Pediatric drug-related problems: a multicenter study in four French-speaking countries.

BACKGROUND: Pediatric intensive care patients represent a population at high risk for drug-related problems. There are few studies that compare the activity of clinical pharmacists between countries. OBJECTIVE: To describe the drug-related problems identified and interventions by four pharmacists in a pediatric cardiac and intensive care unit. SETTING: Four pediatric centers in France, Quebec, Switzerland and Belgium. METHOD: This was a six-month multicenter, descriptive and prospective study conducted from August 1, 2009 to January 31, 2010. Drug-related problems and clinical interventions were compiled from four pediatric centers in France, Quebec, Switzerland and Belgium. Data on patients, drugs, intervention, documentation, approval and estimated impact were compiled. MAIN OUTCOME MEASURE: Number and type of drug-related problems encountered in a large pediatric inpatient population. RESULTS: A total of 996 interventions were recorded: 238 (24 %) in France, 278 (28 %) in Quebec, 351 (35 %) in Switzerland and 129 (13 %) in Belgium. These interventions targeted 270 patients (median 21 months old, 53 % male): 88 (33 %) in France, 56 (21 %) in Quebec, 57 (21 %) in Switzerland and 69 (26 %) in Belgium. The main drug-related problems were inappropriate administration technique (29 %), untreated indication (25 %) and supra-therapeutic dose (11 %). The pharmacists' interventions were mostly optimizing the mode of administration (22 %), dose adjustment (20 %) and therapeutic monitoring (16 %). The two major drug classes that led to interventions were anti-infectives for systemic use (23 %) and digestive system and metabolism drugs (22 %). Interventions mainly involved residents and all clinical staff (21 %). Among the 878 (88 %) proposed interventions requiring physician approval, 860 (98 %) were accepted. CONCLUSION: This descriptive study illustrates drug-related problems and the ability of clinical pharmacists to identify and resolve them in pediatric intensive care units in four French-speaking countries.

Pediatric and adult eosinophilic esophagitis: similarities and differences.

Early in the 1990s, several case series described adults suffering from dysphagia and children with refractory reflux symptoms, both accompanied by an eosinophil-predominant infiltration, thereby conclusively distinguishing it from gastroesophageal reflux disease. Eosinophilic esophagitis (EoE) was recognized as its own entity in the adult and in the pediatric literature. In the last decade, evidence has accumulated that EoE represents a T-helper (Th)2-type inflammatory disease. Remodeling of the esophagus is a hallmark of EoE, leading to esophageal dysfunction and bolus impaction. Familial occurrence and disease association with single-nucleotide polymorphisms underscore the influence of genetics in this disease. Eosinophilic esophagitis may affect individuals at any age, although the clinical presentation is highly age dependent. There is a significant allergic bias in the EoE population, with the majority of patients having concurrent allergic rhinitis, asthma, eczema, and/or a history of atopy. One noteworthy difference is that in children, EoE seems to be primarily a food antigen-driven disease, whereas in adults, mainly aeroallergen sensitization has been observed. Treatment modalities for EoE include the 3Ds: drugs, diet, and dilation. The crucial question of whether adult and pediatric EoE are different phenotypes of one single entity or whether we are confronted with two different diseases is still open. Here, we review similarities and differences between EoE in adults and children.

An epidemiological evaluation of pediatric long bone fractures - a retrospective cohort study of 2716 patients from two Swiss tertiary pediatric hospitals.

BACKGROUND: Children and adolescents are at high risk of sustaining fractures during growth. Therefore, epidemiological assessment is crucial for fracture prevention. The AO Comprehensive Injury Automatic Classifier (AO COIAC) was used to evaluate epidemiological data of pediatric long bone fractures in a large cohort. METHODS: Data from children and adolescents with long bone fractures sustained between 2009 and 2011, treated at either of two tertiary pediatric surgery hospitals in Switzerland, were retrospectively collected. Fractures were classified according to the AO Pediatric Comprehensive Classification of Long Bone Fractures (PCCF). RESULTS: For a total of 2716 patients (60% boys), 2807 accidents with 2840 long bone fractures (59% radius/ulna; 21% humerus; 15% tibia/fibula; 5% femur) were documented. Children's mean age (SD) was 8.2 (4.0) years (6% infants; 26% preschool children; 40% school children; 28% adolescents). Adolescent boys sustained more fractures than girls (p < 0.001). The leading cause of fractures was falls (27%), followed by accidents occurring during leisure activities (25%), at home (14%), on playgrounds (11%), and traffic (11%) and school accidents (8%). There was boy predominance for all accident types except for playground and at home accidents. The distribution of accident types differed according to age classes (p < 0.001). Twenty-six percent of patients were classed as overweight or obese - higher than data published by the WHO for the corresponding ages - with a higher proportion of overweight and obese boys than in the Swiss population (p < 0.0001). CONCLUSION: Overall, differences in the fracture distribution were sex and age related. Overweight and obese patients seemed to be at increased risk of sustaining fractures. Our data give valuable input into future development of prevention strategies. The AO PCCF proved to be useful in epidemiological reporting and analysis of pediatric long bone fractures.

Pediatric advance care planning: a systematic review.

BACKGROUND AND OBJECTIVES: Advance care planning (ACP) is increasingly regarded as the gold standard in the care of patients with life-limiting illnesses. Research has focused on adults, but ACP is also being practiced in pediatrics. We conducted a systematic review on empirical literature on pediatric ACP (pACP) to assess current practices, effects, and perspectives of pACP. METHODS: We searched PubMed, BELIT, and PSYCinfo for empirical literature on pACP, published January 1991 through January 2012. Titles, abstracts, and full texts were screened by 3 independent reviewers for studies that met the predefined criteria. The evidence level of the studies was assessed. Relevant study outcomes were retrieved according to predefined questions. RESULTS: We included 5 qualitative and 8 quantitative studies. Only 3 pACP programs were identified, all from the United States. Two of them were informed by adult programs. Major pACP features are discussions between families and care providers, as well as advance directives. A chaplain and other providers may be involved if required. Programs vary in how well they are evaluated; only 1 was studied by using a randomized controlled trial. Preliminary data suggest that pACP can successfully be implemented and is perceived as helpful. It may be emotionally relieving and facilitate communication and decision-making. Major challenges are negative reactions from emergency services, schools, and the community. CONCLUSIONS: There are few systematic pACP programs worldwide and none in Europe. Future research should investigate the needs of all stakeholders. In particular, the perspective of professionals has so far been neglected.

Human disease and drug pharmacology, complex as real life

In the past decades drug discovery practice has escaped from the complexity of the formerly used phenotypic screening in animals to focus on assessing drug effects on isolated protein targets in the search for drugs that exclusively and potently hit one selected target, thought to be critical for a given disease, while not affecting at all any other target to avoid the occurrence of side-effects. However, reality does not conform to these expectations, and, conversely, this approach has been concurrent with increased attrition figures in late-stage clinical trials, precisely due to lack of efficacy and safety. In this context, a network biology perspective of human disease and treatment has burst into the drug discovery scenario to bring it back to the consideration of the complexity of living organisms and particularly of the (patho)physiological environment where protein targets are (mal)functioning and where drugs have to exert their restoring action. Under this perspective, it has been found that usually there is not one but several disease-causing genes and, therefore, not one but several relevant protein targets to be hit, which do not work on isolation but in a highly interconnected manner, and that most known drugs are inherently promiscuous. In this light, the rationale behind the currently prevailing single-target-based drug discovery approach might even seem a Utopia, while, conversely, the notion that the complexity of human disease must be tackled with complex polypharmacological therapeutic interventions constitutes a difficult-torefuse argument that is spurring the development of multitarget therapies.

2 years' review of pediatric emergencies admitted in the resuscitation room of a Swiss university hospital

Introduction: Paediatric resuscitation is an intense, stressful andchallenging process performed in a specific surrounding. In theresuscitation room (RR), a dedicated pediatric team is not alwaysavailable and its composition varies according to local resources. Aregular review of the children admitted in the resuscitation room andthe assessment of various outcome measures are the basis of qualitycontrol (QC). The epidemiology of Potentially Life ThreateningPaediatric (LTP) emergencies admitted in a Swiss university hospitalhas never been reported. The aims of this study were to review theLTP emergency population with regards to origin, patients'demographics, reason for admission and final diagnosis, treatmentmodalities, critical events and outcome.Methods: A retrospective observational cohort study of prospectivelycollected data was conducted, including all LTP emergencies admittedover a period of 2 years in the RR of a Swiss university hospitalfunctioning as a tertiary level referral centre. Multiple variablesincluding indication for transfer, mode of pre-hospital transportation,diagnosis and the time spent in RR were assessed. Data assessmenttook place 2 years after the implementation of a quality control (QC)team assessing the pediatric resuscitations occurring within theinstitution on a monthly basis.Results: Out of 60 939 pediatric emergencies treated in LausanneUniversity Medical center over 2 years, a total of 277 LTP emergencies(0.46%) were admitted to the RR, including 160 boys and 117 girls,aged 6 days to 15.95 years (mean 6.69 years, median 5.06). The tablebelow illustrates in more details the identified problems, average age,time in hospital and outcome of both surgical and medical groups ofpatients.Conclusions: With the need for health care quality improvement andfinancial restrictions, an excellent knowledge of the characteristics ofLTP emergencies is unavoidable. A thorough understanding of theresuscitation process and humans resources involved can be achievedwith a systematic review of the cases. A dedicated quality control teamevaluating LTP emergencies in a hospital will identify areas forimprovement. A LTP registry at the national level would be of greatvalue in Switzerland.

Purpura de Henoch-Schönlein: une prise en charge entre pédiatre et néphrologue pédiatre [Henoch-Schönlein Purpura a dual follow up between pediatrician and pediatric nephrologist].

Henoch-Schönlein purpura is a well known paediatric disease characterized by the classic triad: purpura, arthritis and abdominal pain. Short term prognosis is excellent and is mostly dependant on abdominal complications. Long term morbidity depends essentially on the severity of renal involvement which occurs in 35% of cases. Microhematuria and light proteinuria are the only signs in 80% of cases. The remaining 20% presents with nephrotic or nephritic syndrome and acute renal insufficiency. Among patients with Henoch-Schönlein nephritis the risk of developing renal insufficiency varies between 11-30% of cases. Currently, the follow up guidelines are multiple and the optimal treatment of nephritis is controversial; this is what this article proposes to discuss.

Pediatric reference intervals for plasma free and total metanephrines established with a parametric approach: Relevance to the diagnosis of neuroblastoma.

BACKGROUND: Urine catecholamines, vanillylmandelic, and homovanillic acid are recognized biomarkers for the diagnosis and follow-up of neuroblastoma. Plasma free (f) and total (t) normetanephrine (NMN), metanephrine (MN) and methoxytyramine (MT) could represent a convenient alternative to those urine markers. The primary objective of this study was to establish pediatric centile charts for plasma metanephrines. Secondarily, we explored their diagnostic performance in 10 patients with neuroblastoma. PROCEDURE: We recruited 191 children (69 females) free of neuroendocrine disease to establish reference intervals for plasma metanephrines, reported as centile curves for a given age and sex based on a parametric method using fractional polynomials models. Urine markers and plasma metanephrines were measured in 10 children with neuroblastoma at diagnosis. Plasma total metanephrines were measured by HPLC with coulometric detection and plasma free metanephrines by tandem LC-MS. RESULTS: We observed a significant age-dependence for tNMN, fNMN, and fMN, and a gender and age-dependence for tMN, fNMN, and fMN. Free MT was below the lower limit of quantification in 94% of the children. All patients with neuroblastoma at diagnosis were above the 97.5th percentile for tMT, tNMN, fNMN, and fMT, whereas their fMN and tMN were mostly within the normal range. As expected, urine assays were inconstantly predictive of the disease. CONCLUSIONS: A continuous model incorporating all data for a given analyte represents an appealing alternative to arbitrary partitioning of reference intervals across age categories. Plasma metanephrines are promising biomarkers for neuroblastoma, and their performances need to be confirmed in a prospective study on a large cohort of patients. Pediatr Blood Cancer 2015;62:587-593. © 2015 Wiley Periodicals, Inc.

The effects of losartan on renal function in the newborn rabbit.

The low GFR of newborns is maintained by various factors including the renin-angiotensin system. We previously established the importance of angiotensin II in the newborn kidney, using the angiotensin-converting enzyme inhibitor perindoprilat. The present study was designed to complement these observations by evaluating the role of angiotensin-type 1 (AT(1)) receptors, using losartan, a specific AT(1)-receptor blocker. Increasing doses of losartan were infused into anesthetized, ventilated, newborn rabbits. Renal function and hemodynamic variables were assessed using inulin and para-aminohippuric acid clearances as markers of GFR and renal plasma flow, respectively. Losartan 0.1 mg/kg slightly decreased mean blood pressure (-11%) and increased diuresis (+22%). These changes can be explained by inhibition of the AT(1)-mediated vasoconstrictive and antidiuretic effects of angiotensin, and activation of vasodilating and diuretic AT(2) receptors widely expressed in the neonatal period. GFR and renal blood flow were not modified. Losartan 0.3 mg/kg decreased mean blood pressure significantly (-15%), probably by inhibiting systemic AT(1) receptors. GFR significantly decreased (-25%), whereas renal blood flow remained stable. The decrease in filtration fraction (-21%) indicates predominant efferent vasodilation. At 3 mg/kg, the systemic hypotensive effect of losartan was marked (mean blood pressure, -28%), with decreased GFR and renal blood flow (-57% and -51%, respectively), a stable filtration fraction, and an increase in renal vascular resistance by 124%. The renal response to this dose can be considered as reflex vasoconstriction of afferent and efferent arterioles, rather than specific receptor antagonism. We conclude that under physiologic conditions, the renin-angiotensin is critically involved in the maintenance of GFR in the immature kidney.

Acute norovirus-induced agranulocytosis in a pediatric kidney transplant recipient.

Norovirus (NoV) infection is usually limited to the gastrointestinal (GI) tract. However, in immunocompromised patients, this infection might lead to severe life-threatening complications. We herein describe a pediatric kidney transplant patient who presented with an acute NoV infection complicated by febrile agranulocytosis that resolved with improvement of her GI illness. This unusual presentation has not been described before, to our knowledge. The aim of this article is to highlight the sometimes dramatic clinical presentation of NoV infection in immunosuppressed patients, and the importance of including this infection in the differential diagnosis of neutropenia in that specific population.