Intranasal ketamine for procedural sedation in children: An open-label multicenter clinical trial.

INTRODUCTION: There are limited options for pain and distress management in children undergoing minor procedures, without the burden of an intravenous line insertion. Prior to this study, we conducted a dose-escalation study and identified 6 mg/kg as a potentially optimal initial dose of intranasal ketamine. OBJECTIVE: To assess the efficacy and safety of intranasal ketamine at a dose of 6 mg/kg for procedural sedation to repair lacerations with sutures in children in the emergency department. METHODS: We conducted a single-arm, open-label multicenter clinical trial for intranasal ketamine for laceration repair with sutures in children aged 1 to 12 years. A convenience sample of 30 patients received 6 mg/kg of intranasal ketamine for their procedural sedation. The primary outcome was the proportion (95% CI) of patients who achieved an effective procedural sedation. RESULTS: We recruited 30 patients from April 2018 to December 2019 in two pediatric emergency departments in Canada. Lacerations repaired were mostly facial in 21(70%) patients and longer than 2 cm in 20 (67%) patients. Sedation was effective in 18/30 (60% [95% CI 45, 80]) children and was suboptimal in 5 (17%) patients but procedure was completed in them with minimal difficulties. Sedation was poor in the remaining 7 (23%) patients, with 3 (10%) of them required additional sedative agents. No serious adverse events were reported. CONCLUSIONS: Using a single dose of 6 mg/kg of intranasal Ketamine for laceration repair led to successful sedation in 60% of patients according to our a priori definition. An additional 17% of patients were considered suboptimal, but their procedure was still completed with minimal difficulty. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT03053947).

Wnt/ß-catenin pathway inhibitors, bone metabolism and vascular health in kidney transplant patients.

BACKGROUND AND OBJECTIVES: Sclerostin, dickkopf-related protein 1 (DKK1), fibroblast growth factor-23 (FGF23) and α-klotho have been shown to play an important role in bone and vascular disease of chronic kidney disease. We aimed to evaluate the evolution of these bone markers in newly kidney transplanted patients, and whether they are associated with bone metabolism and vascular stiffness. DESIGN, SETTING, PARTICIPANTS AND MEASUREMENTS: This is a longitudinal single-center observational cohort study. Circulating levels of Wnt/ß-catenin pathway inhibitors (sclerostin, DKK1, FGF23 and α-klotho), arterial stiffness (carotid-femoral pulse-wave velocity (PWV), carotid-radial PWV, PWV ratio, augmented index) and bone parameters were assessed before (M0), and at 3 (M3) and 6 months (M6) after transplantation. Generalized estimating equations were conducted for comparative analyses between the three time points. We used a marginal structural model for repeated measures for the impact of changes in bone markers on the evolution of arterial stiffness. Multivariate linear regression analyses were performed for the associations between Wnt/ß-catenin pathway inhibitors and mineral metabolism parameters. RESULTS: We included 79 patients (70% male; median age of 53 (44-60) years old). The levels of sclerostin (2.06 ± 1.18 ng/mL at M0 to 0.88 ± 0.29 ng/mL at M6, p ≤ 0.001), DKK1 (364.0 ± 266.7 pg/mL at M0 to 246.7 ± 149.1 pg/mL at M6, p ≤ 0.001), FGF23 (5595 ± 9603 RU/mL at M0 to 137 ± 215 RU/mL at M6, p ≤ 0.001) and α-klotho (457.6 ± 148.6 pg/mL at M0 to 109.8 ± 120.7 pg/mL at M6, p < 0.05) decreased significantly after kidney transplant. Sclerostin and FGF23 were positively associated with carotid-femoral (standardized ß = 0.432, p = 0.037 and standardized ß = 0.592, p = 0.005) and carotid-radial PWV (standardized ß = 0.259, p = 0.029 and standardized ß = 0.242, p = 0.006) throughout the 6 months of follow-up. The nature of the associations between bone markers and bone metabolism parameters varies after kidney transplant. CONCLUSIONS: The circulating levels of Wnt/ß-catenin pathway inhibitors and α-klotho significantly decrease after kidney transplantation, while sclerostin and FGF23 levels might be associated with improvement of vascular stiffness and blood pressure.

Very Early Diagnosis and Management of Congenital Erythropoietic Porphyria.

Congenital erythropoietic porphyria (CEP), a rare form of porphyria, is caused by a defect in the heme biosynthesis pathway of the enzyme uroporphyrinogen III synthase (UROS). Uroporphyrinogen III synthase deficiency leads to an accumulation of nonphysiological porphyrins in bone marrow, red blood cells, skin, bones, teeth, and spleen. Consequently, the exposure to sunlight causes severe photosensitivity, long-term intravascular hemolysis, and eventually, irreversible mutilating deformities. Several supportive therapies such as strict sun avoidance, physical sunblocks, red blood cells transfusions, hydroxyurea, and splenectomy are commonly used in the management of CEP. Currently, the only available curative treatment of CEP is hematopoietic stem cell transplantation (HSCT). In this article, we present a young girl in which precocious genetic testing enabled early diagnosis and allowed curative treatment with HSCT for CEP at the age of 3 months of age, that is, the youngest reported case thus far.

Post-procedural bleeding rate and haemostatic treatment use for dental procedures before and after the implementation of a standardized protocol for people with inherited bleeding disorders.

INTRODUCTION: Persons with inherited bleeding disorders are at a substantial risk of bleeding following dental procedures. AIM: To compare the outcomes and use of haemostatic treatment pre- and post-implementation of a standardized protocol for dental procedures at a Hemophilia Treatment Centre. METHODS: We conducted a retrospective cohort study of outpatient and inpatient dental procedures and maxillofacial surgeries sustained by people with bleeding disorders treated at a comprehensive Hemophilia Treatment Centre (2013-2020), comparing patients' outcomes before and after the introduction of the protocol in 2018. The protocol, built using a multidisciplinary approach, suggested haemostatic treatment based on the invasiveness of the dental procedure and the proposed anaesthesia. Our primary outcome was the rate of procedural bleeding leading to medical or dental reintervention within 10 days. Secondary outcomes included the use of systemic haemostatic treatment and treatment-related adverse effects. RESULTS: Overall, 137 dental procedures in 95 patients (median age: 29 years; 78% males; 74% haemophilia, 14% von Willebrand disease, 12% other disorders) were included. Seventeen procedural bleedings were reported (12.4%). Procedural bleeding occurred in 14.8% and 8.9% of patients in the control and intervention groups (p = .304). No major bleeding occurred. Tranexamic acid was used more consistently after protocol implementation (72.8% vs. 89.3%, p = .019), while factor concentrates use decreased (65.4% vs. 44.6%, p = .016), and desmopressin use remained constant (46.4% vs. 32.1%, p = .100). No treatment-related adverse effects were reported. CONCLUSION: The use of a standardized protocol increased the use of tranexamic acid, with a nonstatistically significant reduction in procedural bleeding rate.

A randomized double-blind trial comparing the effect on pain of an oral sucrose solution versus placebo in children 1-3 months old needing bladder catheterization.

OBJECTIVE: The efficacy of oral sweet solutions to decrease pain in infants during painful procedures remains uncertain. This study aimed to compare the efficacy of an oral sucrose solution versus placebo in reducing pain during bladder catheterization in infants in the Emergency Department (ED). METHODS: A randomized, double-blind clinical trial was conducted in a pediatric university-affiliated hospital ED. Infants 1-3 months old were recruited and randomly allocated to receive 2 ml of sucrose or placebo, 2 min before bladder catheterization. The primary outcome measure was the difference in pain scores as assessed by the Face, Legs, Activity, Cry and Consolability (FLACC) Pain Scale during procedure. Secondary outcome measures were the difference in pain scores using the Neonatal Infant Pain Scale (NIPS), crying time, variations in heart rate and adverse events. RESULTS: Eighty-three participants were recruited and completed the study, 41 and 42 in the sucrose and placebo groups, respectively. The mean difference in FLACC scores compared to baseline was 5.3 in the sucrose group vs. 6.4 in the placebo group during catheterization. There were no differences in FLACC scores or NIPS scores measured at 1, 3 and 5 min post procedure. Mean crying times were similar: 97 vs. 110 s. No significant difference was found in participants' heart rate variations. No adverse events were reported. CONCLUSIONS: In infants undergoing bladder catheterization in the ED, administration of an oral sweet solution was not associated with lower pain as measured by the FLACC and NIPS scales. Participants' heart rate variations and crying times did not change when sucrose was provided.

RéSUMé: OBJECTIF: L'efficacité des solutions sucrées orales pour diminuer la douleur chez les nourrissons pendant les procédures douloureuses reste incertaine. Cette étude visait à comparer l'efficacité d'une solution de saccharose orale par rapport à un placebo pour réduire la douleur pendant le cathétérisme vésical chez les nourrissons dans le service d'urgence. MéTHODES: Un essai clinique randomisé en double aveugle a été mené dans les urgences d'un hôpital universitaire pédiatrique. Des nourrissons âgés de 1 à 3 mois ont été recrutés et répartis au hasard pour recevoir 2 ml de sucrose ou de placebo, 2 minutes avant le cathétérisme vésical. La principale mesure des résultats était la différence dans les scores de douleur évalués par l'échelle de douleur FLACC (Face, Legs, Activity, Cry and Consolability) pendant la procédure. Les mesures de résultats secondaires étaient la différence des scores de douleur en utilisant l'échelle de douleur du nourrisson néonatal (NIPS), la durée des pleurs, les variations de la fréquence cardiaque et les événements indésirables. RéSULTATS: Quatre-vingt-trois participants ont été recrutés et ont terminé l'étude, 41 et 42 dans les groupes sucrose et placebo, respectivement. La différence moyenne des scores FLACC par rapport à la ligne de base était de 5,3 dans le groupe sucrose contre 6,4 dans le groupe placebo pendant le cathétérisme. Il n'y avait aucune différence dans les scores FLACC ou NIPS mesurés à 1, 3 et 5 minutes après la procédure. La durée moyenne des pleurs était similaire : 97 contre 110 secondes. Aucune différence significative n'a été constatée dans les variations de la fréquence cardiaque des participants. Aucun événement indésirable n'a été signalé. CONCLUSIONS: Chez les nourrissons soumis à un cathétérisme vésical aux urgences, l'administration d'une solution sucrée orale n'était pas associée à une douleur moindre, telle que mesurée par les échelles FLACC et NIPS. Les variations de la fréquence cardiaque et les temps de pleurs des participants ne changeaient pas lorsque du saccharose était administré.

Effect on Pain of an Oral Sucrose Solution vs. Placebo in Children 1 to 3 Months Old Needing Nasopharyngeal Aspiration: A Randomized Controlled Trial.

BACKGROUND: Oral sweet solutions have been proposed as effective pain-reducing agents for procedures. OBJECTIVES: To compare the efficacy of an oral sucrose solution vs. placebo in alleviating pain in children (1-3 months) during nasopharyngeal aspiration (NPA). METHODS: A randomized, double-blind, controlled clinical trial was conducted in a pediatric hospital emergency department. Participants (aged 1-3 months) requiring NPA were randomly allocated to receive 2 mL of 88% sucrose (SUC) or 2 mL of a placebo (PLA) 2 min prior to the procedure. The primary outcome was the mean difference in pain scores at 1 min post NPA as assessed by the Face, Legs, Activity, Cry and Consolability (FLACC) Pain Scale. RESULTS: Seventy-two participants completed the study, 37 receiving SUC and 35 PLA. The mean difference in FLACC scores compared with baseline was 3.3 (2.5-4.1) for SUC vs. 3.2 (2.3-4.1) for PLA (p = .094) at 1 min and -1.2 (-1.7-0.7) for SUC vs. -0.8 (-1.5 to -0.1) for PLA (p = 0.66) at 3 min after NPA. For the Neonatal Infant Pain Scale scores, it was 2.3 (1.6-3.0) (SUC) vs. 2.5 (1.8-3.2) (PLA) (p = .086) at 1 min and -1.2 (-1.6 to -0.8) (SUC) vs. -0.8 (-1.3 to 0.2) (PLA) (p = 0.59) 3 min after NPA. There was no difference in the mean crying time, 114 (98-130) s, SUC vs. 109 (92-126) s, PLA (p = 0.81). No significant difference was found in participants' heart rate at 1 min 174 (154-194) beats/min in SUC vs. 179 (160-198) beats/min in PLA (p = 0.32). CONCLUSIONS: In infants (1-3 months) undergoing NPA, administration of an oral sweet solution did not statistically decrease pain scores.

Evaluation of bedside sonography performed by emergency physicians to detect intussusception in children in the emergency department.

OBJECTIVE: The aim of our study was to evaluate the test characteristics of point-of-care ultrasound (POCUS) performed by emergency physicians with varying levels of experience among children having undergone diagnostic radiology ultrasound for intussusception in a pediatric emergency department (PED). METHODS: This was a subanalysis of a prospective cohort study conducted at a tertiary care PED. The study population was a sample of children younger than 5 years old who required an abdominal ultrasound for suspected intussusception. Participating physicians had varying levels of POCUS experience. They received a 1-hour didactic and practical training session on intussusception ultrasound. All POCUS was performed following the initial physical examination and prior to further radiologic evaluation. The final outcome was determined by radiologic evaluation performed by a pediatric radiologist. Test characteristics were calculated for POCUS compared with the criterion standard of ultrasound read by a pediatric radiologist. A secondary analysis compared test characteristics of POCUS performed by physicians with different level of POCUS training. RESULTS: A total of 131 children were evaluated by POCUS, of whom 45 (34%) had an intussusception. Twenty-four physicians performed between one and 25 POCUS procedures. POCUS identified 39 of 45 intussusception cases, with a sensitivity of 0.87 (95% confidence interval [CI] = 0.74 to 0.94). A normal or inconclusive POCUS was reported for 83 of the 86 negative studies, with a specificity of 0.97 (95% CI = 0.90 to 0.99). When excluding the 28 patients for whom the physician reported an inconclusive examination, the sensitivity improved to 0.98 (95% CI = 0.97 to 1.00) and the specificity to 0.94 (95% CI = 0.85 to 0.99). The accuracy of diagnosis using POCUS was 42 of 43 (98%) for experienced sonographers in comparison to 81 of 88 (92%) for novices. CONCLUSION: This study demonstrated a very good sensitivity and specificity of POCUS for intussusception in children when performed by multiple emergency physicians with varying POCUS experience.

Emergency physician performed ultrasound-assisted lumbar puncture in children: A randomized controlled trial.

BACKGROUND AND OBJECTIVE: Lumbar puncture (LP) is one of the most common procedures performed in pediatric emergency departments but first-attempt success rates remain low and traumatic LP remains frequent. The aim of this study was to determine if ultrasound performed by emergency physicians improves the probability of first-attempt success for lumbar puncture in children. METHODS: This was a prospective randomized controlled trial conducted in two tertiary care, pediatric, university-affiliated emergency departments in 2017-2018. Eligible participants were children younger than 19 years old requiring an LP in the emergency department. They were randomized to either the standard landmark-based LP (SLP) or ultrasound-assisted LP (UALP) groups. Our primary outcome was the first-attempt LP success rate. RESULTS: 166 patients were enrolled, with 84 in the UALP and 82 in the SLP group. A total of 23 physicians performed ultrasounds in the study. The proportion of successful first-attempt LP was higher in the ultrasound group (60/84; 68%) than for the standard procedure (52/82; 60%), but this failed to reach statistical significance (difference: 8.1%; 95% CI: -6.4 to 22.2). CONCLUSION: Our study does not support the routine use of ultrasound for performing lumbar puncture in children. Considering the minimal harm and ease of performance, ultrasound may be used as an adjunct and teaching tool in certain clinical situations.

Prognostic Value of Carotid and Radial Artery Reservoir-Wave Parameters in End-Stage Renal Disease.

Background Reservoir-wave approach is an alternative model of arterial hemodynamics based on the assumption that measured arterial pressure is composed of volume-related (reservoir pressure) and wave-related components (excess pressure). However, the clinical utility of reservoir-wave approach remains debatable. Methods and Results In a single-center cohort of 260 dialysis patients, we examined whether carotid and radial reservoir-wave parameters were associated with all-cause and cardiovascular mortality. Central pulse pressure and augmentation index at 75 beats per minute were determined by radial arterial tonometry through generalized transfer function. Carotid and radial reservoir-wave analysis were performed to determine reservoir pressure and excess pressure integral. After a median follow-up of 32 months, 171 (66%) deaths and 88 (34%) cardiovascular deaths occurred. In Cox regression analysis, carotid excess pressure integral was associated with a hazard ratio of 1.33 (95% CI , 1.14-1.54; P<0.001 per 1 SD) for all-cause and 1.45 (95% CI : 1.18-1.75; P<0.001 per 1 SD) for cardiovascular mortality. After adjustments for age, heart rate, sex, clinical characteristics and carotid-femoral pulse wave velocity, carotid excess pressure integral was consistently associated with increased risk of all-cause (hazard ratio per 1 SD, 1.30; 95% CI : 1.08-1.54; P=0.004) and cardiovascular mortality (hazard ratio per 1 SD, 1.31; 95% CI : 1.04-1.63; P=0.019). Conversely, there were no significant associations between radial reservoir-wave parameters, central pulse pressure, augmentation index at 75 beats per minute, pressure forward, pressure backward and reflection magnitude, and all-cause or cardiovascular mortality after adjustment for comorbidities. Conclusions These observations support the clinical value of reservoir-wave approach parameters of large central elastic vessels in end-stage renal disease.

Point-of-care ultrasound before attempting clean-catch urine collection in infants: a randomized controlled trial.

OBJECTIVE: A new non-invasive bladder stimulation technique has been described to obtain clean-catch urine specimens in infants. This study aimed to evaluate if point-of-care ultrasound (POCUS) guided feeding protocol to measure bladder volume prior to stimulation techniques improves clean-catch urine collection success. METHODS: A prospective randomized controlled trial study was conducted in a tertiary care pediatric emergency department. Infants aged less than 6 months needing a urine sample were randomized to either POCUS group or feeding group (standard procedure) before performing a standardized clean-catch urine stimulation technique. In the POCUS group, a feeding period was permitted if the bladder width was less than 2 cm, otherwise the clean-catch urine was performed immediately. The primary outcome was the success of the procedure defined by the collection of at least 2 mL of urine, obtained within 300 seconds of bladder stimulation manoeuvres. It was estimated that the recruitment of 200 children was necessary to yield 80% power to identify an improvement of 20% in the success rate. RESULTS: A total of 201 infants were included. The procedure was not more successful in the POCUS group (48%) compared to the feeding group (54%) (Difference: 6.5%; 95% CI: -7.3 to 19.8%). The mean time to collect urine samples from randomization to sample collection was not different between the two groups. CONCLUSIONS: Our study failed to show a benefit of using POCUS to improve the success rate of stimulated clean-catch urine. Moreover, the importance of the feeding period prior to clean-catch urine manoeuvres should be evaluated further. CLINICAL TRIAL REGISTRATION: NCT02751671.

OBJECTIF: Une nouvelle technique de prélèvement urinaire non-invasive par mi-jet stimulé fut décrite pour les nourrissons. L'étude visait à évaluer si un protocole d'allaitement guidé par l'échographie au chevet (EC), avant stimulation, pour mesurer le volume de la vessie, permettait d'accroître le taux de réussite du recueil d'urine par mi-jet. MÉTHODE: Un essai comparatif, prospectif et à répartition aléatoire a été mené dans un service des urgences pédiatriques de soins tertiaires. Des nourrissons âgés de moins de 6 mois chez qui devait être pratiqué un prélèvement d'urine ont été répartis au hasard dans le groupe de l'EC ou dans le groupe d'allaitement (méthode courante) avant que ne soit pratiquée la technique de stimulation uniforme de recueil d'urine par mi-jet. Dans le groupe de l'EC, l'allaitement était permis si la largeur de la vessie était < 2 cm; sinon, l'on procédait immédiatement au recueil d'urine par mi-jet stimulé. Le principal critère d'évaluation consistait en la réussite du prélèvement, défini comme le recueil d'au moins 2 ml d'urine pendant les manœuvres de stimulation de la vessie, d'une durée maximum de 300 secondes. D'après l'évaluation des chercheurs, le nombre de sujets nécessaire pour que l'étude atteigne une puissance de 80% et mette ainsi en évidence une augmentation de 20% du taux de réussite devait s'élever à 200. RÉSULTATS: Au total, 201 nourrissons ont participé à l'étude. Le recueil d'urine n'était pas plus élevé dans le groupe de l'EC (48%) que dans le groupe d'allaitement (54%) (écart : 6,5%; IC à 95% : -7,3% à 19,8%). Il n'y avait de différence non plus entre les deux groupes quant au temps moyen écoulé depuis la répartition aléatoire des sujets jusqu'au prélèvement d'urine. CONCLUSION: La supériorité de l'EC dans l'accroissement du taux de réussite du recueil d'urine non souillée par stimulation n'a pas été démontrée dans l'étude. Il faudrait aussi évaluer davantage l'importance de la durée de l'allaitement avant les manœuvres de recueil d'urine non souillée. NO D'ENREGISTREMENT DES ESSAIS CLINIQUES: NCT02751671.

Impact of kidney transplantation on aortic stiffness and aortic stiffness index ß0.

BACKGROUND: In chronic kidney disease, the enhanced aortic stiffness increases risk of cardiovascular events. Kidney transplantation (KTx) may improve aortic stiffness; however, it is unclear whether the improvement of aortic stiffness is merely the outcome of the reduction of blood pressure (BP) post-KTx. Furthermore, the long-term trajectory of aortic stiffness remains uncertain, as activation of the immune system may have a negative long-term impact on arterial wall property. METHOD: Using aortic stiffness ß0 as a BP-independent stiffness parameter, and a statistical adjustment for BP, we aimed to examine the early vs. late changes in aortic stiffness, and to define the characteristics of patients with favourable and unfavourable long-term trajectories of aortic stiffness. In this longitudinal study, aortic stiffness was assessed before, 3, 6 and 24 months after KTx in 79 individuals. Aortic stiffness was determined by carotid-femoral pulse wave velocity (cf-PWV), and aortic stiffness index ß0 was obtained by applying the stiffness parameter ß0 theory to cf-PWV based on Bramwell-Hill's equation using a reference pressure. RESULTS: There was an early reduction of ß0 3 months after KTx (29.0 ±â€Š2.0 to 25.8 ±â€Š1.2, P = 0.033) followed by a gradual increase at 6 (28.0 ±â€Š1.4, P = 0.005 vs. 3 months) and 24 months (28.3 ±â€Š1.3, P = 0.003 vs. 3 months). A late increase in ß0 was associated with higher levels of the interleukin-6 (P = 0.029) even after adjustment for potential cofounders. Using statistical adjustments for BP showed similar results. CONCLUSION: Reduction of aortic stiffness index ß0 3 months after KTx suggests that KTx leads to an early de-stiffening of the intrinsic mechanical properties of aorta. However, this improvement is followed by a later stiffening, which is associated with increased interleukin-6, suggesting that activation of the immune system may be involved in arterial wall remodelling in kidney recipients.

Aortic-Brachial Pulse Wave Velocity Ratio: A Measure of Arterial Stiffness Gradient Not Affected by Mean Arterial Pressure.

BACKGROUND: Aortic stiffness, measured by carotid-femoral pulse wave velocity (cf-PWV), is used for the prediction of cardiovascular risk. This mini-review describes the nonlinear relationship between cf-PWV and operational blood pressure, presents the proposed methods to adjust for this relationship, and discusses a potential place for aortic-brachial PWV ratio (a measure of arterial stiffness gradient) as a blood pressure-independent measure of vascular aging. SUMMARY: PWV is inherently dependent on the operational blood pressure. In cross-sectional studies, PWV adjustment for mean arterial pressure (MAP) is preferred, but still remains a nonoptimal approach, as the relationship between PWV and blood pressure is nonlinear and varies considerably among individuals due to heterogeneity in genetic background, vascular tone, and vascular remodeling. Extrapolations from the blood pressure-independent stiffness parameter ß (ß0) have led to the creation of stiffness index ß, which can be used for local stiffness. A similar approach has been used for cardio-ankle PWV to generate a blood pressure-independent cardio-ankle vascular index (CAVI). It was recently demonstrated that stiffness index ß and CAVI remain slightly blood pressure-dependent, and a more appropriate formula has been proposed to make the proper adjustments. On the other hand, the negative impact of aortic stiffness on clinical outcomes is thought to be mediated through attenuation or reversal of the arterial stiffness gradient, which can also be influenced by a reduction in peripheral medium-sized muscular arteries in conditions that predispose to accelerate vascular aging. Arterial stiffness gradient, assessed by aortic-brachial PWV ratio, is emerging to be at least as good as cf-PWV for risk prediction, but has the advantage of not being affected by operating MAP. KEY MESSAGES: The negative impacts of aortic stiffness on clinical outcomes are proposed to be mediated through attenuation or reversal of arterial stiffness gradient. Aortic-brachial PWV ratio, a measure of arterial stiffness gradient, is independent of MAP.

Bedside Sonography Performed by Emergency Physicians to Detect Appendicitis in Children.

OBJECTIVE: The aim of this study was to evaluate the ability of emergency physicians with various levels of point-of-care ultrasound (POCUS) experience to detect appendicitis with POCUS among children visiting a pediatric emergency department (ED). METHODS: A prospective cohort study was conducted in an urban, tertiary care pediatric ED. Children aged 2 to 18 years old who presented with acute abdominal pain suggesting appendicitis were included. Patients were excluded if they had a history of appendectomy or hemodynamic instability requiring resuscitation or were transferred with proven diagnosis of appendicitis. Participating physicians had various levels of POCUS experience. Four of the 22 physicians were experienced in bowel sonography while the others had basic experience in abdominal POCUS. All the participating physicians received a 1-hour didactic and practical training session on appendix ultrasound. The treating physician performed POCUS following initial physical examination, before further radiologic evaluation. POCUS examinations were recorded as positive for appendicitis, normal, or inconclusive, with normal or inconclusive studies considered negative. Final outcomes were determined by pathology and/or operative reports for surgical cases and telephone follow-up at 3 weeks for those who did not have surgery. The primary analysis was a simple proportion for sensitivity and specificity for POCUS. Expecting a sensitivity of 80% based on previous studies, we calculated that a sample size of 50 cases would provide a 95% confidence interval (CI) ranging from 66% to 90%. RESULTS: Of the 140 approached patients, 121 accepted to participate and were recruited. After four patients were excluded for missing POCUS data, 117 patients were included in the primary analysis, of whom 51 (44%) had appendicitis. Twenty-two physicians performed between one and 20 POCUS procedures. The POCUS was positive in 39, negative in nine, and inconclusive in 69 patients. POCUS was interpreted as positive in 27 of 51 appendicitis for a sensitivity of 0.53 (95% CI = 0.40-0.66). A negative or inconclusive POCUS was reported for 54 of 66 patients without appendicitis (specificity = 0.82; 95% CI = 0.71-0.89). CONCLUSION: This study shows limited sensitivity and specificity of POCUS for appendicitis in children, with a high proportion of inconclusive examinations, when performed by emergency physicians with various level of experience in POCUS.

Association of interleukin-6 with aortic stiffness in end-stage renal disease.

Cardiovascular disease (CVD) is the leading cause of mortality in patients with chronic kidney disease (CKD). Aortic stiffness, a nontraditional risk factor, is associated with high rate of mortality in CKD. Using a CKD animal model with medial vascular calcification, we previously reported increased mRNA expression of interleukin-6 (IL-6), tumor necrosis factor (TNF), and interleukin-1ß (IL-1ß) in calcified aorta. The aim of the study was to investigate the association between IL-6, TNF, IL-1ß, and aortic stiffness in end-stage renal disease patients. In a cross-sectional study, we enrolled 351 patients on dialysis. Aortic stiffness was assessed by carotid-femoral pulse wave velocity (cf-PWV), while central pulse pressure and augmentation index were assessed using generalized transfer function applied to the radial artery pressure wave form. Plasma IL-6, TNF, and IL-1ß were measured by enzyme-linked immunosorbent assay. IL-6 was associated with cf-PWV adjusted for mean blood pressure (MBP) (standardized ß = 0.270; P < .001). In a multivariate adjusted model for age, diabetes, hypertension, CVD, and MBP, IL-6 was still associated with cf-PWV (standardized ß = 0.096; P = .026). The impact of age, diabetes, and CVD on cf-PWV was partially mediated by IL-6 in a mediation analysis. However, there were no associations between TNF, IL-1ß, and aortic stiffness. While IL-6 was associated with augmentation index (standardized ß = 0.224; P < .001) and central pulse pressure (standardized ß = 0.162; P = .001) when adjusted for MBP and heart rate, this relationship was not significant after adjusting for potential confounders.This study suggests a potential role of IL-6 for CKD-related aortic stiffness.

A Randomized Double-Blind Trial Comparing the Effect on Pain of an Oral Sucrose Solution vs. Placebo in Children 1 to 3 Months Old Undergoing Simple Venipuncture.

BACKGROUND: Few clinical trials evaluating the efficacy of oral sweet solutions for procedures in the emergency department (ED) have been published. OBJECTIVES: To compare the efficacy of an oral sucrose solution vs. a placebo in reducing pain in infants undergoing venipuncture without cannulation. METHODS: A randomized, double-blinded clinical trial was conducted in a pediatric ED. Infants 1 to 3 months old were randomly allocated to receive 2 mL of 88% sucrose or 2 mL of placebo, 2 min prior to venipuncture. The outcome measures were the difference in pain levels as assessed by the Face, Legs, Activity, Cry and Consolability Pain Scale (FLACC) and Neonatal Infant Pain Scale (NIPS) scores, crying time, and variations in heart rate. RESULTS: Eighty-two participants were recruited. Data were analyzed for 38 patients from each group (excluding protocol deviations). The mean difference in FLACC scores 1 min post venipuncture compared with baseline was 2.84 ± .64 (sucrose) vs. 2.71 ± .62 (placebo) (p = 0.98). For the NIPS score, it was 2.32 ± .47 (sucrose) vs. 1.63 ± .49 (placebo) (p = 0.60). The difference in the median crying time was not statistically significant between the two groups: 63.0 ± 3 (sucrose) vs. 48.5 ± 5 s (placebo) (p = 0.17). No significant difference was found in participants' heart rates 1 min post venipuncture compared with baseline: 33 ± 6 (sucrose) vs. 24 ± 5 beats per minute (placebo) (p = 0.44). CONCLUSIONS: In infants 1 to 3 months of age undergoing simple venipuncture, administration of an oral sweet solution did not statistically decrease pain scores, and participants' heart rate variations and crying time were not significantly changed.

Reduction of Arterial Stiffness After Kidney Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: End-stage kidney disease is associated with increased arterial stiffness. Although correction of uremia by kidney transplantation (KTx) could improve arterial stiffness, results from clinical studies are unclear partly due to small sample sizes. METHOD AND RESULTS: We conducted a systematic review and meta-analysis of before-after design studies performed in adult KTx patients with available measures of arterial stiffness parameters (pulse wave velocity [PWV], central pulse pressure [PP], and augmentation index) before and at any time post-KTx. Mean difference of post- and pre-KTx values of different outcomes were estimated using a random effect model with 95% confidence interval. To deal with repetition of measurement within a study, only 1 period of measurement was considered per study by analysis. Twelve studies were included in meta-analysis, where a significant decrease of overall PWV by 1.20 m/s (95% CI 0.67-1.73, I2=72%), central PWV by 1.20 m/s (95% CI 0.16-2.25, I2=83%), peripheral PWV by 1.17 m/s (95% CI 0.17-2.17, I2=79%), and brachial-ankle PWV by 1.21 m/s (95% CI 0.66-1.75, I2=0%) was observed. Central PP (reported in 4 studies) decreased by 4.75 mm Hg (95% CI 0.78-10.28, I2=50%). Augmentation index (reported in 7 studies) decreased by 10.5% (95% CI 6.9-14.1, I2=64%). A meta-regression analysis showed that the timing of assessment post-KTx was the major source of the residual variance. CONCLUSIONS: This meta-analysis suggests a reduction of the overall arterial stiffness in patients with end-stage kidney disease after KTx.

Levels of Angiopoietin-Like-2 Are Positively Associated With Aortic Stiffness and Mortality After Kidney Transplantation.

BACKGROUND: Angiopoietin-like-2 (ANGPTL2) is a secreted proinflammatory glycoprotein that promotes endothelial dysfunction, atherosclerosis, and cardiovascular disease (CVD). Circulating ANGPTL2 is increased in chronic kidney disease (CKD), where the risk of CVD is amplified. The objectives of the present study were to (i) examine whether kidney transplantation (KTx) reduces ANGPTL2 levels, (ii) identify the determinants of ANGPTL2 after KTx, (iii) study the association of ANGPTL2 with aortic stiffness, and (iv) assess the impact of ANGPTL2 on mortality after KTx. METHODS: In 75 patients, serum ANGPTL2 levels were measured at baseline and 3 months after KTx. Aortic stiffness was determined by carotid-femoral pulse wave velocity, glomerular filtration rate was estimated by CKD-EPI formula, and serum cytokines and endothlin-1 levels were determined 3 months after KTx. Survival analysis was performed using Kaplan-Meier and Cox regression after a median follow-up of 90 months. RESULTS: After 3 months of KTx, ANGPTL2 levels decreased from 71 ng/ml (53-95) to 11 ng/ml (9-15) (P < 0.001). In multivariate analysis, age, lower renal function, and endothelin-1 were independently associated with higher post-KTx ANGPTL2 levels. ANGPTL2 was positively associated with aortic stiffness after KTx, even when adjusted for mean blood pressure (standardized ß = 0.314; P = 0.008). During follow-up, 13 deaths occurred. The group of patients with higher post-KTx ANGPTL2 levels had a hazard ratio for mortality of 3.9 (95% confidence interval: 1.07-14.4; P = 0.039). CONCLUSION: KTx significantly reduced serum ANGPTL2 levels. The positive association between post-KTx ANGPTL2, aortic stiffness and mortality, suggests that ANGPTL2 may play a biological role in CKD-related CVD.

Association Between Dehydration and Fever During the First Week of Life.

BACKGROUND: Trying to differentiate serious bacterial infection (SBI) from a self-limiting illness in febrile infants seen in the pediatric emergency department (PED) is a significant challenge. The aim of the study was to determine the prevalence of dehydration and its relationship to SBI in febrile full-term newborns under 1 week of age seen in a PED. METHODS: A retrospective observational study was carried out on all children younger than 8 days of age with fever who presented to a single, tertiary care, PED from January 2009 to April 2014. Dehydration was defined as plasma sodium >150 mmol/L or >10% loss of birth weight. SBI was defined by the presence of a positive culture in the blood, urine, cerebrospinal fluid; osteoarticular infection; bacterial enteritis; or pneumonia. The primary analysis was the proportion of children with dehydration. A secondary analysis compared proportion of infection according to hydration status. RESULTS: Of the 895 children under 8 days of age who visited the PED, 69 consulted for fever. Seven patients were excluded because they were transferred from another hospital. Sixty-two eligible patients were included in the final analysis. Of these, 17 (27%) were dehydrated according to our definition. Only 2 patients had an SBI while 2 others had a final diagnosis of viral myocarditis and encephalitis, respectively. None of the 4 children with serious infection fulfilled our definition of dehydration, and all had a plasma sodium level lower than 145 mmol/L. CONCLUSIONS: Dehydration is frequently associated with fever in infants younger than 8 days of age seen in a PED. Early identification of dehydration may be useful in limiting the aggressive intervention in some of these infants.

Aortic-Brachial Pulse Wave Velocity Ratio: A Blood Pressure-Independent Index of Vascular Aging.

Aortic stiffness, a cardiovascular risk factor, depends on the operating mean arterial pressure (MAP). The impact of aortic stiffness on cardiovascular outcomes is proposed to be mediated by the attenuation or the reversal of the arterial stiffness gradient. We hypothesized that arterial stiffness gradient is less influenced by changes in MAP. We aimed to study the relationship between MAP and aortic stiffness, brachial stiffness, and arterial stiffness gradient. In a cross-sectional study of a dialysis cohort (group A, n=304) and a cohort of hypertensive or kidney transplant recipient with an estimated glomerular filtration rate of >45 mL/min/1.73 m2 (group B, n=114), we assessed aortic and brachial stiffness by measuring carotid-femoral and carotid-radial pulse wave velocities (PWV). We used aortic-brachial PWV ratio as a measure of arterial stiffness gradient. Although there was a positive relationship between MAP and carotid-femoral PWV (R2=0.10 and 0.08; P<0.001 and P=0.003) and MAP and carotid-radial PWV (R2=0.22 and 0.12; P<0.001 and P<0.001), there was no statistically or clinically significant relationship between MAP and aortic-brachial PWV ratio (R2=0.0002 and 0.0001; P=0.8 and P=0.9) in group A and B, respectively. Dialysis status and increasing age increased the slope of the relationship between MAP and cf-PWV. However, we found no modifying factor (age, sex, dialysis status, diabetes mellitus, cardiovascular disease, and class of antihypertensive drugs) that could affect the lack of relationship between MAP and aortic-brachial PWV ratio. In conclusion, these results suggest that aortic-brachial PWV ratio could be considered as a blood pressure-independent measure of vascular aging.