Evaluation of Immunomodulatory Biomarkers in a Pressure Overload Model of Heart Failure

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90380/1/phco.27.4.504.pd

Nonpharmacologic Treatments for Childhood Constipation:Systematic Review

OBJECTIVE: To summarize the evidence and assess the reported quality of studies concerning nonpharmacologic treatments for childhood constipation, including fiber, fluid, physical movement, prebiotics, probiotics, behavioral therapy, multidisciplinary treatment, and forms of alternative medicine. METHODS: We systematically searched 3 major electronic databases and reference lists of existing reviews. We included systematic reviews and randomized controlled trials (RCTs) that reported on nonpharmacologic treatments. Two reviewers rated the methodologic quality independently. RESULTS: We included 9 studies with 640 children. Considerable heterogeneity across studies precluded meta-analysis. We found no RCTs for physical movement, multidisciplinary treatment, or alternative medicine. Some evidence shows that fiber may be more effective than placebo in improving both the frequency and consistency of stools and in reducing abdominal pain. Compared with normal fluid intake, we found no evidence that water intake increases or that hyperosmolar fluid treatment is more effective in increasing stool frequency or decreasing difficulty in passing stools. We found no evidence to recommend the use of prebiotics or probiotics. Behavioral therapy with laxatives is not more effective than laxatives alone. CONCLUSIONS: There is some evidence that fiber supplements are more effective than placebo. No evidence for any effect was found for fluid supplements, prebiotics, probiotics, or behavioral intervention. There is a lack of well-designed RCTs of high quality concerning nonpharmacologic treatments for children with functional constipation. Pediatrics 2011;128:753-76

Value of Abdominal Radiography, Colonic Transit Time, and Rectal Ultrasound Scanning in the Diagnosis of Idiopathic Constipation in Children:A Systematic Review

Objective To perform a systematic review evaluating the value of abdominal radiography, colonic transit time (CTT), and rectal ultrasound scanning in the diagnosis of idiopathic constipation in children. Study design Eligible studies were those assessing diagnostic accuracy of abdominal radiography, CTT, or rectal ultrasound scanning in children suspected for idiopathic constipation. Methodological quality of the included studies was assessed with the Quality Assessment of studies of Diagnostic Accuracy included in Systematic reviews checklist. Results One systematic review summarized 6 studies on abdominal radiography until 2004. The additional 9 studies evaluated abdominal radiography (n = 2), CTT (n = 3), and ultrasound scanning (n = 4). All studies except two used a case-control study design, which will lead to overestimation of test accuracy. Furthermore, none of the studies interpreted the results of the abdominal radiography, ultrasound scanning, or CTT without knowledge of the clinical diagnosis of constipation. The sensitivity of abdominal radiography, as studied in 6 studies, ranged from 80% (95% CI, 65-90) to 60%(95% CI, 46-72), and its specificity ranged from 99%(95% CI, 95-100) to 43%(95% CI, 18-71). Only one study presented test characteristics of CTT, and two studies presented test characteristics of ultrasonography. Conclusion We found insufficient evidence for a diagnostic association between clinical symptoms of constipation and fecal loading on abdominal radiographs, CTT, and rectal diameter on ultrasound scanning in children. (J Pediatr 2012; 161: 44-50)

Ciclesonide versus other inhaled corticosteroids for chronic asthma in children

Background Inhaled corticosteroids (ICS) are the cornerstone of asthma maintenance treatment in children. Particularly among parents, there is concern about the safety of ICS as studies in children have shown reduced growth. Small-particle-size ICS targeting the smaller airways have improved lung deposition and effective asthma control might be achieved at lower daily doses. Ciclesonide is a relatively new ICS. This small-particle ICS is a pro-drug that is converted in the airways to an active metabolite and therefore with potentially less local (throat infection) and systemic (reduced growth) side effects. It can be inhaled once daily, thereby possibly improving adherence. Objectives To assess the efficacy and adverse effects of ciclesonide compared to other ICS in the management of chronic asthma in children. Search methods We searched the Cochrane Airways Group Register of trials with pre-defined terms. Additional searches of MEDLINE (via PubMed), EMBASE and Clinicalstudyresults. org were undertaken. Searches are up to date to 7 November 2012. Selection criteria Randomised controlled parallel or cross-over studies were eligible for the review. We included studies comparing ciclesonide with other corticosteroids both at nominally equivalent doses or lower doses of ciclesonide. Data collection and analysis Two review authors independently assessed trial quality and extracted data. Study authors were contacted for additional information. Adverse effects information was collected from the trials. Main results Six studies were included in this review (3256 children, 4 to 17 years of age). Two studies were published as conference abstracts only. Ciclesonide was compared to budesonide and fluticasone. Ciclesonide compared to budesonide (dose ratio 1: 2): asthma symptoms and adverse effect were similar in both groups. Pooled results showed no significant difference in children who experience an exacerbation (risk ratio (RR) 2.20, 95% confidence interval (CI) 0.75 to 6.43). Both studies reported that 24-hour urine cortisol levels showed a statistically significant decrease in the budesonide group compared to the ciclesonide group. Ciclesonide compared to fluticasone (dose ratio 1: 1): no significant differences were found for the outcome asthma symptoms. Pooled results showed no significant differences in number of patients with exacerbations (RR 1.37, 95% CI 0.58 to 3.21) and data from a study that could not be pooled in the meta-analysis reported similar numbers of patients with exacerbations in both groups. None of the studies found a difference in adverse effects. No significant difference was found for 24-hour urine cortisol levels between the groups (mean difference 0.54 nmol/mmol, 95% CI -5.92 to 7.00). Ciclesonide versus fluticasone (dose ratio 1: 2) was assessed in one study and showed similar results between the two corticosteroids for asthma symptoms. The number of children with exacerbations was significantly higher in the ciclesonide group (RR 3.57, 95% CI 1.35 to 9.47). No significant differences were found in adverse effects (RR 0.98, 95% CI 0.81 to 1.14) and 24-hour urine cortisol levels (mean difference 1.15 nmol/mmol, 95% CI 0.07 to 2.23). The quality of evidence was judged 'low' for the outcomes asthma symptoms and adverse events and 'very low' for the outcome exacerbations for ciclesonide versus budesonide (dose ratio 1: 1). The quality of evidence was graded 'moderate' for the outcome asthma symptoms, 'very low' for the outcome exacerbations and 'low' for the outcome adverse events for ciclesonide versus fluticasone (dose ratio 1: 1). For ciclesonide versus fluticasone (dose ratio 1: 2) the quality was rated 'low' for the outcome asthma symptoms and 'very low' for exacerbations and adverse events (dose ratio 1: 2). Authors' conclusions An improvement in asthma symptoms, exacerbations and side effects of ciclesonide versus budesonide and fluticasone could be neither demonstrated nor refuted and the trade-off between benefits and harms of using ciclesonide instead of budesonide or fluticasone is unclear. The resource use or costs of different ICS should therefore also be considered in final decision making. Longer-term superiority trials are needed to identify the usefulness and safety of ciclesonide compared to other ICS. Additionally these studies should be powered for patient relevant outcomes (exacerbations, asthma symptoms, quality of life and side effects). There is a need for studies comparing ciclesonide once daily with other ICS twice daily to assess the advantages of ciclesonide being a pro-drug that can be administered once daily with possibly increased adherence leading to increased control of asthma and fewer side effects

Effects of Hawthorn on the Progression of Heart Failure in a Rat Model of Aortic Constriction

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90301/1/phco.29.6.639.pd

UvA-DARE (Digital Academic Repository) Implementation of an evidence-based guideline on fluid resuscitation: lessons learnt for future guidelines

Implementation of an evidence-based guideline on fluid resuscitation: lessons learnt for future guidelines Tabbers, M.M.; Boluyt, N.; Offringa, M. General rights It is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulations If you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: https://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. Abstract Introduction There is little experience with the nationwide implementation of an evidence-based pediatric guideline on first-choice fluid for resuscitation in hypovolemia. Methods We investigated fluid prescribing behavior at (1) guideline development, (2) after guideline development, and (3) after active implementation and identified potential barriers and facilitators for guideline implementation. In order to minimize costs and to optimize implementation effect, we continuously developed and adjusted implementation strategies according to identified barriers. Implementation success was evaluated using questionnaires, pharmaceutical data, and data from medical records. Discussion The most remarkable change occurred after guideline development and dissemination: Normal saline use by neonatologists increased from 22-89% to 100% and by pediatric intensivists from 43-71% to 88-100%, and synthetic colloid use by pediatric intensivists declined from 29-43% to 0-13% with a reduction in albumin use by neonatologists from 11-44% to 0%. After active guideline implementation, most of specialist's management behavior was according to the guideline. Conclusion Stakeholders involved in the developmental process are of great importance in disseminating recommendations before active implementation. Therefore, to successfully implement guidelines and reduce costs of active implementation, any guideline development should consider implementation right from the beginning. Implementation strategies should target identified barriers and will therefore always be guideline specific

Changes in Gene Expression During the Formation of Bioengineered Heart Muscle

A three-dimensional bioengineered heart muscle (BEHM) construct model had been previously developed, exhibiting contractile forces up to 800 µN. The interest of this study was to determine gene expression levels of biologic markers involved in calcium-handling between BEHM, cell monolayer, and neonatal heart. Cardiac cells were isolated from one litter of F344 rats and organized into groups ( n  = 5): 4-, 7-, 10-day BEHM and cell monolayer; BEHM was evaluated for cell viability and contractility. Groups were then analyzed for mRNA expression of calcium-handling proteins: myosin heavy chain (MHC) α and β, Sarcoplasmic reticulum Ca++ ATPase (SERCA) 2, phospholamban (PBL), and ryanodine receptor. BEHM exhibited electrically stimulated active force (208 ± 12 µN day 4, 361 ± 22 µN day 7, and 344 ± 29 µN day 10) and no decrease in cell number. Real-time polymerase chain reaction (PCR) showed an increase in gene expression of all calcium-handling proteins in BEHM at 7 and 10 days compared with monolayers, for example, comparing BEHM to monolayer (7 and 10 days, respectively), MHC-α: 2600-fold increase and a 100-fold increase; MHC-β: 70-fold increase at 10 days; ryanodine receptor: 74-fold increase at 10 days; SERCA: 19-fold increase and sixfold increase; PBL: 158-fold increase and 24-fold increase. It was concluded that a three-dimensional environment is a better culturing condition of cardiac cells than a monolayer. Also, BEHM constructs demonstrated a high similarity to a native myocardium, and is, thus, a good starting foundation for engineered heart muscle. Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/72077/1/j.1525-1594.2008.00669.x.pd

Implementation of an evidence-based guideline on fluid resuscitation: lessons learnt for future guidelines

There is little experience with the nationwide implementation of an evidence-based pediatric guideline on first-choice fluid for resuscitation in hypovolemia. We investigated fluid prescribing behavior at (1) guideline development, (2) after guideline development, and (3) after active implementation and identified potential barriers and facilitators for guideline implementation. In order to minimize costs and to optimize implementation effect, we continuously developed and adjusted implementation strategies according to identified barriers. Implementation success was evaluated using questionnaires, pharmaceutical data, and data from medical records. The most remarkable change occurred after guideline development and dissemination: Normal saline use by neonatologists increased from 22-89% to 100% and by pediatric intensivists from 43-71% to 88-100%, and synthetic colloid use by pediatric intensivists declined from 29-43% to 0-13% with a reduction in albumin use by neonatologists from 11-44% to 0%. After active guideline implementation, most of specialist's management behavior was according to the guideline. Stakeholders involved in the developmental process are of great importance in disseminating recommendations before active implementation. Therefore, to successfully implement guidelines and reduce costs of active implementation, any guideline development should consider implementation right from the beginning. Implementation strategies should target identified barriers and will therefore always be guideline specifi