The impact of behavioural skills training on the knowledge, skills and well-being of front line staff in the intellectual disability sector: a clustered randomised control trial.

BACKGROUND: Staff with varying backgrounds and educational qualifications can be effectively trained to implement procedures in line with evidence-based practice. Behavioural skills training (BST) is a competency-based training model used to effectively educate a broad selection of professionals, including front line staff, in a range of work-related skills. However, BST has yet to be evaluated in a large group-based experiment. METHODS: This study involved a parallel cluster randomised control trial. Six service sites, with a total of 54 participants, were randomised to the intervention condition using the 'coin toss' method. The intervention condition used BST to coach intellectual disability staff in reinforcement, systematic prompting, functional communication training and task analysis. Six service sites, with a total of 50 participants, were also randomised to a control condition in which generalised training in behavioural interventions was restricted. Recruited service sites were randomly assigned to the intervention condition (N = 6, n = 54) or the control condition (N = 6, n = 50) at one point in time, immediately after recruitment and before baseline testing took place. Allocations were stratified by service type (residential or day) and geographical region. One member of the research team allocated service sites using the 'coin toss' method, and another member, blind to the allocations, decided which experimental arm would receive the intervention and which would be designated as control. It was not possible to mask the intervention from participants, but they were recruited prior to randomisation. RESULTS: Participants in the intervention condition demonstrated statistically significant improvements in their knowledge scores over the study period. Participants in the control condition showed no change or a statistically significant decrease in their knowledge scores. No statistically significant changes to well-being were observed for either group. There was clear evidence of knowledge maintenance, as well as skill acquisition and subsequent generalisation to the workplace environment, among participants in the intervention condition. Participants also evaluated the BST intervention positively. CONCLUSIONS: Results support BST as a method for disseminating evidence-based practice to front line staff working with adults with intellectual and developmental disabilities.

Longitudinal associations between asthma and general and abdominal weight status among Norwegian adolescents and young adults: the HUNT Study.

BACKGROUND: In adolescents the temporal directionality to the asthma and adiposity association remains unclear. Asthma may be a consequence of obesity; however, asthma may increase adiposity. OBJECTIVES: This study aimed to assess the associations between (i) baseline weight status and subsequent asthma and (ii) baseline asthma and subsequent weight status after 4 and 11 years of follow-up (N = 1543 and N = 1596, respectively) using data from three, sequentially enrolled population-based surveys of Norwegians aged 12-30 years from 1995 to 2008. METHODS: Weight status was defined as general (body mass index) or abdominal (waist circumference) underweight, normal weight, overweight or obesity. Self-report physician-diagnosed asthma defined asthma status. RESULTS: Over the longitudinal 11-year follow-up, baseline generally overweight or abdominally obese adolescents had increased risk of asthma. Likewise, baseline asthmatics had increased risk of general overweight or abdominal obesity. After sex stratification, these associations were stronger in males. Generally (odds ratio [OR] 1.90; 95% confidence interval [CI] 1.32, 2.73) or abdominally (OR 1.66; 95% CI 1.13, 2.44) overweight males were at increased risk of asthma. Baseline asthmatic males were also at increased risk of general (OR 2.14; 95% CI 1.54, 2.98) and abdominal (OR 1.77; 95% CI 1.27, 2.47) overweight. CONCLUSIONS: Among Norwegian adolescents, a bidirectional association of asthma and adiposity was observed in males. Each baseline condition increased the risk of the other condition over time. No association was observed in females.

Efficient Computation of Small-Molecule Configurational Binding Entropy and Free Energy Changes by Ensemble Enumeration.

Here we present a novel, end-point method using the dead-end-elimination and A* algorithms to efficiently and accurately calculate the change in free energy, enthalpy, and configurational entropy of binding for ligand-receptor association reactions. We apply the new approach to the binding of a series of human immunodeficiency virus (HIV-1) protease inhibitors to examine the effect ensemble reranking has on relative accuracy as well as to evaluate the role of the absolute and relative ligand configurational entropy losses upon binding in affinity differences for structurally related inhibitors. Our results suggest that most thermodynamic parameters can be estimated using only a small fraction of the full configurational space, and we see significant improvement in relative accuracy when using an ensemble versus single-conformer approach to ligand ranking. We also find that using approximate metrics based on the single-conformation enthalpy differences between the global minimum energy configuration in the bound as well as unbound states also correlates well with experiment. Using a novel, additive entropy expansion based on conditional mutual information, we also analyze the source of ligand configurational entropy loss upon binding in terms of both uncoupled per degree of freedom losses as well as changes in coupling between inhibitor degrees of freedom. We estimate entropic free energy losses of approximately +24 kcal/mol, 12 kcal/mol of which stems from loss of translational and rotational entropy. Coupling effects contribute only a small fraction to the overall entropy change (1-2 kcal/mol) but suggest differences in how inhibitor dihedral angles couple to each other in the bound versus unbound states. The importance of accounting for flexibility in drug optimization and design is also discussed.

Crystal structure of an HSA/FcRn complex reveals recycling by competitive mimicry of HSA ligands at a pH-dependent hydrophobic interface.

The long circulating half-life of serum albumin, the most abundant protein in mammalian plasma, derives from pH-dependent endosomal salvage from degradation, mediated by the neonatal Fc receptor (FcRn). Using yeast display, we identified human serum albumin (HSA) variants with increased affinity for human FcRn at endosomal pH, enabling us to solve the crystal structure of a variant HSA/FcRn complex. We find an extensive, primarily hydrophobic interface stabilized by hydrogen-bonding networks involving protonated histidines internal to each protein. The interface features two key FcRn tryptophan side chains inserting into deep hydrophobic pockets on HSA that overlap albumin ligand binding sites. We find that fatty acids (FAs) compete with FcRn, revealing a clash between ligand binding and recycling, and that our high-affinity HSA variants have significantly increased circulating half-lives in mice and monkeys. These observations open the way for the creation of biotherapeutics with significantly improved pharmacokinetics.

Design of a superior cytokine antagonist for topical ophthalmic use.

IL-1 is a key inflammatory and immune mediator in many diseases, including dry-eye disease, and its inhibition is clinically efficacious in rheumatoid arthritis and cryopyrin-associated periodic syndromes. To treat ocular surface disease with a topical biotherapeutic, the uniqueness of the site necessitates consideration of the agent's size, target location, binding kinetics, and thermal stability. Here we chimerized two IL-1 receptor ligands, IL-1ß and IL-1Ra, to create an optimized receptor antagonist, EBI-005, for topical ocular administration. EBI-005 binds its target, IL-1R1, 85-fold more tightly than IL-1Ra, and this increase translates to an ∼100-fold increase in potency in vivo. EBI-005 preserves the affinity bias of IL-1Ra for IL-1R1 over the decoy receptor (IL-1R2), and, surprisingly, is also more thermally stable than either parental molecule. This rationally designed antagonist represents a unique approach to therapeutic design that can potentially be exploited for other ß-trefoil family proteins in the IL-1 and FGF families.

Efficient calculation of molecular configurational entropies using an information theoretic approximation.

Accurate computation of free energy changes upon molecular binding remains a challenging problem, and changes in configurational entropy are especially difficult due to the potentially large numbers of local minima, anharmonicity, and high-order coupling among degrees of freedom. Here we propose a new method to compute molecular entropies based on the maximum information spanning tree (MIST) approximation that we have previously developed. Estimates of high-order couplings using only low-order terms provide excellent convergence properties, and the theory is also guaranteed to bound the entropy. The theory is presented together with applications to the calculation of the entropies of a variety of small molecules and the binding entropy change for a series of HIV protease inhibitors. The MIST framework developed here is demonstrated to compare favorably with results computed using the related mutual information expansion (MIE) approach, and an analysis of similarities between the methods is presented.

Evaluation of conventional PCR for detection of Strongylus vulgaris on horse farms.

Strongyle parasites are ubiquitous in grazing horses. Of these, the bloodworm Strongylus vulgaris is regarded as most pathogenic. Increasing levels of anthelmintic resistance in strongyle parasites has led to recommendations of decreased treatment intensities, and there is now a pronounced need for reliable tools for detection of parasite burdens in general and S. vulgaris in particular. The only method currently available for diagnosing S. vulgaris in practice is the larval culture, which is laborious and time-consuming, so veterinary practitioners most often pool samples from several horses together in one culture to save time. Recently, molecular tools have been developed to detect S. vulgaris in faecal samples. The aim of this study was to compare the performance of a conventional polymerase chain reaction (PCR) assay with the traditional larval culture and furthermore test the performance of pooled versus individual PCR for farm screening purposes. Faecal samples were obtained from 331 horses on 18 different farms. Farm size ranged from 6 to 56 horses, and horses aged between 2 months and 31 years. Larval cultures and PCR were performed individually on all horses. In addition, PCR was performed on 66 faecal pools consisting of 3-5 horses each. Species-specific PCR primers previously developed were used for the PCR. PCR and larval culture detected S. vulgaris in 12.1 and 4.5% of individual horses, respectively. On the farm level, eight farms tested positive with the larval culture, while 13 and 11 farms were positive with the individual and pooled PCRs, respectively. The individual PCR method was statistically superior to the larval culture, while no statistical difference could be detected between pooled and individual PCR for farm screening. In conclusion, pooled PCR appears to be a useful tool for farm screening for S. vulgaris.

A multifaceted analysis of HIV-1 protease multidrug resistance phenotypes.

BACKGROUND: Great strides have been made in the effective treatment of HIV-1 with the development of second-generation protease inhibitors (PIs) that are effective against historically multi-PI-resistant HIV-1 variants. Nevertheless, mutation patterns that confer decreasing susceptibility to available PIs continue to arise within the population. Understanding the phenotypic and genotypic patterns responsible for multi-PI resistance is necessary for developing PIs that are active against clinically-relevant PI-resistant HIV-1 variants. RESULTS: In this work, we use globally optimal integer programming-based clustering techniques to elucidate multi-PI phenotypic resistance patterns using a data set of 398 HIV-1 protease sequences that have each been phenotyped for susceptibility toward the nine clinically-approved HIV-1 PIs. We validate the information content of the clusters by evaluating their ability to predict the level of decreased susceptibility to each of the available PIs using a cross validation procedure. We demonstrate the finding that as a result of phenotypic cross resistance, the considered clinical HIV-1 protease isolates are confined to ~6% or less of the clinically-relevant phenotypic space. Clustering and feature selection methods are used to find representative sequences and mutations for major resistance phenotypes to elucidate their genotypic signatures. We show that phenotypic similarity does not imply genotypic similarity, that different PI-resistance mutation patterns can give rise to HIV-1 isolates with similar phenotypic profiles. CONCLUSION: Rather than characterizing HIV-1 susceptibility toward each PI individually, our study offers a unique perspective on the phenomenon of PI class resistance by uncovering major multidrug-resistant phenotypic patterns and their often diverse genotypic determinants, providing a methodology that can be applied to understand clinically-relevant phenotypic patterns to aid in the design of novel inhibitors that target other rapidly evolving molecular targets as well.

The importance of nurse-led home visits in the assessment of children with problematic asthma.

OBJECTIVE: To evaluate and identify potentially modifiable factors in children with problematic asthma by a nurse-led assessment and home visit. DESIGN: Observational cohort study. SETTING: A tertiary paediatric respiratory centre. PATIENTS: 71 children, aged 4.5-17.5 years, with problematic asthma currently under follow-up at a tertiary respiratory centre. INTERVENTIONS: A nurse-led hospital visit followed by a home visit. MAIN OUTCOME MEASURES: Identification and attempted change of exacerbating factors so that further investigations and consideration of off-label, potentially toxic, asthma therapies were not necessary. RESULTS: Potentially modifiable factors were identified in 56 (79%) children. Many children had multiple causes for poor control. The most important were ongoing allergen exposure, 22 children (31%); passive or active smoking, 18 children (25%); medication issues including adherence, 34 children (48%); psychosocial factors, 42 families (59%). The home visit contributed valuable information to this assessment. At the home visit house dust mite avoidance measures were found to be inadequate in 84% of those sensitised; medications were not easily available for inspection or were out of date in 23%; 74% of psychology referrals were made after the home visit. In 39 children (55%) the factors identified and the interventions recommended meant that further escalation of treatment was avoided. CONCLUSIONS: Nurse-led assessments including a home visit can help identify potentially modifiable factors for poorly controlled symptoms in children with problematic asthma.

Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity.

Idiosyncratic drug hepatotoxicity represents a major problem in drug development due to inadequacy of current preclinical screening assays, but recently established rodent models utilizing bacterial LPS co-administration to induce an inflammatory background have successfully reproduced idiosyncratic hepatotoxicity signatures for certain drugs. However, the low-throughput nature of these models renders them problematic for employment as preclinical screening assays. Here, we present an analogous, but high-throughput, in vitro approach in which drugs are administered to a variety of cell types (primary human and rat hepatocytes and the human HepG2 cell line) across a landscape of inflammatory contexts containing LPS and cytokines TNF, IFN gamma, IL-1 alpha, and IL-6. Using this assay, we observed drug-cytokine hepatotoxicity synergies for multiple idiosyncratic hepatotoxicants (ranitidine, trovafloxacin, nefazodone, nimesulide, clarithromycin, and telithromycin) but not for their corresponding non-toxic control compounds (famotidine, levofloxacin, buspirone, and aspirin). A larger compendium of drug-cytokine mix hepatotoxicity data demonstrated that hepatotoxicity synergies were largely potentiated by TNF, IL-1 alpha, and LPS within the context of multi-cytokine mixes. Then, we screened 90 drugs for cytokine synergy in human hepatocytes and found that a significantly larger fraction of the idiosyncratic hepatotoxicants (19%) synergized with a single cytokine mix than did the non-hepatotoxic drugs (3%). Finally, we used an information theoretic approach to ascertain especially informative subsets of cytokine treatments for most highly effective construction of regression models for drug- and cytokine mix-induced hepatotoxicities across these cell systems. Our results suggest that this drug-cytokine co-treatment approach could provide a useful preclinical tool for investigating inflammation-associated idiosyncratic drug hepatotoxicity.

MIST: Maximum Information Spanning Trees for dimension reduction of biological data sets.

MOTIVATION: The study of complex biological relationships is aided by large and high-dimensional data sets whose analysis often involves dimension reduction to highlight representative or informative directions of variation. In principle, information theory provides a general framework for quantifying complex statistical relationships for dimension reduction. Unfortunately, direct estimation of high-dimensional information theoretic quantities, such as entropy and mutual information (MI), is often unreliable given the relatively small sample sizes available for biological problems. Here, we develop and evaluate a hierarchy of approximations for high-dimensional information theoretic statistics from associated low-order terms, which can be more reliably estimated from limited samples. Due to a relationship between this metric and the minimum spanning tree over a graph representation of the system, we refer to these approximations as MIST (Maximum Information Spanning Trees). RESULTS: The MIST approximations are examined in the context of synthetic networks with analytically computable entropies and using experimental gene expression data as a basis for the classification of multiple cancer types. The approximations result in significantly more accurate estimates of entropy and MI, and also correlate better with biological classification error than direct estimation and another low-order approximation, minimum-redundancy-maximum-relevance (mRMR). AVAILABILITY: Software to compute the entropy approximations described here is available as Supplementary Material. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Continuous infusion versus intermittent bolus doses of indomethacin for patent ductus arteriosus closure in symptomatic preterm infants.

BACKGROUND: Indomethacin is a prostaglandin inhibitor used for the prevention and the treatment of patent ductus arteriosus (PDA). Although a 3-dose schedule has been commonly used, there is no consensus on optimal dosage and duration of indomethacin therapy for PDA closure. There are potential adverse effects of indomethacin use in premature infants such as a reduction in cerebral, mesenteric and renal blood flow and platelet dysfunction. Administering indomethacin continuously over 36-hours has been suggested as a safer and more effective option to prevent such adverse effects. OBJECTIVES: To compare the efficacy and safety of continuous infusion versus bolus administration of indomethacin in closing a symptomatic PDA in preterm infants. SEARCH STRATEGY: The standard search strategy of Cochrane Neonatal Review was used: MEDLINE and EMBASE (1966 - March 2007), Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 1, 2007), bibliographies of reviews and trials were examined for references to other trials, previous symposia proceedings published in Pediatric Research (Pediatric Academic Societies Annual Meeting Abstract Book, 1972 - 2006). No language restrictions were applied. SELECTION CRITERIA: Randomized and quasi-randomized controlled trials comparing continuous indomethacin infusion to bolus doses for closure of a symptomatic PDA in preterm infants with a symptomatic PDA diagnosed clinically and/or by echocardiography. DATA COLLECTION AND ANALYSIS: The methodological quality of each study was assessed. Authors were contacted regarding missing data as well as to inquire about the outcomes that were not reported. Meta-analysis was performed to calculate relative risk (RR), risk difference (RD) and 95% confidence intervals (CI). MAIN RESULTS: Only two small trials comparing continuous versus bolus indomethacin were eligible. Analysis of these studies showed that, although the primary outcome of PDA closure on days two and five slightly favored bolus administration, there was no statistical difference between the two groups. The estimates for PDA closure were RR 1.57 (95% CI 0.54, 4.60), RD 0.10 (95% CI -0.13, 0.33) for day 2 and RR 2.77 (95% CI 0.33, 23.14), RD 0.15 (95% CI -0.13, 0.42) for day five. There was no statistical difference between the bolus and continuous groups for the secondary outcomes of reopening of PDA, neonatal mortality, intraventricular hemorrhage (IVH) and necrotizing enterocolitis (NEC). These analyses were based on a very small number of events reported by these trials. None of the trials reported on outcomes such as requirement for retreatment with indomethacin or surgical ligation, mortality, bronchopulmonary dysplasia (BPD), retinopathy of prematurity (ROP), neurodevelopmental outcome and isolated intestinal perforation. The review demonstrated that there was a decrease in cerebral blood flow velocity after bolus injections and that the difference between the bolus and continuous infusion groups remained significant for 12 - 24 hour. In one study (Christmann 2002), the decrease in blood flow was maximum at 10 minutes [MD -46.40 (95% CI -75.41, -17.39)], while the other study (Hammerman 1995) reported a maximum drop at 30 minutes [MD -55.60 (95% CI -62.92, -48.28)]. Similar decrease in blood flow to the renal and mesenteric circulations following bolus administration was reported in one study (Christmann 2002). In both of these circulations, the decrease was maximum 30 minutes after the bolus injection [typical estimates for renal and mesenteric circulations, respectively: MD -42.00 (95% CI -76.59, -7.41) and MD -26.50 (95% CI -45.34, -7.66)] and lasted about two hours. None of the trials detected predefined levels of decreased urine output and increased levels of BUN and creatinine. AUTHORS' CONCLUSIONS: Due to a paucity of events and lack of precision, the available data was found to be insufficient to draw conclusions regarding the efficacy of continuous indomethacin infusion versus bolus injections for the treatment of PDA. Although continuous indomethacin seems to cause less alterations in cerebral, renal and mesenteric circulations, the clinical meaning of this effect is unclear. Definitive recommendations about the preferred method of indomethacin administration i.e. continuous versus bolus infusions for the treatment of PDA in premature infants cannot be made based on the current findings of this review.

A systematic review: antipsychotic augmentation with treatment refractory obsessive-compulsive disorder.

As many as half of obsessive-compulsive disorder (OCD) patients treated with an adequate trial of serotonin reuptake inhibitors (SRIs) fail to fully respond to treatment and continue to exhibit significant symptoms. Many studies have assessed the effectiveness of antipsychotic augmentation in SRI-refractory OCD. In this systematic review, we evaluate the efficacy of antipsychotic augmentation in treatment-refractory OCD. The electronic databases of PubMed, PsychINFO (1967-2005), Embase (1974-2000) and the Cochrane Central Register of Controlled Trials (CENTRAL, as of 2005, Issue 3) were searched for relevant double-blind trials using keywords 'antipsychotic agents' or 'neuroleptics' and 'obsessive-compulsive disorder'. Search results and analysis were limited to double-blind, randomized control trials involving the adult population. The proportion of subjects designated as treatment responders was defined by a greater than 35% reduction in Yale Brown Obsessive-Compulsive Scale (Y-BOCS) rating during the course of augmentation therapy. Nine studies involving 278 participants were included in the analysis. The meta-analysis of these studies demonstrated a significant absolute risk difference (ARD) in favor of antipsychotic augmentation of 0.22 (95% confidence interval (CI): 0.13, 0.31). The subgroup of OCD patients with comorbid tics have a particularly beneficial response to this intervention, ARD=0.43 (95% CI: 0.19, 0.68). There was also evidence suggesting OCD patients should be treated with at least 3 months of maximal-tolerated therapy of an SRI before initiating antipsychotic augmentation owing to the high rate of treatment response to continued SRI monotherapy (25.6%). Antipsychotic augmentation in SRI-refractory OCD is indicated in patients who have been treated for at least 3 months of maximal-tolerated therapy of an SRI. Unfortunately, only one-third of treatment-refractory OCD patients show a meaningful treatment response to antipsychotic augmentation. There is sufficient evidence in the published literature, demonstrating the efficacy of haloperidol and risperidone, and evidence regarding the efficacy of quetiapine and olanzapine is inconclusive. Patients with comorbid tics are likely to have a differential benefit to antipsychotic augmentation.

The influence of air conditioning, humidity, temperature and other household characteristics on mite allergen concentrations in the northeastern United States.

BACKGROUND: Information about the influence of housing and occupant characteristics on mite allergen concentrations is crucial to determine which methods could be used to decrease exposure of susceptible subjects. OBJECTIVES: To identify housing and occupant characteristics that are associated with mite allergen concentrations in house dust collected from living rooms and mattresses. METHODS: We collected dust samples from 750 homes in the northeastern US. The influence of various characteristics on concentrations of mite allergens (Der p 1 and Der f 1) was studied using multiple linear regression analysis. RESULTS: Some characteristics, like absence of air conditioners, the presence of mold or mildew, and a lower temperature were consistently associated with higher concentrations of both mite allergens in dust from all sampling locations. However, none of these factors changed Der p 1 or Der f 1 concentrations by more than a factor of 2. People of white ethnic background had roughly two times higher mite allergen concentrations, while family income, family size, and education level only marginally influenced mite allergen concentrations. CONCLUSIONS: Various housing characteristics have some influence on mite allergen concentrations, and could possibly be used to decrease exposure of susceptible subjects. However, only a limited percentage of the variation in mite allergen concentrations was explained by these characteristics.

Coastal oceanography sets the pace of rocky intertidal community dynamics.

The structure of ecological communities reflects a tension among forces that alter populations. Marine ecologists previously emphasized control by locally operating forces (predation, competition, and disturbance), but newer studies suggest that inputs from large-scale oceanographically modulated subsidies (nutrients, particulates, and propagules) can strongly influence community structure and dynamics. On New Zealand rocky shores, the magnitude of such subsidies differs profoundly between contrasting oceanographic regimes. Community structure, and particularly the pace of community dynamics, differ dramatically between intermittent upwelling regimes compared with relatively persistent down-welling regimes. We suggest that subsidy rates are a key determinant of the intensity of species interactions, and thus of structure in marine systems, and perhaps also nonmarine communities.

Steroids for acute spinal cord injury.

BACKGROUND: Acute spinal cord injury is a devastating condition typically affecting young people with a preponderance being male. Steroid treatment in the early hours of the injury is aimed at reducing the extent of permanent paralysis during the rest of the patient's life. OBJECTIVES: To review randomized trials of steroids for acute spinal cord injury. SEARCH STRATEGY: The review draws on the search strategy developed by the Cochrane Injuries Group. In addition, files of the National Acute Spinal Cord Injury Study have been reviewed and a Medline search conducted. SELECTION CRITERIA: All published or unpublished randomized controlled trials of steroid treatment for acute spinal cord injury in any language. DATA COLLECTION AND ANALYSIS: Data have been abstracted from original trial reports. For the NASCIS, Japanese and French trials, additional data (e.g. SDs) have been obtained from the original authors. MAIN RESULTS: There are few trials in this area of medical care. Only one steroid has been extensively studied, methylprednisolone sodium succinate, which has been shown to improve neurologic outcome up to one year post injury if administered within eight hours of injury and in a dose regimen of: bolus 30mg/kg administered over 15 minutes with a maintenance infusion of 5.4 mg/kg per hour infused for 23 hours. The initial North American trial was replicated in a Japanese trial but not in the one from France. Data has been obtained from the latter studies to permit appropriate meta-analysis of all three trials. This analysis indicates significant recovery in motor function after methylprednisolone therapy when administration commences within eight hours of injury. A more recent trial indicates that if methylprednisolone therapy is given for an additional 24 hours (for a total of 48 hours), additional improvement in motor neurologic function and functional status is observed. This is particularly observed if treatment cannot be started until between three to eight hours after injury. The same methylprednisolone therapy has been found effective in whiplash injuries and a modified regimen found to improve recovery after surgery for lumbar disc disease. REVIEWER'S CONCLUSIONS: High dose methylprednisolone steroid therapy is the only pharmacological therapy shown to have efficacy in a Phase Three randomized trial when it can be administered within eight hours of injury. A recent trial indicates additional benefit by extending the maintenance dose from 24 to 48 hours if start of treatment must be delayed to between three and eight hours after injury. There is an urgent need for more randomized trials of pharmacological therapy for acute spinal cord injury.

Bronchodilator therapy and hyperactivity in preschool children.

The common report of parents of asthmatic children that inhaled/nebulised salbutamol causes overactive behaviour was investigated. Nineteen children were assessed in a standardised setting before and after the administration of nebulised salbutamol and placebo. Neither parental report nor observer ratings suggested any significant increase in the child's level of activity.