species produced ENNs, MON, the sphingosine analog 2-amino-14,16-dimethyloctadecan-3-ol (AOD), and the toxic pigment aurofusarin (AUR) on a cracked corn kernel substrate. Interestingly, the five earliest diverging species in the FTSC phylogeny (i.e., F. iranicum, F. flocciferum, F. torulosum, and Fusarium spp. FTSC 8 and 24) failed to produce AOD and MON, but synthesized ENNs and/or AUR. Moreover, our reassessment of nine published phylogenetic studies on the FTSC identified 11 additional novel taxa, suggesting this complex comprises at least 36 species.
What Obstetrician–Gynecologists Should Know About Substance Use Disorders in the Perinatal Period
Authors: Smid Marcela C. , Terplan Mishka
Published: January 2022

Substance use in pregnancy is common; nearly one of five of pregnant individuals have past-month nicotine, alcohol, or illicit substance use, and more than one in 10 meet criteria for a substance use disorder (SUD). Substance use disorders are among the most stigmatized and poorly understood medical conditions, particularly in the perinatal period. The obstetrician–gynecologist (ob-gyn) is a critical member of the health care and social support team for pregnant and postpartum individuals with SUD. Yet, many do not feel knowledgeable in screening and treating SUD, hampering efforts to identify and treat this population. In this review, we focus on practices that ob-gyns can incorporate into daily care. We start with the unique vulnerabilities of the perinatal period and discuss overdose as a leading cause of maternal death in the United States. We then review the basic tenets of addiction medicine including person-centered language and current medical terminology as well as best practices for substance use screening. We provide a review of maternal, fetal, and child effects of the most common substances including tobacco, alcohol, cannabis, opioids, stimulants, and benzodiazepines and their respective treatment recommendations, so that ob-gyns can incorporate basic addiction management into their daily practice.
Effects of the Zishen Yutai Pill Compared With Placebo on Live Births Among Women in a Fresh Embryo Transfer Cycle
Authors: Chen Xiaoli , Hao Cuifang , Deng Weifen , Bai Haiyan , Li Yu , Wang Zhuran , Shi Yuhua , Zhang Hanwang , Zhu Yimin , Zhang Haiying , Liu Fenghua , Li Lu , Li Xinlin , Tan Li , Tan Jichun , Lu Weiying , Luo Jia , Yang Shuo , Miao Congxiu , Chen Xuemei , Zhang Heping , Yang Dongzi
Published: January 2022

OBJECTIVE:

To assess the efficacy of the Zishen Yutai Pill compared with placebo on live birth rates among women after fresh embryo transfer cycles.

METHODS:

We conducted a double-blind, multicenter, placebo-controlled, randomized trial to investigate whether administration of the Zishen Yutai Pill would improve pregnancy outcomes among women undergoing fresh embryo transfer after in vitro fertilization or intracytoplasmic sperm injection. The primary outcome was live birth rate. Secondary outcomes were rates of implantation, biochemical pregnancy, clinical pregnancy, pregnancy loss, cycle cancellation, and maternal, fetal, and neonatal complications. A total sample size of 2,265 women (1:1 in two groups) was used to detect a live birth rate difference between the Zishen Yutai Pill and placebo. Participants were enrolled and randomized to receive 5 g of the Zishen Yutai Pill or placebo orally, three times per day during the study.

RESULTS:

Recruitment was completed between April 2014 and June 2017, with 2,580 patients screened. Two thousand two hundred sixty-five patients were randomized: 1,131 to the Zishen Yutai Pill and 1,134 to placebo. Characteristics were similar between groups. In intention-to-treat analysis, the rates of live birth in the Zishen Yutai Pill (ZYP) group and placebo group were 26.8% and 23.0% (rate ratio [RR], 1.16; 95% CI 1.01–1.34; P=.038), respectively. The implantation rates were 36.8% and 32.6% in the ZYP and placebo groups, respectively (RR 1.13; 95% CI 1.01–1.25; P=.027). The biochemical pregnancy rate for the ZYP group was 35.5% compared with 31.1% in the placebo group (RR 1.14; 95% CI 1.02–1.28; P=.026). The rates of clinical pregnancy in the ZYP and placebo groups were 31.2% compared with 27.3%, respectively (RR 1.14; 95% CI 1.00–1.30; P=.043). There were no significant between-group differences in the rates of pregnancy loss, maternal, or neonatal complications (all P>.05).

CONCLUSION:

The Zishen Yutai Pill increased the rate of live birth after fresh embryo transfer compared with placebo.

CLINICAL TRIAL REGISTRATION:

Chictr.org.cn, Chictr-TRC-14004494.
Experiences of New Mothers During the Coronavirus Disease 2019 (COVID-19) Pandemic
Authors: Critchlow Elizabeth , Birkenstock Lyena , Hotz Melanie , Sablone Lauren , Riley Amy Henderson , Mercier Rebecca , Frasso Rosemary
Published: January 2022

OBJECTIVE:

To describe postpartum experiences of women who gave birth during the coronavirus disease 2019 (COVID-19) pandemic, to identify short-term and long-term opportunities to address maternal–child health during this pandemic.

METHODS:

This qualitative photo-elicitation study asked 30 women between 3 and 10 weeks postpartum to take photographs that encompassed their experience as a new mother during the pandemic. Two trained interviewers elicited elements of this experience using the photos as an anchor during virtual, hour-long interviews. Interview transcripts were analyzed using directed content analysis, including open coding to identify key ideas, codebook development, and codebook refinement. Half of transcripts were team coded to ensure coding accuracy. After coding, the study team organized codes to inform the development of an explanatory model.

RESULTS:

Interviews identified important stressors new mothers experienced that were worsened during the pandemic, namely fear, child care, older children, loss, isolation, and employment. Interviews also highlighted key support structures (self-care, interpersonal, and structural supports) that were at times helpful in alleviating stressors and at others were inadequate to counter stress and even enhanced stress.

CONCLUSION:

For postpartum individuals overall, the pandemic resulted in increased strain during an already stressful time. These findings demonstrate inadequacy of support systems for postpartum women and may highlight action items for stakeholders to improve postpartum care during the pandemic and in the future.
Association Between Menstrual Cycle Length and Coronavirus Disease 2019 (COVID-19) Vaccination
Authors: Edelman Alison , Boniface Emily R. , Benhar Eleonora , Han Leo , Matteson Kristen A. , Favaro Carlotta , Pearson Jack T. , Darney Blair G.
Published: January 2022

OBJECTIVE:

To assess whether coronavirus disease 2019 (COVID-19) vaccination is associated with changes in cycle or menses length in those receiving vaccination as compared with an unvaccinated cohort.

METHODS:

We analyzed prospectively tracked menstrual cycle data using the application “Natural Cycles.” We included U.S. residents aged 18–45 years with normal cycle lengths (24–38 days) for three consecutive cycles before the first vaccine dose followed by vaccine-dose cycles (cycles 4–6) or, if unvaccinated, six cycles over a similar time period. We calculated the mean within-individual change in cycle and menses length (three prevaccine cycles vs first- and second-dose cycles in the vaccinated cohort, and the first three cycles vs cycles four and five in the unvaccinated cohort). We used mixed-effects models to estimate the adjusted difference in change in cycle and menses length between the vaccinated and unvaccinated cohorts.

RESULTS:

We included 3,959 individuals (vaccinated 2,403; unvaccinated 1,556). Most of the vaccinated cohort received the Pfizer-BioNTech vaccine (55%) (Moderna 35%, Johnson & Johnson/Janssen 7%). Overall, COVID-19 vaccine was associated with a less than 1-day change in cycle length for both vaccine-dose cycles compared with prevaccine cycles (first dose 0.71 day-increase, 98.75% CI 0.47–0.94; second dose 0.91, 98.75% CI 0.63–1.19); unvaccinated individuals saw no significant change compared with three baseline cycles (cycle four 0.07, 98.75% CI −0.22 to 0.35; cycle five 0.12, 98.75% CI −0.15 to 0.39). In adjusted models, the difference in change in cycle length between the vaccinated and unvaccinated cohorts was less than 1 day for both doses (difference in change: first dose 0.64 days, 98.75% CI 0.27–1.01; second dose 0.79 days, 98.75% CI 0.40–1.18). Change in menses length was not associated with vaccination.

CONCLUSION:

Coronavirus disease 2019 (COVID-19) vaccination is associated with a small change in cycle length but not menses length.
A Cost-effectiveness Analysis Comparing Pembrolizumab-Axitinib, Nivolumab-Ipilimumab, and Sunitinib for Treatment of Advanced Renal Cell Carcinoma
Authors: Chan Alan , Dang Carolyn , Wisniewski Jessica , Weng Xiuhua , Hynson Edward , Zhong Lixian , Wilson Leslie
Published: January 2022

Objectives:

The US Food and Drug Administration (FDA) approved nivolumab-ipilimumab and pembrolizumab-axitinib as first-line treatments for metastatic, clear-cell, renal cell carcinoma (mRCC) based on results from CheckMate 214 and KEYNOTE-426. Our objective was to compare the adjusted, lifetime cost-effectiveness between nivolumab-ipilimumab, pembrolizumab-axitinib, and sunitinib for patients with mRCC.

Materials and Methods:

A 3-state Markov model was developed comparing nivolumab-ipilimumab and pembrolizumab-axitinib to each other and sunitinib, over a 20-year lifetime horizon from a US medical center perspective. The clinical outcomes of nivolumab-ipilimumab and pembrolizumab-axitinib were compared using matching-adjusted indirect comparison. Costs of drug treatment, adverse events, and utilities associated with different health states and adverse events were determined using national sources and published literature. Our outcome was incremental cost-effectiveness ratio (ICER) using quality-adjusted life years (QALY). One-way and probabilistic sensitivity analyses were conducted.

Results:

Nivolumab-ipilimumab was the most cost-effective option in the base case analysis with an ICER of $34,190/QALY compared with sunitinib, while the pembrolizumab-axitinib ICER was dominated by nivolumab-ipilimumab and was not cost-effective (ICER=$12,630,828/QALY) compared with sunitinib. The mean total costs per patient for the nivolumab-ipilimumab and pembrolizumab-axitinib arms were $284,683 and $457,769, respectively, compared with sunitinib at $241,656. QALY was longer for nivolumab-ipilimumab (3.23 QALY) than for adjusted pembrolizumab-axitinib (1.99 QALY), which was longer than sunitinib’s (1.98 QALY). These results were most sensitive to treatment cost in both groups, but plausible changes did not alter the conclusions.

Conclusions:

The base case scenario indicated that nivolumab-ipilimumab was the most cost-effective treatment option for mRCC compared with pembrolizumab-axitinib and sunitinib.
Traversing academic rank promotion for nurse practitioner faculty
Authors: Stager Sharon L. , Douglass Brenda , Mitchell Sheryl , Wise Barbara , Buchholz Susan W.
Published: January 2022

The relatively rapid increase of nurse practitioner (NP) programs across the United States has necessitated schools and colleges of nursing to hire and support NP faculty through the promotion process to sustain their programs. Nurse practitioner faculty engaged in clinical practice often face barriers in obtaining rank promotion. The purpose of this article was to provide NP faculty an evidence-based pathway to support academic rank promotion. An additional aim was to recognize implicit biases and barriers, while offering guidance for overcoming challenges. Using Boyer (1990) and American Association of Colleges of Nursing (2018) as a foundation, this article outlines a pathway to synergistically highlight and weave clinical practice experiences within academic expectations of promotion. The categories of academic rank promotion identified and highlighted within this article include scholarship, teaching, practice, and service. The Stager & Douglass Pathway to Preparation for Traversing Academic Rank for Clinical Faculty provides steps for a well-developed plan and comprehensive dossier in supporting successful promotion. These steps include understanding institutional promotional guidelines, developing focused priorities, defining the clinical practice role in the progression of promotion, partnering with a mentor, gathering supportive materials early, and developing a comprehensive dossier, leading to a successful academic rank promotion process. Preparing the dossier early leverages time for the NP faculty to strategize with academic leaders and colleague mentors to develop focused priorities. In addition, identified biases and barriers may be mitigated to support successful academic rank promotion.
What Laboratory Tests and Physiologic Triggers Should Guide the Decision to Administer a Platelet or Plasma Transfusion in Critically Ill Children and What Product Attributes Are Optimal to Guide Specific Product Selection? From the Transfusion and Anemia EXpertise Initiative–Control/Avoidance of Bleeding
Authors: Delaney Meghan , Karam Oliver , Lieberman Lani , Steffen Katherine , Muszynski Jennifer A. , Goel Ruchika , Bateman Scot T. , Parker Robert I. , Nellis Marianne E. , Remy Kenneth E. ,   for the Pediatric Critical Care Transfusion and Anemia EXpertise Initiative–Control/Avoidance of Bleeding (TAXI-CAB), in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: January 2022

Objectives:

To present consensus statements and supporting literature for plasma and platelet product variables and related laboratory testing for transfusions in general critically ill children from the Transfusion and Anemia EXpertise Initiative–Control/Avoidance of Bleeding.

Design:

Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children.

Setting:

Not applicable.

Patients:

Critically ill pediatric patients at risk of bleeding and receiving plasma and/or platelet transfusions.

Interventions:

None.

Measurements and Main Results:

A panel of 10 experts developed evidence-based and, when evidence was insufficient, expert-based statements for laboratory testing and blood product attributes for platelet and plasma transfusions. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative - Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed five expert consensus statements and two recommendations in answer to two questions: what laboratory tests and physiologic triggers should guide the decision to administer a platelet or plasma transfusion in critically ill children; and what product attributes are optimal to guide specific product selection?

Conclusions:

The Transfusion and Anemia EXpertise Initiative–Control/Avoidance of Bleeding program provides some guidance and expert consensus for the laboratory and blood product attributes used for decision-making for plasma and platelet transfusions in critically ill pediatric patients.
Plasma and Platelet Transfusion Strategies in Critically Ill Children Following Noncardiac Surgery and Critically Ill Children Undergoing Invasive Procedures Outside the Operating Room: From the Transfusion and Anemia EXpertise Initiative–Control/Avoidance of Bleeding
Authors: Tucci Marisa , Crighton Gemma , Goobie Susan M. , Russell Robert T. , Parker Robert I. , Haas Thorsten , Nellis Marianne E. , Vogel Adam M. , Lacroix Jacques , Stricker Paul A. ,   for the Pediatric Critical Care Transfusion and Anemia EXpertise Initiative–Control/Avoidance of Bleeding (TAXI-CAB), in collaboration with the Pediatric Critical Care Blood Research Network (BloodNet), and the Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network
Published: January 2022

Objectives:

To present consensus statements and supporting literature for plasma and platelet transfusions in critically ill children following noncardiac surgery and critically ill children undergoing invasive procedures outside the operating room from the Transfusion and Anemia EXpertise Initiative - Control/Avoidance of Bleeding.

Design:

Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children.

Setting:

Not applicable.

Patients:

Critically ill children undergoing invasive procedures outside of the operating room or noncardiac surgery.

Interventions:

None

Measurements and Main Results:

A panel of 10 experts developed evidence-based and, when evidence was insufficient, expert-based statements for plasma and platelet transfusions in critically ill children following noncardiac surgery or undergoing invasive procedures outside of the operating room. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative–Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed eight expert consensus statements focused on the critically ill child following noncardiac surgery and 10 expert consensus statements on the critically ill child undergoing invasive procedures outside the operating room.

Conclusions:

Evidence regarding plasma and platelet transfusion in critically ill children in this area is very limited. The Transfusion and Anemia EXpertise Initiative–Control/Avoidance of Bleeding Consensus Conference developed 18 pediatric specific consensus statements regarding plasma and platelet transfusion management in these critically ill pediatric populations.
Virtual Developmental Screening After Invasive Mechanical Ventilation in Children: A Prospective Cohort Pilot Study
Authors: Bartel Nicholas J. , Boyle David W. , Hines Abbey C. , Tomlin Angela M. , Nitu Mara E. , Szczepaniak Dorota , Abu-Sultaneh Samer M. A.
Published: January 2022

OBJECTIVES:

With decreasing PICU mortality, survivor morbidity has increased. This study aims to evaluate feasibility of virtual PICU-led follow-up of patients at risk for pediatric postintensive care syndrome.

DESIGN:

Prospective cohort study.

SETTING:

Single-center, quaternary children’s hospital.

PATIENTS:

Children less than or equal to 4 years without known preexisting neurodevelopmental deficits requiring greater than or equal to 12 hours mechanical ventilation.

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Age-appropriate Ages and Stages Questionnaires, Third Edition (ASQ-3) were administered via a web-based system at 3, 6, and 12 months following PICU discharge. Primary-care physicians were notified of results; at-risk patients were referred to early developmental intervention. Forty-eight patients enrolled with median age 11.5 months (interquartile range [IQR], 2–19.5 mo) and median mechanical ventilation duration 92.5 hours (IQR, 40.5–147 hr). Fifty-eight percent completed greater than or equal to 1 ASQ-3. Lower caregiver educational achievement, lower income, and single-caregiver status were associated with lower ASQ-3 completion rates. Of those completing any ASQ-3, 50% flagged as at-risk for developmental delay and referred to early developmental intervention. There was no association between patient characteristics and abnormal ASQ-3.

CONCLUSIONS:

Virtual caregiver-completed surveillance is a promising method to screen children for neurodevelopmental abnormalities following PICU hospitalization and facilitate early referral for developmental intervention, but special attention must be dedicated to families with limited resources for follow-up.
Weaning Dexmedetomidine in Non-ICU Areas: An Implementation Effort
Authors: Solodiuk Jean C. , Sweet Erin , Greco Christine , Manzi Shannon F. , Giangregorio Maeve , Homoki Adam , Li Liza , Mansfield Laura , Mahoney Judy , Kleinman Monica E.
Published: January 2022

OBJECTIVES:

To develop and implement clinical practice guidelines for safely weaning dexmedetomidine infusions in non-ICU areas.

DESIGN:

Development, implementation, and analysis of effectiveness of clinical practice guidelines.

SETTING:

Quaternary care academic free-standing pediatric hospital.

PATIENTS:

Children, otherwise medically ready for transfer to non-ICU areas, who were undergoing a planned wean of a dexmedetomidine infusion.

INTERVENTIONS:

Subject matter experts developed evidence-based guidelines for weaning dexmedetomidine in patients whose critical phase of illness had resolved.

MEASUREMENTS AND MAIN RESULTS:

Searches identified no prospective studies of dexmedetomidine weaning. We identified two retrospective reviews of withdrawal symptoms and one on the use of clonidine. There were case studies on withdrawal symptoms. Guidelines were piloted on a cohort of 24 patients while in the ICU. The guidelines were then implemented in non-ICU areas for patients undergoing dexmedetomidine weaning after ICU transfer. Over a 2-year period (October 1, 2018, to September 30, 2020), 63 patients (1 mo to 18 yr old) successfully weaned dexmedetomidine in non-ICU areas. The median time to discontinuation of dexmedetomidine after transfer to non-ICU areas was 5.8 days (interquartile range, 4.75–15 d). Fifty-eight percent (n = 41) of all patients were considered high risk for dexmedetomidine withdrawal based on the dose, duration of exposure, and the risk of experiencing physiologic detriment with more than mild withdrawal. Twenty-nine patients (46%) exhibited no signs or symptoms of withdrawal while weaning per guidelines. For those with signs and symptoms of withdrawal, the most common were tachycardia (n = 26, 40%), agitation (n = 9, 14%), and hypertension (n = 9, 11%).

CONCLUSIONS:

Weaning dexmedetomidine in non-ICU areas is feasible and can be accomplished safely even among pediatric patients at high risk for withdrawal using standardized weaning guidelines. At our institution, implementation was associated with reduced ICU length of stay for patients recovering from critical illness.
Balanced Versus Unbalanced Fluid in Critically Ill Children: Systematic Review and Meta-Analysis*
Authors: Lehr Anab Rebecca , Rached-d’Astous Soha , Barrowman Nick , Tsampalieros Anne , Parker Melissa , McIntyre Lauralyn , Sampson Margaret , Menon Kusum
Published: January 2022

OBJECTIVES:

The ideal crystalloid fluid bolus therapy for fluid resuscitation in children remains unclear, but pediatric data are limited. Administration of 0.9% saline has been associated with hyperchloremic metabolic acidosis and acute kidney injury. The primary objective of this systematic review was to compare the effect of balanced versus unbalanced fluid bolus therapy on the mean change in serum bicarbonate or pH within 24 hours in critically ill children.

DATA SOURCES:

We searched MEDLINE including Epub Ahead of Print, In-Process & Other Non-Indexed Citations, Embase, CENTRAL Trials Registry of the Cochrane Collaboration, ClinicalTrials.gov, and World Health Organization International Clinical Trials Registry Platform.

STUDY SELECTION:

Using the Preferred Reporting Items for Systematic Review and Meta-analysis Protocols guidelines, we retrieved all controlled trials and observational cohort studies comparing balanced and unbalanced resuscitative fluids in critically ill children. The primary outcome was the change in serum bicarbonate or blood pH. Secondary outcomes included the prevalence of hyperchloremia, acute kidney injury, renal replacement therapy, and mortality.

DATA EXTRACTION:

Study screening, inclusion, data extraction, and risk of bias assessments were performed independently by two authors.

DATA SYNTHESIS:

Among 481 references identified, 13 met inclusion criteria. In the meta-analysis of three randomized controlled trials with a population of 162 patients, we found a greater mean change in serum bicarbonate level (pooled estimate 1.60 mmol/L; 95% CI, 0.04–3.16; p = 0.04) and pH level (pooled mean difference 0.03; 95% CI, 0.00–0.06; p = 0.03) after 4–12 hours of rehydration with balanced versus unbalanced fluids. No differences were found in chloride serum level, acute kidney injury, renal replacement therapy, or mortality.

CONCLUSIONS:

Our systematic review found some evidence of improvement in blood pH and bicarbonate values in critically ill children after 4–12 hours of fluid bolus therapy with balanced fluid compared with the unbalanced fluid. However, a randomized controlled trial is needed to establish whether these findings have an impact on clinical outcomes before recommendations can be generated.
Inpatient Early Intervention for Serious Mental Illnesses Is Associated With Fewer Rehospitalizations Compared With Treatment as Usual in a High-volume Public Psychiatric Hospital Setting
Authors: Warner Alia R. , Lavagnino Luca , Glazier Stephen , Hamilton Jane E. , Lane Scott D.
Published: January 2022

Objective:

High-acuity publicly funded inpatient psychiatric settings usually feature short lengths of stay and high readmission rates. This study examined the influence of an early intervention program for serious mental illnesses (SMI) on readmissions at 6 and 12 months postdischarge at a high-volume, urban public inpatient psychiatric hospital.

Methods:

The Early Onset Treatment Program (EOTP) is a cost-free, 90-day inpatient multidisciplinary service intervention program for uninsured patients who are within 5 years of SMI onset, funded as a pilot program by the Texas state legislature. Rehospitalization rates at 6 and 12 months were extracted from electronic medical records for EOTP participants (n=165) and comparison patients matched on demographics and diagnosis (n=155). The comparison group received treatment as usual at the same psychiatric hospital. Group re-admission rates were compared using logistic and Poisson regression analyses.

Results:

Group membership was a significant predictor of rehospitalization (P<0.0001) at both 6 and 12 months. Expressed as 1/odds ratio (OR), the EOTP group was less likely to readmit once and more than once at 6 months postdischarge (1/OR=3.82 and 4.74, respectively) compared with the non-EOTP group. The EOTP group was also less likely to readmit once and more than once at 12 months postdischarge (1/OR=2.96 and 3.51, respectively).

Conclusions:

The results suggest that participation in the EOTP service in this high-acuity setting was significantly related to reduced likelihood of rehospitalization at 6 and 12 months. Several variables may account for this observation, including length of stay, longer medication adherence, environmental stability, and more individualized and extensive psychotherapy treatment.
Utility of Nipple Markers in the Era of Digital Imaging
Authors: Lee Elizabeth , Sayyouh Mohamed , Aslam Anum , Sella Edith , Kazerooni Ella , Agarwal Prachi
Published: January 2022

Purpose:

Nipple markers maybe used to decrease the recall of patients undergoing chest radiography by aiding in distinguishing between a nipple shadow and lung nodule. We evaluated the use of digital chest radiographs in clinical practice including accuracy of placement and markers that do not contribute to interpretation (ie, projected outside the lung fields). We also evaluated the recall rate for additional imaging in patients who received nipple markers compared to those who did not.

Material and Methods:

In this Institutional Review Board approved retrospective study, 1000 consecutive outpatient frontal and lateral chest radiographs performed in 2018 for which nipple markers were provided to patients formed the study group. Three cardiothoracic radiologists evaluated the images for the presence of markers and accuracy of placement. The recall rate was calculated over a 3-year period from March 21, 2016 and March 21, 2019.

Results:

One or both markers were missing without an explanation (such as mastectomy), misplaced or outside the lung fields in 57.8% (578/1000) of studies. The 3-year recall rate for all chest radiographs was very low (0.03%; 42/135,792) and was lower for patients provided nipple markers (0.007%; 5/62,587) than those who were not (0.05%; 37/73,205) (P<0.001).

Conclusions:

The low overall recall rate and high prevalence of inaccurate marker placement or markers that do not contribute to interpretation (ie, outside the lung fields) does not justify the routine use of nipple markers for chest radiography.
Significance of Right-to-Left Ventricular Ratio as a Quantitative Computed Tomography Biomarker in Patients With Negative Computed Tomography Pulmonary Angiograms
Authors: Tang Anji , Hunsaker Andetta , Hammer Mark
Published: January 2022

Purpose:

The purpose of our study was to determine if the ratio of right–to-left ventricular diameter (RV/LV ratio) on computed tomography (CT) pulmonary angiograms (CTPA) is predictive of 90-day mortality in patients without pulmonary embolism (PE).

Materials and Methods:

This Institutional Review Board-approved single-institution retrospective study was performed on patients who underwent CTPA in the emergency or inpatient setting over a 1-year period. Right and left ventricular diameters were measured and RV/LV ratios calculated for patients without acute PE. Ratios greater than or equal to 0.9 were considered abnormal. Univariate analysis was performed for the outcome of death within 90 days of CT. Multivariable analysis was also performed to control for age, sex, and lung disease.

Results:

Of the 423 patients included in the study, 55 patients died within 90 days of CT. An RV/LV ratio ≥0.9 was predictive of 90-day mortality: of the 226 patients with RV/LV ≥0.9, 42 (18.6%) died within 90 days, compared with 13 of 197 patients without abnormal ratio (6.6%), with odds ratio (OR) of 3.23 (95% confidence interval [CI]: 1.68-6.22; P<0.01). In multivariate analysis, RV/LV ratio had an OR of 5.19 per unit increase (95%CI: 1.06-25.42; P=0.04); age had an OR of 1.04 per year increase (95% CI: 1.01-1.06; P<0.01).

Conclusion:

Increased RV/LV ratio is a negative prognostic factor even in patients without acute PE and may be a useful CT biomarker to include in radiology reports for all patients undergoing CTPA.
Computed Tomography-derived Characterization of Pericoronary, Epicardial, and Paracardial Adipose Tissue and Its Association With Myocardial Ischemia as Assessed by Computed Fractional Flow Reserve
Authors: Duncker Hendrik , Achenbach Stephan , Moshage Maximilian , Dey Damini , Bittner Daniel O. , Ammon Fabian , Marwan Mohamed , Goeller Markus
Published: January 2022

Background:

Increased pericoronary adipose tissue (PCAT) attenuation derived from coronary computed tomography (CT) angiography (CTA) relates to coronary inflammation and cardiac mortality. We aimed to investigate the association between CT-derived characterization of different cardiac fat compartments and myocardial ischemia as assessed by computed fractional flow reserve (FFRCT).

Methods:

In all, 133 patients (median 64 y, 74% male) with coronary artery disease (CAD) underwent CTA including FFRCT measurement followed by invasive FFR assessment (FFRINVASIVE). CT attenuation and volume of PCAT were quantified around the proximal right coronary artery (RCA), left anterior descending artery (LAD), and left circumflex artery (LCX). Epicardial adipose tissue (EAT) and paracardial adipose tissue (PAT; all intrathoracic adipose tissue outside the pericardium) were quantified in noncontrast cardiac CT datasets.

Results:

Median FFRCT was 0.86 [0.79, 0.91] and median FFRINVASIVE was 0.87 [0.81, 0.93]. Subjects with the presence of myocardial ischemia (n=26) defined by an FFRCT-threshold of ≤0.75 showed significantly higher RCA PCAT attenuation than individuals without myocardial ischemia (n=107) (−75.1±10.8 vs. −81.1±10.6 HU, P=0.011). In multivariable analysis adjusted for age, body mass index, sex and risk factors, increased RCA PCAT attenuation remained a significant predictor of myocardial ischemia. Between individuals with myocardial ischemia compared with individuals without myocardial ischemia, there was no significant difference in the volume and CT attenuation of EAT and PAT or in the PCAT volume of RCA, LAD, and LCX.

Conclusions:

Increased RCA PCAT attenuation is associated with the presence of myocardial ischemia as assessed by FFR, while PCAT volume, EAT, and PAT are not.
Urine leaks in children sustaining blunt renal trauma
Authors: Ghani Muhammad Owais Abdul , Snyder Elizabeth , Xu Mark C. , McKay Katlyn G. , Foster Jarrett , Tong Carmen , Clayton Douglas B. , Greeno Amber , Azam Bassil , Zhao Shilin , Hernanz-Schulman Marta , Lovvorn Harold N.
Published: January 2022

BACKGROUND

Few consensus statements exist to guide the timely diagnosis and management of urine leaks in children sustaining blunt renal trauma (BRT). The aims of this study were to characterize kidney injuries among children who sustain BRT, evaluate risk factors for urine leaks, and describe the negative impact of urinoma on patient outcomes and resource consumption.

METHODS

A retrospective review was performed of 347 patients, younger than 19 years, who presented with BRT to a single American College of Surgeons–verified Level I Pediatric Trauma Center between 2005 and 2020. Frequency of and risk factors for urine leak after BRT were evaluated, and impact on patient outcomes and resource utilization were analyzed.

RESULTS

In total, 44 (12.7%) patients developed urine leaks, which exclusively presented among injury Grade 3 (n = 5; 11.4%), Grade 4 (n = 27; 61.4%), and Grade 5 (n = 12; 27.3%). A minority of urine leaks (n = 20; 45.5%) were discovered on presenting CT scan but all within 3 days. Kidney-specific operative procedures (nephrectomy, cystoscopy with J/ureteral stent, percutaneous nephrostomy) were more common among urine leak patients (n = 17; 38.6%) compared with patients without urine leaks (n = 3; 1.0%; p = 0.001). Patients with urine leak had more frequent febrile episodes during hospital stay (n = 24; 54.5%; p = 0.001) and showed increased overall 90-day readmission rates (n = 14; 33.3%; p < 0.001). Independent risk factors that associated with urine leak were higher grade (odds ratio [OR], 7.9; 95% confidence interval [CI], 2.6–24.3; p < 0.001), upper-lateral quadrant injuries (OR, 2.9; 95% CI, 1.2–7.1; p = 0.02), and isolated BRT (OR, 2.6; 95% CI, 1.0–6.5; p = 0.04).

CONCLUSION

In a large cohort of children sustaining BRT, urine leaks result in considerable morbidity, including more febrile episodes, greater 90-day readmission rates, and increased operative or image-guided procedures. This study is the first to examine the relationship between kidney quadrant injury and urine leaks. Higher grade (Grade 4–5) injury, upper lateral quadrant location, and isolated BRT were independently predictive of urine leaks.

LEVEL OF EVIDENCE

Therapeutic/Care Management; Level III.