JAK Inhibitor Therapy in a Child with Inherited USP18 Deficiency.

Deficiency of ubiquitin-specific peptidase 18 (USP18) is a severe type I interferonopathy. USP18 down-regulates type I interferon signaling by blocking the access of Janus-associated kinase 1 (JAK1) to the type I interferon receptor. The absence of USP18 results in unmitigated interferon-mediated inflammation and is lethal during the perinatal period. We describe a neonate who presented with hydrocephalus, necrotizing cellulitis, systemic inflammation, and respiratory failure. Exome sequencing identified a homozygous mutation at an essential splice site on USP18. The encoded protein was expressed but devoid of negative regulatory ability. Treatment with ruxolitinib was followed by a prompt and sustained recovery. (Funded by King Saud University and others.).

Feasibility and efficacy of sepsis management guidelines in a pediatric intensive care unit in Saudi Arabia: a quality improvement initiative.

OBJECTIVES: Evaluation of feasibility and effectiveness of Surviving Sepsis Campaign (SSC) Guidelines implementation at a Pediatric Intensive Care Unit (PICU) in Saudi Arabia to reduce severe sepsis associated mortality. DESIGN: Retrospective data analysis for a prospective quality improvement (QI) initiative. SETTINGS: PICU at King Saud University Medical City, Saudi Arabia. PARTICIPANTS: Children ≤14 years of age admitted to the PICU from July 2010 to March 2011 with suspected or proven sepsis. Comparisons were made to a previously admitted group of patients with sepsis from October 2009 to June 2010. INTERVENTIONS: Adaptation and implementation of the Surviving Sepsis Campaign-Clinical Practice Guidelines (SSC-CPGs) through AGREE instrument and ADAPTE process. MAIN OUTCOME MEASURES: We reported pre- and post-implementation outcome of interest for this QI initiative, annual sepsis-related mortality rate. Furthermore, we reported follow-up of annual mortality rate until December 2016. RESULTS: Sixty-five patients was included in the study (42 in post-guidelines implementation group and 23 in pre-guidelines implementation group). Mortality was insignificantly lower in the post-implementation group (26.2% vs. 47.8%; P = 0.079). However, when adjusted for severity, identified by number of failing organs in the multivariate regression analysis, the mortality difference was favorable for the post-implementation group (P = 0.006). The lower sepsis-related mortality rate was also sustained, with an average mortality rate of 15.11% for the subsequent years (2012-16). CONCLUSIONS: Adaptation and implementation of SSC Guidelines in our setting support its feasibility and potential benefits. However, a larger study is recommended to explore detailed compliance rates.

Respiratory support attitudes among pediatric intensive care staff for spinal muscular atrophy patients in Saudi Arabia.

OBJECTIVE: To explore therapeutic attitude of healthcare providers practicing in pediatric critical care in Saudi Arabia toward patients with Spinal Muscular Atroph (SMA) Type I, and to explore their awareness about the International Consensus statement for SMA care. METHODS: A cross-sectional survey was conducted in April 2015 during 6th Saudi Critical Care Conference, targeting physicians and respiratory therapists practicing in Pediatric Critical Care. RESULTS: Sixty participants accepted to participate in this survey. Out of those who answered the questionnaire, 44 were included in the analysis. Majority (66%) of participants were unaware of the International Consensus guidelines for SMA. Endotracheal intubation was reported as an acceptable intervention in SMA patients with acute respiratory failure by 43% of participants. Similarly, chronic home ventilation was agreed by 41% of participants. CONCLUSION: A nationwide adaptation of the International SMA Consensus guidelines for children with SMA I is recommended, aiming to decrease variability and standardize their management across various healthcare facilities in Saudi Arabia.

Presentations and outcomes of familial hemophagocytic lymphohistiocytosis in the pediatric intensive care units (PICUs).

Objectives: We aimed to describe Familial Hemophagocytic Lymphohistiocytosis (F-HLH) patients' clinical features, intensive care courses, and outcomes. Methods: Multi-center retrospective cohort study of pediatric patients diagnosed with F-HLH from 2015 to 2020 in five tertiary centers in Saudi Arabia. Patients were classified as F-HLH based on their genetic confirmation of known mutation or on their clinical criteria, which include a constellation of abnormalities, early disease onset, recurrent HLH in the absence of other causes, or a family history of HLH. Results: Fifty-eight patients (28 male, 30 female), with a mean age of 21.0 ± 33.9 months, were included. The most common principal diagnosis was hematological or immune dysfunction (39.7%), followed by cardiovascular dysfunction in 13 (22.4%) patients. Fever was the most common clinical presentation in 27.6%, followed by convulsions (13.8%) and bleeding (13.8%). There were 20 patients (34.5%) who had splenomegaly, and more than 70% of patients had hyperferritinemia >500 mg/dl, hypertriglyceridemia >150 mg/dl and hemophagocytosis in bone marrow biopsy. Compared to deceased patients 18 (31%), survivors had significantly lower PT (p = 041), bilirubin level of <34.2 mmol/L (p = 0.042), higher serum triglyceride level (p = 0.036), and lesser bleeding within the initial 6 h of admission (p = 0.004). Risk factors for mortality included requirements of higher levels of hemodynamic (61.1% vs. 17.5%, p = 0.001) and respiratory (88.9% vs. 37.5%, p < 0.001) support, and positive fungal cultures (p = 0.046). Conclusions: Familial HLH still represents a challenge in the pediatric critical care setting. Earlier diagnosis and prompt initiation of appropriate treatment could improve F-HLH survival.

Causes, timing, and modes of death in a tertiary pediatric intensive care unit: Five years' experience.

OBJECTIVES: To identify the causes, modes, and timing of death in a tertiary pediatric intensive care unit (PICU). METHODS: This is a retrospective data analysis of patients older than 48 hours and younger than 15 years who died in the PICU over a 5-year period from January 2012 until December 2016 at a tertiary hospital in Riyadh, Saudi Arabia. RESULTS: There were 101 deaths out of 2295 admissions, representing average crude mortality rate of 4.4%. Sepsis was the most common cause of death in 31 patients (30.7%), followed by lower respiratory tract infections in 19 (18.8%), and cardiac diseases in 12 (11.9%). Failed cardiopulmonary resuscitation was the most common mode of death in 51 patients (50.5%), followed by withholding life-sustaining treatment in 43 (42.6%), and brain death in 7 (6.9%). Although more deaths occurred during after hours (n=70; 69.3%), there was no significant correlation between mode of death and working hours vs. after hours (p>0.05). Among the cohort, 63 patients (62.4%) had an infection-attributed mortality, of which 43 (68.3%) were bacterial, 14 (22.2%) were viral, and 10 (15.9%) were fungal. CONCLUSION: Infections remain a significant cause of death in the PICU. Further improvement of prevention programs and early therapy of severe infections could lower pediatric mortality. This report highlights the need for enhancing palliative care programs. The low rate of brain death diagnoses warrants further investigation.

Effect of lumbar puncture educational video on parental knowledge and self-reported intended practice.

BACKGROUND: Lumbar puncture (LP) remains an essential diagnostic procedure for neurological and infectious diseases. However, it remains a source of anxiety to patients and families. This research aimed to assess the impact of a newly developed educational simplified video about LP, in the parents' native language, that is tailored to their social background and beliefs and to assess whether it can facilitate their consent for the procedure. METHODS: This prospective, interventional study was conducted at the outpatient pediatric clinics at a teaching hospital. The conventional arm used verbal explanation about LP. The second method utilized a standardized video, having the same information as the conventional arm, with streaming of graphic depictions. Parents' knowledge and perceived LP risks were measured before and after the intervention. RESULTS: Two hundred and one parents were enrolled, with no significant differences in the socio-demographic and baseline characteristics. Both verbal and video-based counseling were found to provide a statistically significant increase in knowledge scores, and a Wilcoxon signed-rank test showed that knowledge gains for both groups were statistically significant (Verbal Explanation: W = 2693, n = 83, P < .001 and Video: W = 5538, n = 117, P < .001). However, the conventional verbal counseling resulted in more consistent gain of knowledge (SD = 14.5) as compared to the video group (SD = 18.94). The video group reported higher perceived risk (Mean 8.2, SD 3.59) than the verbal explanation group (Mean 7.12, SD 2.51). The less educated parents perceived LP procedure to be of significantly higher risk after watching the video (P < .001). It was found that 73.6% of persons with perceived intention to refuse LP changed their opinion after either of the counseling interventions, with significant opinion difference pre- and post-counseling intervention (P value .002). CONCLUSIONS: Video education in parents' native language about LP is as effective as conventional verbal education for informed consent, with the additional advantage of reproducibility and more illustrations to give parents better insight. However, this video should be followed by direct interaction with parents to ensure their full understanding and address any further concerns.

Middle East Respiratory Syndrome-Corona Virus (MERS-CoV) associated stress among medical students at a university teaching hospital in Saudi Arabia.

BACKGROUND AND OBJECTIVES: Middle East Respiratory Syndrome Corona Virus (MERS-CoV) outbreak in 2014 was associated with high public anxiety in the affected countries. Media speculations may have increased this psychological distress. The healthcare community was the most distressed because they were at the highest risk of infection. This study is the first to explore MERS-CoV epidemic impact on medical students' perception and determinants of their psychological distress during this outbreak. METHODS: We randomly selected and surveyed 200 students from the College of Medicine at King Saud University, Riyadh, Saudi Arabia. A predesigned questionnaire was answered by participants, and the collected data were statistically analyzed. RESULTS: One hundred and seventy-four (87%) responded. Female students had a significantly higher mean stress level than males (P < 0.001). Participants had a mean GAD score of 2.7 ± 3.1 and a median of 2. Perceived sufficiency of information score was the highest mean and median (17.4 ± 4.2 and 18 respectively). College and hospital announcements were the most common source of information (25.4%). One hundred and thirty-four (77%) reported minimal anxiety, thirty-two (18.4%) reported mild anxiety, 8 (4.6%) reported moderate anxiety, and none of them reported severe anxiety (score >14). The stress level (as reported on 1-10 scale) shows significant correlation with Generalized Anxiety Disorder (GAD-7) score. We found in this study that significant predictors in our model, in terms of more significant to the least, were: an increased self-report on hygienic habits, self-reported social avoidance, the generalized anxiety score and finally being female gander while other variables including numbers of resources access, agreeing with public fear and knowledge score on MERS-CoV all were found to be non-significant. However, the number of accessed resources, as per students, has borderline significant correlation with higher self-reported anxiety from MERS-CoV. CONCLUSIONS: Medical students' psychological needs during the MERS-CoV outbreak should be addressed appropriately. Our results highlight the need to establish psychological support programs for medical students during an infectious disease outbreak.

Long-stay patients in pediatric intensive care units. Five-years, 2-points, cross-sectional study.

OBJECTIVES: To explore the changing patterns of long-stay patients (LSP) to improve the utilization of pediatric intensive care units (PICUs) resources. METHODS: This is a 2-points cross-sectional study (5 years apart; 2014-2019) conducted among PICUs and SCICUs in Riyadh, Saudi Arabia. Children who have stayed in PICU for more than 21 days were included. RESULTS: Out of the 11 units approached, 10 (90%) agreed to participate. The prevalence of LSP in all these hospitals decreased from 32% (48/150) in 2014 to 23.4% (35/149) in 2019. The length of stay ranged from 22 days to 13.5 years. The majority of LSP had a neuromuscular or cardiac disease and were admitted with respiratory compromise. Ventilator-associated pneumonia was the most prevalent complication (37.5%). The most commonly used resources were mechanical ventilation (93.8%), antibiotics (60.4%), and blood-products transfusions (35.4%). The most common reason for the extended stay was medical reasons (51.1%), followed by a lack of family resources (26.5%) or lack of referral to long-term care facilities (22.4%). CONCLUSION: A long-stay is associated with significant critical care bed occupancy, complications, and utilization of resources that could be otherwise utilized as surge capacity for critical care services. Decreasing occupancy in this multicenter study deserves further engagement of the healthcare leaders and families to maximize the utilization of resources.

Middle East Respiratory Syndrome Coronavirus epidemic impact on healthcare workers' risk perceptions, work and personal lives.

INTRODUCTION: Middle East respiratory syndrome coronavirus (MERS-CoV) continues to cause frequent outbreaks in hospitals in Saudi Arabia. Since healthcare workers (HCWs) have a higher risk of acquiring and spreading MERS-CoV, we aimed to evaluate the perceived risk and anxiety level of HCWs in Saudi Arabia regarding MERS. METHODOLOGY: An anonymous, self-administered questionnaire was sent online to HCWs at King Khalid University Hospital in Saudi Arabia. The total knowledge and anxiety scores were calculated. Logistic regression analyses were used to identify predictors of high anxiety scores. RESULTS: Of 591 (70%) HCWs that responded, 284 (55%), 164 (32%), and 68 (13.2%) were physicians, nurses, and technicians, respectively. Physicians obtained a lower median knowledge score (6/9) compared to other professions (7/9). The mean anxiety score was similar for physicians and other HCWs (3/5); however, non-physicians expressed higher levels of anxiety toward the risk of transmitting MERS-CoV to their families, with an anxiety score of 4/5. The ability of the virus to cause severe disease or death was the most frequently reported reason for worry by physicians (89.7%) and non-physicians (87.2%). Overall, 80% of physicians and 90% of non-physicians reported improvement in adherence to hand hygiene and standard precautions while in hospital (p = 0.002). Concern over transmitting MERS-CoV to family members was the most predictive factor for anxiety among non-physician HCWs. CONCLUSION: A significant proportion of HCWs expressed anxiety about the risk of acquiring MERS-CoV infection. Healthcare institutions need to develop an integrated psychological response for HCWs to the occupational and psychological challenge of MERS-CoV outbreaks.

Factors that influence the self-reported confidence of pediatric residents as team leaders during cardiopulmonary resuscitation: A national survey.

OBJECTIVE: The leadership skills of pediatric residents during cardiopulmonary resuscitation (CPR) may have major impacts on their performance. These skills should be addressed during the pediatric residency training program. Therefore, we aimed to identify the perceptions of residents regarding their level of confidence in providing or leading a real pediatric CPR code, and to identify different factors that might influence their self-confidence when assuming the role of a team leader during a real CPR. DESIGN & SETTING: Cross-sectional paper-based and online electronic surveys were conducted in February 2017, which included all Saudi pediatric residency program trainees. INTERVENTIONS: A survey questionnaire was distributed to Saudi pediatric residency trainees throughout the Kingdom. The main aim was to assess their perceived level of confidence when running a real pediatric CPR code either as a team leader or as a team member. RESULTS: The survey was distributed and sent by email to 1052 residents, where it was received by 640 and 231 responded (response rate = 36%). Almost one-fifth of the respondents (19.5%) did not have a valid pediatric advanced life support (PALS) certificate. The most frequently reported obstacles to life support training were lack of time (45.8%) and its financial cost (22.7%). The mean self-reported confidence as a CPR team member was reported significantly more frequently than being a CPR team leader (mean standard deviation, SD) = 7.8 (2.1) and 6.7 (2.4) respectively, P < .001). The self-reported confidence as a CPR team leader was reported significantly more frequently in males compared with female respondents (mean ±â€¯SD = 6.7 ±â€¯2.4 and 5.9 ±â€¯2.4, respectively; P < .013). There was a significant positive effect of recent attendance at a real CPR event on the perceived self-rated confidence of residents as a CPR team leader (P < .001). Residents who reported that they had often assumed a real CPR leadership role had significantly greater perceived self-confidence compared with those who assumed a member role (P < .05). Furthermore, residents without a valid PALS certificate had significantly less confidence in leading CPR teams than their peers who were recently certified (P < .05). CONCLUSIONS: The self-reported confidence as team leader during CPR was higher among residents who were certified in life support courses, exposed to CPR during their training, and those who assumed the role of a team leader during CPR. Our findings suggests the need to incorporate life support training courses and simulation-based mock code programs with an emphasis on the leadership in the curriculum of the pediatric residency training program.

Neurologic Complications in Children With Scorpionism: A Retrospective Study in Upper Egypt.

Scorpion envenomation is a life-threatening health problem in tropical and subtropical regions, particularly among children. The aim of this study was to describe the epidemiologic characteristics, clinical profile, and prognosis of neurologic complications among children with scorpionism in Upper Egypt. In this retrospective study, the neurologic complications of scorpionism in 2 university hospitals were analyzed from the points of epidemiologic and clinical picture and outcomes. The neurologic manifestations were found at a high percentage (85%). Irritability was the main manifestation (83.4%), followed by sweating (81.5%), hyperthermia (33.6%), and priapism (48.2% of males). Moreover, convulsion and coma were found in 14.7% and 11% of children, respectively. Neurologic manifestations were common in children with scorpionism and they correlated with poor outcome. Identification of epidemiologic and clinical features of central nervous system complications of scorpionism in children provide important data, helping in development of management policies aiming at preventive control of scorpionism and decrease its mortality.

A comparative study of propranolol versus silver nitrate cautery in the treatment of recurrent primary epistaxis in children.

BACKGROUND: Epistaxis is a common medical problem in pediatric population. Although in most cases it is mild and self-limiting, a proportion of childhood epistaxis is massive, recurrent, or resistant to conventional management. OBJECTIVE: To compare effectiveness of propranolol as a treatment option for childhood epistaxis versus conventional silver nitrate cautery. STUDY DESIGN AND METHODOLOGY: This is a prospective interventional comparative study that was carried out during a period of 1 year (January 1, 2013 to December 31, 2013) at Qena University Hospital and Assiut University Children's Hospital. One hundred children aged 6-12 years who presented with epistaxis to Qena University Hospital and Assiut University Children's Hospital during the study period and fulfilling the inclusion criteria were included in the study. They were randomly assigned into one of two interventional groups, where 50 children were treated with oral propranolol (propranolol treatment group) and another 50 children were treated with conventional silver nitrate cautery (cauterization treatment group) for their epistaxis. Propranolol was given at a dose of 1.5-2 mg/kg/day (divided into three doses). Patients were followed for 6 months after their discharge for recurrence of epistaxis. RESULTS: Both groups of patients showed minimal recurrent epistaxis with rates of 14% for propranolol treated group and 12% for cauterization group, with no statistically significant difference between both groups. Local pain was found to be more in patients treated with silver nitrate cauterization. CONCLUSION: Treatment of primary epistaxis with propranolol or silver nitrate cautery showed equal rates of recurrence, and local nasal pain was slightly more among silver nitrate cauterization treated group. Propranolol could be a favorable treatment option for patients with primary epistaxis. Further studies that include multiple centers and larger number of patients are recommended for more clarification of the effectiveness of such treatment option.

Pediatric pain management: More opportunities for better comfort.

Pediatric pain assessment is vital for optimal pediatric practice. After a year of implementation of pediatric pain assessment tools at a tertiary university hospital (King Saud University Medical City, Riyadh, Saudi Arabia), the physicians in the Department of Pediatrics were invited to participate in an interactive lecture about pediatric pain management to assess their awareness about using these tools. Their responses demonstrated that almost half of them were not using any pain scale in their daily practice. These findings highlight the need for a new strategy of implementation. The improvement of pain assessment and management necessitates extensive educational campaign for all health care providers and early audit in order to improve the physicians' awareness and compliance with these changes.

Therapeutic benefits and side effects of Azathioprine and Aspirin in treatment of childhood primary arterial stroke.

BACKGROUND: Childhood primary angiitis of central nervous system (cPACNS) is rare idiopathic vasculitis most frequently in adults. Children with this disorder can present with a range of neurological symptoms and signs including decreased consciousness, seizures, hemiparesis, cranial nerve deficits, and cognitive deficits. Delayed diagnosis and treatment may compromise the outcome. Therapeutic modalities including Anti-Platelet agents, Corticosteroids, Azathioprine, Cyclophosphamide and other Immunomodulatory agents have been used with variable success. PURPOSE: We wanted to study a cohort of children with childhood primary angiitis of Central Nervous System (cPACNS); and evaluate efficacy and safety of their management. METHODS: Current study is an observational cohort study that included 68 patients admitted with acute ischemic strokes (AIS) within 14 days of symptoms onset at Department of Neurosciences at Children's Hospital, Lahore, Pakistan from January 2009 to December 2010 with an age ≤16 years. They were subjected to physical examination laboratory and neuroimaging evaluation. They received pulses of intravenous steroids and/or Immunoglobulins for 4 weeks with maintenance dose of Azathioprine and low dose Aspirin for 24 months and kept on follow for 2 years. RESULTS: Sixty eight patients were included; 42 (62.76%) boys and 26 (38.23%) girls whose mean age was 8.5 ± 3.5 years. Presenting symptoms and signs included fever (20%), headache (64%), disturbed consciousness (30%), seizures 55%, hemiparesis (60%), and motor deficit (70%). Neuroimaging studies revealed ischemic strokes in 50 patients (73.5%), hemorrhagic strokes in 10 (14.7%) and ischemic-hemorrhagic lesions in 8 (11.8%). Males with, deep coma and raised intracranial pressure were poor prognostic signs. Mortality was encountered in 12 patients (17.64%) with normal outcome in 11 (16.17%), minor disabilities in 14 (20.59%), moderate disabilities in 11 (16.17%) and severe disabilities in 20 (29.41%). CONCLUSIONS: Characteristic features of cPACNS on presentation may predict later progression and outcome, identify high-risk patients which may guide selection of patients for immunosuppressive therapy. Further studies are required to substantiate our findings regarding immunosuppressive therapy for such patients.