Two methods for assessing the risk-factor composition of the HIV-1 epidemic in heterosexual women: southeast England, 1988-1991.

OBJECTIVE: The prevalence of HIV-1 in the heterosexual population in southeast England between 1988 and 1991 was examined using two methods. DESIGN AND METHODS: First, district neonatal seroprevalence was compared on a geographical basis to social and demographic variables reflecting risk-factor prevalence. Second, over the same period eight children who developed AIDS within the first 12 months of life were born. RESULTS: The differences in seroprevalence between districts could be explained by the proportion of livebirths to women born in parts of Africa. An estimated 92% of neonatal seropositives could be associated with this demographic variable. The proportions of livebirths to women born in other countries, the prevalence of notified injecting drug use, and area measures of social deprivation, were only poorly related to HIV seroprevalence, and had no additional explanatory value. Seven of the eight (87.5%) children who developed AIDS in the first year were born to black women from Africa. CONCLUSIONS: Both methods suggest that a high proportion of heterosexually transmitted HIV in southeast England has been imported.

Thyroid antoantibodies and the response to thyrotropin releasing hormone in patients with subclinical hypothyroidism.

AIM: To evaluate the clinical usefulness of the thyrotropin releasing hormone (TRH) test and estimation of thyroid autoantibody concentrations in patients with borderline raised thyroid stimulating hormone (TSH). METHODS: The records of 34 consecutive patients with persistent borderline increased TSH (4.4-9.9 mU/l) referred to the Medical Investigation Unit were reviewed. The response of patients with thyroid autoantibodies to the TRH test was compared with that of patients with a negative antibody screen. RESULTS: Eleven (44%) of 25 patients with positive anti-thyroid microsomal and/or thyroglobulin antibody tests and three (33%) of nine patients with a negative antibody screen had hypothyroid responses to TRH. Neither age nor sex affected the response to TRH. Basal TSH alone was poorly correlated with these indices. Twelve (35%) patients who had elevated basal TSH had a normal response to the TRH test. CONCLUSION: Patients with positive or negative thyroid autoantibodies and an exaggerated response to the TRH test should be regarded as hypothyroid and treated with thyroxine. Patients with positive thyroid autoantibodies and normal TSH response may subsequently develop hypothyroidism and should be given long term follow up.

Newborn screening for inborn errors of metabolism: a systematic review.

OBJECTIVES. To establish a database of literature and other evidence on neonatal screening programmes and technologies for inborn errors of metabolism. To undertake a systematic review of the data as a basis for evaluation of newborn screening for inborn errors of metabolism. To prepare an objective summary of the evidence on the appropriateness and need for various existing and possible neonatal screening programmes for inborn errors of metabolism in relation to the natural history of these diseases. To identify gaps in existing knowledge and make recommendations for required primary research. To make recommendations for the future development and organisation of neonatal screening for inborn errors of metabolism in the UK. HOW THE RESEARCH WAS CONDUCTED. There were three parts to the research. A systematic review of the literature on inborn errors of metabolism, neonatal screening programmes, new technologies for screening and economic factors. Inclusion and exclusion criteria were applied, and a working database of relevant papers was established. All selected papers were read by two or three experts and were critically appraised using a standard format. Seven criteria for a screening programme, based on the principles formulated by Wilson and Jungner (WHO, 1968), were used to summarise the evidence. These were as follows. Clinically and biochemically well-defined disorder. Known incidence in populations relevant to the UK. Disorder associated with significant morbidity or mortality. Effective treatment available. Period before onset during which intervention improves outcome. Ethical, safe, simple and robust screening test. Cost-effectiveness of screening. A questionnaire which was sent to all newborn screening laboratories in the UK. Site visits to assess new methodologies for newborn screening. The classical definition of an inborn error of metabolism was used (i.e., a monogenic disease resulting in deficient activity in a single enzyme in a pathway of intermediary metabolism). RESEARCH FINDINGS. INBORN ERRORS OF METABOLISM. Phenylketonuria (PKU) (incidence 1:12,000) fulfilled all the screening criteria and could be used as the 'gold standard' against which to review other disorders despite significant variation in methodologies, sample collection and timing of screening and inadequacies in the infrastructure for notification and continued care of identified patients. Of the many disorders of organic acid and fatty acid metabolism, a case can only be made for the introduction of newborn screening for glutaric aciduria type 1 (GA1; estimated incidence 1:40,000) and medium-chain acyl CoA dehydrogenase (MCAD) deficiency (estimated incidence 1:8000-1:15,000). Therapeutic advances for GA1 offer prevention of neurological damage but further investigation is required into the costs and benefits of screening for this disorder. MCAD deficiency is simply and cheaply treatable, preventing possible early death and neurological handicap. Neonatal screening for these diseases is dependent upon the introduction of tandem mass spectrometry (tandem MS). This screening could however also simultaneously detect some other commonly-encountered disorders of organic acid metabolism with a collective incidence of 1:15,000.(ABSTRACT TRUNCATED)

Secondary analysis of economic data: a review of cost-benefit studies of neonatal screening for phenylketonuria.

STUDY OBJECTIVE: To estimate the net financial benefit of neonatal screening for phenylketonuria (PKU): by a simple pooling of cost data from the literature; and by a more complex modelling approach. DESIGN: A systematic literature review was conducted to identify papers containing data on the monetary costs and benefits of neonatal screening for PKU. The methodological quality of the studies was appraised, and data were extracted on resource use and expenditure. Monetary data were converted to common currency units, and standardised to UK incidence rates. Net benefits were calculated for median, best case and worst case scenarios, and the effect of excluding poor quality studies and data was tested. The net benefit was also estimated from a model based on data from the literature and assumptions appropriate for the current UK situation. Extensive sensitivity analysis was conducted. MAIN RESULTS: The direct net benefit of screening based on the median costs and benefits from the 13 studies identified was 143,400 Pounds per case detected and treated (39,000 Pounds and 241,800 Pounds for worst case and best case scenarios respectively). The direct net benefit obtained by the modelling approach was lower at 93,400 Pounds per case detected and treated. Screening remained cost saving under sensitivity analysis, except with low residential care costs (less than 12,300 Pounds per annum), or very low incidence rates (less than 1 in 27,000). CONCLUSIONS: The economic literature on PKU screening is of variable quality. The two methods of secondary analysis lead to the same conclusion: that neonatal PKU screening is worthwhile in financial terms alone in the UK, and that it justifies the infrastructure for collecting and testing neonatal blood samples. This result cannot necessarily be extrapolated to other countries.

Use of anonymous newborn serosurveys to evaluate antenatal HIV screening programmes.

OBJECTIVE: To evaluate the extent to which antenatal HIV screening programmes identify HIV infected women who go to term. DESIGN: Comparison of results of two surveillance systems. An anonymous neonatal HIV serosurvey was used to estimate the numbers of HIV infected women giving birth; reporting by obstetricians was used to assess the proportion who had been identified. SETTING: Three Thames regions. RESULTS: 729,105 neonatal blood samples were tested, of which 484 were HIV seropositive. Newborn HIV seroprevalence is increasing, at different rates, in inner London, suburban London, and in non-metropolitan districts. During the past four years the proportion of infected women who have been identified before delivery is 16.9%, but less than half of these were diagnosed during pregnancy. In 1993 only five of the 128 (4%) previously undiagnosed infected women delivering babies were identified by antenatal screening. CONCLUSION: Despite increased emphasis on antenatal testing for HIV in areas of higher prevalence the number of undiagnosed women delivering babies continues to increase. Consideration should be given to alternative strategies for offering antenatal HIV testing. Antenatal screening programmes should be monitored continuously by comparing anonymous neonatal seroprevalence with clinical reports from obstetricians.

The response of evidential breath alcohol testing instruments with subjects exposed to organic solvents and gases. I. Toluene, 1,1,1-trichloroethane and butane.

Experimental work has been undertaken to investigate the potential interference of toluene, 1,1,1-trichloroethane and butane with the evidential breath alcohol testing instruments used in Great Britain (Lion Intoximeter 3000 and Camic Breath Analyser). Volunteers inhaled the volatile substances in an exposure chamber for up to 4 hours, at concentrations of 100, 350 and 600ppm respectively. Subsequently breath was tested on leaving the chamber. No interference was observed with the breath alcohol instruments when the subjects were exposed to toluene and 1,1,1-trichloroethane. A short-term response immediately after exposure was observed for subjects exposed to butane. Further analytical work involving blood and breath samples demonstrated that all three volatile substances were absorbed during exposure and were detectable in blood for at least 3 hours post-exposure. Their elimination post-exposure followed an exponential decay.

The response of evidential breath alcohol testing instruments with subjects exposed to organic solvents and gases. II. White spirit and nonane.

Following exposure to white spirit vapour, the effect of the expired solvent on evidential breath alcohol equipment was investigated under controlled exposure chamber conditions and in a simulated painting exercise. Five volunteers inhaled the solvent in an exposure chamber at a concentration of 100ppm for periods up to 4h 17min. Two other volunteers were exposed to white spirit while painting with domestic gloss paint in an unventilated room under which conditions exposure concentrations reached 185ppm for 20min. Following all white spirit exposures, volunteers underwent breath tests with the Lion Intoximeter 3000. In all instances the apparent alcohol responses were very small and never exceeded a reading of 1 microgram/100ml for breath samples more than 10min post-exposure. Simultaneous analytical work was conducted to demonstrate that white spirit was absorbed during exposure and was present in the breath and blood after the volunteers had left the exposure atmospheres. A further study involved the exposure of a volunteer to nonane vapour at 100ppm, demonstrating that this compound, being one of the principal components of white spirit, appears to be a good model for studying the uptake and elimination of white spirit.

The use of the Rapignost strip for estimating urinary amylase levels.

The Rapignost-Amylase urinary test strip (Behringwerke Laboratories) provides an estimation of urine amylase which takes a few minutes and is easy to perform. During a period of 9 months, 84 patients had their urine tested with this strip by casualty officers in the Accident and Emergency Department of St George's Hospital, London. In addition, urine amylase, and plasma amylase and creatinine were measured in the chemical pathology laboratory. In all but one instance, the result of the strip test agreed with the laboratory result. The Rapignost strip should prove useful in screening for acute pancreatitis in situations where there is likely to be a delay in obtaining a laboratory amylase result.

Erythrocyte ouabain binding in patients receiving thyroxine.

Thyroid hormone action at the cellular level was investigated in euthyroid women who were receiving replacement thyroxine, and whose plasma T4 levels were above the upper reference limit for healthy subjects. There is evidence that erythrocyte sodium pump sites are reduced in number in patients with hyperthyroidism. These sites were measured by the ouabain binding capacity. Plasma T4, free T3 and TSH were also measured, the latter by a high sensitivity fluoroimmunoassay. Three groups of women were investigated; 30 patients receiving T4 with elevated plasma T4 concentrations, 30 age-matched healthy women, and 10 untreated thyrotoxic patients. Erythrocyte ouabain binding was significantly reduced in the thyroxine treated patients, although not to the degree observed in the thyrotoxic patients. Plasma free T3 concentration was increased in 12 of 30 treated patients. TSH was undetectable in 23 of 30 treated patients. The ouabain binding results provide some evidence for increased thyroid hormone action at cellular level in thyroxine treated patients.

Prevalence of maternal HIV infection based on unlinked anonymous testing of newborn babies.

This pilot study established that unlinked anonymous testing of dried blood spots routinely collected on Guthrie cards for neonatal screening is a feasible method for monitoring HIV prevalence in women at the time of delivery. The method was sensitive, specific, and less expensive than more conventional ELISAs. 114,515 dried blood spots taken from cards collected in three Thames regions were tested for antibody to HIV-1. 28 samples were confirmed to be antibody positive by western blot (seroprevalence 0.24 per 1000). Unlinked anonymous screening of newborn babies should be extended to monitor the spread of HIV infection in the heterosexual population and to target preventive strategies and provision of health care.

Prevalence of maternal HIV-1 infection in Thames regions: results from anonymous unlinked neonatal testing.

To monitor the spread of human immunodeficiency virus (HIV) in the heterosexual population, residues of blood samples collected routinely on absorbent paper for neonatal screening (Guthrie cards) in NE, NW, and SW Thames Regions in England have been tested for antibodies to HIV-1 since June, 1988. 323,369 dried blood spots were analysed to end March, 1991. Prevalence of anti-HIV-1 in newborn babies has remained stable in outer London and non-metropolitan districts whereas prevalence in inner London has increased from 1 in 2000 in the 12 months beginning June, 1988, to 1 in 500 in the first 3 months of 1991. Either exponential or linear growth in the numbers of new seropositives could account for the results. That obstetricians were aware of maternal HIV infection in only 20% of infected pregnancies, indicates the extent to which HIV infection goes unrecognised in the heterosexual community.

A systematic review of evidence for the appropriateness of neonatal screening programmes for inborn errors of metabolism.

BACKGROUND: Developments in screening technology and increased understanding of the natural history and treatment of inborn errors of metabolism (IEMs) have produced pressure to extend neonatal screening programmes. This review aims to assess the evidence for the appropriateness of such programmes. METHODS: A formal systematic literature review was conducted. Exclusion and inclusion criteria were used to select papers for critical appraisal by pairs of reviewers. Standard criteria were used to assess the appropriateness of neonatal screening for various IEMs. Site visits were conducted to assess new technologies for newborn screening. RESULTS: A total of 1866 papers were identified and 407 systematically selected for full critical appraisal. Published evidence confirmed that universal newborn screening for phenylketonuria (PKU) meets all of the screening criteria and justifies the expense and infrastructure necessary for the collection and testing of neonatal blood spots. There was insufficient evidence in the literature to assess the cost-effectiveness of screening for any other IEMs. There was reasonable evidence to support inclusion in extended neonatal screening of four other IEMs: biotinidase deficiency, congenital adrenal hyperplasia (CAH), medium-chain acyl CoA dehydrogenase (MCAD) deficiency and glutaric aciduria type 1 (GA1). CONCLUSIONS: Large-scale trials of screening for biotinidase, CAH, MCAD and GA1 should be conducted, with careful evaluation to establish their clinical effectiveness and cost-effectiveness in practice. Screening for the latter two disorders would be dependent upon the use of tandem mass spectrometry (tandem MS). The application of tandem MS to newborn screening requires further evaluation. The extension of neonatal screening programmes to other IEMs is not currently justified.

Maternal prevalence of Toxoplasma antibody based on anonymous neonatal serosurvey: a geographical analysis.

A total of 12,902 neonatal samples collected on absorbent paper for routine metabolic screening were tested anonymously for antibodies to toxoplasma. Seroprevalence varied from 19.5% in inner London, to 11.6% in suburban London, and 7.6% in non-metropolitan districts. Much of this variation appeared to be associated with the proportions of livebirths in each district to women born outside the UK. However, additional geographical variation remained and seroprevalence in UK-born women was estimated to be 12.7% in inner London, 7.5% in suburban London, and 5.5% in non-metropolitan areas. These estimates are considerably lower than any previously reported in antenatal sera in the UK. The wide geographical variation highlights a need for further research to determine the relative importance of different routes of transmission.