Lack of expansion of triplet repeats in the FMR1, FRAXE,and FRAXF loci in male multiplex families with autism and pervasive developmental disorders

Sib, twin, and family studies have shown that a genetic cause exists in many cases of autism, with a portion of cases associated with a fragile X chromosome. Three folate-sensitive fragile sites in the Xq27→Xq28 region have been cloned and found to have polymorphic trinucleotide repeats at the respective sites; these repeats are amplified and methylated in individuals who are positive for the different fragile sites. We have tested affected boys and their mothers from 19 families with two autistic/PDD boys for amplification and/or instability of the triplet repeats at these loci and concordance of inheritance of alleles by affected brothers. In all cases, the triplet repeat numbers were within the normal range, with no individuals having expanded or premutation-size alleles. For each locus, there was no evidence for an increased frequency of concordance, indicating that mutations within these genes are unlikely to be responsible for the autistic/PDD phenotypes in the affected boys. Thus, we think it is important to retest those autistic individuals who were cytogenetically positive for a fragile X chromosome, particularly cases where there is no family history of the fragile X syndrome, using the more accurate DNA-based testing procedures. © 1996 Wiley-Liss, Inc.     

Audit and academic departments of general practice: a survey in the United Kingdom and Eire.

A questionnaire and telephone survey was carried out in April 1991 of all 31 academic departments of general practice in the United Kingdom and Eire; 30 departments responded. The aim of the study was to assess the departments' level of involvement in teaching about audit in the undergraduate curriculum, their role in the development of audit in primary care including involvement with medical audit advisory groups, whether they undertook teaching about audit to other health professionals and whether they were involved in audit related research. Eleven of 27 responding undergraduate departments provided formal teaching about audit and five intended to introduce it in the near future. Respondents expressed concerns about teaching audit to undergraduates, including lack of time in the curriculum, difficulties making the teaching relevant and interesting, and a lack of expertise and knowledge of the subject among the staff. All 29 departments in the UK were represented on medical audit advisory groups, and audit related research was being carried out in 24 undergraduate departments. The role of academic departments of general practice in the development of audit in primary care is discussed.     

The incidence of bleeding complications associated with warfarin treatment in general practice in the United Kingdom.

The aim of this study was to estimate and explore the incidence of warfarin-related bleeding in a representative sample of patients in the United Kingdom. We identified 3958 patients aged 40 to 84 years, newly treated with warfarin and with no prior history of bleeding from the General Practice Research Database, and followed them for 12 months. The overall incidence of first-time, idiopathic bleeding was 15.2 per 100 patient-years of current warfarin exposure: the incidence of fatal/hospitalised and referred bleeding was 3.5 and 2.6 per 100 patient-years, respectively.     

A national audit of the laboratory diagnosis of tuberculosis and other mycobacterial diseases within the United Kingdom

In order to audit United Kingdom laboratory diagnostic and reference services including novel molecular methods for tuberculosis, a questionnaire was sent to laboratories submitting specimens to the PHLS Mycobacterium Reference Unit (MRU) and regional centres and to the Scottish Mycobacteria Reference Laboratory (SMRL) in 1996-7. Nationally, 67.2% of laboratories responded. Most UK laboratories were fully or conditionally CPA accredited and take part in the NEQAS proficiency scheme. On average only 3.3% of primary samples submitted for mycobacterial diagnosis in 1995 produced a mycobacterial culture from approximately half as many patients (that is, a mean of 1488 specimens producing 49 isolates from 23 patients). Potentially over 380,000 specimens are processed for mycobacteria in the UK each year. The majority of laboratories use 4% NaOH +/- NALC for specimen decontamination. Culture on solid media was used by most laboratories and 62.9% also use liquid media. Most laboratories incubated cultures for eight weeks. Few laboratories use molecular diagnostic methods. Laboratories were most likely to use molecular methods for diagnosing tuberculous meningitis and for specimens from immunocompromised patients, although usage was strongly influenced by cost. Within England and Wales 43.9% (47/107) and 56% (61/109) of laboratories wanted a rapid service for rifampicin resistance detection in M tuberculosis from immunocompetent and immunocompromised patients, respectively. In regard to a tuberculous meningitis service, 80.5% (43/112) and 84.3% (102/121) of laboratories wanted this service for immunocompetent and immunocompromised patients, respectively. The quality of reference services was rated as "very good"/"good" by 85.6% of respondents nationally. Rapid molecular amplification diagnostic services were established at the PHLS MRU for rifampicin drug resistance detection nationally and for tuberculous meningitis at the MRU.     

Quality deviations in cancer diagnosis: prevalence and time to diagnosis in general practice

Background

High quality in every phase of cancer diagnosis is important to optimise the prognosis for the patient. General practice plays an important role in this phase.

Aim

The aim was to describe the prevalence and the types of quality deviations (QDs) that arise during the diagnostic pathway in general practice as assessed by GPs and to analyse the association between these QDs, the cancer type, and the GP’s interpretation of presenting symptoms as well as the influence on the diagnostic interval.

Design and setting

A Danish retrospective cohort study based on questionnaire data from 1466 GPs on 5711 incident patients with cancer identified in the Danish National Patient Registry (response rate = 71.4%). The GP was involved in diagnosing in 4036 cases.

Method

Predefined QDs were prompted with the possibility for free text. QD prevalence was estimated as was the association between QDs and diagnosis, the GP’s symptom interpretation, and time to diagnosis.

Results

QDs were present for 30.4% (95% confidence interval [CI] = 29.0 to 31.9) of cancer patients. The most prevalent QD was ‘retrospectively, one or more of my clinical decisions were less optimal’. QDs were most prevalent among patients with vague symptoms (24.1% for alarm symptoms versus 39.5% for vague symptoms [P<0.001]). QD presence implied a 41-day (95% CI = 38.4 to 43.6) longer median diagnostic interval.

Conclusion

GPs noted at least one QD, which often involved clinical decisions, for one-third of all cancer patients. QDs were more likely among patients with vague symptoms and increased the diagnostic interval considerably.     

Lack of benefit of a single dose of synthetic human secretin in the treatment of autism and pervasive developmental disorder

BACKGROUND: Secretin is a peptide hormone that stimulates pancreatic secretion. After recent publicity about a child with autism whose condition markedly improved after a single dose of secretin, thousands of children with autistic disorders may have received secretin injections. METHODS: We conducted a double-blind, placebo-controlled trial of a single intravenous dose of synthetic human secretin in 60 children (age, 3 to 14 years) with autism or pervasive developmental disorder. The children were randomly assigned to treatment with an intravenous infusion of synthetic human secretin (0.4 microg per kilogram of body weight) or saline placebo. We used standardized behavioral measures of the primary and secondary features of autism, including the Autism Behavior Checklist, to assess the degree of impairment at base line and over the course of a four-week period after treatment. RESULTS: Of the 60 children, 4 could not be evaluated - 2 received secretin outside the study, and 2 did not return for follow-up. Thus, 56 children (28 in each group) completed the study. As compared with placebo, secretin treatment was not associated with significant improvements in any of the outcome measures. Among the children in the secretin group, the mean total score on the Autism Behavior Checklist at base line was 59.0 (range of possible values, 0 to 158, with a larger value corresponding to greater impairment), and among those in the placebo group it was 63.2. The mean decreases in scores over the four-week period were 8.9 in the secretin group and 17.8 in the placebo group (mean difference, -8.9; 95 percent confidence interval, -19.4 to 1.6; P=0.11). None of the children had treatment-limiting adverse effects. After they were told the results, 69 percent of the parents of the children in this study said they remained interested in secretin as a treatment for their children. CONCLUSIONS: A single dose of synthetic human secretin is not an effective treatment for autism or pervasive developmental disorder.     

Sleep problems in children with autism spectrum disorders, developmental delays, and typical development: a population-based study

This study compared parent-reported sleep characteristics in 2- to 5-year-old children with autism spectrum disorders (ASD) to children with other developmental delays (DD) and typical development (TD). We included 529 children (303 ASD [167 males], 63 DD [46 males], and 163 TD [134 males]) enrolled in the CHARGE study, an ongoing population-based case-control study. The mean age of participants was 3.6 years (standard deviation, 0.8 years). ASD diagnosis was confirmed with Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedules (ADOS). Cognitive and adaptive functioning was assessed using Mullen Scales of Early Learning (MSEL) and Vineland Adaptive Behavior Scales (VABS), respectively. Demographic, medical and sleep history information were ascertained from California birth records, telephone interview, medical assessments at clinic visit, and parent-administered questionnaires. Fifty-three percent of children with ASD had at least one frequent sleep problem, followed by 46% of children with DD, and 32% of the TD group (P < 0.0001). Exploratory factor analyses of sleep history data yielded two factors: sleep onset problems and night waking. Children with ASD had marginally higher sleep onset factor scores and significantly higher night waking factor scores compared with the TD group. Factor scores for children with DD were intermediate between the ASD and TD groups. Cognitive or adaptive development did not predict severity of sleep problems in the ASD group.     

The prevalence of PTEN mutations in a clinical pediatric cohort with autism spectrum disorders,developmental delay,and macrocephaly

PurposeTo define the prevalence of PTEN mutations in a clinical cohort of pediatric subjects with autism spectrum disorders (ASDs), developmental delay/mental retardation (DD/MR), and/or macrocephaly and to assess genotype–phenotype correlations.MethodsMedical records of patients who had clinical PTEN gene sequencing ordered through our institution between January 1, 2005 and December 31, 2007 were abstracted to confirm genetic test results and medical diagnoses. Phenotypic information related to the diagnoses, prenatal history, early developmental milestones, physical characteristics, and family history for those with a confirmed PTEN mutation was also recorded.ResultsOne hundred fourteen patients were tested during this time period for indications of ASDs (N = 60), DD/MR (N = 49), or macrocephaly only (N = 5). Eleven mutations were identified: five in patients with ASDs and six in those with DD/MR, resulting in a prevalence of 8.3% and 12.2% in these respective clinical populations. All individuals with a PTEN mutation had significant macrocephaly (>2.0 SD)ConclusionsThese data illustrate that PTEN gene sequencing has a high diagnostic yield when performed in a selected population of individuals with ASDs or DD/MR and macrocephaly. Germline mutations in PTEN are an important, identifiable etiology among these patients.     

Review of egg-related salmonellosis and reduction strategies in United States,Australia, United Kingdom and New Zealand

Globally, Salmonella enterica subsp. enterica is one of the most commonly reported causes of foodborne illness in humans. Contaminated food products of animal origin, particularly egg and egg products are frequently implicated in outbreaks of human salmonellosis. Salmonella enteritidis is frequently involved in egg and egg products-associated foodborne outbreaks in the USA and UK. However, in Australia and New Zealand, human infections caused by this serovar occur as a result of infection acquired while overseas travel, with Salmonella typhimurium being a predominant cause of local foodborne outbreaks. In this paper, an overview of Salmonella epidemiology on laying farms, egg-related Salmonella outbreaks in humans, and regulatory practises to control Salmonella across USA, UK, Australia and New Zealand is provided. Considering the estimated production of eggs in the USA, UK, Australia and New Zealand in 2015, the risk of foodborne illness in general is quite low for humans consuming eggs. Salmonella diagnostics, reporting and surveillance systems have improved over the years and will continue to improve in the years to come. However, given the number of different emerging Salmonella serovars a regular review of Salmonella control strategies from farm to fork is required.