[Show abstract][Hide abstract] ABSTRACT: The aim of this study was to assess the effect of intravenous (IV) insulin administration in children with severe acute asthma (SAA) and hyperglycemia on IV salbutamol consumption and length of stay (LOS) in a pediatric intensive care unit (PICU).
Retrospective, descriptive study of the clinical course before and after implementation of an insulin protocol for the treatment of hyperglycemia (i.e. blood glucose >8 mmol/L or 144 mg/dL, respectively) in the PICU of a tertiary care university hospital. Admissions between 1994 and 2010 were reviewed. The insulin protocol was introduced in 2006.
A total of 131 pediatric patients with SAA complicated by hyperglycemia requiring IV salbutamol were included. Severity of illness before and after implementation of the insulin protocol did not significantly differ. The insulin-treated patient group had significantly higher maximum blood glucose levels and higher cumulative IV salbutamol dose than the non-treated group. There were no differences between these groups in the duration of IV salbutamol administration and LOS.
In view of the lack of difference in outcomes and considering that the insulin protocol is labor-intensive, the question is whether this protocol is efficacious for the treatment of pediatric SAA associated with hyperglycemia.
Journal of Asthma 05/2015; 52(7):1-6. DOI:10.3109/02770903.2015.1008139 · 1.80 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Asthma guidelines recommend monitoring of asthma control. However, in a substantial proportion of children, asthma is poorly controlled and the best monitoring strategy is not known.
We studied two monitoring strategies for their ability to improve asthma outcomes in comparison with standard care (SC): web-based monthly monitoring with the (Childhood) Asthma Control Test (ACT or C-ACT) and 4-monthly monitoring of FENO.
In this randomised controlled, partly blinded, parallel group multicentre trial with a 1-year follow-up, children aged 4-18 years with a doctor's diagnosis of asthma treated in seven hospitals were randomised to one of the three groups. In the web group, treatment was adapted according to ACT obtained via a website at 1-month intervals; in the FENO group according to ACT and FENO, and in the SC group according to the ACT at 4-monthly visits. The primary endpoint was the change from baseline in the proportion of symptom-free days (SFD).
Two-hundred and eighty children (mean age 10.4 years, 66% boys) were included; 268 completed the study. Mean changes from baseline in SFD were similar between the groups: -2.1% (web group, n=90), +8.9% (FENO group, n=91) versus 0.15% (SC, n=87), p=0.15 and p=0.78. Daily dose of inhaled corticosteroids (ICS) decreased more in the web-based group compared with both other groups (-200 μg/day, p<0.01), while ACT and SFD remained similar.
The change from baseline in SFD did not differ between monitoring strategies. With web-based ACT monitoring, ICS could be reduced substantially while control was maintained.
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[Show abstract][Hide abstract] ABSTRACT: We prospectively studied the incidence and clinical course of hypertriglyceridemia and hypercholesterolemia during very prolonged use of asparaginase or in relation to asparaginase activity levels in children with acute lymphoblastic leukemia. Also, incidence of pancreatitis, thrombosis, hyperammonemia and central neurotoxicity and their association with asparaginase activity levels were evaluated. 89 patients were treated according to Dutch Childhood Oncology Group Acute Lymphoblastic Leukemia 10 medium-risk intensification protocol, which includes 15 doses PEGasparaginase(2,500 IU/m2) for 30 weeks. Erwinia-asparaginase(20,000 IU/m2) was administered when allergy to or silent inactivation of PEGasparaginase occurred. Triglyceride/cholesterol/ammonia levels increased rapidly in children with PEGasparaginase and remained temporary elevated, but normalized after finishing the last asparaginase dose. Hypertriglyceridemia and hypercholesterolemia(grade 3/4) were found in 47% and in 25%, respectively, of PEGasparaginase-treated patients. Studying the correlations between PEGasparaginase activity levels and triglyceride levels showed the strongest correlation at week 5 (Spearman correlation coefficient=0.36, p=0.005). Children >10 years had higher triglyceride levels as compared to younger patients(<10 years) adjusted for asparaginase preparations: median 4.9 mmol/L versus 1.6 mmol/L(p<0.001). In patients receiving Erwinia-asparaginase, triglyceride levels increased in the first weeks as well, but no grade 3/4 dyslipidemia was found. Hyperammonemia(grade 3/4) was only found in Erwinia-asparaginase treated patients(9%). Thrombosis occurred in 4.5%, pancreatitis in 7 %, and central neurotoxicity in 9 % of patients using each of both agents; these toxicities were not related to asparaginase activity levels nor to triglyceride levels. Severe dyslipidemia occurred frequently, but was temporary and was not associated with relevant clinical events and therefore should not be considered a reason for asparaginase treatment modifications. Only dyslipidemia was related to asparaginase activity levels.
[Show abstract][Hide abstract] ABSTRACT: The aim of this cross-sectional study was to analyze the incidence of incisional hernia after liver transplantation (LT), to determine potential risk factors for their development and to assess their impact of incisional hernia on health-related quality of life (HRQoL).Patients who underwent LT through a J-shaped incision with a minimum follow-up of 3 months were included. Follow-up was conducted at the outpatient clinic. Short form 36 (SF-36) and body image questionnaire (BIQ) were used for the assessment of HRQoL.A total of 140 patients was evaluated. The mean follow-up period was 33 (SD 20) months. Sixty patients (43%) were diagnosed with an incisional hernia. Multivariate analysis revealed surgical site infection (OR 5.27, p = 0.001), advanced age (OR 1.05, p = 0.003), and prolonged ICU stay (OR 1.54, p = 0.022) to be independent risk factors for development of incisional hernia after LT. Patients with an incisional hernia experienced significantly diminished HRQoL with respect to physical, social, and mental aspects.In conclusion, patients who undergo LT exhibit a high incidence of incisional hernia, which has a considerable impact on HRQoL. Development of incisional hernia was shown to be related to surgical site infection, advanced age and prolonged ICU stay.This article is protected by copyright. All rights reserved.
[Show abstract][Hide abstract] ABSTRACT: Background:
Aim of the study was to validate commonly used bedside right-ventricular (RV) impedance parameters, which are utilized in determining heart-lung interactions during mechanical ventilation.
Fifteen pigs were equally assigned to either an open or a closed pericardium group. In all animals, an inflatable vascular occluder and a flow probe were placed around the main pulmonary artery, which allowed for a gradual increase in pulmonary vascular impedance with banding of the pulmonary artery. A median sternotomy was performed for the open pericardium group, and a lateral thoracotomy was performed for the closed pericardium group.
In the open pericardium group, mean acceleration time (ACmean) and the slope of the pulmonary artery flow correlated significantly with Poiseuille resistance over the banding (r=0.67 and r=0.65, respectively). In the closed pericardium group, the ratio of the right to left ventricular area, eccentricity index, and tricuspid annular plane systolic excursion did not correlate with resistance over the banding, only the ACmean showed a significant correlation with resistance over the banding (r=0.88).
ACmean is a reliable parameter of RV impedance that can be used to study the heart-lung interactions during mechanical ventilation.
[Show abstract][Hide abstract] ABSTRACT: This study prospectively analyzed the efficacy of very prolonged PEGasparaginase and Erwinia asparaginase (Erwinia-asp) courses in pediatric acute lymphoblastic leukemia (ALL) patients.
Patients received 15 PEGasparaginase infusions (2,500 IU/m2 q2 weeks) in intensification after receiving native E.coli asparaginase in induction. In case of allergy to or silent inactivation of PEGasparaginase, Erwinia-asp (20,000 IU/m2 2-3 times weekly) was given.
Eighty-nine patients were enrolled in the "PEGasparaginase study". Twenty(22%) of the PEGasparaginase-treated patients developed an allergy; seven (8%) showed silent inactivation. PEGasparaginase level was zero in all allergic patients (grade 1-4). Patients without hypersensitivity to PEGasparaginase had serum mean trough levels of 899 U/L. Fifty-nine patients were included in the "Erwinia-asp study", two (3%) developed an allergy and none silent inactivation. Ninety-six percent had at least one trough level ≥100 U/L. Serum asparagine level was not always completely depleted with Erwinia-asp in contrast to PEGasparaginase. Presence of asparaginase-antibodies was related to allergies and silent inactivation, but with low specificity (64%).
Use of native E.coli asparaginase in induction leads to high hypersensitivity rates to PEGasparaginase in intensification. Therefore, PEGasparaginase should be used already in induction and we suggest that the dose could be lowered. Switching to Erwinia-asp leads to effective asparaginase levels in most patients. Therapeutic drug monitoring has been added to our ALL-11-protocol to individualize asparaginase therapy.
[Show abstract][Hide abstract] ABSTRACT: This study prospectively analyzed the efficacy of very prolonged PEGasparaginase and Erwinia-asparaginase (Erwinia-asp) courses in pediatric acute lymphoblastic leukemia (ALL) patients. Patients received 15 PEGasparaginase infusions (2,500IU/m(2) q2 weeks) in intensification after receiving native E.coli-asparaginase in induction. In case of allergy to or silent-inactivation of PEGasparaginase, Erwinia-asp(20,000IU/m(2) 2-3 times weekly) was given. Eighty-nine patients were enrolled in the "PEGasparaginase study". Twenty(22%) of the PEGasparaginase-treated patients developed an allergy; seven(8%) showed silent inactivation. PEGasparaginase level was zero in all allergic patients(grade 1-4). Patients without hypersensitivity to PEGasparaginase had serum mean trough levels of 899 U/L. Fifty-nine patients were included in the "Erwinia-asp study", two(3%) developed an allergy and none silent-inactivation. Ninety-six percent had at least one trough level ≥100 U/L. Serum asparagine level was not always completely depleted with Erwinia-asp in contrast to PEGasparaginase. Presence of asparaginase-antibodies was related to allergies and silent-inactivation, but with low specificity(64%). Use of native E.coli-asparaginase in induction leads to high hypersensitivity rates to PEGasparaginase in intensification. Therefore, PEGasparaginase should be used already in induction and we suggest that the dose could be lowered. Switching to Erwinia-asp leads to effective asparaginase levels in most patients. Therapeutic-drug-monitoring has been added to our ALL-11-protocol to individualize asparaginase therapy.
[Show abstract][Hide abstract] ABSTRACT: Prolonged prednisolone treatment for the initial episode of childhood nephrotic syndrome may reduce relapse rate, but whether this results from the increased duration of treatment or a higher cumulative dose remains unclear. We conducted a randomized, double-blind, placebo-controlled trial in 69 hospitals in The Netherlands. We randomly assigned 150 children (9 months to 17 years) presenting with nephrotic syndrome to either 3 months of prednisolone followed by 3 months of placebo (n=74) or 6 months of prednisolone (n=76), and median follow-up was 47 months. Both groups received equal cumulative doses of prednisolone (approximately 3360 mg/m(2)). Among the 126 children who started trial medication, relapses occurred in 48 (77%) of 62 patients who received 3 months of prednisolone and 51 (80%) of 64 patients who received 6 months of prednisolone. Frequent relapses, according to international criteria, occurred with similar frequency between groups as well (45% versus 50%). In addition, there were no statistically significant differences between groups with respect to the eventual initiation of prednisolone maintenance and/or other immunosuppressive therapy (50% versus 59%), steroid dependence, or adverse effects. In conclusion, in this trial, extending initial prednisolone treatment from 3 to 6 months without increasing cumulative dose did not benefit clinical outcome in children with nephrotic syndrome. Previous findings indicating that prolonged treatment regimens reduce relapses most likely resulted from increased cumulative dose rather than the treatment duration.
Journal of the American Society of Nephrology 12/2013; 24(1):149-59. DOI:10.1681/ASN.2012070646 · 9.34 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To elucidate incidence and risk factors of bone mineral density and fracture risk in children with Acute Lymphoblastic Leukemia (ALL).
Prospectively, cumulative fracture incidence, calculated from diagnosis until one year after cessation of treatment, was assessed in 672 patients. This fracture incidence was compared between subgroups of treatment stratification and age subgroups (Log-Rank test). Serial measurements of bone mineral density of the lumbar spine (BMDLS) were performed in 399 ALL patients using dual energy X-ray absorptiometry. We evaluated risk factors for a low BMD (multivariate regression analysis). Osteoporosis was defined as a BMDLS≤-2 SDS combined with clinical significant fractures.
The 3-years cumulative fracture incidence was 17.8%. At diagnosis, mean BMDLS of ALL patients was lower than of healthy peers (mean BMDLS=-1.10 SDS, P<0.001), and remained lower during/after treatment (8months: BMDLS=-1.10 SDS, P<0.001; 24months: BMDLS=-1.27 SDS, P<0.001; 36months: BMDLS=-0.95 SDS, P<0.001). Younger age, lower weight and B-cell-immunophenotype were associated with a lower BMDLS at diagnosis. After correction for weight, height, gender and immunophenotype, stratification to the high risk (HR)-protocol arm and older age lead to a larger decline of BMDLS (HR group: β=-0.52, P<0.01; age: β=-0.16, P<0.001). Cumulative fracture incidences were not different between ALL risk groups and age groups. Patients with fractures had a lower BMDLS during treatment than those without fractures. Treatment-related bone loss was similar in patients with and without fractures (respectively: ΔBMDLS=-0.36 SDS and ΔBMDLS=-0.12 SDS; interaction group time, P=0.30). Twenty of the 399 patients (5%) met the criteria of osteoporosis.
Low values of BMDLS at diagnosis and during treatment, rather than the treatment-related decline of BMDLS, determines the increased fracture risk of 17.8% in children with ALL.
Bone 11/2013; 59. DOI:10.1016/j.bone.2013.11.017 · 3.97 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: After a more successful treatment of pediatric cancer, the number of childhood cancer survivors is progressively increasing. Consequently, awareness of psychological late sequelae is important.
The Hospital Anxiety and Depression Scale (HADS) was used as a screening tool for emotional distress in a single center cohort of 652 childhood cancer survivors (median age 23 y [range, 15 to 46 y], median follow-up time 15 y [range, 5 to 42 y]). Results were compared with a control group of 440 Dutch subjects. A higher HADS score linearly reflect a higher level of emotional distress, and a score ≥15 is indicative of clinically significant emotional distress.
Mean HADS score of the childhood cancer survivors was not different from the control group (P=0.38). Survivors exposed to global central nervous system (CNS) irradiation had a significantly higher HADS score than the control group (8.3±6.6; P=0.05) as well as other survivors (P=0.01). Forty-three survivors (7%) had a HADS score ≥15. Survivors with a HADS score ≥15 were variously spread over the diagnostic-related and treatment-related subgroups. Linear regression analysis showed that high educational achievement (β=-1.28; P<0.01) and age at the time of the study (β=0.08; P=0.03) were both significantly associated with the HADS score.
Emotional distress does not occur more often in childhood cancer survivors than in the normal population. No disease-related or treatment-related variable was independently associated with emotional distress.
[Show abstract][Hide abstract] ABSTRACT: Randomized studies support the closure of midline incisions with a suture length to wound length ratio (SL:WL) of more than 4, accomplished with small tissue bites and short stitch intervals to decrease the risk of incisional hernia and wound infection. We investigated practical aspects of this technique possibly hampering the introduction of this technique. Patient data, operative variables and SL:WL ratio were collected at two hospitals: Sundsvall Hospital (SH) and Erasmus University Medical Center (EMC). A structured implementation of the technique had been performed at SH but not at EMC. Personnel were interviewed by questionnaire. At each hospital, 18 closures were analyzed. Closure time was significantly longer (p = 0.023) at SH (median 18 minutes, range: 9-59) than at EMC (median 13 minutes, range: 5-23). An SL:WL ratio of more than 4 was achieved in 8 of 18 cases at EMC and in all 18 cases at SH. We conclude that calculation of an SL:WL ratio is easily performed. Suturing with the small bite-short stitch interval technique of SH required 5 minutes extra, outweighing the morbidity of incisional hernia. Without a structured implementation to suture with an SL:WL ratio of more than 4, a lower ratio is often achieved.
[Show abstract][Hide abstract] ABSTRACT: Background:
In chronic obstructive pulmonary disease (COPD), there is a poor correlation between forced expiratory volume in 1 s (FEV1) and dyspnea following bronchodilator use. Better correlations have been observed between inspiratory lung function parameters (ILPs) and dyspnea, which drives our interest in ILPs. However, the acute and prolonged effects of long-acting bronchodilators and oral corticosteroids on ILPs have not been well investigated. Therefore, the aim of this study was to investigate the effects of these treatments on the ILPs, FEV1, dyspnea (visual analog scale (VAS)) and clinical COPD questionnaire (CCQ).
Twenty-eight stable COPD patients had their ILPs and FEV1 measured both before and 2 h after the use of a single dose of 18 mcg bronchodilator tiotropium and 50 mcg salmeterol. Thereafter, the patients were randomized to 2 weeks of treatment with 30 mg oral prednisolone once daily or oral placebo in combination with daily treatment with these two bronchodilators. Four weeks after the cessation of the randomized treatment, the ILPs and FEV1 were again measured. After each intervention, any change in the VAS score was assessed.
With both bronchodilators, significant improvements in ILPs were demonstrated (p < 0.005), with the exception of changes in ILPs inspiratory capacity (IC) and forced inspiratory flow at 50% of the vital capacity (FIF50) after tiotropium inhalation. After 2 weeks of treatment with prednisolone, significant differences were found for ILP forced inspiratory volume in 1 s (FIV1) and FEV1 compared with placebo. These differences were no longer present 4 weeks after the cessation of prednisolone. Significant relationships between ILPs and VAS scores were only found after 2 weeks of treatment with prednisolone or placebo.
After a single dose of long-acting bronchodilator salmeterol, significant improvements are observed in all ILPs and in FIV1 and PIF after tiotropium. Two weeks of oral corticosteroid treatment improved the FIV1 and FEV1. The dyspnea VAS score was only significantly correlated with the ILPs after 2 weeks of oral corticosteroid treatment.