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Aims: Beta‐lactam dose optimization in critical care is a current priority. We aimed to review the pharmacokinetics (PK) of three commonly used beta‐lactams (amoxicillin ± clavulanate, piperacillin–tazobactam and meropenem) to compare PK parameters reported in critically and noncritically ill neonates, children and adults, and to investigate whether allometric and maturation scaling principles could be applied to describe changes in PK parameters through life. Methods: A systematic review of PK studies of the three drugs was undertaken using MEDLINE and EMBASE. PK parameters and summary statistics were extracted and scaled using allometric principles to 70 kg individual for comparison. Pooled data were used to model clearance maturation and decline using a sigmoidal (Hill) function. Results: A total of 130 papers were identified. Age ranged from 29 weeks to 82 years and weight from 0.9–200 kg. PK parameters from critically ill populations were reported with wider confidence intervals than those in healthy volunteers, indicating greater PK variability in critical illness. The standard allometric size and sigmoidal maturation model adequately described increasing clearance in neonates, and a sigmoidal model was also used to describe decline in older age. Adult weight‐adjusted clearance was achieved at approximately 2 years postmenstrual age. Changes in volume of distribution were well described by the standard allometric model, although amoxicillin data suggested a relatively higher volume of distribution in neonates. Conclusions: Critical illness is associated with greater PK variability than in healthy volunteers. The maturation models presented will be useful for optimizing beta‐lactam dosing, although a prospective, age‐inclusive study is warranted for external validation. [ABSTRACT FROM AUTHOR]

Whilst new drug technologies like biologics have begun a revolution in the treatment of cancer and autoimmune disease, there has been a conspicuous absence of new classes of antibiotic over the last 30 years. Mgbeahurulike et al. [[6]] utilize another strategy for developing new antimicrobial treatments by combining a novel synergistic compound with an established antibiotic. Suay-Garcia and Pérez-Gracia [[7]] provide a concise summary of the history, epidemiology and resistance mechanisms of these pathogens, and outline the treatment strategies that may be employed to treat them. [Extracted from the article]

Since the development of the Adult Attachment Interview (AAI) in 1985, more than 26,000 AAIs have been administered, coded, and reported, representing 170 (wo-)man-years of work. We used multinomial tests and analyses of correspondence to compare the AAI distributions in various cultural and age groups, in mothers, fathers, high-risk, and clinical samples with the combined samples of North American non-clinical, non-risk mothers (22% dismissing, 53% secure, 8% preoccupied, and 17% unresolved loss or other trauma). Males were more often classified as dismissing and less frequently classified as secure compared to females (except adoptive fathers), and females were more frequently classified as unresolved (but not more often preoccupied) compared to males. A combination of high scores on the unresolved and insecure-preoccupied dimensions was shared by borderline personality disorder, autism spectrum disorders, and gender dysphoria, while combined high scores on the unresolved and insecure-dismissing dimensions characterized anxiety problems, obsessive-compulsive and thought disorders.

A growing body of research suggests that, compared with single parent-child attachment relationships, child developmental outcomes may be better understood by examining the configurations of child-mother and child-father attachment relationships (i.e., attachment networks). Moreover, some studies have demonstrated an above-chance level chance of concordance between the quality of child-mother and child-father attachment relationships, and child temperament has been offered as a plausible explanation for such concordance. To assess whether temperament plays a role in the development of different attachment network configurations, in this preregistered individual participant data meta-analysis we tested the degree to which the temperament dimension of negative emotionality predicts the number of secure, insecure-avoidant, insecure-resistant, and disorganized attachment relationships a child has with mother and father. Data included in the linear mixed effects analyses were collected from seven studies sampling 872 children (49% female; 83% White). Negative emotionality significantly predicted the number of secure ( d = -0.12) and insecure-resistant ( d = 0.11), but not insecure-avoidant ( d = 0.04) or disorganized ( d = 0.08) attachment relationships. Nonpreregistered exploratory analyses indicated higher negative emotionality in children with insecure-resistant attachment relationships with both parents compared to those with one or none ( d = 0.19), suggesting that temperament plays a small yet significant role in child-mother/child-father insecure-resistant attachment relationships concordance. Taken together, results from this study prompt a more in-depth examination of the mechanism underlying the small yet significantly higher chance that children with increased negative emotionality have for developing multiple insecure-resistant attachment relationships. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Background: The standard vancomycin regimen for term neonates is 45 mg/kg/day. However, the optimal starting vancomycin dosing for achieving therapeutic levels in young infants in cardiac intensive care units remains unknown. Moreover, data on the association of supratherapeutic vancomycin levels with acute kidney injury (AKI) are limited., Methods: Retrospective study of infants ≤3 months old, receiving vancomycin following congenital heart surgery at postoperative intensive care unit admission. Assessed were vancomycin dosing, achievement of therapeutic trough concentration of 10-20 mg/L and development of AKI, based on the modified Kidney Disease Improving Global Outcomes criteria., Results: Inclusion criteria were met by 109 patients with a median age of 8 days (IQR: 6-16). The mean (SD) vancomycin dose required for achieving therapeutic concentration was 28.9 (9.1) mg/kg at the first postoperative day. Multivariate logistic regression identified higher preoperative creatinine levels and shorter cardiopulmonary bypass time as predictors of supratherapeutic vancomycin concentrations (c-index 0.788). During the treatment course, 62 (56.9%) developed AKI. Length of stay and mortality were higher in those who developed AKI as compared with those who did not. Multivariate logistic regression identified higher vancomycin concentration as a predictor for postoperative AKI, OR, 3.391 (95% CI: 1.257-9.151), P = 0.016 (c-index 0.896)., Conclusion: Our results support a lower starting vancomycin dose of ~30 mg/kg/day followed by an early personalized therapeutic approach, to achieve therapeutic trough concentrations of 10-20 mg/L in cardiac postoperative term infants. Supratherapeutic concentrations are associated with an increased risk for AKI, which is prevalent in this population and associated with adverse outcomes., Competing Interests: The authors have no funding or conflicts of interest to disclose., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: While the contribution of environmental factors including smoking, overweight and stress has been validated, data mining for the association between socioeconomic status (SES) and psoriasis prevalence has yielded contradicting observations., Objective: To evaluate the association between psoriasis prevalence and SES., Methods: This was a nationwide population-based cross-sectional retrospective study that included all patients insured by the "Clalit" Health Services (N=4,604,994). Univariable and multivariable logistic regression analyses were conducted to explore the association between psoriasis and SES while controlling for potential sociodemographic and clinical confounders., Results: The study population included 129,855 patients with psoriasis and 4,475,139 individuals without psoriasis. Higher SES was associated with an increased prevalence of psoriasis; in a fully adjusted model, Clalit members within the highest SES were 1.43-fold more likely to have psoriasis (95% CI, 1.39-1.48; P< 0.001), and those at medium SES were 1.2-fold more likely to have psoriasis, compared to those at the lowest SES group (95% CI, 1.18-1.26; P< 0.001; P for linear trend <0.001)., Conclusions: Positive correlation was found between SES and psoriasis prevalence. Further investigation is warranted to elucidate the factors accounting for this observation., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Tumor depth of invasion is a known prognostic factor in several head and neck cancers, but data on early laryngeal squamous cell carcinoma (SCC) are sparse. In this study, we aim to determine whether radiological tumor thickness serves as a prognostic factor in early SCC of the glottis treated with radiation., Methods: One hundred thirty-two adult patients (age >18 years) underwent pretreatment computed tomography (CT) and were treated with radiation for pathologically proven early stage (T1 or T2) glottic SCC. Thirty-eight were excluded because the tumor could not be correctly identified on the CT scan, and an additional three patients because of insufficient data., Results: The final cohort consisted of 91 patients, 84 (90.3%) men and 7 (9.7%) women aged 39.86-86.53 (mean 65.55 ± 12.76) years. Mean tumor thickness was 0.59 ± 0.19 cm in patients with T1 tumors and 0.79 ± 0.21 cm in patients with T2 tumors. The optimal cutoff value for 5-year disease-free survival (DFS), using the Youden index (sensitivity: 81.2%, specificity 65.3%), was 0.7 cm. A significant advantage in 5-year overall survival (OAS) and 5-year DFS for tumor thickness of <0.7 cm (P = 0.01 and P < 0.01, respectively) was found, these findings were consistent also when each stage was examined separately (T1 vs T2)., Conclusion: Radiological tumor thickness appears to significantly predict OAS and DFS in early glottic SCC patients., Implication for Practice: Tumor thickness may be considered as an auxiliary aid in deciding follow-up time and frequency, proper treatment, and determining prognosis., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Voice Foundation. Published by Elsevier Inc. All rights reserved.)

Background and Objectives: Extracorporeal membrane oxygenation (ECMO) serves as cardiopulmonary therapy in critically ill patients with respiratory/heart failure and often necessitates multiple blood product transfusions. The administration of platelet transfusions during ECMO is triggered by the presence or risk of significant bleeding. Most paediatric ECMO programmes follow guidelines that recommend a platelet transfusion threshold of 80-100 × 10 9 /L. To reduce exposure to platelets, we developed a practice to dynamically lower the threshold to ~20 × 10 9 /L. We describe our experience with patient-tailored platelet thresholds and related bleeding outcomes., Materials and Methods: We retrospectively evaluated our platelet transfusion policy, bleeding complications and patient outcome in 229 ECMO-supported paediatric patients in our unit., Results: We found that more than 97.4% of patients had a platelet count <100 × 10 9 /L at some point during their ECMO course. Platelets were transfused only on 28.5% of ECMO days; and 19.2% of patients never required a platelet transfusion. The median lowest platelet count in children who had bleeding events was 25 × 10 9 /L as compared to 33 × 10 9 /L in children who did not bleed (p < 0.001). Our patients received fewer platelet transfusions and did not require more red blood cell transfusions, nor did they experience more haemorrhagic complications., Conclusion: We have shown that a restrictive, 'patient-tailored' rather than 'goal-directed' platelet transfusion policy is feasible and safe, which can greatly reduce the use of platelet products. Although there was a difference in the lowest platelet counts in children who bled versus those who did not, the median counts were much lower than current recommendations., (© 2024 The Authors. Vox Sanguinis published by John Wiley & Sons Ltd on behalf of International Society of Blood Transfusion.)

Attachment theorists claim that the quality of parental support is internalized as a mental representation of early relationship experiences. Increasingly, the content of attachment representations is evaluated by studying the extent to which adults demonstrate knowledge of the secure base script , either in the context of the Attachment Script Assessment (ASA) or during the Adult Attachment Interview (AAI sbs ). Preliminary evidence from a high-risk sample showed that AAI sbs was more strongly associated with the quality of antecedent caregiving than was the more traditional approach to the measurement of adult attachment focused on the coherence of adults' AAI discourse (Waters, et al., 2017). Drawing on new coding of data from the NICHD Study of Early Child Care and Youth Development (SECCYD), we found that AAI sbs around age 18 years was significantly predicted by observations of maternal ( r = .21) and paternal ( r = .12) sensitivity assessed prospectively through age 15 years, and with attachment security in the first three years of life ( r =.08). AAI sbs was also associated with existing measures of adult attachment ( r s = .31-.42). Pre-registered analyses revealed that AAI sbs performed in a manner roughly comparable to traditional, though more labor intensive approaches to coding the AAI. Based on all available evidence from the SECCYD and the pragmatic challenges and advantages of different narrative methods for assessing adult attachment representations (Booth-LaForce & Roisman, 2014; Steele et al., 2014), researchers seeking to measure attachment representations should strongly consider the strengths of the ASA in term of practicality, performance, and adaptability to various age groups across development (Waters & Waters, 2021).

Natural human behavior arises from continuous interactions between the cognitive and motor domains. However, assessments of cognitive abilities are typically conducted using pen and paper tests, i.e., in isolation from "real life" cognitive-motor behavior and in artificial contexts. In the current study, we aimed to assess cognitive-motor task performance in a more naturalistic setting while recording multiple motor and eye tracking signals. Specifically, we aimed to (i) delineate the contribution of cognitive and motor components to overall task performance and (ii) probe for a link between cognitive-motor performance and pupil size. To that end, we used a virtual reality (VR) adaptation of a well-established neurocognitive test for executive functions, the 'Color Trails Test' (CTT). The VR-CTT involves performing 3D reaching movements to follow a trail of numbered targets. To tease apart the cognitive and motor components of task performance, we included two additional conditions: a condition where participants only used their eyes to perform the CTT task (using an eye tracking device), incurring reduced motor demands, and a condition where participants manually tracked visually-cued targets without numbers on them, incurring reduced cognitive demands. Our results from a group of 30 older adults (>65) showed that reducing cognitive demands shortened completion times more extensively than reducing motor demands. Conditions with higher cognitive demands had longer target search time, as well as decreased movement execution velocity and head-hand coordination. We found larger pupil sizes in the more cognitively demanding conditions, and an inverse correlation between pupil size and completion times across individuals in all task conditions. Lastly, we found a possible link between VR-CTT performance measures and clinical signatures of participants (fallers versus non-fallers). In summary, performance and pupil parameters were mainly dependent on task cognitive load, while maintaining systematic interindividual differences. We suggest that this paradigm opens the possibility for more detailed profiling of individual cognitive-motor performance capabilities in older adults and other at-risk populations., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

An individual participant data meta-analysis was conducted to test pre-registered hypotheses about how the configuration of attachment relationships to mothers and fathers predicts children's language competence. Data from seven studies (published between 1985 and 2014) including 719 children (M age : 19.84 months; 51% female; 87% White) were included in the linear mixed effects analyses. Mean language competence scores exceeded the population average across children with different attachment configurations. Children with two secure attachment relationships had higher language competence scores compared to those with one or no secure attachment relationships (d = .26). Children with two organized attachment relationships had higher language competence scores compared to those with one organized attachment relationship (d = .23), and this difference was observed in older versus younger children in exploratory analyses. Mother-child and father-child attachment quality did not differentially predict language competence, supporting the comparable importance of attachment to both parents in predicting developmental outcomes., (© 2023 The Authors. Child Development © 2023 Society for Research in Child Development.)

Background: Ventricular assist devices (VADs) play a critical and increasing role in treating end-stage heart failure in pediatric patients. A growing number of patients are supported by VADs as a bridge to heart transplantation. Experience with VADs in the pediatric population is limited, and experience in Israel has not been published., Objectives: To describe this life-saving technology and our experience with VAD implantation in children with heart failure, including characteristics and outcomes., Methods: We conducted a retrospective chart review of all patients who underwent VAD implantation at Schneider Children's Medical Center from 2018 to 2023., Results: We analyzed results of 15 children who underwent VAD implantation. The youngest was 2.5 years old and weighed 11 kg at implantation. In eight patients, HeartMate 3, a continuous-flow device, was implanted. Seven patients received Berlin Heart, a pulsatile-flow device. Three children required biventricular support; 11 underwent heart transplants after a median duration of 169 days. Two patients died due to complications while awaiting a transplant; two were still on VAD support at the time of submission of this article. Successful VAD support was achieved in 86.6% of patients. In the last 5 years,79% of our heart transplant patients received VAD support prior to transplant., Conclusions: Circulatory assist devices are an excellent bridge to transplantation for pediatric patients reaching end-stage heart failure. VADs should be carefully selected, and implantation techniques tailored to patient's weight and diagnosis at a centralized pediatric cardiac transplantation center. Israeli healthcare providers should be cognizant of this therapeutic alternative.

Background: Partial Tonsillectomy (PT) is an alternative method to treat sleep disordered breathing (SDB) and/or obstructive sleep apnea (OSA). The current guidelines do not differentiate it from traditional tonsillectomy. Thus, children younger than 3 years old undergoing PT are admitted for surveillance similar to traditional tonsillectomy due to possible postoperative complications. The aim of this study is to assess the risks of PT in children 3 years old and younger, compared to older children., Methods: Children underwent inpatient partial tonsillectomy and/or adenoidectomy, due to SDB/OSA, from 2018 to 2020. A special protocol was designed, including follow-up at 2-, 4-, 6-, 8- and 24-h after surgery. Variables analyzed included visual analogue pain score, oral intake, oxygen saturation, pulse rate, postoperative hemorrhage, urine output, temperature, analgesics and fluid administration. Furthermore, major interventions were recorded. Comparison of all variables between children younger than 3 years old with older children was performed., Results: Ninety-two children were included; mean age of the whole cohort was 44.5 ± 21.9 months. Thirty-five (38%) children were 3-years old or younger and n = 57 (62%) were older than 3 years old, with no significant statistical difference in sex (p = 0.22). Mean age in the younger group was 25.7 ± 6.9 months, and 56.1 ± 20.1 months in the older group. In total we had 7 children with post-operative complications; 4 with fever, 3 with low intake. There were no major interventions recorded in either group. The complications were more common in the older group (n = 5) than the younger group (n = 2) without a statistical significance (p = 0.59). There were no differences in VAS, use of painkillers, oral intake, urine output, oxygen saturation and tachycardia among the two groups., Conclusion: This study supports that children undergoing ambulatory PT may be at low risk of complications, regardless of age., (© 2023. Canadian Society Of Otolaryngology-Head & Neck Surgery.)

Objectives: To evaluate the safety and outcomes of powered intracapsular tonsillotomy and adenoidectomy (PITA) for the treatment of sleep disordered breathing in infants up to 36 months of age compared to older children., Methods: This retrospective analysis included children who underwent PITA from 2013 to 2019 at a single tertiary care medical center. The patients were divided into 2 groups: up to 36 months, and 36 to 72 months. The data were collected from electronic medical records and from a telephone survey based on a modified version of the OSA-18 questionnaire. Post-operative complications, and short- and long-term outcomes were compared., Results: A total of 48 patients met the inclusion criteria for the main study group (up to 36 months of age). They were compared to 59 children 36 to 72 months of age. There were no differences in subjective outcomes between age groups ( P  = .65). There were no differences in the frequency of post-operative complications between age groups ( P  = .8) or in the number of hospitalization days ( P  = .91)., Conclusion: The short- and long-term outcomes and safety of PITA for the treatment of sleep disordered breathing in infants up to 36 months of age are similar to those of older children.

Objective: Blood stream infections (BSIs) are well described in pediatric cardiac intensive care units (PCICU). We noted that postoperative high-risk patients may develop BSI after a preceding clinical event (PCE). The study aim was to investigate whether high-risk patients who developed bacteremia experienced more PCEs than a similar group of high-risk patients. Design: Retrospective case-control study. Setting: Referral pediatric center. Patients: We enrolled patients who developed bacteremia from March 2010 to November 2019, after undergoing open-heart surgery at a pediatric center. The control group was comprised of case-matched patients with immediate consecutive same surgery. Interventions: None. Measurements: We recorded operative data, common risk factors, postoperative indicators of organ dysfunction, mortality, and PCEs 72 to 24 h before bacteremia emerged. Main results: A total of 200 patients were included (100 with bacteremia and 100 controls). Key demographic and operative parameters were matched. Bacteremia emerged on average on postoperative day 12.8. Skin-associated Gram-positive bacteria were cultured in 10% and Gram-negative bacteria in 84% of the patients. Average central-venous lines (CVL) duration was 9.5 ± 8.4 days. Postoperatively (72 h), indicators of organ dysfunction were significantly worse in patients with bacteremia, with a higher rate of postoperative complications during PCICU length-of-stay (LOS). In the bacteremia group, 72 to 24 h prior to the development of bacteremia, 92 (92%) PCEs were recorded, as compared to 21 (21%) in controls during their entire LOS (odds ratio [OR] 43.3, confidence interval [CI] 18.2-103.1, P  < .0001). Conclusions: We propose a 3-hit model demonstrating that high-risk patients undergoing open-heart surgery have significantly higher risk for bacteremia after a PCE.