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Abstract Background Eating disorders (EDs) are among the most difficult psychiatric disorders to treat in normal conditions. They are likely even more difficult to manage in at-risk conditions such as the COVID-19 pandemic. Currently there is limited evidence about the particular needs and recommended treatment of adolescents with EDs during the COVID-19 outbreak, in particular regarding the use of telemedicine and the involvement of the family in long distance-treatment. Aims We sought to discuss the advantages and problems associated with the use of multi-professional long-distance telemedicine treatment in the management of adolescents with EDs and their families during the COVID-19 outbreak. Methods We gathered data about the treatment of adolescents with EDs in our pediatric ED-treatment center in Israel during the COVID-19 outbreak in the first 10 months of 2020, and compared it to the respective period in the past five years (2015–2019). Second, we described the management of four young females with anorexia nervosa (AN), treated in the ambulatory, daycare and inpatient facilities of our center during the COVID-19 pandemic. Findings Slightly less patients were treated in our center during the COVID-19 pandemic than in the respective period in the past five years. These patients received at that time considerably more treatment sessions from all treatment providers (psychiatrists, clinical nutritionists and psychotherapists). This was related, in part, to the extensive use of telemedicine during that period (more than as third of all sessions were carried out with telemedicine in comparison to no use of long-distance treatment in the previous years). The condition of the four adolescents with AN was compromised at the start of the COVID-19 quarantine. The use of multi-disciplinary long-distance telemedicine treatment resulted in an improvement in the condition in three of the four adolescents, living in well-organized families, with the motivation and ability to adjust to the new conditions, but not in one adolescent whose family experienced more problems. These families might require the use of face-to-face interventions even during pandemic conditions. Conclusion The choice of the mode of treatment for adolescents with EDs during pandemic times (telemedicine vs. face-to-face) should consider the functioning of the family.

Objective: Traditionally, pediatric tracheostomy has been viewed as a technically demanding procedure with a high complication rate, requiring the routine use of a formal operating room. Pediatric bedside tracheostomy in an intensive care unit (ICU) setting has not been widely reported, in contrast to the widespread adult bedside ICU tracheostomy. Transport of these critically ill, multiple life support systems dependent patients can be technically difficult, labor intensive, and potentially risky for these patients. Our study aimed to demonstrate the safety and efficacy of bedside tracheostomy in the pediatric ICU. Materials and Methods: A retrospective analysis of all pediatric patients undergoing tracheostomy at a tertiary care center, between 1st of January 2013 and 31st of December 2019. Results: During the study period, 117 pediatric patients underwent tracheostomy, 57 (48.7%) were performed bedside while 60 (51.3%) were performed in the operating room. Patients' ages ranged from 2 weeks to 17 years of age, with a median age of 16 months. No case of bedside tracheostomy necessitated a shift to the operating room. There was no difference in 30-day morbidity and mortality between the 2 groups. Conclusions: Our results suggest that pediatric open bedside tracheostomy in an ICU setting is a safe procedure, with similar complications and outcomes compared to tracheostomy performed in the operating room. [ABSTRACT FROM AUTHOR]

Background: Acute pain and anxiety management during pediatric burn dressing change is very challenging. There are limited data regarding feasibility and safety of sedation administration by nonanesthesiologists. We sought to describe the implementation of a sedation protocol for pediatric residents during burn dressing changes in the pediatric ward. Methods: An analgesia and sedation protocol was designed and implemented in the pediatric wards in 2015. Retrospective data were collected on all children who were sedated by pediatric residents for burns in the pediatric wards over a 4‐year period in our hospital. Demographics, burn characteristics, and data regarding adverse events were collected from patients' electronic medical records. The main outcomes were successful procedure completion and safety. Results: During the study period, 1130 sedations were performed in 272 patients by pediatric residents. The median age was 2.5 years (IQR 1.3–9.1). Sixty‐two percent (695/1130) of the patients were male. The majority of the burns (84%, 955/1130) were <20%, and the majority of the patients (91%, 1030/1130) had an ASA (American Society of Anesthesiologists) score of 1. The incidence rate of adverse events was 4.3% (49/1130) and 1.3% (15/1130) for serious adverse events. There were no statistically significant differences in gender, age, ASA, or burn degree between patients with or without adverse events. Conclusions: We designed and implemented an analgesia and sedation protocol for pediatric residents to be applied in patients during burn dressing change. The implemented protocol in the pediatric wards was found to be feasible and with a low incidence of adverse events. [ABSTRACT FROM AUTHOR]

Background: Genetic conditions contribute a significant portion of disease etiologies in children admitted to general pediatric wards worldwide. While exome sequencing (ES) has improved clinical diagnosis and management over a variety of pediatric subspecialties, it is not yet routinely used by general pediatric hospitalists. We aim to investigate the impact of exome sequencing in sequencing-naive children suspected of having monogenic disorders while receiving inpatient care. Methods: We prospectively employed exome sequencing in children admitted to the general pediatric inpatient service at a large tertiary medical center in Israel. Genetic analysis was triggered by general and/or subspecialist pediatricians who were part of the primary inpatient team. We determined the diagnostic yield among children who were referred for exome sequencing and observed the effects of genetic diagnosis on medical care. Results: A total of fifty probands were evaluated and exome sequenced during the study period. The most common phenotypes included were neurodevelopmental (56%), gastrointestinal (34%), and congenital cardiac anomalies (24%). A molecular diagnosis was reached in 38% of patients. Among seven patients (37%), the molecular genetic diagnosis influenced subsequent clinical management already during admission or shortly following discharge. Conclusion: We identified a significant fraction of genetic etiologies among undiagnosed children admitted to the general pediatric ward. Our results support that early application of exome sequencing may be maximized by pediatric hospitalists' high index of suspicion for an underlying genetic etiology, prompting an in-house genetic evaluation. This framework should include a multidisciplinary co-management approach of the primary care team working alongside with subspecialties, geneticists and bioinformaticians. [ABSTRACT FROM AUTHOR]

In the course of primary infection with herpes simplex virus 1 (HSV-1), children with inborn errors of toll-like receptor 3 (TLR3) immunity are prone to HSV-1 encephalitis (HSE) (1-3). We tested the hypothesis that the pathogenesis of HSE involves non-haematopoietic CNS-resident cells. We derived induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of TLR3- and UNC-93B-deficient patients and from controls. These iPSCs were differentiated into highly purified populations of neural stem cells (NSCs), neurons, astrocytes and oligodendrocytes. The induction of interferon-β (IFN-β) and/or IFN-λ1 in response to stimulation by the dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) was dependent on TLR3 and UNC-93B in all cells tested. However, the induction of IFN-β and IFN-λ1 in response to HSV-1 infection was impaired selectively in UNC-93B-deficient neurons and oligodendrocytes. These cells were also much more susceptible to HSV-1 infection than control cells, whereas UNC-93B-deficient NSCs and astrocytes were not. TLR3-deficient neurons were also found to be susceptible to HSV-1 infection. The rescue of UNC-93B- and TLR3deficient cells with the corresponding wild-type allele showed that the genetic defect was the cause of the poly(I:C) and HSV-1 phenotypes. The viral infection phenotype was rescued further by treatment with exogenous IFN-a or IFN-β (IFN-α/β) but not IFN-λ1. Thus, impaired TLR3- and UNC-93B-dependent IFN-α/β intrinsic immunity to HSV-1 in the CNS, in neurons and oligodendrocytes in particular, may underlie the pathogenesis of HSE in children with TLR3-pathway deficiencies., Childhood HSE is a rare, life-threatening, central nervous system (CNS)-restricted complication of primary infection with HSV-1, an almost ubiquitous virus that is typically innocuous4. Children with HSE are not unusually [...]

Cytosolic phospholipase [A.sub.2] (cPL[A.sub.2])-generated arachidonic acid (AA) has been shown to be an essential requirement for the activation of NADPH oxidase, in addition to its being the major enzyme involved in the formation of eicosanoid at the nuclear membranes. The mechanism by which cPL[A.sub.2] regulates NADPH oxidase activity is not known, particularly since the NADPH oxidase complex is localized in the plasma membranes of stimulated cells. The present study is the first to demonstrate that upon stimulation cPL[A.sub.2] is transiently recruited to the plasma membranes by a functional NADPH oxidase in neutrophils and in granulocyte-like PLB-985 cells. Coimmunoprecipitation experiments and double labeling immunofluorescence analysis demonstrated the unique colocalization of cPL[A.sub.2] and the NADPH oxidase in plasma membranes of stimulated cells, in correlation with the kinetic burst of superoxide production. A specific affinity in vitro binding was detected between GST-[p47.sup.phox] or GST-[p67.sup.phox] and cPL[A.sub.2] in lysates of stimulated cells. The association between these two enzymes provides the molecular basis for AA released by cPL[A.sub.2] to activate the assembled NADPH oxidase. The ability of cPL[A.sub.2] to regulate two different functions in the same cells (superoxide generation and eicosanoid production) is achieved by a novel dual subcellular localization of cPL[A.sub.2] to different targets.

Objective: To identify COVID-19 work-related stressors and experiences associated with sleep difficulties in HCW, and to assess the role of depression and traumatic stress in this association. Methods: A cross-sectional study of HCW using self-report questionnaires, during the first peak of the pandemic in Israel (April 2020), conducted in a large tertiary medical center in Israel. Study population included 189 physicians and nurses working in designated COVID-19 wards and a comparison group of 643 HCW. Mean age of the total sample was 41.7 ± 11.1, 67% were female, 42.1% physicians, with overall mean number of years of professional experience 14.2 ± 20. The exposure was working in COVID-19 wards and related specific stressors and negative experiences. Primary outcome measurement was the Insomnia Severity Index (ISI). Secondary outcomes included the Primary Care-Post Traumatic Stress Disorder Screen (PC-PTSD-5); the Patient Health Questionnaire-9 (PHQ-9) for depression; the anxiety module of the Patient-Reported Outcomes Measurement Information System (PROMIS); Pandemic-Related Stress Factors (PRSF) and witnessing patient suffering and death. Results: Compared with non-COVID-19 HCW, COVID-19 HCW were more likely to be male (41.3% vs. 30.7%) and younger (36.91 ± 8.81 vs. 43.14 ± 11.35 years). COVID-19 HCW reported higher prevalence of sleep difficulties: 63% vs. 50.7% in the non-COVID group (OR 1.62, 95% CI 1.15–2.29, p = 0.006), mostly difficulty maintaining sleep: 26.5% vs. 18.5% (OR 1.65, 95% CI 1.11–2.44, p = 0.012). Negative COVID-19 work-related experiences, specifically witnessing patient physical suffering and death, partially explained the association. Although past psychological problems and current depression and PTSD were associated with difficulty maintaining sleep, the main association remained robust also after controlling for those conditions in the full model. Conclusion and Relevance: COVID-19 frontline HCW were more likely to report sleep difficulties, mainly difficulty maintaining sleep, as compared with non-COVID-19 HCW working at the same hospital. Negative patient-care related experiences likely mediated the increased probability for those difficulties. Future research is needed to elucidate the long-term trajectories of sleep difficulties among HCW during large scale outbreaks, and to identify risk factors for their persistence. [ABSTRACT FROM AUTHOR]

One of the major challenges for healthcare systems during the Coronavirus-2019 (COVID-19) pandemic was the inability to successfully predict which patients would require mechanical ventilation (MV). Angiotensin-Converting Enzyme 2 (ACE2) and TransMembrane Protease Serine S1 member 2 (TMPRSS2) are enzymes that play crucial roles in SARS-CoV-2 entry into human host cells. However, their predictive value as biomarkers for risk stratification for respiratory deterioration requiring MV has not yet been evaluated. We aimed to evaluate whether serum ACE2 and TMPRSS2 levels are associated with adverse outcomes in COVID-19, and specifically the need for MV. COVID-19 patients admitted to an Israeli tertiary medical center between March--November 2020, were included. Serum samples were obtained shortly after admission (day 0) and again following one week of admission (day 7). ACE2 and TMPRSS2 concentrations were measured with ELISA. Of 72 patients included, 30 (41.6%) ultimately required MV. Serum ACE2 concentrations >7.8 ng/mL at admission were significantly associated with the need for MV (p = 0.036), inotropic support, and renal replacement therapy. In multivariate logistic regression analysis, elevated ACE2 at admission was associated with the need for MV (OR = 7.49; p = 0.014). To conclude, elevated serum ACE2 concentration early in COVID-19 illness correlates with respiratory failure necessitating mechanical ventilation. We suggest that measuring serum ACE2 at admission may be useful for predicting the risk of severe disease. [ABSTRACT FROM AUTHOR]

BACKGROUND: There is limited data on the longitudinal trajectories of psychiatric disorders in children with cancer and risk factors for their persistence. The current study aimed to longitudinally assess the trajectories and risk factors for anxiety and depressive symptoms and disorders in children and adolescents with cancer. METHODS: Children and adolescents with cancer and their parents completed the Patient-Reported Outcomes Measurement Information System (PROMIS) Depression and Anxiety Module and were interviewed by the semi-structured Affective and Anxiety Modules of the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children (K-SADS), at 4 time points, 1, 4, 7, and 12 months following the diagnosis of cancer. RESULTS: Of the 99 patients enrolled, 48% met criteria for anxiety and/or depressive disorders at least once during the follow-up period. There was a significant decrease in PROMIS pediatric and parent anxiety and depression scores (all p's < 0.01) and in the rate of depressive disorders over time (p = 0.02), while rates of anxiety disorders remained stable. Anxiety PROMIS pediatric and parent scores at baseline, having brain tumors and being in the acute treatment phase significantly predicted the presences of anxiety disorders at endpoint. CONCLUSIONS: Our results highlight the importance of screening for anxiety and disorders in children with cancer, especially among those with brain tumors and at the acute phase of treatment. [ABSTRACT FROM AUTHOR]

Objective: This case study examines the implementation of inpatient telemedicine in COVID-19 intensive care units (ICUs) and explores the impact of shifting forms of visibility on the management of the unit, staff collaboration, and patient care. Background: The COVID-19 crisis drove healthcare institutions to rapidly develop new models of care based on integrating digital technologies for remote care with transformations in the hospital-built environment. The Sheba Medical Center in Israel created COVID-19 ICUs in an underground structure with an open-ward layout and telemedicine control rooms to remotely supervise, communicate, and support the operations in the contaminated zones. One unit had a physical visual connection between the control room and the contaminated zone through a window, while the other had only a virtual connection with digital technologies. Methods: The findings are based on semistructured interviews with Sheba medical staff, telemedicine companies, and the architectural design team and observations at the COVID-19 units during March–August 2020. Results: The case study illustrates the implications of virtual and physical visibility on the management of the unit, staff collaboration, and patient care. It demonstrates the correlations between patterns of visibility and the users' sense of control, orientation in space, teamwork, safety, quality of care, and well-being. Conclusions: The case study demonstrates the limitations of current telemedicine technologies that were not designed for inpatient care to account for the spatial perception of the unit and the dynamic use of the space. It presents the potential of a hybrid model that balances virtual and physical forms of visibility and suggests directions for future research and development of inpatient telemedicine. [ABSTRACT FROM AUTHOR]

Abstract Background Circulating endothelial cells may serve as novel markers of angiogenesis. These include a subset of hem-endothelial progenitor cells that play a vital role in vascular growth and repair. The presence and clinical implications of circulating RNA levels as an expression for hematopoietic and endothelial-specific markers have not been previously evaluated in preterm infants. This study aims to determine circulating RNA levels of hem-endothelial marker genes in peripheral blood of preterm infants and begin to correlate these findings with prenatal complications. Methods Peripheral blood samples from seventeen preterm neonates were analyzed at three consecutive post-delivery time points (day 3–5, 10–15 and 30). Using quantitative reverse transcription-polymerase chain reaction we studied the expression patterns of previously established hem-endothelial-specific progenitor-associated genes (AC133, Tie-2, Flk-1 (VEGFR2) and Scl/Tal1) in association with characteristics of prematurity and preterm morbidity. Results Circulating Tie-2 and SCL/Tal1 RNA levels displayed an inverse correlation to gestational age (GA). We observed significantly elevated Tie-2 levels in preterm infants born to mothers with amnionitis, and in infants with sustained brain echogenicity on brain sonography. Other markers showed similar expression patterns yet we could not demonstrate statistically significant correlations. Conclusion These preliminary findings suggest that circulating RNA levels especially Tie2 and SCL decline with maturation and might relate to some preterm complication. Further prospective follow up of larger cohorts are required to establish this association.

Background: Healthcare workers (HCW) treating coronavirus disease 2019 (COVID-19) patients face high levels of psychological stress. We aimed to compare mental health outcomes, risk and protective factors for posttraumatic stress symptoms (PTSS), probable depression, and anxiety between HCW working in COVID-19 and non-COVID-19 wards. Methods: A self-report survey, administered in a large tertiary hospital in Israel during the peak of the COVID-19 outbreak was completed by 828 HCW (42.2% physicians, 57.8% nurses. Patient-Reported Outcomes Measurement Information System; the Patient Health Questionnaire-9; the Primary Care-Post Traumatic Stress Disorder Screen for DSM-5 (PC-PTSD-5) were used for assessing anxiety, depression, and PTSS, respectively. Pandemic-related stress factors, negative experiences, and potential protective factors were also assessed. Results: Median PC-PTSD scores differed significantly between study teams (X2 [5] = 17.24; p = .004). Prevalence of probable depression and anxiety were similar in both groups. Risk factors for mental health outcomes included mental exhaustion, anxiety about being infected and infecting family. Overall, higher proportion of the COVID-19 team witnessed patient deaths as compared to the non-COVID-19 team (50.2% vs. 24.7%). Witnessing patient death at the COVID-19 wards was associated with a four-fold increased likelihood of PTSS (odds ratio [OR] = 3.97; 95% confidence interval [CI], 1.58-9.99; p = .0007), compared with the non-COVID-19 wards (OR 0.91; 95% CI, 0.51-1.61; p = .43). Conclusions: Witnessing patient death appears to be a risk factor for PTSS unique to HCW directly engaged in treating patients with COVID-19. Our findings suggest that helping HCW cope with COVID-19 related deaths might reduce their risk of posttraumatic stress. [ABSTRACT FROM AUTHOR]

Background: While focusing on the management and care of COVID-19 patients, the mental health of these patients and their relatives is being overlooked. The aim of the current study was to measure anxiety and depression, and to assess their association with socio-demographic and pandemic-related stress factors in COVID-19 patients and their relatives during the initial stage of hospitalization. Methods: We assessed isolated hospitalized patients (N = 90) and their relatives (adults and children, N = 125) by phone, 25–72 h following patients' admission. The quantitative measures included the Anxiety and Depression modules of the Patient-Reported Outcomes Measurement Information System (PROMIS) and pandemic-related stress factors. Qualitative measures included questions exploring worries, sadness, and coping modes. Results: Both patients and relatives suffer from high levels of anxiety and related pandemic worries, with lower levels of depressive symptoms. Compared to adult relatives, child relatives reported significantly lower anxiety. The multivariable logistic regression analysis revealed an increased risk for anxiety among females and a decreased risk among ultra-orthodox participants. While increased anxiety among patients was associated with feelings of isolation, increased anxiety among relatives was associated with a feeling of not being protected by the hospital. Conclusions: Patients and relatives experience similar high anxiety levels which are more robust in women and lower in ultra-orthodox participants. Our findings indicate that anxiety symptoms of both patients and adult relatives should be addressed. [ABSTRACT FROM AUTHOR]

Background: Physicians play a crucial frontline role in the COVID‐19 pandemic, which may involve high levels of anxiety. We aimed to investigate the association between pandemic‐related stress factors (PRSF) and anxiety and to evaluate the potential effect of resilience on anxiety among physicians. Methods: A self‐report digital survey was completed by 1106 Israeli physicians (564 males and 542 females) during the COVID‐19 outbreak. Anxiety was measured by the 8‐item version of the Patient‐Reported Outcomes Measurement Information System. Resilience was evaluated by the 10‐item Connor–Davidson Resilience Scale. Stress was assessed using a PRSF inventory. Results: Physicians reported high levels of anxiety with a mean score of 59.20 ± 7.95. We found an inverse association between resilience and anxiety. Four salient PRSF (mental exhaustion, anxiety about being infected, anxiety infecting family members, and sleep difficulties) positively associated with anxiety scores. Conclusions: Our study identified specific PRSF including workload burden and fear of infection that are associated with increased anxiety and resilience that is associated with reduced anxiety among physicians. [ABSTRACT FROM AUTHOR]