Assessment of data quality in a multi-centre cross-sectional study of participation and quality of life of children with cerebral palsy

Background: SPARCLE is a cross-sectional survey in nine European regions, examining the relationship of the environment of children with cerebral palsy to their participation and quality of life. The objective of this report is to assess data quality, in particular heterogeneity between regions, family and item non-response and potential for bias. Methods: 1,174 children aged 8–12 years were selected from eight population-based registers of children with cerebral palsy; one further centre recruited 75 children from multiple sources. Families were visited by trained researchers who administered psychometric questionnaires. Logistic regression was used to assess factors related to family non-response and self-completion of questionnaires by children. Results: 431/1,174 (37%) families identified from registers did not respond: 146 (12%) were not traced; of the 1,028 traced families, 250 (24%) declined to participate and 35 (3%) were not approached. Families whose disabled children could walk unaided were more likely to decline to participate. 818 children entered the study of which 500 (61%) self-reported their quality of life; children with low IQ, seizures or inability to walk were less likely to self-report. There was substantial heterogeneity between regions in response rates and socio-demographic characteristics of families but not in age or gender of children. Item non-response was 2% for children and ranged from 0.4% to 5% for questionnaires completed by parents. Conclusion: While the proportion of untraced families was higher than in similar surveys, the refusal rate was comparable. To reduce bias, all analyses should allow for region, walking ability, age and socio-demographic characteristics. The 75 children in the region without a population based register are unlikely to introduce bias

Mutational analysis of the active centre of coronavirus 3C-like proteases.

Formation of the coronavirus replication-transcription complex involves the synthesis of large polyprotein precursors that are extensively processed by virus-encoded cysteine proteases. In this study, the coding sequence of the feline infectious peritonitis virus (FIPV) main protease, 3CL(pro), was determined. Comparative sequence analyses revealed that FIPV 3CL(pro) and other coronavirus main proteases are related most closely to the 3C-like proteases of potyviruses. The predicted active centre of the coronavirus enzymes has accepted unique replacements that were probed by extensive mutational analysis. The wild-type FIPV 3CL(pro) domain and 25 mutants were expressed in Escherichia coli and tested for proteolytic activity in a peptide-based assay. The data strongly suggest that, first, the FIPV 3CL(pro) catalytic system employs His(41) and Cys(144) as the principal catalytic residues. Second, the amino acids Tyr(160) and His(162), which are part of the conserved sequence signature Tyr(160)-Met(161)-His(162) and are believed to be involved in substrate recognition, were found to be indispensable for proteolytic activity. Third, replacements of Gly(83) and Asn(64), which were candidates to occupy the position spatially equivalent to that of the catalytic Asp residue of chymotrypsin-like proteases, resulted in proteolytically active proteins. Surprisingly, some of the Asn(64) mutants even exhibited strongly increased activities. Similar results were obtained for human coronavirus (HCoV) 3CL(pro) mutants in which the equivalent Asn residue (HCoV 3CL(pro) Asn(64)) was substituted. These data lead us to conclude that both the catalytic systems and substrate-binding pockets of coronavirus main proteases differ from those of other RNA virus 3C and 3C-like proteases.

Influence of prolonged hospitalization on overall bed occupancy: a five-year single-centre study

Background: Effective bed use is crucial to an efficient NHS. Current targets suggest a decrease in mean occupancy as the most appropriate method of improving overall efficiency. The elderly and those suffering from complex medical problems are thought to account for a high proportion of overall bed occupancy.

Aim: To assess the effect of prolonged hospital stay (>100 days) on overall bed occupancy in a modern teaching hospital.

Design: Retrospective analysis.

Methods: Analysis of all admission episodes (n = 117 178) over a five-year period in a large teaching hospital in a single UK region, serving a population of approximately 200 000. A logistic regression multi-factorial model was used to assess the effect of demographic and diagnostic variables on duration of stay.

Results: A prolonged stay (>100 days) was seen in 648 admission episodes (0.6%). These accounted for 11% of the overall bed occupancy over the 5-year period. Excluding all prolonged admission episodes from our analysis made no difference to the overall median length of stay.

Discussion: Prolonged hospitalizations have a significant impact on bed occupancy. Targeting these very long (>100 days) hospital stays may better improve overall efficiency, compared to targeting mean or median length of stay.

Frequency of participation of 8-12 year old children with cerebral palsy: a multi-centre cross sectional European study

Participation in home, school and community is important for all children; and little is known about the frequency of participation of disabled children. Frequency of participation is a valuable outcome measure for evaluating habilitation programmes for disabled children and for planning social and health services.

We investigated how frequency of participation varied between children with cerebral palsy and the general population; and examined variation across countries to understand better how the environmental factors such as legislation, public attitudes and regulation in different countries might influence participation.

We undertook a multi-centre, population-based study in children with and without cerebral palsy. Working from the Life-H instrument, we developed a questionnaire to capture frequency of participation in 8–12-year-old children. In nine regions of seven European countries, parents of 813 children with cerebral palsy and 2939 children from the general populations completed the questionnaire.

Frequency of participation for each question was dichotomised about the median; multivariable logistic regressions were carried out.

In the general population, frequency of participation varied between countries. Children with cerebral palsy participated less frequently in many but not all areas of everyday life, compared with children from the general population. There was regional variation in the domains with reduced participation and in the magnitude of the differences. We discuss how this regional variation might be explained by the different environments in which children live. Attending a special school or class was not associated with further reduction in participation in most areas of everyday life.

Health status of children with cerebral palsy living in Europe: a multi-centre study

Aim The aim of this report is to describe the health status of 8–12-year-old children with cerebral palsy (CP) of all severities in Europe using the Child Health Questionnaire (CHQ).

Method A total of 818 children with CP from nine centres in defined geographical areas participated. CP type, gross and fine motor function, additional impairments were classified and family data were obtained. The CHQ was used to measure the parent's perception of their child's physical (PHY) and psychosocial (PSY) health.

Results PHY scores were lower than the reference samples with a median of 46. The severity of gross motor function influenced the CHQ scores significantly in the PHY scale with the lowest scores for children with least gross motor function. There were significant differences between the CP types in PHY with the higher scores for children with unilateral spastic and the lowest scores for children with bilateral spastic and dyskinetic CP type. Fine motor function severity significantly affected both the PHY and PSY scales. The severity of intellectual impairment was significantly associated with CHQ scores in most dimensions with higher scores for higher IQ level in PHY and PSY. Children with seizures during the last year had a significantly lower health compared with children without seizures. The results of the multivariate regression analyses (forward stepwise regression) of CHQ scores on CP subtype, gross and fine motor function, cognitive function, additional impairments, seizures, parental education and employment revealed gross motor function, cognitive level and type of school attended were significant prognostic factors.

Conclusion This report is based on the largest sample to date of children with CP. Health status as measured using the CHQ was affected in all children and was highly variable. Gross motor function level correlates with health from the PHY well-being perspective but the PSY and emotional aspects do not appear to follow the same pattern.

Deuterium in the Galactic Centre as a result of recent infall of low-metallicity gas

The Galactic Centre is the most active and heavily processed region of the Milky Way, so it can be used as a stringent test for the abundance of deuterium (a sensitive indicator of conditions in the first 1,000 seconds in the life of the Universe). As deuterium is destroyed in stellar interiors, chemical evolution models 1 predict that its Galactic Centre abundance relative to hydrogen is D/H = 5 x 10(-12), unless there is a continuous source of deuterium from relatively primordial (low-metallicity) gas. Here we report the detection of deuterium (in the molecule DCN) in a molecular cloud only 10 parsecs from the Galactic Centre. Our data, when combined with a model of molecular abundances, indicate that D/H = (1.7 +/- 0.3) x 10(-6), five orders of magnitude larger than the predictions of evolutionary models with no continuous source of deuterium. The most probable explanation is recent infall of relatively unprocessed metal-poor gas into the Galactic Centre (at the rate inferred by Wakker(2)). Our measured D/H is nine times less than the local interstellar value, and the lowest D/H observed in the Galaxy. We conclude that the observed Galactic Centre deuterium is cosmological, with an abundance reduced by stellar processing and mixing, and that there is no significant Galactic source of deuterium.