<b><i>Background:</i></b> Off-label drug use is associated with an increased risk of adverse drug reactions. It is common in pediatrics and in rare diseases, which are two characteristics applying to vascular anomalies (VA). <b><i>Objectives:</i></b> The aim of this work was to quantify off-label drug use in VA and assess its safety. <b><i>Methods:</i></b> A review was conducted to extract a list of drugs used in VA management. A drug was considered to have significant safety concerns if a black box warning was present or if a serious adverse drug reaction (SADR) was reported in at least 1% of the patients (SADR is defined as a noxious and unintended response to a drug that occurs at any dose and results in hospitalization, prolongation of existing hospitalization, congenital malformation, persistent or significant disability or incapacity, life-threatening condition, or death). The labelling status and safety of each drug was assessed based on the product monograph, Micromedex, and the FDA data. <b><i>Results:</i></b> We found that 98.9% of the inventoried drugs were used off-label or unlicensed for VA management. Only the oral solution of propranolol hydrochloride (Hemangeol®) for the treatment of infantile hemangiomas is approved. Significant safety issues concerned 73% of the drugs and were more frequent among systemic than locally delivered drugs. <b><i>Conclusions:</i></b> Off-label drug use in VA is the rule and not the exception. Significant safety concerns are common. It is necessary to carefully weigh risk and benefits for every patient when using systemic and local treatments carrying safety concerns. Patients should be openly informed and involved in the decision-making process.
Denys-Drash syndrome (DDS), a condition caused by mutations in the tumor-suppressor gene WT-1, is associated with a triad of disorders: ambiguous genitalia, nephrotic syndrome leading to end-stage renal disease (ESRD), and Wilms’ tumor. Given the variable disease course, management is challenging. We aimed to describe the evolution of DDS and the range of management strategies by summarizing the clinical courses of cases collected from a questionnaire sent to the international pediatric nephrology community. 15 respondents provided information on 23 patients; 21 DDS cases were confirmed and analyzed. At DDS diagnosis, 6 patients had a Wilms’ tumor (group A) and 15 had no Wilms’ tumor (group B). Three group A patients had unilateral nephrectomy. Two of these still had renal function, with no second tumor, at 36 months and 16 years of age, and 1 progressed to ESRD. Three had bilateral nephrectomy before ESRD. Eight group B patients progressed to ESRD, all of whom later had all renal tissue removed. Two group B patients subsequently developed a unilateral Wilms’ tumor and had bilateral nephrectomy pre-ESRD. Three had bilateral nephrectomy prior to reaching ESRD without ever having a Wilms’ tumor. Two group B patients remained tumor-free with renal function at last follow-up. Two main management approaches were taken: pre-emptive nephrectomy prior to ESRD and conservative surveillance. Based on the known risks associated with ESRD in infants and young children, the variable course of DDS, and the relatively good prognosis associated with Wilms’ tumor, a guiding principle of preservation of renal function is most logical. Most would advocate bilateral prophylactic nephrectomy after ESRD is reached due to the high tumor risk, which is likely heightened after transplant.
Primary Subject area Neonatal-Perinatal Medicine Background During neonatal resuscitation, use of an electrocardiogram (ECG) provides a more reliable measurement of heart rate than auscultation or pulse oximetry. Having an ECG monitor may, however, provide a false sense of security in the unlikely scenario of a newborn with pulseless rhythms. This could delay critical resuscitative steps during neonatal resuscitation. Objectives The aim of this study is to evaluate whether the presence of ECG monitoring has an impact on the resuscitative steps of neonatal resuscitation providers. Design/Methods We conducted a prospective crossover randomized controlled trial, which took place at Sainte-Justine University Health Center in Montreal, Quebec, Canada. Residents, fellows, attending physicians, transport nurses, and respiratory therapists were recruited in teams of three. They participated in two simulation scenarios (pulseless electrical activity [PEA] with and without ECG monitoring). Teams were randomized to one of the scenarios and then crossed over. A debriefing session followed the two scenarios. All sessions were video-recorded. The primary outcome was the time to pulse check once the simulated mannequin was programmed to become pulseless. Secondary outcomes were the number of pulse checks, time to intubation, time to start of chest compressions, and time to administration of epinephrine. Results Preliminary results (n=5 groups, 10 scenarios) showed that the time to check the pulse once the mannequin was pulseless was longer when ECG electrodes were used (98.0 vs 55.6 sec, p = 0.07). There was a statistically significant decreased number of pulse checks with the ECG compared to without (2.4 vs 5.6, p = 0.004). Time to start of positive pressure ventilation (31.3 vs 27 sec), intubation (182.4 vs 179.2 sec), chest compressions (235.2 vs 227.6 sec), and epinephrine administration (340.8 vs 241.5 sec), were all increased in the presence ECG monitoring, but the difference between groups was not statistically significant. Conclusion ECG monitoring may alter the behaviour of individuals and delay recognition of a pulseless state, but preliminary data suggest that clinical endpoints are not affected.
Introduction: Genetically targeted drugs in vascular anomalies (VA) are used despite the absence of a validated severity score. The aim of this study was to evaluate the feasibility of grouping phenotypic VA clinical characteristics into a single severity score. Methods: A systematic literature review including children treated with sirolimus accompanied by a detailed description of phenotype and management was conducted. Demographic data and clinical features were extracted to define distinct categories of phenotypes.Results: Children with VA display two main phenotypes regardless of VA subtype, which may overlap. A systemic phenotype results from direct invasion and compression of vital structures generally leading to hospitalization and aggressive management in infancy. A functional phenotype is associated with chronic pain and disability manifesting mainly during early adolescence and managed in the outpatient setting.
Primary Subject area Clinical Pharmacology and Toxicology Background Vascular anomalies (VA) represent a heterogeneous group of disorders associated with an abnormal development and proliferation of blood and/or lymphatic vessels displaying variable clinical presentations and severity. Infantile hemangiomas, venous, and lymphatic malformations, for example, are commonly encountered in children. Other, less frequent diagnostics include Klippel-Trenaunay syndrome and PIK-3CA-related overgrowth spectrum (PROS). Severe phenotypes can alter organ function and/or lead to pain and chronic functional impairment, and are associated with significant morbidity and mortality. Management includes surgical, interventional radiology, and pharmacologic modalities. Drugs are administered by systemic (e.g., oral, intravenous) or local (topical, intralesional) routes, or by sclerotherapy (endovascular or percutaneous venous, lymphatic, or arterial injection). Off-label drug use is common in pediatrics and in rare diseases, two characteristics applying to vascular anomalies (VA). Off-label use is associated with an increased risk of adverse drug reactions. Objectives To quantify off-label drug use in VA and assess its safety. Design/Methods A guidelines search was conducted to extract a list of drugs used in VA management. The labelling status and safety of each drug was assessed based on the product monograph, Micromedex, and the FDA data. A drug was considered to have significant safety concerns if a black box warning (the FDA’s most stringent warning dedicated to serious or life-threatening risks) or if a serious adverse drug reaction was reported in at least 1% of the patients (leading to hospitalization, congenital malformation, persistent or significant disability or incapacity, life-threatening condition, or death). Results Among 87 drugs, 13 were unlicensed and 73 off-label. Figure 1 describes the reason for considering the 73 drugs off-label. Among 74 licensed drugs, only the oral solution of propranolol hydrochloride (Hemangeol®) for the treatment of infantile hemangiomas (IH) is approved. 98.9% of the drugs are used off-label or unlicensed. Except infantile hemangioma, all other VA are exclusively treated with off-label drugs. Significant safety issues concerned 73% of the drugs and were more frequent among systemic than locally delivered drugs (Figure 2). Conclusion This first study determining the rate of off-label drug use in vascular anomalies shows that off-label drug use in VA is the rule and not the exception. Significant safety concerns are common. It is needed to carefully weigh risk and benefits for every patient when using systemic and local treatments carrying safety concerns. Patients and families should be openly informed and involved in the decision-making process.
Objective: Assess the educational and clinical impact of a tiny baby intubation team (TBIT).Study Design: Retrospective study comparing endotracheal intubation (ETI) performed: pre-implementation of a TBIT (T1), six months post-implementation (T2), and four years post-implementation (T3).Results: Post-implementation of a TBIT, rst attempt success rate in tiny babies increased (44% in T1 vs. 59% in T2; p=0.046) and the proportion of ETIs performed by residents decreased (53% in T1 vs. 37% in T2; p=0.002). After an educational quality improvement intervention (prioritizing non-tiny baby ETIs to residents, systematic simulation training and ETI using videolaryngoscopy), residents' overall (63% in T2 vs. 79% in T3; p=0.03) and non-tiny baby ETI success rate improved (63% in T2 vs. 82% in T3; p=0.02). Conclusion:A TBIT improves success rate of ETIs in ELBW infants but decreases educational exposure of residents. Educational strategies helps maintain residents' procedural exposure without impacting on quality of care.
Objective: Assess the educational and clinical impact of a tiny baby intubation team (TBIT).Study Design: Retrospective study comparing endotracheal intubation (ETI) performed: pre-implementation of a TBIT (T1), six months post-implementation (T2), and four years post-implementation (T3).Results: Post-implementation of a TBIT, first attempt success rate in tiny babies increased (44% in T1 vs. 59% in T2; p=0.046) and the proportion of ETIs performed by residents decreased (53% in T1 vs. 37% in T2; p=0.002). After an educational quality improvement intervention (prioritizing non-tiny baby ETIs to residents, systematic simulation training and ETI using videolaryngoscopy), residents’ overall (63% in T2 vs. 79% in T3; p=0.03) and non-tiny baby ETI success rate improved (63% in T2 vs. 82% in T3; p=0.02).Conclusion: A TBIT improves success rate of ETIs in ELBW infants but decreases educational exposure of residents. Educational strategies helps maintain residents’ procedural exposure without impacting on quality of care.
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