A randomised trial of low dose folic acid to prevent neural tube defects. The Irish Vitamin Study Group.

A randomised trial was initiated in Ireland in 1981 to determine if periconceptional supplementation with either folic acid alone or a multivitamin preparation alone could reduce the recurrence risk of neural tube defects (NTDs) in women with a previously affected pregnancy from 5.0% to 1.0% or less. The trial was concluded before the initial target number of study subjects was reached and without a clear treatment effect being observed. A total of 354 women were randomised to receive one of three treatments: folic acid, multivitamins without folic acid, and folic acid plus multivitamins. At the end of the trial 257 women had had a first trial pregnancy outcome (261 infants/fetuses) where the presence or absence of NTDs was ascertainable. There was one NTD recurrence in the 89 infants/fetuses of women in the multivitamin group and no recurrence in the 172 infants/fetuses of women in the folic acid groups, a non-significant difference. Otherwise eligible women who were pregnant when first contacted constituted a non-randomised control group; there were three recurrences among the 103 infants in this group. The difference in the recurrence rate between the folic acid groups and the non-randomised controls was statistically significant but we have reservations about the validity of this comparison. Although our findings do not provide clear evidence of a protective effect of folic acid supplementation they are consistent with those of the Medical Research Council (MRC) trial which demonstrated the efficacy of folic acid in preventing recurrence of NTDs and they raise the possibility that folic acid may be protective at a much lower dosage than that used in the MRC trial.

Respiratory disability in ex-flax workers.

Acute respiratory effects occur in a high proportion of subjects exposed to textile dusts. The extent to which these lead to permanent respiratory symptoms and loss of lung function is unknown. A survey of random population samples was therefore conducted in ten towns in Northern Ireland in which flax processing had been a major source of employment. The MRC questionnaire on respiratory symptoms was administered and Vitalograph tracings recorded on subjects aged 40 to 74 inclusive. An occupational history was taken at the end of each interview. Lung function in ex-flax workers was slightly lower than in control subjects never exposed to flax dust, but the presence of a positive interaction with age meant that differences were apparent only in the younger subjects. Over about the age of 65 the lung function in the ex-flax workers was comparable with that of the controls and overall the loss was at most about half that due to light smoking (1-14 cigarettes a day). The association between a "dust exposure score" and lung function was inconsistent in the two sexes. In men there was a small decrement with increasing dust exposure. In women there was also a small decrement, but a positive interaction with age meant that the women with the highest dust exposure scores had a lower loss with increasing age than the women with the least dust exposure. There was an excess in symptoms in the ex-flax workers but the size of the excess was greater than would be expected from the lung function results. It is possible that, although the survey was conducted without explicit reference to the flax industry, knowledge throughout Northern Ireland that many flax workers have been awarded compensation on the grounds of respiratory disablement may have led to an increased reporting of symptoms in the ex-flax workers.

Deaths from ischaemic heart disease in Belfast.

There were 1323 deaths due to ischaemic heart disease in Belfast from 20 July 1981 to 19 July 1982. Some 496 (37%) of these were in persons aged less than 70 years. By World Health Organisation criteria 247 (19%) of these deaths were classified as definite myocardial infarction and 749 (57%) as possible myocardial infarction. Dyspnoea, collapse, and typical pain were the main symptoms at the onset of the fatal attack. In hospital only 12% of deaths in persons aged less than 70 years and 14% of those aged greater than or equal to 70 years were due to presumed primary rhythm disturbance, whereas outside hospital these proportions were 78% and 59% respectively. The median survival time was 84 minutes and was shortest in men aged less than 70 years (62 minutes). Outside hospital a relative was the most likely aid sought initially (70%) and the median delay time from onset of symptoms to calling for medical aid was eight minutes. Among 128 witnessed deaths in persons aged less than 70 years occurring outside hospital due to presumed primary rhythm disturbance the median survival time was 8 X 25 minutes. Improvements in facilities available for resuscitation including public education could result in the prevention of a proportion of deaths caused by primary rhythm disturbances.

Certification of death from ischaemic heart disease in Belfast.

All death certificates over a one-year period (20 July 1981 to 19 July 1982) for residents of Belfast were examined in order to ascertain those due to ischaemic heart disease. Some 1654 were included for further investigation of which 1288 (78%) were coded by ICD Nos 410-414 (9th revision). Additional data were obtained from hospital records, ECGs, cardiac enzyme measurements, post mortems, general practitioners and from relatives of the deceased. Some 108 deaths coded by 410-414 and 223 deaths coded by other rubrics were eventually excluded. For people aged less than 70 years the net effect of excluding these deaths and including some coded under rubrics other than 410-414 was very small representing a change from 498 to 496 deaths (-0.4%). For people aged 70 years and above the net effect also was small, namely an increase from 790 to 827 (+4.4%). We conclude that the total number of deaths recorded as being due to IHD in Belfast was reasonably accurate. While 76% of deaths registered under ICD Nos 410-414 had been coded by ICD No 410 (acute myocardial infarction) only 19% of all deaths due to IHD could be classified as definite myocardial infarction using World Health Organization criteria.

Myocardial infarction: hospital and home management in Northern Ireland.

Some 262 general practitioners in the Belfast area were asked to complete a questionnaire about their attitudes and practice regarding the management of myocardial infarction at home. Of the 211 responders, only nine per cent would sometimes consider home care for patients under 65 years of age, although 55 per cent would sometimes consider home care for those over 65 years and three per cent preferred home management for this age group. In the year preceding this study, seven per cent of these general practitioners treated only 22 myocardial infarction patients under 65 years of age at home (two per cent of all cases in the area). Home care for myocardial infarction patients appears to be less popular in Belfast than in other parts of the United Kingdom. The views of the general practitioners concerning home care are discussed.

Very early intervention with metoprolol in suspected acute myocardial infarction.

A double blind randomized study of 800 patients was carried out to determine if very early intervention with metoprolol (15 mg I.V. followed by oral administration) in suspected acute myocardial infarction affected overall mortality in selected subgroups, (age, site of infarct, delay to intervention). Sudden death occurred less frequently in patients allocated to metoprolol but there was no significant difference in total mortality on discharge, at three months and at twelve months. Ventricular fibrillation after intervention was not significantly reduced. Adverse reactions did not occur significantly more frequently in patients assigned to metoprolol.

Investigation of area differences in the prevalence at birth of anencephalus in Belfast.

A retrospective case-control study comparing social and biological factors relating to all stillbirths and liveborn infants with anencephalus (n = 433) and a 10% random sample of all livebirths (n = 107 346) born to women resident in Belfast between 1957 and 1969 was carried out. The aim was to determine whether the large difference in the prevalence rate at birth of anencephalus within this city could be explained by any previously identified risk factors. For the 15 electoral wards the average rate over the study period was lowest in Windsor ward and highest in Court ward--rates 2.7 and 8.0 per 1000 livebirths respectively. Also, for one particular group of women who lived in certain areas of Belfast and who had an abnormal reproductive history the anencephalic rate was between 7.1 and 10.1 per 1000 livebirths depending on their parity. Although reproductive history was significantly associated with the risk of anencephalus this did not explain the area differences in rates within the city. These findings together with other work suggest that there are at least two separate sets of factors influencing the occurrence of anencephalus. One set relates to area of residence and may reflect adverse social circumstances and diet; the second set relates to maternal reproductive history, acts largely independently of the first and may have a genetic basis. Although this hypothesis accounts for a number of observations relating to anencephalus the excess of affected females cannot be adequately explained.

Diagnosis of myocardial infarction from serum creatine kinase MB isoenzyme (CKMB) measurement.

The cardiospecific isoenzyme MB of creatine kinase (CKMB) has previously been shown to be of value in the diagnosis of myocardial infarction (MI). We studied 418 admissions to a coronary care unit (CCU) with suspected MI and calculated the sensitivity, specificity and positive and negative predictive values for several CKMB test functions. Several functions performed better than any combination of the other enzymes in common use. 97% of patients achieving a CKMB activity of at least 15 U/l did so between 6 and 30 h following the onset of symptoms. The present study confirms that the use of the CKMB isoenzyme leads to an earlier and more accurate diagnosis or exclusion of MI compared to the "cardiac enzyme series". The timing of blood sampling for CKMB estimation is also discussed.

Effect of very early intervention with metoprolol on myocardial infarct size.

All patients with a presumptive diagnosis of myocardial infarction, who were seen within six hours of the onset of symptoms and had no reason for exclusion, were considered for entry into a trial to compare the effects of metoprolol and placebo on creatine kinase MB isoenzyme release. The trial was randomised and double blind. The median time from onset of symptoms to receiving trial drug was just under two hours. Two hundred and four patients (of whom 120 had myocardial infarction) received metoprolol and 187 (of whom 105 had myocardial infarction) received placebo. Infarct size was estimated semiquantitatively using cumulative release of the cardiospecific isoenzyme, creatine kinase MB. Mean creatine kinase MB isoenzyme was less in patients who received metoprolol, but the reduction did not achieve statistical significance. Clinical problems related to early intravenous metoprolol were uncommon.

International variation in the prevalence at birth of anencephalus in relation to maternal factors.

Information from series of cases of anencephalus and corresponding random samples of all livebirths showed that the prevalence rate at birth per 1000 livebirths for anencephalus was 4.02 in Belfast (from 1957 to 1969), compared to 1.36 in mothers of Scots-Irish origin resident in 14 selected Canadian cities (from 1950 to 1969). For each of these two populations, anencephalus was associated with the number of previous livebirths, stillbirths, and child deaths. However, these maternal factors did not account for any appreciable portion of the difference in prevalence rates between the two populations, showing that a different set of factors must cause the international difference in rates.

The flax industry in Northern Ireland twenty years on.

In 1961-62 a survey of respiratory symptoms in 2528 workers in flax mills in Northern Ireland and of dust levels in the mills was conducted. The workers were followed up in 1978, because recent developments suggested that an upturn in the industry was likely. Flax dust has an acute, reversible effect on the respiratory system, and byssinosis is a prescribed disease under the Industrial Injuries Act (1965). However, the follow-up study found no evidence of an effect on survival of either exposure to dust or byssinosis. The number of applications to compensation panels for assessment and certification of byssinosis has increased greatly in Northern Ireland. Although certification is independent of any subsequent common law claim by a worker for compensation on the grounds of disablement consequent on negligence by his employer, it must weight heavily in such a claim. About 50 common law claims have been settled out of court for large sums in Northern Ireland, and 950 claims are waiting to be heard. The future cost to the industry is estimated to be at least 16 million pounds. Since byssinosis appears not to cause excess mortality, it is unlikely to cause serious long-term morbidity. Although workers should be compensated for disablement due to negligence, in the absence of unequivocal evidence of disablement caused by byssinosis the financial settlements being reached in Northern Ireland seem unreasonable.

Associations between pelvic anatomy, height and year of birth of men and women in Belfast.

Standardized radiological pelvimetry was used to examine 242 male and 314 female adults attending the out-patient departments of the Royal Victoria Hospital, Belfast, Seven indices of pelvic size and shape were measured from X-rays on each individual together with social and biological factors including age, height and year of birth. The aims were to quantify any differences in pelvic anatomy between the sexes and to measure correlations between these pelvic indices and selected biosocial factors. Pelvic indices for men and women of similar stature were significantly different, with the exception of the brim index, and these anatomical changes were correlated with year of birth. The similarity of the findings in both sexes suggests common environmental factors such as nutrition are the most likely causes, rather than factors specifically associated with pregnancy and childbirth.

Mortality of flax workers.

A total of 2528 workers in flax mills in Northern Ireland were followed up for 16 years. Follow-up was 97% complete. Deaths were identified and date and cause ascertained. Expected deaths were calculated on the basis of age and sex specific rates for Northern Ireland. Both male and female workers had fewer deaths than expected, and mortality showed no clear relationship with type of work. There was a small excess in the mortality of the workers who had had byssinosis at the time of the original survey, but there was no evidence that the more severe grades of byssinosis were associated with higher mortality than the less severe grades. Workers who smoke are known to have an increased risk of developing byssinosis, and cigarette smoking may be responsible for most of the excess deaths in the workers with byssinosis.