Showing papers in "BMJ in 1991"

Fetal and infant growth and impaired glucose tolerance at age 64.

Abstract: OBJECTIVE--To discover whether reduced fetal and infant growth is associated with non-insulin dependent diabetes and impaired glucose tolerance in adult life. DESIGN--Follow up study of men born during 1920-30 whose birth weights and weights at 1 year were known. SETTING--Hertfordshire, England. SUBJECTS--468 men born in east Hertfordshire and still living there. MAIN OUTCOME MEASURES--Fasting plasma glucose, insulin, proinsulin, and 32-33 split pro-insulin concentrations and plasma glucose and insulin concentrations 30 and 120 minutes after a 75 g glucose drink. RESULTS--93 men had impaired glucose tolerance or hitherto undiagnosed diabetes. They had had a lower mean birth weight and a lower weight at 1 year. The proportion of men with impaired glucose tolerance fell progressively from 26% (6/23) among those who had weighted 18 lb (8.16 kg) or less at 1 year to 13% (3/24) among those who had weighed 27 lb (12.25 kg) or more. Corresponding figures for diabetes were 17% (4/23) and nil (0/24). Plasma glucose concentrations at 30 and 120 minutes fell with increasing birth weight and weight at 1 year. Plasma 32-33 split proinsulin concentration fell with increasing weight at 1 year. All these trends were significant and independent of current body mass. Blood pressure was inversely related to birth weight and strongly related to plasma glucose and 32-33 split proinsulin concentrations. CONCLUSIONS--Reduced growth in early life is strongly linked with impaired glucose tolerance and non-insulin dependent diabetes. Reduced early growth is also related to a raised plasma concentration of 32-33 split proinsulin, which is interpreted as a sign of beta cell dysfunction. Reduced intrauterine growth is linked with high blood pressure, which may explain the association between hypertension and impaired glucose tolerance.

Association between infection with Helicobacter pylori and risk of gastric cancer: evidence from a prospective investigation.

Abstract: OBJECTIVE--To investigate the association between gastric cancer and prior infection with Helicobacter pylori. DESIGN--Case-control comparison of prevalence of IgG antibodies to H pylori in blood samples collected prospectively, before diagnosis of gastric cancer in the cases. Presence of H pylori antibody (greater than 10 micrograms IgG/ml) determined by enzyme linked immunosorbent assay (ELISA). SUBJECTS--29 men with a subsequent diagnosis of gastric cancer and 116 aged matched controls selected from over 22,000 middle aged men participating in two ongoing cohort studies (the British United Provident Association study and the Caerphilly collaborative heart disease study), who had provided blood samples during 1975-1982. RESULTS--20 of the 29 cases (69%) and 54 of the 116 controls (47%) were positive for H pylori specific antibody. The median specific IgG concentration was significantly higher in the cases than controls (90 micrograms/ml v 3.6 micrograms/ml, p less than 0.01). The estimated odds ratio for the risk of gastric cancer in those with a history of infection with H pylori was 2.77 (95% confidence interval 1.04 to 7.97, 2p = 0.039). CONCLUSIONS--H pylori infection may be an important cause of gastric cancer; between 35% and 55% of all cases may be associated with such an infection.

Fetal and infant origins of adult disease.

Abstract: live births and this includes both familial and non-familial cases. There were 1068 children born in Seascale between 1950 and 1983.2 There would have to be a 20-fold increase in incidence before a single case was expected in this population. It is nonsense to state that retinoblastoma should be \"generally more common in Seascale.\" Similar arguments apply to Millom rural district. It is the extreme rarity of retinoblastoma that makes the observation of five cases linked to Seascale so extraordinary and noteworthy. The ideas in our paper are neither confusing nor contradictory. The data, in fact, strongly suggest a link between retinoblastoma and residence in Seascale. The nature of the association remains to be determined, but it is wrong to imply that radiation can be excluded as the causative agent.

Relation of birth weight and childhood respiratory infection to adult lung function and death from chronic obstructive airways disease.

Abstract: OBJECTIVE--To examine whether birth weight, infant weight, and childhood respiratory infection are associated with adult lung function and death from chronic obstructive airways disease. DESIGN--Follow up study of men born during 1911-30 whose birth weights, weights at 1 year, and childhood illnesses were recorded at the time by health visitors. SETTING--Hertfordshire, England. SUBJECTS--5718 men born in the county during 1911-30 and a subgroup of 825 men born in the county during 1920-30 and still living there. MAIN OUTCOME MEASURES--Death from chronic obstructive airways disease, mean forced expiratory volume in one second (FEV1) and forced vital capacity (FVC), and respiratory symptoms. RESULTS--55 men died of chronic obstructive airways disease. Death rates fell with increasing birth weight and weight at 1 year. Mean FEV1 at age 59 to 70 years, adjusted for height and age, rose by 0.06 litre (95% confidence interval 0.02 to 0.09) with each pound (450 g) increase in birth weight, independently of smoking habit and social class. Bronchitis or pneumonia in infancy was associated with a 0.17 litre (0.02 to 0.32) reduction in adult FEV1 and with an increased odds ratio of wheezing and persistent sputum production in adult life independently of birth weight, smoking habit, and social class. Whooping cough in infancy was associated with a 0.22 litre (0.02 to 0.42) reduction in adult FEV1. CONCLUSIONS--Lower birth weight was associated with worse adult lung function. Intrauterine influences which retard fetal weight gain may irrecoverably constrain the growth of the airways. Bronchitis, pneumonia, or whooping cough in infancy further reduced adult lung function. They also retarded infant weight gain. Consistent with this, death from chronic obstructive airways disease in adult life was associated with lower birth weight and weight at 1 year. Promoting lung growth in fetuses and infants and reducing the incidence of lower respiratory tract infection in infancy may reduce the incidence of chronic obstructive airways disease in the next generation.

Validation of information recorded on general practitioner based computerised data resource in the United Kingdom.

Abstract: OBJECTIVE--To determine the extent of agreement between clinical information recorded on surgery computers of selected general practitioners and similar information in manual records of letters received from hospital consultants and kept in the general practitioners9 files. DESIGN--Hospital consultants9 letters in the manual records of selected general practitioners were photocopied and the consultants9 clinical diagnoses were compared with diagnoses recorded on computer. SETTING--General practices in the United Kingdom using computers provided by VAMP Health for recording clinical information. SUBJECTS--2491 patients who received one of three non-steroidal anti-inflammatory drugs and who attended 58 practices whose computer recorded data were considered after a preliminary review to be of satisfactory quality. RESULTS--Among 1191 patients for whom consultants9 letters were forwarded a clinical diagnosis reflecting the diagnosis noted on a consultant letter was present on the computer record for 1038 (87%). CONCLUSION--Clinical information available on the computer records of the general practitioners who participated in this study is satisfactory for many clinical studies.

Doctor-patient communication: the Toronto consensus statement.

Abstract: This report was compiled on behalf of the staff at the Northern General Hospital, Sheffield, the staff at the Royal Hallamshire Hospital, Sheffield, and the many people who helped at the scene. The efforts of hundreds of professionals and volunteers were vital and greatly appreciated. We thank Neil Appleyard, David Edbrooke, David Dawson, Stuart Yates, Ian Winston, John Duncan, G A Baker, Charlie Cooper, Kath Sherry, Tim Shaw, and A Moss for access to the neuropsychological reports on some of the survivors.

Surveys of patients satisfaction: I--Important general considerations.

Abstract: was 46%, then introducing the protocol saved the radiology department almost £500 a year. The protocol also resulted in an increase in the number of patients reviewed and hence the work of the accident and emergency department. In terms of the patients reviewed in the department, however, the total numbers (an extra 36 over the eight weeks) were small, amounting to an extra four or five patients a week in a department with an average new-patient attendance each week of about 800. Eleven of the patients reviewed in the department were referred to the soft tissue clinic, six of whom required physiotherapy. This suggests that, as had been suspected, before the protocol was introduced patients with ligamentous injuries had been undertreated; this seems to justify the small increase in the number of patients reviewed. After introducing the protocol the number of patients reattending of their own accord fell from five to one, supporting the view that the protocol improved the treatment of patients with ligamentous injuries. The protocol also resulted in a reduction of the work of the fracture clinics as inappropriate referrals were reduced by 53%. The two patients who were referred by their general practitioners for radiography show the importance of informing local general practitioners of changes in treatment policy. At the end of the study no changes were required in the protocol, and the algorithm is now included in the notes of any patient attending with an ankle injury. The algorithm proved an effective means of improving treatment of ankle injuries and algorithms may improve treatment of other conditions in accident and emergency departments.

Serum cholesterol concentration and coronary heart disease in population with low cholesterol concentrations.

Abstract: OBJECTIVE--To examine the relation between serum cholesterol concentration and mortality (from coronary heart disease and from other causes) below the range of cholesterol values generally seen in Western populations. DESIGN--Prospective observational study based on 8-13 years of follow up of subjects in a population with low cholesterol concentrations. SETTING--Urban Shanghai, China. SUBJECTS--9021 Chinese men and women aged 35-64 at baseline. MAIN OUTCOME MEASURE--Death from coronary heart disease and other causes. RESULTS--The average serum cholesterol concentration was 4.2 mmol/l at baseline examination, and only 43 (7%) of the deaths that occurred during 8-13 years of follow up were attributed to coronary heart disease. There was a strongly positive, and apparently independent, relation between serum cholesterol concentration and death from coronary heart disease (z = 3.47, p less than 0.001), and within the range of usual serum cholesterol concentration studied (3.8-4.7 mmol/l) there was no evidence of any threshold. After appropriate adjustment for the regression dilution bias, a 4 (SD 1)% difference in usual cholesterol concentration was associated with a 21 (SD 6)% (95% confidence interval 9% to 35%) difference in mortality from coronary heart disease. There was no significant relation between serum cholesterol concentration and death from stroke or all types of cancer. The 79 deaths due to liver cancer or other chronic liver disease were inversely related to cholesterol concentration at baseline. CONCLUSION--Blood cholesterol concentration was directly related to mortality from coronary heart disease even in those with what was, by Western standards, a "low" cholesterol concentration. There was no good evidence of an adverse effect of cholesterol on other causes of death.

Impact of variability among surgeons on postoperative morbidity and mortality and ultimate survival.

Abstract: OBJECTIVE--To assess the differences among surgeons in postoperative complications, postoperative mortality, and survival in patients undergoing surgery for colorectal cancer. DESIGN--Prospective study of patients with colorectal cancer managed by one of 13 consultant surgeons, none of whom had a special interest in colorectal surgery. SETTING--Royal Infirmary, Glasgow. PATIENTS--645 sequential patients with colorectal cancer presenting over the six years from 1974 to 1979. MAIN OUTCOME MEASURES--Postoperative complications, postoperative mortality (within 30 days), and survival (up to 10 years); predictive factors for postoperative mortality and survival; and relative hazard rate ratios for individual surgeons. RESULTS--The proportion of patients undergoing apparently curative resection varied among surgeons from 40% to 76%; overall postoperative mortality varied from 8% to 30%. After curative resection postoperative mortality varied from 0% to 20%, local recurrence from 0% to 21%, and the rate of anastomotic leak from 0% to 25%. Survival at 10 years in patients who underwent curative resection varied from 20% to 63%, two year survival in those who underwent palliative resection varied from 7% to 32%, and median survival in those who underwent palliative diversion varied from one to eight months. The hazard rate ratios among individual surgeons, taking into account the identified risk factors, varied from 0.56 to 2.03, from 0.17 to 1.92, and from 0.57 to 1.50 for curative resection, palliative resection, and palliative diversion, respectively. CONCLUSION--There were significant variations in patient outcome among surgeons after surgery for colorectal cancer; such differences compromise survival. A considerable improvement in overall survival might be achieved if such surgery were undertaken by surgeons with a special interest in colorectal surgery or surgical oncology.

Clinical trials of homoeopathy.

Abstract: OBJECTIVE--To establish whether there is evidence of the efficacy of homoeopathy from controlled trials in humans. DESIGN--Criteria based meta-analysis. Assessment of the methodological quality of 107 controlled trials in 96 published reports found after an extensive search. Trials were scored using a list of predefined criteria of good methodology, and the outcome of the trials was interpreted in relation to their quality. SETTING--Controlled trials published world wide. MAIN OUTCOME MEASURES--Results of the trials with the best methodological quality. Trials of classical homoeopathy and several modern varieties were considered separately. RESULTS--In 14 trials some form of classical homoeopathy was tested and in 58 trials the same single homoeopathic treatment was given to patients with comparable conventional diagnosis. Combinations of several homoeopathic treatments were tested in 26 trials; isopathy was tested in nine trials. Most trials seemed to be of very low quality, but there were many exceptions. The results showed a positive trend regardless of the quality of the trial or the variety of homeopathy used. Overall, of the 105 trials with interpretable results, 81 trials indicated positive results whereas in 24 trials no positive effects of homoeopathy were found. The results of the review may be complicated by publication bias, especially in such a controversial subject as homoeopathy. CONCLUSIONS--At the moment the evidence of clinical trials is positive but not sufficient to draw definitive conclusions because most trials are of low methodological quality and because of the unknown role of publication bias. This indicates that there is a legitimate case for further evaluation of homoeopathy, but only by means of well performed trials.

By how much does dietary salt reduction lower blood pressure? III--Analysis of data from trials of salt reduction.

Abstract: OBJECTIVE--To determine whether the reduction in blood pressure achieved in trials of dietary salt reduction is quantitatively consistent with estimates derived from blood pressure and sodium intake in different populations, and, if so, to estimate the impact of reducing dietary salt on mortality from stroke and ischaemic heart disease. DESIGN--Analysis of the results of 68 crossover trials and 10 randomised controlled trials of dietary salt reduction. MAIN OUTCOME MEASURE--Comparison of observed reductions in systolic blood pressure for each trial with predicted values calculated from between population analysis. RESULTS--In the 45 trials in which salt reduction lasted four weeks or less the observed reductions in blood pressure were less than those predicted, with the difference between observed and predicted reductions being greatest in the trials of shortest duration. In the 33 trials lasting five weeks or longer the predicted reductions in individual trials closely matched a wide range of observed reductions. This applied for all age groups and for people with both high and normal levels of blood pressure. In people aged 50-59 years a reduction in daily sodium intake of 50 mmol (about 3 g of salt), attainable by moderate dietary salt reduction would, after a few weeks, lower systolic blood pressure by an average of 5 mm Hg, and by 7 mm Hg in those with high blood pressure (170 mm Hg); diastolic blood pressure would be lowered by about half as much. It is estimated that such a reduction in salt intake by a whole Western population would reduce the incidence of stroke by 22% and of ischaemic heart disease by 16% [corrected]. CONCLUSIONS--The results from the trials support the estimates from the observational data in the accompanying two papers. The effect of universal moderate dietary salt reduction on mortality from stroke and ischaemic heart disease would be substantial--larger, indeed, than could be achieved by fully implementing recommended policy for treating high blood pressure with drugs. However, reduction also in the amount of salt added to processed foods would lower blood pressure by at least twice as much and prevent some 75,000 [corrected] deaths a year in Britain as well as much disability.

Role of peak bone mass and bone loss in postmenopausal osteoporosis: 12 year study.

Abstract: OBJECTIVE--To examine the role of peak bone mass and subsequent postmenopausal bone loss in the development of osteoporosis and the reliability of identifying women at risk from one bone mass measurement and one biochemical assessment of the future bone loss. DESIGN--Population based study. SETTING--Outpatient clinic for research into osteoporosis. SUBJECTS--178 healthy early postmenopausal women who had participated in a two year study in 1977. 154 of the women underwent follow up examination in 1989, of whom 33 were excluded because of diseases or taking drugs known to affect calcium metabolism. MAIN OUTCOME MEASURES--Bone mineral content of the forearm and values of biochemical markers of bone turnover. RESULTS--The average reduction in bone mineral content during 1977-89 was 20%, but the fast losers had lost 10.0% more than had the slow loser group (mean loss 26.6% in fast losers and 16.6% in slow losers; p less than 0.001). Prediction of future bone mineral content using baseline bone mineral content and estimated rate of loss gave results almost identical with the actual bone mineral content measured in 1989. Seven women had had a Colles' fracture and 20 a spinal compression fracture. The group with Colles' fracture had low baseline bone mineral content (34.7 (95% confidence interval 31.3 to 38.1) units v 39.4 (38.1 to 40.8) units in women with no fracture) whereas the group with spinal fracture had a normal baseline bone mineral content (38.1 (35.0 to 41.1) units) but an increased rate of loss (-2.4 (-3.5 to -1.3)%/year v -1.8 (-2.1 to -1.5)%/year in women with no fracture). CONCLUSIONS--One baseline measurement of bone mass combined with a single estimation of the rate of bone loss can reliably identify the women at menopause who are at highest risk of developing osteoporosis later in life. The rate of loss may have an independent role in likelihood of vertebral fracture.

Ethnic differences in mortality from ischaemic heart disease and cerebrovascular disease in England and Wales.

Abstract: OBJECTIVE--To examine mortality from ischaemic heart disease and cerebrovascular disease in England and Wales by country of birth of the deceased. DESIGN--Standardised mortality ratios were computed by country of birth groups for ischaemic heart disease and cerebrovascular disease for 1979-83 and 1970-2 by using the five year age-sex specific rates for England and Wales for 1979-83 as standard. SETTING--England and Wales 1970-2 and 1979-83. RESULTS--In 1979-83 mortality from ischaemic heart disease was highest in men and women born in the Indian subcontinent (standardised mortality ratio 136 and 146 respectively). Young Indian men suffered the greatest excess (313 at ages 20-29). Other groups with raised mortality included Irish, Scottish, and Polish born immigrants. Those born in the Caribbean, the old Commonwealth, west Europe, and the United States had low death rates. In England and Wales mortality from ischaemic heart disease declined by 5% in men and 1% in women between 1970-2 and 1979-83, with greatest percentage declines in immigrants born in the United States, South Africa, the old Commonwealth, the Caribbean, and France. immigrant groups with raised mortality in the earlier period showed little improvement, and mortality from ischaemic heart disease increased among Indians (6% in men and 13% in women). In 1979-83 mortality from cerebrovascular disease was highest in Caribbeans (standardised mortality ratios 176 in men and 210 in women), followed by Africans, Indians, and Irish. Rates were low in west Europeans. Mortality from stroke declined by 28% overall in this period, a rate of decline shared by most groups. Men from the Indian subcontinent showed a decline of only 3%. CONCLUSION--In the 1980s mortality from ischaemic heart disease and cerebrovascular disease differed significantly between ethnic groups in England and Wales. In general, ethnic groups that experienced lower mortality from ischaemic heart disease in the 1970s showed the greatest improvement over the following decade.

Efficacy of captopril in postponing nephropathy in normotensive insulin dependent diabetic patients with microalbuminuria.

Abstract: OBJECTIVE--To assess the effectiveness of angiotensin converting enzyme inhibition in preventing the development of diabetic nephropathy (albuminuria greater than 300 mg/24h). DESIGN--Open randomised controlled study of four years' duration. SETTING--Outpatient diabetic clinic in tertiary referral centre. PATIENTS--44 normotensive (mean blood pressure 127/78 (SD 12/10) mm Hg) insulin dependent diabetic patients with persistent microalbuminuria (30-300 mg/24h). INTERVENTIONS--The treatment group (n = 21) was initially given captopril (25 mg/24 h). The dose was increased to 100 mg/24 h during the first 16 months and thiazide was added after 30 months. The remaining 23 patients were left untreated. MAIN OUTCOME MEASURES--Albuminuria, kidney function, development of diabetic nephropathy (albuminuria greater than 300 mg/24 h), and arterial blood pressure. RESULTS--Clinical and laboratory variables were comparable at baseline. Urinary excretion of albumin was gradually reduced from 82 (66-106) to 57 (39-85) mg/24 h (geometric mean (95% confidence interval)) in the captopril treated group, whereas an increase from 105(77-153) to 166 (83-323) mg/24 h occurred in the control group (p less than 0.05). Seven of the untreated patients progressed to diabetic nephropathy, whereas none of the captopril treated patients developed clinical overt diabetic nephropathy (p less than 0.05). Systemic blood pressure, glomerular filtration rate, haemoglobin A1c concentration, and urinary excretion of sodium and urea remained practically unchanged in the two groups. CONCLUSIONS--The findings suggest that angiotensin converting enzyme inhibition postpones the development of clinical overt diabetic nephropathy in normotensive insulin dependent diabetic patients with persistent microalbuminuria.

Intravenous acetylcysteine in paracetamol induced fulminant hepatic failure: a prospective controlled trial.

Abstract: OBJECTIVE--To see whether intravenous acetylcysteine would improve outcome in patients with fulminant hepatic failure after paracetamol overdose. DESIGN--A prospective randomised controlled study. SETTING--The Institute of Liver Studies, King's College Hospital, London. PATIENTS--50 consecutive patients (21 male) aged 16-60 with fulminant hepatic failure after paracetamol overdose who had not previously received acetylcysteine. INTERVENTIONS--Conventional intensive liver care plus either acetylcysteine (25 patients) in the same dose regimen as used early after a paracetamol overdose, except that the infusion was continued until recovery from encephalopathy or death, or an equivalent volume of 5% dextrose (25 patients). MAIN OUTCOME MEASURES--Survival; incidence of cerebral oedema, renal failure, and hypotension requiring inotropic support; liver function as assessed by prolongation of the prothrombin time; and degree of encephalopathy. RESULTS--The rate of survival was significantly higher in the acetylcysteine treated group than in the controls (48% (12/25 patients) v 20% (5/25); p = 0.037, 95% confidence interval for difference in proportions surviving 3% to 53%). Acetylcysteine treated patients had a lower incidence of cerebral oedema (40% (10/25) v 68% (17/25); p = 0.047, 95% confidence interval for difference in incidence 2% to 54%), and fewer developed hypotension requiring inotropic support (48% (12/25) v 80% (20/25); p = 0.018, 95% confidence interval 7% to 57%). Rates of deterioration and recovery of liver function, however, were similar in the two groups. No adverse reactions to acetylcysteine were seen. CONCLUSIONS--Acetylcysteine is safe and effective in fulminant hepatic failure after paracetamol overdose.

Prevalence of asthma in Melbourne schoolchildren: changes over 26 years.

Abstract: OBJECTIVES--To determine the prevalence of asthma in the past 12 months in Melbourne schoolchildren aged 7, 12, and 15 years and to compare the prevalence of a history of asthma with that of 26 years ago. DESIGN--A questionnaire on respiratory symptoms was distributed to children for completion by parents and return to the school. Subjects were selected by a stratified cluster design. SETTING--Government and non-government schools in the greater Melbourne area, Australia. SUBJECTS--10,981 children. Parents completed questionnaires for 3324 children aged 7, 2899 aged 12, and 2968 aged 15. The overall response rate was 90%. MAIN OUTCOME MEASURES--History of wheeze or asthma in the past 12 months and in lifetime. RESULTS--The prevalences of wheeze in the past 12 months were 23.1%, 21.7%, and 18.6% for 7, 12, and 15 year olds respectively. A history of wheeze was more common in boys than in girls at age 7 (443/1711 v 324/1614) and 12 (418/1767 v 322/1718) but not at age 15. Overall, 78% (1548) of those reporting wheeze also reported a history of asthma and 83% (1611) had used a bronchodilator. The prevalence of a history of asthma among 7 year olds was 46% compared with 19.1% in the 1964 survey, an increase of 141%. CONCLUSIONS--The current prevalence of asthma in Melbourne schoolchildren is high and has risen substantially over the past 26 years.

Delaying childbearing: effect of age on fecundity and outcome of pregnancy.

Abstract: Objectives - To study the age of the start of the fall (critical age) in fecundity; the probability of a pregnancy leading to a healthy baby taking into account the age of the woman; and, combining these results, to determine the age dependent probability of getting a healthy baby. Design - Cohort study of all women who had entered a donor insemination programme. Setting - Two fertility clinics serving a large part of The Netherlands. Subjects - Of 1637 women attending for artificial insemination 751 fulfilled the selection criteria, being married to an azoospermic husband and nulliparous and never having received donor insemination before. Main ontcome measures - The number of cycles before pregnancy (a positive pregnancy test result) or stopping treatment; and result of the pregnancy (successful outcome). Results - Of the 751 women, 555 became pregnant and 461 had healthy babies. The fall in fecundity was estimated to start at around 31 years (critical age); after 12 cycles the probability of pregnancy in a woman aged >31 was 0.54 compared with 0.74 in a woman aged 20-31. After 24 cycles this difference had decreased (probability of conception 0.75 in women >31 and 0.85 in women 20-31). The probability of having a healthy baby also decreased - by 3.5% a year after the age of 30. Combining both these age effects, the chance of a woman aged 35 having a healthy baby was about half that of a woman aged 25. Conclusion - After the age of 31 the probability of conception falls rapidly, but this can be partly compensated for by continuing insemination for more cycles. In addition, the probability of an adverse pregnancy outcome starts to increase at about the same age. This study examined the age of the start of the fall (critical age) in fecundity, the probability of a pregnancy leading to a healthy baby taking into account the age of the women, and, by combining all of the results, the determination of the age-dependent probability of getting a healthy baby. 2 fertility clinics serving a large part of the Netherlands provided the 751 women who fulfilled the selection criteria. In this cohort study of all women who entered a donor insemination program, those who fulfilled the selection criteria were married to azoospermic husbands, were nulliparous, and never received donor insemination previously. Main outcome measures studied were the number of cycles prior to a pregnancy (positive pregnancy result) or the cessation of treatment and the result of the pregnancy (successful outcome). Of 751 women, 555 became pregnant and 461 had healthy babies. The drop in fecundity was estimated to begin at around age 31 (critical age); after 12 cycles, the probability of pregnancy in a woman age 31 was 0.54 compared with 0.74 in a woman age 20-31. After 24 cycles, this difference had decreased (probability of conception 0.75 in women 31 and 0.85 in women age 20-31). The probability of having a healthy baby also decreased, by 3.5% a year after the age of 30. Combining both of these age effects, the chance of a woman age 35 having a healthy baby was about 1.2 that of a woman age 25. After the age of 31, the probability of conception falls rapidly; however, this can be compensated for partly by continuing insemination for more cycles. In addition, the probability of an adverse pregnancy outcome begins to increase at about the same age.

Alcohol and cardiovascular disease: the status of the U shaped curve.

Abstract: Alcohol is responsible for considerable morbidity and mortality and for considerable social problems. Excess mortality associated with alcohol consumption has been estimated at 28 000 per year in England and Wales,' and the annual cost of alcohol associated illness in Britain was calculated to be £167 million in 1986; this is in addition to a social cost of about £1600 million. The public health importance of limiting alcohol consumption is not questioned. This is the context within which to place the debate on the effect of moderate levels of alcohol consumption on morbidity and mortality associated with coronary heart disease. This debate has centred on the so called U shaped curve describing the relation of alcohol consumption to risk of death from all causes. Heavy drinkers have an increased risk ofdeath compared with moderate drinkers, but moderate drinkers have a lower mortality than abstainers. One commentator, surprisingly, labelled this U shaped curve a myth.' It is not mythical. Its existence is now not seriously in doubt. It is due largely to the lower death rate from coronary heart disease among moderate drinkers. What has been questioned is whether this is a consequence of a protective effect of alcohol. Abstainers include people who have stopped drinking because of ill health ("sick quitters") and people who are at higher risk for other reasons. Either of these groups may account for the higher risk among non-drinkers. The only major prospective study that failed to show that moderate drinkers had a lower risk of cardiovascular disease was that from Alameda County.' On p 553 in a follow up to this study, Lazarus et al have reported that among the women former drinkers had a higher risk of death than lifetime non-drinkers, but this was not true for the men. Among the men lifetime abstainers had a higher relative risk estimate than drinkers, although the confidence limits overlapped.4 A study from New Zealand reported recently in this journal showed that moderate drinkers had a lower incidence and mortality from coronary heart disease compared with both former drinkers and never drinkers. ' What then is the status of the U shaped curve? Does it represent causation? Is moderate drinking protective? Against the possible protective effect of moderate alcohol consumption on the risk of coronary heart disease has to be set the direct effect on blood pressure and the possible effect on risk of stroke.

Incidence of venous thromboembolism verified by necropsy over 30 years.

Abstract: OBJECTIVE--To determine the incidence of venous thromboembolism in all necropsy reports over 30 years. DESIGN--Study of all necropsies in one hospital in 1987 and longitudinal analysis of results of necropsy in 1957, 1964, 1975, and 1987. SETTING--Departments of general surgery, infectious diseases, internal medicine, oncology, and orthopaedics in a Swedish general hospital. MAIN OUTCOME MEASURE--Number of cases of venous thromboembolism. RESULTS--About a third of all necropsies showed venous thromboembolism. In 1987, 260 of 347 necropsies showing venous thromboembolism found pulmonary embolism, of which 93 were classified as fatal, 90 as contributory, and 77 as incidental. Only 21 contributory or fatal postoperative pulmonary emboli were seen. In only 106 of 260 patients with pulmonary embolism did routine necropsy not show the source of embolism. Calf veins were not routinely examined. Deep venous thrombosis was seen in 239 patients in 1987. The incidence of venous thromboembolism in the four years studied was remarkably stable except in the department of orthopaedics, where the proportion fell from 60.7% in 1975 to 32.2% in 1987 (p less than 0.05), although there were only a few patients. CONCLUSIONS--The overall incidence of venous thromboembolism has not changed over 30 years. During this period the proportion of the population aged over 65 has doubled, and this may have masked the beneficial effects of prophylaxis and early mobilisation. Prevalences corrected for age are needed.

Fatal myocardial infarction in the Scottish adjuvant tamoxifen trial. The Scottish Breast Cancer Committee.

Abstract: OBJECTIVE--To investigate the incidence of fatal myocardial infarction in women in the two randomised arms of the Scottish adjuvant tamoxifen trial. DESIGN--Retrospective review of hospital notes to determine with the greatest possible certainty women who had died of an acute myocardial infarction. SETTING--Scottish Cancer Trials Office, the University of Edinburgh. PATIENTS--1070 postmenopausal women with operable breast cancer who were randomised to receive either adjuvant tamoxifen for five years or until relapse (539 patients) or tamoxifen for at least six weeks on the confirmation of first recurrence (531 patients). MAIN OUTCOME MEASURES--Incidence of fatal myocardial infarction in women with no known or suspected systemic cancer. RESULTS--Of the 200 women who died in the adjuvant tamoxifen arm of the trial, 44 were free of cancer at death and 10 of these died of myocardial infarction. In the observation arm 251 women died, of whom 61 showed no evidence of systemic cancer and 25 had a fatal myocardial infarction. The incidence of fatal myocardial infarction in the two groups was significantly different (chi 2 = 6.88, p = 0.0087). CONCLUSION--Tamoxifen given for at least five years as adjuvant therapy for breast cancer seems to have a cardioprotective oestrogen-like effect in postmenopausal women.

By how much does dietary salt reduction lower blood pressure? II--Analysis of observational data within populations.

Abstract: OBJECTIVE--To determine whether the estimates of the size of the association between blood pressure and sodium intake derived from studies of individuals within populations can be quantitatively reconciled with our estimates derived from comparisons of the average blood pressure and sodium intake between different populations. DESIGN--Examination of data from 14 published studies that correlated blood pressure recordings in individuals against measurements of their 24 hour sodium intake (within population studies). MAIN OUTCOME MEASURE--Comparison of observed differences in blood pressure per 100 mmol/24 h difference in sodium intake in each within population study with predicted differences calculated from the between population data, after allowing for the underestimation of the true association of blood pressure with sodium intake caused by the large day to day variation in 24 hour sodium intake within individuals. RESULTS--The underestimation bias inherent in the within populations studies reduced the regression slope of blood pressure on single measures of 24 hour sodium intake to between a half and a quarter of the true value (for example, in one study from 6.0 to 2.4 mm Hg/100 mmol/24 h). Estimates from between population comparisons of the regression slope of blood pressure on sodium intake, after adjustment to take this underestimation bias into account, were similar to the values actually observed in the within population studies. CONCLUSION--The within population studies confirm our estimates from between population comparisons of the magnitude of the association between blood pressure and sodium intake.

The new NHS.

Abstract: With the new NHS almost upon us should we be looking backwards, forwards, or sideways? Nostalgia for the time before the NHS review has its attractions, and mourning the loss of the \"good old days\" is a common enough response to enforced change. But idealising the past also helps us to avoid dealing with the good old problems that faced the NHS. Not that the new reforms manage to address all or even the most important of these problems. The obvious omission is the underfunding of the NHS, which the government has never accepted despite its role in triggering the review. Instead the government redefined the problems of the NHS as the need to find ways to control costs in the face of limitless demands for health care, identify value for money, and increase consumer choice. This was a highly selective interpretation, particularly as spending on health in the United Kingdom was not escalating (6-09% ofgross domestic product in 1981; 5 98% in 1988, the year of the review). As the BMA has been saying for the past two years, not everything that emerged from the review was bad. Its focus was not entirely on efficiency and the crude cost cutting mechanisms of old: health outcomes and ways of identifying a \"good buy\" replaced the past emphasis on manipulating inputs. And while accepting the principle of public funding, the review Qorrectly challenged two assumptions on which our public service organisations have been based. The first is that large hierarchically managed institutions have enough flexibility to respond to the diverse demands of heterogeneous populations. The second is the assumption that employing highly trained health professionals ensures that users get what they want. In practice, these assumptions have led to patterns of NHS spending that are linked more closely to the status of medical specialties and powerful doctors' research interests than to the health needs of communities. This is the \"provider capture\" of resource planning within the NHS, which contributes to the pressure to extend services-acute hospital services in particularwithout reference to their relative benefits to the public health. That this government should have chosen market forces to remedy this is not surprising, although no evidence exists that competition alone reduces costs.' In fact, the opposite is more often found as competing providers invest heavily in improving quality, which drives up the price. Recent experience in the United States suggests, however, that having competing providers and powerful, discriminating purchasers may reduce costs without compromising outcomes in acute care.2 These were the conditions that the NHS reforms attempted to recreate here. District health authorities will shop around competing providers, buying health care for their population. Authorities will be funded according to the size and needs of their population (weighted capitation), not the size of their acute hospitals. Previously doctors have \"known what's best\" for their patients, but now purchasing health authorities will become the people's advocates. A new group of professionals will act as discriminating purchasers of services by becoming expert in assessing health needs and in monitoring the quality and effectiveness of health care. Anyone hoping for greater public accountability-which was meant to be part of the deal-will be disappointed. So what will happen from 1 April. Firstly, funding of health authorities by weighted capitation will not be introduced fully until 1992-3. Secondly, much of the information needed by purchasers to compare relative costs and benefits does not exist.3 (Ironically the NHS's failure to invest in information and audit is one of the reasons why its costs are so low by international standards.) Thirdly, closer examination of what happens in the United States shows that the \"powerful, discriminating purchasers\" are more generously funded and can buy from providers with surplus capacity-conditions that do not apply here after decades of underfunding. Finally, true separation between purchasers and providers within the district health authority is impossible. District general managers, responsible both for buying the best possible services for their population and keeping their directly managed units solvent, are unlikely to shift business away from their local units, thereby bankrupting them. As for contracting, it seems right that public money should be accounted for openly. Inevitably, given the lack of investment in information systems and the very slow development of medical and care audit in the NHS, detailed service specifications will not be available from 1 April. Skills needed by discriminating purchasers-such as those for negotiating and commissioning service agreements-also need developing. Service agreements, with or without expensive billing procedures, could enable us to challenge the current practice of paying for care that is of untested value, inappropriate, unnecessary, or unkind-while starving more valuable services. To become discriminating district health authorities will need adequate investment to support their public health functions, which have long been neglected. Without this contracts may merely reflect the status quo or reduce what counts in the complexities of providing care to what can be counted.

Usefulness of immunotherapy in patients with severe summer hay fever uncontrolled by antiallergic drugs.

Abstract: OBJECTIVE--To evaluate the efficacy and safety of immunotherapy (hyposensitisation) in patients with severe summer hay fever. DESIGN--A randomised, double blind, placebo controlled study of a biologically standardised depot grass pollen extract. SETTING--Allergy clinic, Royal Brompton and National Heart Hospital, London. PATIENTS--40 adults (mean age 35 years) with a history of severe grass pollen allergy uncontrolled by standard antiallergic drugs. Patients with perennial asthma were specifically excluded. INTERVENTION--Patients were randomised to receive either an active preparation (Alutard SQ, a grass pollen (Phleum pratense) extract) or placebo at a rate of two subcutaneous injections a week in increasing doses until a maintenance dose was reached. This maintenance dose was given once a month. MAIN OUTCOME MEASURES--Clinical efficacy was evaluated by symptom and drug diary cards, visual analogue scores during the grass pollen season, and a postseasonal assessment by the patients and a doctor. Conjunctival and skin sensitivity to local allergen provocation was measured before and after eight months of treatment. RESULTS--There was a highly significant decrease (median Alutard SQ v median placebo (95% confidence interval for difference between medians] in total symptom scores (p=0.001) in the Alutard SQ treated group (360 v 928 (238 to 825]. Significant differences were also found in total drug use (p=0.002, 129 v 627 (178 to 574]. Visual analogue symptom scores were also reduced in the active group (p=0.02, 2.2 v 5.5 (-4.8 to -0.5]. The postseasonal assessment, by either the doctor or the patients, showed a large improvement (p less than 0.001) in favour of Alutard SQ. Provocation tests showed a greater than 10-fold reduction for the active group in immediate conjunctival allergen sensitivity (p=0.001), a 40% decrease in early phase response (p=0.02), and a 57% decrease in the late phase (p=0.001) cutaneous response after intradermal allergen. A total of 523 active injections were given. There was one systemic reaction at 10 minutes after injection, which was rapidly reversed with intramuscular adrenaline. There was one mild delayed urticarial reaction at 2 1/2 hours. CONCLUSION--Immunotherapy is effective in patients with severe summer hay fever, but immediate anaphylactic reactions limit its use to specialised centres. Patient selection is extremely important, and chronic perennial asthma should be specifically excluded. As serious reactions occur within minutes a two hour wait for all patients after each injection seems unnecessary.

Fluoxetine and suicide: a meta-analysis of controlled trials of treatment for depression.

Abstract: OBJECTIVE--A comprehensive meta-analysis of clinical trial data was performed to assess the possible association of fluoxetine and suicidality (suicidal acts and ideation). DESIGN--Retrospective analysis of pooled data from 17 double blind clinical trials in patients with major depressive disorder comparing fluoxetine (n = 1765) with a tricyclic antidepressant (n = 731) or placebo (n = 569), or both. MAIN OUTCOME MEASURES--Multiple data sources were searched to identify patients with suicidal acts. Suicidal ideation was assessed with item 3 of the Hamilton depression rating scale, which systematically rates suicidality. Emergence of substantial suicidal ideation was defined as a change in the rating of this item from 0 or 1 at baseline to 3 or 4 during double blind treatment; worsening was defined as any increase from baseline; improvement was defined as a decrease from baseline at the last visit during the treatment. RESULTS--Suicidal acts did not differ significantly in comparisons of fluoxetine with placebo (0.2% v 0.2%, p = 0.494, Mantel-Haenszel adjusted incidence difference) and with tricyclic antidepressants (0.7% v 0.4%, p = 0.419). The pooled incidence of suicidal acts was 0.3% for fluoxetine, 0.2% for placebo, and 0.4% for tricyclic antidepressants, and fluoxetine did not differ significantly from either placebo (p = 0.533, Pearson's chi 2) or tricyclic antidepressants (p = 0.789). Suicidal ideation emerged marginally significantly less often with fluoxetine than with placebo (0.9% v 2.6%, p = 0.094) and numerically less often than with tricyclic antidepressants (1.7% v 3.6%, p = 0.102). The pooled incidence of emergence of substantial suicidal ideation was 1.2% for fluoxetine, 2.6% for placebo, and 3.6% for tricyclic antidepressants. The incidence was significantly lower with fluoxetine than with placebo (p = 0.042) and tricyclic antidepressants (p = 0.001). Any degree of worsening of suicidal ideation was similar with fluoxetine and placebo (15.4% v 17.9%, p = 0.196) and with fluoxetine and tricyclic antidepressants (15.6% v 16.3%, p = 0.793). The pooled incidence of worsening of suicidal ideation was 15.3% for fluoxetine, 17.9% for placebo, and 16.3% for tricyclic antidepressants. The incidence did not differ significantly with fluoxetine and placebo (p = 0.141) or tricyclic antidepressants (p = 0.542). Suicidal ideation improved significantly more with fluoxetine than with placebo (72.0% v 54.8%, p less than 0.001) and was similar to the improvement with tricyclic antidepressants (72.5% v 69.8%, p = 0.294). The pooled incidence of improvement of suicidal ideation was 72.2% for fluoxetine, 54.8% for placebo, and 69.8% for tricyclic antidepressants. The incidence with fluoxetine was significantly greater than with placebo (p less than 0.001) and did not differ from that with tricyclic antidepressants (p = 0.296). CONCLUSIONS--Data from these trials do not show that fluoxetine is associated with an increased risk of suicidal acts or emergence of substantial suicidal thoughts among depressed patients.

Critical appraisal of published research: introductory guidelines.

Abstract: Reading medical journals can be time consuming, and most doctors have become adept at skimming contents by reading titles and perusing abstracts. Getting to grips with the details of papers and conducting a critical appraisal of the research may be a task many find difficult because there are not research experts and have not had training in the appraisal of papers during medical education. This difficulty may be particularly acute for junior doctors embarking on their first research towards a higher degree.

Effects of feedback of information on clinical practice: a review.

Abstract: OBJECTIVE--To establish what is known about the role of feedback of statistical information in changing clinical practice DESIGN--Review of 36 studies of interventions entailing the use of statistical information for audit or practice review, which used a formal research design SUBJECTS--Papers identified from computer searches of medical and health service management publications, of which 36 describing studies of interventions designed to influence clinical care and including information feedback from clinical or administrative data systems were reviewed MAIN OUTCOME MEASURES--Evidence for effect of information feedback on change in clinical practice RESULTS--Information feedback was most likely to influence clinical practice if it was part of strategy to target decision makers who had already agreed to review their practice A more direct effect was discernable if the information was presented close to the time of decision making The questions of the optimum layout and quantity of information were not addressed; the 36 papers were insufficient for defining good formats for information to be used for audit or quality assurance CONCLUSIONS--Given the cost of information processing and the current emphasis on closing the audit loop in the health services, it is important that the use of information in the audit process should be critically evaluated

Risk of epilepsy after febrile convulsions: a national cohort study

Abstract: OBJECTIVE--To identify children with febrile convulsions, classify their febrile convulsions into simple and complex, and determine the number and type of subsequent afebrile seizures in those children. DESIGN--National population based study. SETTING--United Kingdom. SUBJECTS--16,004 neonatal survivors born during one week in April 1970. MAIN OUTCOME MEASURES--Information about febrile and afebrile seizures obtained from questionnaires at 5 and 10 years of age and from hospital records. RESULTS--Information was available for 14,676 of the cohort children. 398 (2.7%) of them had had at least one febrile convulsion. 16 children were known to be neurologically or developmentally abnormal before the first attack. Of the remaining 382 children, 305 had had a simple first febrile convulsion and 77 a complex first febrile convulsion. Thirteen of the 382 had had one or more afebrile seizures, nine of whom had developed epilepsy (recurrent afebrile seizures). A higher proportion of children with complex febrile convulsions (6/95) rather than simple febrile convulsions (3/287) developed epilepsy, the risk being highest for those who had had focal febrile convulsions (5/17; chi 2 = 39.9, p less than 0.001). Three of the 32 children who had prolonged febrile convulsions developed afebrile complex partial seizures. CONCLUSIONS--The risk of epilepsy after febrile convulsions is much less than reported in many hospital studies, and if febrile convulsions cause brain damage that leads to later epilepsy this is a rare occurrence.

Treatment needs of prisoners with psychiatric disorders

Abstract: OBJECTIVE--To describe the prevalence of psychiatric disorder and the treatment needs of sentenced prisoners in England and Wales. DESIGN--Population survey based on a 5% sample of men serving prison sentences. SETTING--Sixteen prisons for adult males and nine institutions for male young offenders representative of all prisons in prison type, security levels, and length of sentences. SUBJECTS--406 young offenders and 1478 adult men, 404 and 1365 of whom agreed to be interviewed. MAIN OUTCOME MEASURES--History of psychiatric disorder, clinical diagnosis of psychiatrist, and required treatment. RESULTS--652 (37%) men had psychiatric disorders diagnosed, of whom 15 (0.8%) had organic disorders, 34 (2%) psychosis, 105 (6%) neurosis, 177 (10%) personality disorder, and 407 (23%) substance misuse. 52 (3%) were judged to require transfer to hospital for psychiatric treatment, 96 (5%) required treatment in a therapeutic community setting, and a further 176 (10%) required further psychiatric assessment or treatment within prison. CONCLUSIONS--By extrapolation the sentenced prison population includes over 700 men with psychosis, and around 1100 who would warrant transfer to hospital for psychiatric treatment. Provision of secure treatment facilities, particularly long term medium secure units, needs to be improved. Services for people with personality, sexual, and substance misuse disorders should be developed in both prisons and the health service.

Effects of intravenous magnesium in suspected acute myocardial infarction: overview of randomised trials.

Abstract: OBJECTIVE--To investigate the effect of intravenous magnesium on mortality in suspected acute myocardial infarction. DESIGN--Systematic overview of all available randomised trials in which patients were allocated to receive either intravenous magnesium or otherwise similar treatment without magnesium. SETTING--Coronary care units of several hospitals. PATIENTS--1301 patients in seven randomised trials. MAIN OUTCOME MEASURE--Short term mortality. RESULTS--Considering the seven trials collectively there were 25 (3.8%) deaths among 657 patients allocated to receive magnesium and 53 (8.2%) deaths among 644 patients allocated control, generally during hospital follow up. This represents a 55% reduction in the odds of death (p less than 0.001) with 95% confidence intervals ranging from about one third to about two thirds. 70 of 648 patients allocated magnesium compared with 109 of 641 controls had serious ventricular arrhythmias, suggesting that magnesium reduces the incidence, though the definition varied among trials. Other adverse effects were rare in the limited number of patients for whom this data were available. CONCLUSION--Despite the limited number of patients randomised this overview suggests that intravenous magnesium therapy may reduce mortality in patients with acute myocardial infarction. Further large scale trials to confirm (or refute) these findings are desirable.

Chemotherapy in advanced ovarian cancer: An overview of randomised clinical trials

Abstract: OBJECTIVES--To consider the role of platinum and the relative merits of single agent and combination chemotherapy in the treatment of advanced ovarian cancer. DESIGN--Formal quantitative overview using updated individual patient data from all available randomised trials (published and unpublished). SUBJECTS--8139 patients (6408 deaths) included in 45 different trials. RESULTS--No firm conclusions could be reached. Nevertheless, the results suggest that in terms of survival immediate platinum based treatment was better than non-platinum regimens (overall relative risk 0.93; 95% confidence interval 0.83 to 1.05); platinum in combination was better than single agent platinum when used in the same dose (overall relative risk 0.85; 0.72 to 1.00); and cisplatin and carboplatin were equally effective (overall relative risk 1.05; 0.94 to 1.18). CONCLUSIONS--In the past, randomised clinical trials of chemotherapy in advanced ovarian cancer have been much too small to detect the degree of benefit which this overview suggests is realistic for currently available chemotherapeutic regimens. Hence a new trial comparing cisplatin, doxorubicin, and cyclophosphamide (CAP) with carboplatin has been launched and plans to accrue 2000 patients.