How to follow the guidelines, when the appropriate fluid is missing?

Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care. Recently paediatric societies have produced evidence-based practice guidelines that recommend the use of balanced isotonic fluid when prescribing IV-MFT in both acute and critical paediatric care. Unfortunately, the applicability of these guidelines could be called into question when a ready-to-use glucose-containing balanced isotonic fluid is not available. The main objective of this study was to describe the availability of glucose-containing balanced isotonic fluids in European and Middle Eastern paediatric acute and critical care settings. This work is an ancillary study of the survey dedicated to IV-MFT practices in the paediatric acute and critical care settings in Europe and Middle East, a cross-sectional electronic 27-item survey, emailed in April–May 2021 to paediatric critical care physicians across 34 European and Middle East countries. The survey was developed by an expert multi-professional panel within the European Society of Peadiatric and Neonatal Intensive Care (ESPNIC). Balanced isotonic fluid with glucose 5% was available for only 32/153 (21%) responders. Balanced isotonic fluid with glucose 5% was consistently available in the UK (90%) but not available in France, Greece, The Netherlands and Turkey.    Conclusion: Ready-to-use isotonic balanced IV solutions containing glucose in sufficient amount exist but are inconsistently available throughout Europe. National and European Medication Safety Incentives should guarantee the availability of the most appropriate and safest IV-MFT solution for all children. What is Known:• Intravenous maintenance fluid therapy (IV-MFT) is probably the most prescribed drug in paediatric hospital care.• Balanced isotonic fluid is recommended when prescribing IV-MFT in both acute and critical paediatric care. What is New:• Balanced isotonic fluid with glucose 5% is available for less than 25% of the prescribers in Europe and the Middle East. Availability of balanced isotonic fluid with glucose 5% varies from one country to another but can also be inconsistent within the same country.• Clinicians who have access to a ready-to-use balanced isotonic fluid with glucose 5% are more likely to consider its use than clinicians who do not have access to such an IV solution

ESPNIC clinical practice guidelines: intravenous maintenance fluid therapy in acute and critically ill children- a systematic review and meta-analysis

PURPOSE Intravenous maintenance fluid therapy (IV-MFT) prescribing in acute and critically ill children is very variable among pediatric health care professionals. In order to provide up to date IV-MFT guidelines, the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) undertook a systematic review to answer the following five main questions about IV-MFT: (i) the indications for use (ii) the role of isotonic fluid (iii) the role of balanced solutions (iv) IV fluid composition (calcium, magnesium, potassium, glucose and micronutrients) and v) and the optimal amount of fluid. METHODS A multidisciplinary expert group within ESPNIC conducted this systematic review using the Scottish Intercollegiate Guidelines Network (SIGN) grading method. Five databases were searched for studies that answered these questions, in acute and critically children (from 37 weeks gestational age to 18 years), published until November 2020. The quality of evidence and risk of bias were assessed, and meta-analyses were undertaken when appropriate. A series of recommendations was derived and voted on by the expert group to achieve consensus through two voting rounds. RESULTS 56 papers met the inclusion criteria, and 16 recommendations were produced. Outcome reporting was inconsistent among studies. Recommendations generated were based on a heterogeneous level of evidence, but consensus within the expert group was high. "Strong consensus" was reached for 11/16 (69%) and "consensus" for 5/16 (31%) of the recommendations. CONCLUSIONS Key recommendations are to use isotonic balanced solutions providing glucose to restrict IV-MFT infusion volumes in most hospitalized children and to regularly monitor plasma electrolyte levels, serum glucose and fluid balance

Impaired IL-23-dependent induction of IFN-gamma underlies mycobacterial disease in patients with inherited TYK2 deficiency

Human cells homozygous for rare loss-of-expression (LOE) TYK2 alleles have impaired, but not abolished, cellular responses to IFN-alpha/beta (underlying viral diseases in the patients) and to IL-12 and IL-23 (underlying mycobacterial diseases). Cells homozygous for the common P1104A TYK2 allele have selectively impaired responses to IL-23 (underlying isolated mycobacterial disease). We report three new forms of TYK2 deficiency in six patients from five families homozygous for rare TYK2 alleles (R864C, G996R, G634E, or G1010D) or compound heterozygous for P1104A and a rare allele (A928V). All these missense alleles encode detectable proteins. The R864C and G1010D alleles are hypomorphic and loss-of-function (LOF), respectively, across signaling pathways. By contrast, hypomorphic G996R, G634E, and A928V mutations selectively impair responses to IL-23, like P1104A. Impairment of the IL-23-dependent induction of IFN-gamma is the only mechanism of mycobacterial disease common to patients with complete TYK2 deficiency with or without TYK2 expression, partial TYK2 deficiency across signaling pathways, or rare or common partial TYK2 deficiency specific for IL-23 signaling.ANRS Nord-Sud ; CIBSS ; CODI ; Comité para el Desarrollo de la Investigación ; Fulbright Future Scholarshi

Inborn errors of type I IFN immunity in patients with life-threatening COVID-19.

Clinical outcome upon infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ranges from silent infection to lethal coronavirus disease 2019 (COVID-19). We have found an enrichment in rare variants predicted to be loss-of-function (LOF) at the 13 human loci known to govern Toll-like receptor 3 (TLR3)- and interferon regulatory factor 7 (IRF7)-dependent type I interferon (IFN) immunity to influenza virus in 659 patients with life-threatening COVID-19 pneumonia relative to 534 subjects with asymptomatic or benign infection. By testing these and other rare variants at these 13 loci, we experimentally defined LOF variants underlying autosomal-recessive or autosomal-dominant deficiencies in 23 patients (3.5%) 17 to 77 years of age. We show that human fibroblasts with mutations affecting this circuit are vulnerable to SARS-CoV-2. Inborn errors of TLR3- and IRF7-dependent type I IFN immunity can underlie life-threatening COVID-19 pneumonia in patients with no prior severe infection

Predictors and Direct Cost Estimation of Long Stays in Pediatric Intensive Care Units in Saudi Arabia: A Mixed Methods Study

Mohamad-Hani Temsah,1,2,* Noura Abouammoh,2,3,* Ayman Al-Eyadhy,1,2 Yazed AlRuthia,4,5 Marwah Hassounah,3 Fahad Alsohime,1,2 Ali Alhaboob,1,2 Mohammed Almazyad,1,2 Majed Alabdulhafid,1,2 Fadi Aljamaan,2,6 Khalid Alhasan,1,2 Amr Jamal2,3,7 1Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 2King Saud University Medical City, King Saud University, Riyadh, Saudi Arabia; 3Family and Community Medicine Department, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 4Department of Clinical Pharmacy, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 5Pharmacoeconomics Research Unit, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; 6Department of Critical Care, College of Medicine, King Saud University, Riyadh, Saudi Arabia; 7Evidence-Based Health Care & Knowledge Translation Research Chair, King Saud University, Riyadh, Saudi Arabia*These authors contributed equally to this workCorrespondence: Amr Jamal Email [email protected]: Several factors influence patients’ length of stay (LOS) in pediatric intensive care units (PICUs). This study explored the factors and cost associated with long LOS among pediatric patient population across various PICUs and pediatric surgical cardiac intensive care units (SCICUs).Methods: This is a multi-center concurrent mixed-methods study that was conducted in different PICUs and SCICUs in Riyadh, Saudi Arabia. The units’ leaders were qualitatively interviewed to explore the potential factors contributing to long LOSs in PICUs and SCICUs, and deductive content analysis was used. Microcosting was utilized to estimate the inpatient costs for a sample of long-stay patients (LSPs) and the potential cost savings if those patients were transferred to step-down care units (SDUs) for those who stayed ≥ 60 days.Results: Ten (90%) leaders of PICUs and SCICUs who were invited had participated. Changing the admission criteria, patient transfer to SDUs, family engagement in the decision-making process, and adopting a national do-not-resuscitate (DNR) policy were factors contributing to short LOSs. On the other hand, administrative constraints, staff avoidance of code status decisions, lack of palliative care resources, and complex patient characteristics were factors associated with long LOSs. The mean inpatient cost per patient was SAR 3.63 million (USD 0.97 million), and the total cost for the 48 patients was SAR 172.95 million (USD 46.12 million).Conclusion: If the recommendation to transfer LSPs after a 60-day PICU stay to SDUs is taken, the estimated cost savings among this sample of patients alone can be as high as SAR 109.47 million (USD 29.19 million). Therefore, future studies should examine the factors contributing to long LOSs in PICUs and SCICUs as well as the effectiveness of different policies aimed at improving the resource allocation and management using more robust study designs and diverse patient population.Keywords: pediatric critical care, long-stay patients, cost of long-stay patients, content analysi

The clinical utility of rapid exome sequencing in a consanguineous population

Abstract Background The clinical utility of exome sequencing is now well documented. Rapid exome sequencing (RES) is more resource-intensive than regular exome sequencing and is typically employed in specialized clinical settings wherein urgent molecular diagnosis is thought to influence acute management. Studies on the clinical utility of RES have been largely limited to outbred populations. Methods Here, we describe our experience with rapid exome sequencing (RES) in a highly consanguineous population. Clinical settings included intensive care units, prenatal cases approaching the legal cutoff for termination, and urgent transplant decisions. Results A positive molecular finding (a pathogenic or likely pathogenic variant that explains the phenotype) was observed in 80 of 189 cases (42%), while 15 (8%) and 94 (50%) received ambiguous (variant of uncertain significance (VUS)) and negative results, respectively. The consanguineous nature of the study population gave us an opportunity to observe highly unusual and severe phenotypic expressions of previously reported genes. Clinical utility was observed in nearly all (79/80) cases with positive molecular findings and included management decisions, prognostication, and reproductive counseling. Reproductive counseling is a particularly important utility in this population where the overwhelming majority (86%) of identified variants are autosomal recessive, which are more actionable in this regard than the de novo variants typically reported by RES elsewhere. Indeed, our cost-effectiveness analysis shows compelling cost savings in the study population. Conclusions This work expands the diversity of environments in which RES has a demonstrable clinical utility

ESPNIC clinical practice guidelines: intravenous maintenance fluid therapy in acute and critically ill children- a systematic review and meta-analysis

PURPOSE: Intravenous maintenance fluid therapy (IV-MFT) prescribing in acute and critically ill children is very variable among pediatric health care professionals. In order to provide up to date IV-MFT guidelines, the European Society of Pediatric and Neonatal Intensive Care (ESPNIC) undertook a systematic review to answer the following five main questions about IV-MFT: (i) the indications for use (ii) the role of isotonic fluid (iii) the role of balanced solutions (iv) IV fluid composition (calcium, magnesium, potassium, glucose and micronutrients) and v) and the optimal amount of fluid. METHODS: A multidisciplinary expert group within ESPNIC conducted this systematic review using the Scottish Intercollegiate Guidelines Network (SIGN) grading method. Five databases were searched for studies that answered these questions, in acute and critically children (from 37 weeks gestational age to 18 years), published until November 2020. The quality of evidence and risk of bias were assessed, and meta-analyses were undertaken when appropriate. A series of recommendations was derived and voted on by the expert group to achieve consensus through two voting rounds. RESULTS: 56 papers met the inclusion criteria, and 16 recommendations were produced. Outcome reporting was inconsistent among studies. Recommendations generated were based on a heterogeneous level of evidence, but consensus within the expert group was high. "Strong consensus" was reached for 11/16 (69%) and "consensus" for 5/16 (31%) of the recommendations. CONCLUSIONS: Key recommendations are to use isotonic balanced solutions providing glucose to restrict IV-MFT infusion volumes in most hospitalized children and to regularly monitor plasma electrolyte levels, serum glucose and fluid balance