Drooling is a common problem for children with cerebral palsy (CP). This can be distressing for these children as well as for their parents and caregivers. The consequences of drooling include risk of social rejection, damp and soiled clothing, unpleasant odour, irritated chapped skin, mouth infections, dehydration, interference with speech, damage to books, communication aids, computers, and the risk of social isolation (Blasco 1992; Van der Burg 2006). A range of interventions exist that aim to reduce or eliminate drooling. There is a lack of consensus regarding which interventions are most effective for children with CP.
(1) To evaluate the effectiveness and safety of interventions aimed at reducing or eliminating drooling in children with cerebral palsy. (2) To provide the best available evidence to inform clinical practice. (3) To assist with future research planning.
We searched the following databases from inception to December 2010 : Cochrane Central Register of Controlled Trials (CENTRAL); Medline via Ovid; EMBASE; CINAHL; ERIC; Psych INFO; Web of Science; Web of Knowledge; AMED; SCOPUS; Dissertation Abstracts.We searched for ongoing clinical trials in the Clinical Trials web site (http://clinicaltrials.gov.) and in the Current Controlled Trials web site (http://www.controlled-trials.com/). We hand searched a range of relevant journals and conference proceeding abstracts.
Only randomised controlled trials (RCTs) and controlled clinical trials (CCTs) were included.
Data were extracted independently by MW, MS and LP and differences resolved through discussion.
Six studies were eligible for inclusion in the review. Four of these studies were trials using botulinum toxin-A (BoNT-A) and two were trials on the pharmacological interventions, benztropine and glycopyrrolate. No RCTs or CCTs were retrieved on surgery, physical, oro-motor and oro-sensory therapies, behavioural interventions, intra-oral appliances or acupuncture. In the studies eligible for review, there was considerable heterogeneity within and across interventions and a meta-analysis was not possible. A descriptive summary of each study is provided. All studies showed some statistically significant change for treatment groups up to 1 month post intervention. However, there were methodological flaws associated with all six studies.
It was not possible to reach a conclusion on the effectiveness and safety of either BoNT-A or the pharmaceutical interventions, benztropine and glycopyrrolate. There is insufficient evidence to inform clinical practice on interventions for drooling in children with CP. Directions for future research are provided.
[Show abstract][Hide abstract] ABSTRACT: We consider the possibility of engineering metabolic pathways in a chassis organism in order to synthesize novel target compounds that are heterologous to the chassis. For this purpose, we model metabolic networks through hypergraphs where reactions are represented by hyperarcs. Each hyperarc represents an enzyme-catalyzed reaction that transforms set of substrates compounds into product compounds. We follow a retrosynthetic approach in order to search in the metabolic space (hypergraphs) for pathways (hyperpaths) linking the target compounds to a source set of compounds.
To select the best pathways to engineer, we have developed an objective function that computes the cost of inserting a heterologous pathway in a given chassis organism. In order to find minimum-cost pathways, we propose in this paper two methods based on steady state analysis and network topology that are to the best of our knowledge, the first to enumerate all possible heterologous pathways linking a target compounds to a source set of compounds. In the context of metabolic engineering, the source set is composed of all naturally produced chassis compounds (endogenuous chassis metabolites) and the target set can be any compound of the chemical space. We also provide an algorithm for identifying precursors which can be supplied to the growth media in order to increase the number of ways to synthesize specific target compounds.
We find the topological approach to be faster by several orders of magnitude than the steady state approach. Yet both methods are generally scalable in time with the number of pathways in the metabolic network. Therefore this work provides a powerful tool for pathway enumeration with direct application to biosynthetic pathway design.
BMC Systems Biology 02/2012; 6(1):10. DOI:10.1186/1752-0509-6-10 · 2.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Aim The aim of this paper was to systematically review the efficacy and safety of botulinum toxin (BoNT) injections to the salivary glands to treat drooling in children with cerebral palsy and neurodevelopmental disability.
Method A systematic search of The Cochrane Central Register of Controlled Trials, PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), EMBASE, and the Physiotherapy Evidence Database (PEDro) was conducted (up to 1 October 2011). Data sources included published randomized controlled trials (RCTs) and prospective studies.
Results Sixteen studies met inclusion criteria. Three outcome measures support the effectiveness of BoNT for drooling. One RCT found an almost 30% reduction in the impact of drooling on patients’ lives, as measured by the Drooling Impact Scale (mean difference −27.45; 95% confidence interval [CI] −35.28 to −19.62). There were sufficient data to pool results on one outcome measure, the Drooling Frequency and Severity Scale, which supports this result (mean difference −2.71; 95% CI −4.82 to −0.60; p<0.001). There was a significant reduction in the observed number of bibs required per day. The incidence of adverse events ranged from 2 to 41%, but was inconsistently reported. One trial was terminated early because of adverse events.
Interpretation BoNT is an effective, temporary treatment for sialorrhoea in children with cerebral palsy. Benefits need to be weighed against the potential for serious adverse events. More studies are needed to address the safety of BoNT and to compare BoNT with other treatment options for drooling.
[Show abstract][Hide abstract] ABSTRACT: Objectives
Botulinum toxin has emerged as an effective approach for the management of sialorrhea. This study presents a critical literature review and meta-analysis to determine the impact of botulinum toxin on drooling severity in patients with sialorrhea.Data SourcesOvid MEDLINE and the Cochrane databases.Review Methods
The above sources were searched to identify studies examining botulinum toxin for the treatment of sialorrhea. Included studies were randomized, placebo-controlled trials. Excluded studies failed to report quantifiable outcome measures of drooling severity at 4 weeks postintervention.ResultsEight studies involving 181 patients (83 placebo; 98 active) were included in the analysis. Botulinum toxin was found to significantly decrease the severity of drooling in patients with sialorrhea (standardized mean difference [SMD], -1.54; 95% confidence interval [CI], -2.05 to -1.04; P = .06; I(2) = 48%) when compared with placebo control using random effects models. The effect was significant in both adult (SMD, -1.29; 95% CI, -1.88 to -0.71) and pediatric (SMD, -1.84; 95% CI, -2.67 to -1.00) populations. Both botulinum toxin A (SMD, -1.53; 95% CI, -2.27 to -0.79) and B (SMD, -1.56; 95% CI, -2.32 to -0.79) produced similar effects. Botulinum toxin doses greater than 50 U (SMD, -3.81; 95% CI, -6.19 to -1.43) produced much stronger effects compared with doses less than or equal to 50 U (SMD, -1.32; 95% CI, -2.28 to -0.36).Conclusion
Botulinum toxin is a clinically effective therapy that improves drooling severity in patients with sialorrhea. Future studies will need to further evaluate the technique and examine dosages required to achieve optimal outcomes.
Otolaryngology Head and Neck Surgery 10/2012; 148(2). DOI:10.1177/0194599812465059 · 2.02 Impact Factor
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