Cross-sectional study of 168 patients with hepatorenal tyrosinaemia and implications for clinical practice

Background: Hepatorenal tyrosinaemia (Tyr 1) is a rare inborn error of tyrosine metabolism. Without treatment, patients are at high risk of developing acute liver failure, renal dysfunction and in the long run hepatocellular carcinoma. The aim of our study was to collect cross-sectional data. Methods. Via questionnaires we collected retrospective data of 168 patients with Tyr 1 from 21 centres (Europe, Turkey and Israel) about diagnosis, treatment, monitoring and outcome. In a subsequent consensus workshop, we discussed data and clinical implications. Results: Early treatment by NTBC accompanied by diet is essential to prevent serious complications such as liver failure, hepatocellular carcinoma and renal disease. As patients may remain initially asymptomatic or develop uncharacteristic clinical symptoms in the first months of life newborn mass screening using succinylacetone (SA) as a screening parameter in dried blood is mandatory for early diagnosis. NTBC-treatment has to be combined with natural protein restriction supplemented with essential amino acids. NTBC dosage should be reduced to the minimal dose allowing metabolic control, once daily dosing may be an option in older children and adults in order to increase compliance. Metabolic control is judged by SA (below detection limit) in dried blood or urine, plasma tyrosine (<400 μM) and NTBC-levels in the therapeutic range (20-40 μM). Side effects of NTBC are mild and often transient. Indications for liver transplantation are hepatocellular carcinoma or failure to respond to NTBC. Follow-up procedures should include liver and kidney function tests, tumor markers and imaging, ophthalmological examination, blood count, psychomotor and intelligence testing as well as therapeutic monitoring (SA, tyrosine, NTBC in blood). Conclusion: Based on the data from 21 centres treating 168 patients we were able to characterize current practice and clinical experience in Tyr 1. This information could form the basis for clinical practice recommendations, however further prospective data are required to underpin some of the recommendations.

A cross-sectional study of neuropsychiatric symptoms in 435 patients with Alzheimer's disease

OBJECTIVES: The behavioral and psychological symptoms of Alzheimer's disease (AD) are associated with significant patient and caregiver distress and increased likelihood of institutionalization. We attempted to characterize in detail these symptoms and the distress they cause to caregivers. METHODS: Patients with probable AD were assessed with the Mini-Mental State Exam (MMSE), Functional Assessment Staging (FAST), and the Neuropsychiatric Inventory With Caregiver Distress (NPI-D). RESULTS: Four hundred and thirty-five patients were recruited. Neuropsychiatric symptoms of all types were highly prevalent. The most common and most persistent symptom was apathy (75%). Delusional symptoms were the least persistent. Depressive and apathetic symptoms were the earliest to appear, and hallucinations, elation/euphoria, and aberrant motor behavior were the latest symptoms to emerge. Hallucinations were significantly more common in severe dementia. Symptoms of irritability were most prevalent in early disease. Total Neuropsychiatric Symptom score was significantly correlated with MMSE and FAST score. Caregivers rated their own emotional distress levels as moderate or severe for 10 out of 12 symptom domains. The sum total of caregiver distress was strongly correlated with total NPI-D but not cognition or functional state. Distress levels did not vary when analyzed according to the patients' place of residence. CONCLUSIONS: Potentially treatable neuropsychiatric symptoms are common in AD and represent a major source of distress among caregivers. The extent of neuropsychiatric symptomatology is seen to correlate with the level of functional and cognitive disability although some symptoms are variably persistent and related to disease stage.

Risk adjustment for hospital use using social security data: cross sectional small area analysis

Objectives: To identify demographic and socioeconomic determinants of need for acute hospital treatment at small area level. To establish whether there is a relation between poverty and use of inpatient services. To devise a risk adjustment formula for distributing public funds for hospital services using, as far as possible, variables that can be updated between censuses. Design: Cross sectional analysis. Spatial interactive modelling was used to quantify the proximity of the population to health service facilities. Two stage weighted least squares regression was used to model use against supply of hospital and community services and a wide range of potential needs drivers including health, socioeconomic census variables, uptake of income support and family credit, and religious denomination. Setting: Northern Ireland. Main outcome measure: Intensity of use of inpatient services. Results: After endogeneity of supply and use was taken into account, a statistical model was produced that predicted use based on five variables: income support, family credit, elderly people living alone, all ages standardised mortality ratio, and low birth weight. The main effect of the formula produced is to move resources from urban to rural areas. Conclusions: This work has produced a population risk adjustment formula for acute hospital treatment in which four of the five variables can be updated annually rather than relying on census derived data. Inclusion of the social security data makes a substantial difference to the model and to the results produced by the formula.

Recognizing and reporting child physical abuse: a cross sectional survey of primary health care professionals

Objectives: To assess primary health care professionalsâ?? ability to recognise child physical abuse within their everyday practice. Design: Cross-sectional survey Participants: A stratified random sample of 979 nurses, doctors, and dentists working in primary care in NI. Results: Four hundred and thirty one primary health care professionals responded [44% response rate]. Thirty two per cent were doctors, 35% were dentists and 33% were nurse professionals. The mean age was 41.63 years. Fifty-nine percent (251) stated that they had seen a suspicious case of child physical abuse and 47% (201) said they had reported it. Seventy-two per cent (310) of participants were aware of the mechanisms for reporting child physical abuse. Ability and willingness to recognise and report abuse discriminated the three professions. Conclusions: The findings suggest a professional reluctance to engage in recognising and reporting abuse. Barriers could be reduced by providing training and professional support for the primary care professionals.

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

Self-reported quality of life of 8-12 year old children with cerebral palsy: a cross-sectional European Study

Background

Little is known about the quality of life (QoL) of disabled children. We describe self-reported QoL of children with cerebral palsy, factors that influence it, and how it compares with QoL of the general population.

Methods

1174 children aged 8–12 years were randomly selected from eight population-based registers of children with cerebral palsy in six European countries and 743 (63%) agreed to participate; one further region recruited 75 children from multiple sources. Researchers visited these 818 children. 318 (39%) with severe intellectual impairment could not self-report; 500 (61%) reported their QoL using KIDSCREEN, an instrument with scores in ten domains, each with SD=10. Multivariable regression was used to relate QoL to impairments, pain, and sociodemographic characteristics. Comparisons were made with QoL data from the general population.

Findings

Impairments were not significantly associated with six KIDSCREEN domains. Comparison of least and most able groups showed that severely limited self-mobility was significantly associated with reduced mean score for physical wellbeing (7·6, 95% CI 2·7–12·4); intellectual impairment with reduced mean for moods and emotions (3·7, 1·5–5·9) and autonomy (3·3, 0·9–5·7); and speech difficulties with reduced mean for relationships with parents (4·5, 1·9–7·1). Pain was common and associated with lower QoL on all domains. Impairments and pain explained up to 3% and 7%, respectively, of variation in QoL. Children with cerebral palsy had similar QoL to children in the general population in all domains except schooling, in which evidence was equivocal, and physical wellbeing, in which comparison was not possible.

Interpretation

Parents can be reassured that most children aged 8–12 years with cerebral palsy will have similar QoL to other children. This finding should guide social and educational policy to ensure that disabled children participate fully in society. Because of its association with QoL, children's pain should be carefully assessed.

Psychological problems in children with cerebral palsy: A cross-sectional European study

Objectives: To describe psychological symptoms in 8–12-year-old children with cerebral palsy; to investigate predictors of these symptoms and their impact on the child and family.

Design: A cross-sectional multi-centre survey.

Participants: Eight hundred and eighteen children with cerebral palsy, aged 8–12 years, identified from population-based registers of cerebral palsy in eight European regions and from multiple sources in one further region.

Main outcome measures: The Strengths and Difficulties Questionnaire (SDQ)P4-16 and the Total Difficulties Score (TDS) dichotomised into normal/borderline (TDS = 16) versus abnormal (TDS > 16).

Statistical analysis: Multilevel, multivariable logistic regression to relate the presence of psychological symptoms to child and family characteristics.

Results: About a quarter of the children had TDS > 16 indicating significant psychological symptoms, most commonly in the domain Peer Problems. Better gross motor function, poorer intellect, more pain, having a disabled or ill sibling and living in a town were independently associated with TDS > 16. The risk of TDS > 16 was odds ratio (OR) = .2 (95% CI: .1 to .3) comparing children with the most and least severe functional limitations; OR = 3.2 (95%CI: 2.1 to 4.8) comparing children with IQ < 70 and others; OR = 2.7 (95% CI: 1.5 to 4.6) comparing children in severe pain and others; OR = 2.7 (95% CI:1.6 to 4.6) comparing children with another disabled sibling or OR = 1.8 (95%CI: 1.2 to 2.8) no siblings and others; OR = 1.8 (95% CI: 1.1 to 2.8) comparing children resident in a town and others. Among parents who reported their child to have psychological problems, 95% said they had lasted over a year, 37% said they distressed their child and 42% said they burdened the family at least ‘quite a lot’.

Conclusions: A significant proportion of children with cerebral palsy have psychological symptoms or social impairment sufficiently severe to warrant referral to specialist services. Care must be taken in the assessment and management of children with cerebral palsy to ensure psychological problems are not overlooked and potentially preventable risk factors like pain are treated effectively. The validity of the SDQ for children with severe disability warrants further assessment.

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.