Showing papers in "BMJ in 1988"

Intersalt: An international study of electrolyte excretion and blood pressure. Results for 24 hour urinary sodium and potassium excretion

Abstract: The relations between 24 hour urinary electrolyte excretion and blood pressure were studied in 10,079 men and women aged 20-59 sampled from 52 centres around the world based on a highly standardised protocol with central training of observers, a central laboratory, and extensive quality control. Relations between electrolyte excretion and blood pressure were studied in individual subjects within each centre and the results of these regression analyses pooled for all 52 centres. Relations between population median electrolyte values and population blood pressure values were also analysed across the 52 centres. Sodium excretion ranged from 0.2 mmol/24 h (Yanomamo Indians, Brazil) to 242 mmol/24 h (north China). In individual subjects (within centres) it was significantly related to blood pressure. Four centres found very low sodium excretion, low blood pressure, and little or no upward slope of blood pressure with age. Across the other 48 centres sodium was significantly related to the slope of blood pressure with age but not to median blood pressure or prevalence of high blood pressure. Potassium excretion was negatively correlated with blood pressure in individual subjects after adjustment for confounding variables. Across centres there was no consistent association. The relation of sodium to potassium ratio to blood pressure followed a pattern similar to that of sodium. Body mass index and heavy alcohol intake had strong, significant independent relations with blood pressure in individual subjects.

Randomised trial of prophylactic daily aspirin in British male doctors

Abstract: A six year randomised trial was conducted among 5139 apparently healthy male doctors to see whether 500 mg aspirin daily would reduce the incidence of and mortality from stroke, myocardial infarction, or other vascular conditions Though total mortality was 10% lower in the treated than control group, this difference was not statistically significant and chiefly involved diseases other than stroke or myocardial infarction Likewise, there was no significant difference in the incidence of non-fatal myocardial infarction or stroke—indeed, disabling strokes were somewhat commoner among those allocated aspirin The lower confidence limit for the effect of aspirin on non-fatal stroke or myocardial infarction, however, was a substantial 25% reduction Migraine and certain types of musculoskeletal pain were reported significantly less often in the treated than control group, but as the control group was not given a placebo the relevance of these findings was difficult to assess There was no apparent reduction in the incidence of cataract in the treated group The lack of any apparent reduction in disabling stroke or vascular death contrasts with the established value of antiplatelet treatment after occlusive vascular disease

Detecting anxiety and depression in general medical settings.

Abstract: To aid general practitioners and other non-psychiatrists in the better recognition of mental illness short scales measuring anxiety and depression were derived by latent trait analysis from a standardised psychiatric research interview. Designed to be used by non-psychiatrists, they provide dimensional measures of the severity of each disorder. The full set of nine questions need to be administered only if there are positive answers to the first four. When assessed against the full set of 60 questions contained in the psychiatric assessment schedule they had a specificity of 91% and a sensitivity of 86%. The scales would be used by non-psychiatrists in clinical investigations and possibly also by medical students to familiarise them with the common forms of psychiatric illness, which are often unrecognised in general medical settings.

Mammographic screening and mortality from breast cancer: the Malmö mammographic screening trial.

Abstract: STUDY OBJECTIVE--To determine whether mortality from breast cancer could be reduced by repeated mammographic screening. DESIGN--Birth year cohorts of city population separately randomised into study and control groups. SETTING--Screening clinic outside main hospital. PATIENTS--Women aged over 45; 21,088 invited for screening and 21,195 in control group. INTERVENTIONS--Women in the study group were invited to attend for mammographic screening at intervals of 18-24 months. Five rounds of screening were completed. Breast cancer was treated according to stage at diagnosis. END POINT--Mortality from breast cancer. MEASUREMENTS AND MAIN RESULTS--All women were followed up and classed at end point as alive without breast cancer, alive with breast cancer, dead from breast cancer, or dead from other causes. Cause of death was taken from national mortality registry and for patients with breast cancer was validated independently. Mean follow up was 8.8 years. Altogether 588 cases of breast cancer were diagnosed in the study group and 447 in the control group; 99 v 94 women died of all causes and 63 v 66 women died of breast cancer (no significant difference; relative risk 0.96 (95% confidence interval 0.68 to 1.35)). In the study group 29% more women aged less than 55 died of breast cancer (28 v 22; relative risk 1.29 (0.74 to 2.25)). More women in the study group died from breast cancer in the first seven years; after that the trend reversed, especially in women aged greater than or equal to 55 at entry. Overall, women in the study group aged greater than or equal to 55 had a 20% reduction in mortality from breast cancer (35 v 44; relative risk 0.79 (0.51 to 1.24)). OTHER FINDINGS--In the study group 100 (17%) cancers appeared in intervals between screenings and 107 (18%) in non-attenders; 51 of these women died from breast cancer. Cancers classed as stages II-IV comprised 33% (190/579) of cancers in the study group and 52% (231/443) in the control group. CONCLUSIONS--Invitation to mammographic screening may lead to reduced mortality from breast cancer, at least in women aged 55 or over.

Maternal serum screening for Down's syndrome in early pregnancy.

Abstract: The possibility of improving the effectiveness of antenatal screening for Down's syndrome by measuring human chorionic gonadotrophin concentrations in maternal serum during the second trimester to select women for diagnostic amniocentesis was examined. The median maternal serum human chorionic gonadotrophin concentration in 77 pregnancies associated with Down's syndrome was twice the median concentration in 385 unaffected pregnancies matched for maternal age, gestational age, and duration of storage of the serum sample. Measuring human chorionic gonadotrophin in maternal serum was an effective screening test, giving a lower false positive rate (3%) at a 30% detection rate than that for maternal age (5%) and the two existing serum screening tests, unconjugated oestriol (7%) and alpha fetoprotein (11%). The most effective screening results were obtained with all four variables combined; at the same 30% detection rate the false positive rate declined to 0.5%. The new screening method would detect over 60% of affected pregnancies, more than double that achievable with the same amniocentesis rate in existing programmes (5%), and could reduce the number of children born with Down's syndrome in the United Kingdom from about 900 a year to about 350 a year.

Statistics in Medicine: Calculating confidence intervals for relative risks (odds ratios) and standardised ratios and rates

Abstract: Gardner and Alunan explained the rationale for using estimation and confidence intervals in making inferences from analytical studies and described their calculation for means or proportions and their differences.1 In this paper we present methods for calculating confidence intervals for other common statistics obtained from medical investigations. The techniques for obtaining confidence intervals for estimates of relative risk are described. These can come either from an incidence study, where, for example, the frequency of a congenital malformation at birth is compared in two defined groups of mothers, or from a case-control study, where a group of patients with the disease of interest (the cases) is compared with another group of people without the disease (the controls). The methods of obtaining confidence intervals for standardised disease ratios and rates in studies of incidence, prevalence, and mortality are described. Such rates and ratios are commonly calculated to enable appropriate comparisons to be made between study groups after adjustment for confounding factors like age and sex. The most frequently used standardised indices are the standardised incidence ratio (SIR) and the standardised mortality ratio (SMR). A worked example is included for each method. The calculations have been carried out to full arithmetical precision, as is recom? mended practice,2 although intermediate steps are shown as rounded results. Some of the methods given in this paper are large sample approximations and are not reliable for studies with fewer than about 20 cases. Appropriate design principles for these types of study have to be adhered to since confidence intervals convey only the effects of sampling variation on the precision of the estimated statistics and cannot control for other errors such as biases due to the selection of inappropriate controls or in the methods of collecting the data.

Randomised controlled trial of general practitioner intervention in patients with excessive alcohol consumption.

Abstract: OBJECTIVE: To determine effectiveness of advice from general practitioners to heavy drinkers to reduce their excessive alcohol consumption (35 U or more a week for men, 21 U or more for women). DESIGN: Randomised, controlled double blind trial over 12 months with interim assessment at six months. SETTING: Group practices (n = 47; list size averaging 10,000) recruited from Medical Research Council's general practice research framework, mostly in rural or small urban settings. PATIENTS: Patients recruited after questionnaire survey. Of total of 2571 (61.2%) of 4203 patients invited for interview who attended, 909 (35.4%) stated that in past seven days they had drunk above the limits set for study and had not received advice; they were randomised to control and treatment groups. INTERVENTIONS: Patients in treatment group were interviewed by general practitioner (who had had a training session) and received advice and information about how to reduce consumption and also given a drinking diary. END POINT: Study aimed at detecting a reduction in proportion of men with excessive alcohol consumption of 30% in treatment group and 20% in control group (for women 40% and 20%, respectively) with a power of 90% at 5% level of significance. In addition, corroborative measures such as estimation of gamma-glutamyltransferase activity were included. MEASUREMENTS AND MAIN RESULTS: At one year a mean reduction in consumption of alcohol of 18.2 (SE 1.5) U/week had occurred in treated men compared with a reduction of 8.1 (1.6) U/week in controls (p less than 0.001). The proportion of men with excessive consumption at interview had dropped by 43.7% in the treatment group compared with 25.5% in controls (p less than 0.001). A mean reduction in weekly consumption of 11.5 (1.6) U occurred in treated women compared with 6.3 (2.0) U in controls (p less than 0.05), with proportionate reductions of excessive drinkers in treatment and control groups of 47.7% and 29.2% respectively. Reduction in consumption increased significantly with number of general practitioner interventions. At one year the mean value for gamma-glutamyltransferase activity had dropped significantly more in treated men (-2.4 (0.9)IU/l) than in controls (+1.1(1.0)IU/l; t = 2.7, p less than 0.01). Reduction in gamma-glutamyltransferase activity tended to increase with number of intervention sessions in men. Changes in gamma-glutamyltransferase activity in women and changes in other indicators in both sexes did not differ significantly between treatment and control groups. CONCLUSIONS: If the results of this study were applied to the United Kingdom intervention by general practitioners could each year reduce to moderate levels the alcohol consumption of some 250000 men and 67500 women who currently drink to excess. General practitioners and other members of the primary health care team should therefore be encouraged to include counselling about alcohol consumption in their preventive activities.

Adverse neurodevelopmental outcome of moderate neonatal hypoglycaemia.

Abstract: There has been considerable debate over whether asymptomatic neonatal hypoglycaemia results in neurological damage. In a detailed multicentre study of 661 preterm infants hypoglycaemia was found to be common. Moderate hypoglycaemia (plasma glucose concentration less than 2.6 mmol/l) occurred in 433 of the infants and in 104 was found on three to 30 separate days. There was considerable variation among the centres, implying differences in decisions to intervene. The number of days on which moderate hypoglycaemia occurred was strongly related to reduced mental and motor development scores at 18 months (corrected age), even after adjustment for a wide range of factors known to influence development. When hypoglycaemia was recorded on five or more separate days adjusted mental and motor developmental scores at 18 months (corrected age) were significantly reduced by 14 and 13 points respectively, and the incidence of neurodevelopmental impairment (cerebral palsy or developmental delay) was increased by a factor of 3.5 (95% confidence interval 1.3 to 9.4). These data suggest that, contrary to general belief, moderate hypoglycaemia may have serious neurodevelopmental consequences, and reappraisal of current management is urgently required.

Seropositivity for HIV and the development of AIDS or AIDS related condition: three year follow up of the San Francisco General Hospital cohort.

Abstract: The three year actuarial progression rate to the acquired immune deficiency syndrome (AIDS) in a cohort of men in San Francisco who were seropositive for the human immuno-deficiency virus (HIV) was 22%. An additional 26 (19%) developed AIDS related conditions. β 2 Microglobulin concentration, packed cell volume, HIV p24 antigenaemia, and the proportion and number of T4 lymphocytes each independently predicted progression to AIDS. β 2 Microglobulin was the most powerful predictor. The 111 subjects tested who were normal by all predictors (40%) had a three year progression rate of 7%, and the 68 subjects who were abnormal by two or more predictors (24%) had a progression rate of 57%. Two thirds of all men who progressed to AIDS were in the last group. The median T4 lymphocyte count in subjects who did not progress to AIDS fell from 626 × 10 6 to 327 × 10 6 /1. HIV p24 antigenaemia developed in 7% of the subjects per year. The proportion who were abnormal by two or more predictive variables rose to 41%. At three years an estimated two thirds of the seropositive subjects showed clinical AIDS, an AIDS related condition, or laboratory results that were highly predictive of AIDS. It is concluded from the observed rates and the distribution of predictive variables at three years that half of the men who were seropositive for HIV will develop AIDS by six years after the start of the study, and three quarters will develop AIDS or an AIDS related condition.

Causes of venous ulceration: a new hypothesis

Abstract: Previous hypotheses about the causes of venous ulceration are inconsistent with recently published data. In patients with chronic venous insufficiency the number of functioning capillary loops visible in the skin on microscopy fell after the legs had been dependent for 30 minutes. Another study had shown that leucocytes became trapped in the circulation in dependent legs. A new hypothesis linking these two findings proposes that the trapped while cells occlude the capillaries and result in ischaemia of the skin of the leg.

Prevalence of microalbuminuria, arterial hypertension, retinopathy and neuropathy in patients with insulin dependent diabetes

Abstract: Diabetic nephropathy is the main cause of the increased morbidity and mortality in patients with insulin dependent diabetes. The prevalence of microalbuminuria was determined in adults with insulin dependent diabetes of five or more years9 duration that had started before the age of 41. All eligible patients (n=982) attending a diabetes clinic were asked to collect a 24 hour urine sample for analysis of albumin excretion by radio-immunoassay; 957 patients complied. Normoalbuminuria was defined as urinary albumin excretion of ≤30 mg/24 h (n=562), microalbuminuria as 31-299 mg/24 h (n=215), and macroalbuminuria as ≥300 mg/24 h (n=180). The prevalence of microalbuminuria and macroalbuminuria was significantly higher in patients whose diabetes had developed before rather than after the age of 20. The prevalence of arterial hypertension increased with increased albuminuria, being 19%, 30%, and 65% in patients with normoalbuminuria, microalbuminuria, and macroalbuminuria respectively. The prevalence of proliferative retinopathy and blindness rose with increasing albuminuria, being 12% and 1·4%, respectively, in patients with normoalbuminuria, 28% and 5·6% in those with microalbuminuria and 58% and 10·6% in those with macroalbuminuria. An abnormal vibratory perception threshold was more common in patients with microalbuminuria (31%) and macroalbuminuria (50%) than in those with normoalbuminuria (21%). This study found a high prevalence (22%) of microalbuminuria, which is predictive of the later development of diabetic nephropathy. Microalbuminuria is also characterised by an increased prevalence of arterial hypertension, proliferative retinopathy, blindness, and peripheral neuropathy. Thus, urinary excretion of albumin should be monitored routinely in patients with insulin dependent diabetes.

Influence of serum luteinising hormone concentrations on ovulation, conception, and early pregnancy loss in polycystic ovary syndrome.

Abstract: Women with the polycystic ovary syndrome do not respond well to treatment with luteinising hormone releasing hormone. To determine whether this might be due to an underlying endocrine disturbance basal concentrations of luteinising hormone were measured in 54 infertile women treated with pulsatile luteinising hormone releasing hormone and concentrations at the time of maximum follicular growth were measured in 23 of the patients. Forty one patients ovulated. Forty one patients ovulated and 27 conceived, but nine pregnancies terminated within four weeks after ovulation. Basal luteinising hormone concentrations were significantly lower in those who conceived (12.4 (range 1.3-29.0) IU/l) than in those who did not (19.0 (3.5-50.0) IU/l) and in those whose pregnancy progressed (9.6 (1.3-29.0) IU/l) than in those with early loss of pregnancy (17.9 (7.0-29.0) IU/l). Concentrations at the time of maximum follicular growth were significantly lower in women who ovulated (9.4 (2.9-35.4) IU/l) than in those who did not (29.0 (7.0-50.0) IU/l) and in those who conceived (6.2 (2.9-8.5) IU/l) than in those who did not (17.9 (4.0-50.0) IU/l). These results indicate that high concentrations of luteinising hormone during the follicular phase in women with polycystic ovaries have a deleterious effect on rates of conception and may be a causal factor in early pregnancy loss.

Deep vein thrombosis.

Abstract: example is the largest recorded food related outbreak of paratyphoid, which occurred in Birmingham early this year and was successfully dealt with under the present control of infection arrangements. Another example is the outbreak Qf legionnaires' disease in London which Dr Cunningham and her colleagues had to deal witlY. One shudders to think what would have happened if the government had accepted the Acheson recommendations when the report was published. Control of infection has progressed since the major outbreaks of salmonella food poisoning at the Stanley Royd Hospital, Wakefield, and of legionnaires' disease in Stafford. Several models of good practice are now available in the provinces, including Birmingham. Health authorities in London would do well to adopt these practices, which emphasise the important role of local authorities in respect ofcommunicable disease and the link with the medical officer for environmental health in his role as proper officer. The models rely on the effective use of available resources. This is not the time to impose an unnecessary financial commitment on the National Health Service. Besides, historical evidence suggests that the health service would not be able to cope with the demands of the organisation of the nationwide control of infection services outside the National Health Service. No other Western country has abandoned the system built on local authority medical officers of health for controlling infection. It is time that we returned to it. S S BAKHSHI

Physical activity, muscle strength, and calcium intake in fracture of the proximal femur in Britain.

Abstract: Regular exercise and high calcium intake possibly help to preserve bone mass. Little is known, however, about their role in preventing hip fracture. The physical activity and calcium intake of 300 elderly men and women with hip fractures were compared with those of 600 controls matched for age and sex. In both sexes increased daily activity, including standing, walking, climbing stairs, carrying, housework, and gardening protected against fracture. This was independent of other known risk factors, including body mass, cigarette smoking, and alcohol consumption. Strength of grip correlated with activity and was inversely related to the risk of fracture. Calcium intake was not related to the risk of fracture in women. Men with daily calcium intakes above 1g had lower risks. These findings point to the importance of elderly people in Britain maintaining physical activity in their day to day lives.

Prevention of gastroduodenal damage induced by non-steroidal anti-inflammatory drugs: controlled trial of ranitidine.

Abstract: OBJECTIVE: To evaluate the prophylactic effect of ranitidine 150 mg twice daily in patients requiring one of the following non-steroidal anti-inflammatory drugs: naproxen, piroxicam, diclofenac, and indomethacin. In addition, risk factors were studied in order to help in targeting of such treatment to specific groups of patients. DESIGN: Double blind, placebo controlled, randomised, parallel group with endoscopic assessments at 0, 4, and 8 weeks. SETTING: Multicentre outpatient study at secondary referral centres in five European countries. PATIENTS--297 patients with rheumatoid arthritis or osteoarthritis over the age of 18 without lesions in the stomach and duodenum at baseline endoscopy (after one week without taking non-steroidal anti-inflammatory drugs). Those taking other antirheumatic agents, concomitant ulcerogenic drugs, or treatment for peptic ulcers within the previous 30 days were excluded. Age, sex, arthritic disease, and type of non-steroidal anti-inflammatory drug used were comparable in the two treatment groups. In all, 263 patients completed the trial. INTERVENTIONS: Ranitidine 150 mg twice daily or placebo (plus the selected non-steroidal anti-inflammatory drug) was prescribed within five days after the baseline endoscopy for two consecutive periods of four weeks. Paracetamol was permitted during the study, but not antacids. Patients were withdrawn if the most severe grade of damage (including ulceration) was found at the four week endoscopy or when indicated, or with lesser damage at the investigator's discretion. END POINT: Frequency of gastric and duodenal ulceration or lesions, or both. MEASUREMENTS AND MAIN RESULTS: The cumulative incidence of peptic ulceration by eight weeks was 10.3% (27/263); 2 out of 135 (1.5%) developed duodenal ulceration in the ranitidine group, compared with 10 out of 126 (8%) taking placebo. The frequency of gastric ulceration was the same (6%) for the two groups at eight weeks. Though significantly fewer gastric lesions developed in the ranitidine group by eight weeks. The frequency of non-ulcerative lesions in the duodenum did not differ greatly for the two groups at either time point. Twelve out of 75 (16%) patients taking piroxicam developed peptic ulceration, of whom two thirds had duodenal ulceration. Patients with a history of peptic ulcer were particularly susceptible to recurrent ulceration, against which ranitidine offered some protection. CONCLUSIONS: Ranitidine 150 mg twice daily significantly reduced the incidence of duodenal ulceration but not gastric ulceration when prescribed concomitantly with one of four commonly used non-steroidal anti-inflammatory drugs.

Prevention of diabetic nephropathy with enalapril in normotensive diabetics with microalbuminuria.

Abstract: STUDY OBJECTIVE--To assess the effectiveness of inhibition of angiotensin converting enzyme in preventing diabetic nephropathy. DESIGN--Randomised follow up study of normotensive diabetics with persistent microalbuminuria (30-300 mg/24 hours) treated with enalapril or its matched placebo for one year. Double blind for first six months, single blind for last six months. SETTING--Diabetic clinic in tertiary referral centre. PATIENTS--Treatment group and placebo group each comprised 10 normotensive diabetics with persistent microalbuminuria. INTERVENTIONS--Treatment group was given enalapril 20 mg daily and controls matched placebo. Patients were given antihypertensive treatment after one year. END POINT--Albumin excretion, arterial pressure, and renal function. MAIN RESULTS--In last three months of trial three of 10 patients taking placebo had diabetic nephropathy (albumin excretion greater than 300 mg/24 hours). No patients taking enalapril developed nephropathy and five showed normal albumin excretion (less than 30 mg/24 hours) (p = 0.005, Mann-Whitney test). Mean arterial pressure was reduced by enalapril throughout study (p less than 0.005) but increased linearly with placebo (p less than 0.05). Albumin excretion decreased linearly with enalapril but not placebo. An increase in albumin excretion with placebo was positively related to the increase in mean arterial pressure (r = 0.709, p less than 0.05, Spearman's rank test). With enalapril total renal resistances and fractional albumin clearances improved progressively (time effect, p = 0.0001). CONCLUSION--Inhibition of angiotensin converting enzyme prevents development of nephropathy in normotensive diabetics with persistent microalbuminuria. This may be due to reduction in intraglomerular pressure and to prevention of increased systemic blood pressure. Future studies should compare long term effects of inhibitors of converting enzyme with other antihypertensive drugs.

Intravenous tissue plasminogen activator and size of infarct, left ventricular function, and survival in acute myocardial infarction.

Abstract: STUDY OBJECTIVE--To assess effect of intravenous recombinant tissue type plasminogen activator on size of infarct, left ventricular function, and survival in acute myocardial infarction. DESIGN--Double blind, randomised, placebo controlled prospective trial of patients with acute myocardial infarction within five hours after onset of symptoms. SETTING--Twenty six referral centres participating in European cooperative study for recombinant tissue type plasminogen activator. PATIENTS--Treatment group of 355 patients with acute myocardial infarction allocated to receive intravenous recombinant plasminogen activator. Controls comprised 366 similar patients allocated to receive placebo. INTERVENTION--All patients were given aspirin 250 mg and bolus injection of 5000 IU heparin immediately before start of trial. Patients in treatment group were given 100 mg recombinant tissue plasminogen activator over three hours (10 mg intravenous bolus, 50 mg during one hour, and 40 mg during next two hours) by infusion. Controls were given placebo by same method. Full anticoagulation treatment and aspirin were given to both groups until angiography (10-22 days after admission). beta Blockers were given at discharge. END POINT--Left ventricular function at 10-22 days, enzymatic infarct size, clinical course, and survival to three month follow up. MEASUREMENTS AND MAIN RESULTS--Mortality was reduced by 51% (95% confidence interval -76 to 1) in treated patients at 14 days after start of treatment and by 36% (-63 to 13) at three months. For treatment within three hours after myocardial infarction mortality was reduced by 82% (-95 to -31) at 14 days and by 59% (-83 to -2) at three months. During 14 days in hospital incidence of cardiac complications was lower in treated patients than controls (cardiogenic shock, 2.5% v 6.0%; ventricular fibrillation, 3.4% v 6.3%; and pericarditis, 6.2% v 11.0% respectively), but that of angioplasty or artery bypass, or both was higher (15.8% v 9.6%) during the first three months. Bleeding complications were commoner in treated than untreated patients. Most were minor, but 1.4% of treated patients had intracranial haemorrhage within three days after start of infusion. Enzymatic size of infarct, determined by alpha hydroxybutyrate dehydrogenase concentrations, was less (20%, 2p = 0.0018) in treated patients than in controls. Left ventricular ejection fraction was 2.2% higher (0.3 to 4.0) and end diastolic and end systolic volumes smaller by 6.0 ml (-0.2 to -11.9) and 5.8 ml (-0.9 to -10.6), respectively, in treated patients. CONCLUSION--Recombinant tissue type plasminogen activator with heparin and aspirin reduces size of infarct, preserves left ventricular function, and reduces complications and death from cardiac causes but at increased risk of bleeding complications4+

Incidence of non-melanocytic skin cancer treated in Australia.

Abstract: In 1985, as part of a national random household omnibus survey by a market research company, 30 976 Australians (mostly of European origin) were asked whether they had ever been treated by a doctor for skin cancer. The treating doctor or hospital was then approached for confirmation of the diagnosis of all those people who claimed to have been so treated within the past 12 months. Demographic data were also collected, permitting analysis by age, sex, country of birth, current residence, and skin reaction to strong sunlight. Melanomas accounted for less than 5% of the tumours treated. The world standardised incidence of melanoma was 19/100 000 population. The standardised incidence of treated non-melanocytic skin cancer in Australia was estimated to be 823/100 000. The standardised rates for basal cell carcinoma and squamous cell carcinoma were 657 and 166/100 000 respectively, yielding a standardised rate ratio of about 4:1. Standardised rates based on medically confirmed cases only were 555, 443, and 112/100 000 for all non-melanocytic skin cancers, basal cell carcinomas, and squamous cell carcinomas respectively. Significant differences and trends in incidence were noted with respect to age and sex. Rates in men were higher than those in women but significantly so only after the age of 60. People born in Australia had a rate of 936/100 000 compared with 402/100 000 in British migrants. Rates for non-melanocytic skin cancer showed a gradient with respect to latitude within Australia. The rate in people residing north of 29°S was 1242/100 000 compared with a rate of 489/100 000 in those living south of 37°S. A person9s skin reaction to strong sunlight was a good indicator of the risk of skin cancer, tanning ability being inversely related to its incidence. The rate in those who always burnt and never tanned when exposed to strong sunlight was 1764/100 000 compared with a rate of 616/100 000 in those who always tanned and never burnt. These findings have important implications for public education programmes in relation to exposure to sunlight in Australia.

Postmenopausal oestrogen treatment and stroke: a prospective study.

Abstract: STUDY OBJECTIVE--To determine whether post-menopausal oestrogen use affects the risk of dying from stroke. DESIGN--Postal questionnaire survey to elicit details of oestrogen replacement therapy and potential risk modifiers. SETTING--Californian retirement community. PARTICIPANTS--All 22,781 residents of community (white, affluent, well educated) contacted by mail and phone; 13,986 (61%, median age 73) responded, including 8882 women. These formed cohort for mortality follow up, using health department death certification. Only 13 lost to follow up, apparently not deceased, but 34 excluded because no information on oestrogen use. INTERVENTIONS--None. END POINT--Mortality rate from stroke compared in women who did and did not receive oestrogen replacement treatment. MEASUREMENTS AND MAIN RESULTS--Age adjusted mortality rates were computed using internal standard and four age groups. By January 1987 there had been 1019 deaths in the cohort. Twenty out of 4962 women who used oestrogen replacement treatment died from stroke compared with 43 out of 3845 women who did not use oestrogen replacement treatment: relative risk 0.53, 95% confidence interval 0.31 to 0.91. Protection was found in all age groups except the youngest and was unaffected by adjustment for possible confounding factors (hypertension, smoking, alcohol, body mass index, exercise). CONCLUSIONS--Oestrogen replacement treatment protects against death due to stroke.

Reported prevalence of urinary incontinence in women in a general practice

Abstract: To determine the prevalence of urinary incontinence and other urinary symptoms a questionnaire was sent to all women aged 25 and over and to women under 21 taking oral contraceptives registered with a rural practice (n=937); the questionnaire was completed by 833 women (89%). The overall prevalence of urinary incontinence was 41% (343/833); rates were lower in nulliparous and postmenopausal women (30/181 (17%) and 120/344 (35%) respectively) than parous and premenopausal women (313/652 (48%) and 225/479 (47%) respectively). Incontinence was significantly associated with perineal suturing after childbirth, being present in 201 of 376 (53%) women with sutures compared with 113 of 270 (42%) without. Of the 166 women with a history of minor gynaecological surgery, 100 had symptoms of incontinence, compared with 263 of the 657 (37%) without such a history. Incontinence was not related to type of delivery, and postnatal exercises for the pelvic floor were not beneficial. Inappropriate leakage of urine is perceived by many women as common and therefore not serious; thus it is often not reported to the doctor. Nevertheless, the 6% of women who always require protection against leakage could be helped by treatment.

Calculating confidence intervals for some non-parametric analyses.

Abstract: Gardner and Altman1 described the rationale behind the use of confidence intervals and gave methods for their calculation for a population mean and for differences between two population means for paired and unpaired samples. These methods are based on sample means, standard errors, and the t distribution and should strictly be used only for continuous data from Normal distributions (although small deviations from Normality are not important2). For non-Normal continuous data the median of the population or the sample is preferable to the mean as a measure of location. Medians are also appropriate in other situations?for example, when measurements are on an ordinal scale. This paper describes methods of calculating confidence intervals for a population median or for other population quantiles from a sample of observations. Calculations of confidence intervals for the difference between two population medians or means (a non-parametric approach rather than the parametric approach mentioned above) for both unpaired and paired samples are described. Worked examples are given for each situation. Because of the discrete nature of some of the sampling distribu? tions involved in non-parametric analyses it is not usually possible to calculate confidence intervals with exactly the desired level of confidence. Hence, if a 95% confidence interval is wanted the choice is between the lowest possible level of confidence over 95% (a "conservative" interval) and the highest possible under 95%. There is no firm policy on which of these is preferred, but we will mainly describe conservative intervals in this paper. The exact level of confidence associated with any particular approximate level can be calculated from the distribution of the statistic being used. The methods outlined for obtaining confidence intervals are described in more detail in textbooks on non-parametric statistics.3 The calculations can be carried out using the statistical computer package MINITAB.4 A method for calculating confidence intervals for Spearman's rank correlation coefficient is given in an accom? panying paper.5 A confidence interval indicates the precision of the sample statistic as an estimate of the overall population value. Confidence intervals convey the effects of sampling variation but cannot control for non-sampling errors in study design or conduct. They should not be used for basic description of the sample data but only for indicating the uncertainty in sample estimates for population values of medians or other statistics.

Antibody to Saccharomyces cerevisiae (bakers' yeast) in Crohn's disease.

Abstract: Comparaison de 55 cas de maladie de Crohn, 40 de colite ulcerative et 30 temoins normaux. Les titres d'anticorps IgG et IgA contre Saccharomyces cerevisiae sont significativement eleves dans la maladie de Crohn, non dans la colite ulcerative

Protection of kidney function and decrease in albuminuria by captopril in insulin dependent diabetics with nephropathy.

Abstract: STUDY OBJECTIVE--To assess whether long term inhibition of angiotensin converting enzyme with captopril and frusemide or bendrofluazide protects kidney function in diabetic nephropathy. DESIGN--Non-randomised controlled before-after trial of matched hypertensive insulin dependent diabetics with nephropathy treated with captopril and frusemide or bendrofluazide. SETTING--Outpatient diabetic clinic in tertiary referral centre. PATIENTS--Treatment group of 18 hypertensive insulin dependent diabetics with nephropathy (mean age 33), who had not been treated previously. Control group of 13 patients (mean age 32) fulfilling the same entry criteria from a prospective study. INTERVENTIONS--Treatment group was given daily captopril 37.5-100.0 mg and frusemide (mean) 98 mg (10 patients) or bendrofluazide (mean) 4 mg (seven). Treatment was continued for about two and a half years. Controls were not treated. END POINT--Measurement of arterial blood pressure, albuminuria, and glomerular filtration. MEASUREMENTS AND MAIN RESULTS--Baseline values were identical in treated and untreated groups respectively: mean blood pressure 146/93 (SE 3/1) mm Hg v 137/95 (2/1) mm Hg; geometric mean albuminuria 982 (antilog SE 1.2) micrograms/min v 936 (1.2) micrograms/min; and mean glomerular filtration rate 98 (SE 5) ml/min/1.73 m2 v 96 (6) ml/min/1.73 m2. Mean arterial blood pressure fell by 8.7 (1.3) mm Hg with captopril and rose by 6.6 (1.5) mm Hg in controls, (p less than 0.001); Albumin excretion decreased to 390 (1.1) micrograms/min with captopril and rose to 1367 (1.3) micrograms/min in controls (p less than 0.001). The rate of decrease in glomerular filtration rate was lower with captopril (5.8 (0.7) ml/year v 10.0 (1.3) ml/year) (p less than 0.01). Rate of fall in glomerular filtration rate and mean arterial blood pressure were significantly correlated (n = 31, r = 0.37, p less than 0.05). CONCLUSIONS--Captopril is a valuable new drug for treating hypertension in insulin dependent diabetics with nephropathy.

Sustained compression and healing of chronic venous ulcers.

Abstract: STUDY OBJECTIVE--Comparison of four layer bandage system with traditional adhesive plaster bandaging in terms of (a) compression achieved and (b) healing of venous ulcers. DESIGN--Part of larger randomised trial of five different dressings. SETTING--Outpatient venous ulcer clinic in university hospital. PATIENTS--(a) Pressure exerted by both bandage systems was measured in the same 20 patients. (b) Healing with the four layer bandage was assessed in 148 legs in 126 consecutive patients (mean age 71 (SE 2); range 30-96) with chronic venous ulcers that had resisted treatment with traditional bandaging for a mean of 27.2 (SE 8) months. INTERVENTIONS--(a) Four layer bandage system or traditional adhesive plaster bandaging for pressure studies; (b) four layer bandaging applied weekly for studies of healing. END POINTS--(a) Comparison of pressures achieved at the ankle for up to one week; (b) complete healing within 12 weeks. MEASUREMENTS AND MAIN RESULTS--(a) Four layer bandage produced higher initial pressures at the ankle of 42.5 (SE 1) mm Hg compared with 29.8 (1.8) for the adhesive plaster (p less than 0.001; 95% confidence interval 18.5 to 6.9). Pressure was maintained for one week with the four layer bandage but fell to 10.4 (3.5) mm Hg at 24 hours with adhesive plaster bandaging. (b) After weekly bandaging with the four layer bandage 110 of 48 venous ulcers had healed completely within 12 (mean 6.3 (0.4)) weeks. CONCLUSION--Sustained compression of over 40 mm Hg achieved with a multilayer bandage results in rapid healing of chronic venous ulcers that have failed to heal in many months of compression at lower pressures with more conventional bandages.

Early growth delay in diabetic pregnancy: relation to psychomotor development at age 4.

Abstract: Ninety nine consecutive insulin dependent and 101 non-diabetic pregnant women were examined by ultrasonograph to assess early fetal growth. In 42 of the diabetic mothers and three of the non-diabetic mothers the scan showed early intrauterine growth delay. At 4-5 years of age all children available for study were evaluated by the Denver developmental screening test. Only 23 of the 34 children of diabetic mothers with early intrauterine growth delay had normal test scores compared with 46 of the 50 children of diabetic mothers with normal intrauterine growth. The children failed in personal-social development, gross motor development, and particularly in language and speech development. Children of diabetic mothers with normal early fetal growth had scores very similar to those of the children of non-diabetic mothers, of whom 76 of the 86 tested had normal scores. This study suggests that children with a history of growth delay in early diabetic pregnancy should be screened for possible developmental impairment.

Distress and delay associated with urinary incontinence, frequency, and urgency in women

Abstract: Correspondence to: Mr S L Stanton, Urodynamic Unit, Department of Obstetrics and Gynaecology, St George's Hospital, Cranmer Terrace, London SW17 0RE. It is ironic that though many personal topics may be openly discussed with patients or in the media, uro logical symptoms are still largely avoided. Yet urinary complaints are common among women, although exact prevalence is difficult to estimate because various researchers use different definitions of severity and patients have different thresholds for complaint. Nemir and Middleton1 found occasional stress inconti? nence in half of the premenopausal women they studied, and Brocklehurst2 estimated the prevalence of urgency, frequency, and nocturia in elderly women to be 60%. Using stricter criteria, Yarnell et al found that 3-7% of women in the general population complained of "significant" urinary incontinence.3 It seems that patients who present to their doctor complaining of various urinary symptoms, from occasional episodes to constant leakage, share one common factor: the problem has become so personally worrying that the patient is compelled to seek medical advice. Thomas et al found that only a third of women complaining of moderate or severe incontinence were receiving medical care or help from the social services.4 In the study by Yarnell et al of the women who reported that urinary symptoms interfered with social or domestic life, only half had sought medical advice.3 Thus patients with urinary symptoms who seek medical advice represent only the tip of the iceberg, and many who are troubled by their urinary complaints may delay seeking treatment. Although such delay is a common clinical impression, it has not been previously investigated. The purpose of this study was to examine initial delay and reasons for delay in seeking treatment among women who were ultimately referred to a urodynamic clinic. Since delay might be justified if symptoms are not unduly troublesome to the woman restriction of activities and feelings of stigma were also assessed.

Retrospective study of 1000 deaths from injury in England and Wales

Abstract: One thousand consecutive deaths from injury in 11 coroner9s districts in England and Wales were reviewed by four independent assessors, who studied necropsy reports to identify deaths in hospital that might have been preventable. Of 514 patients admitted to hospital alive, 102 deaths (20%) were judged by all four assessors to have been potentially preventable. When those cases in which three out of four assessors considered that the death was preventable were added the total rose to 170 (33%). Nearly two thirds of all non-central nervous system deaths were judged to have been preventable. The median age of the 170 patients whose deaths were preventable was 41, and the mean Injury Severity Score was 29. Further analysis suggested that the preventable deaths were principally the result of failure to stop bleeding and prevent hypoxia and the absence of, or delay in, surgical treatment. The results closely parallel those from similar studies from the United States and suggest that there are serious deficiencies in the services for managing severe injury in England and Wales. Debate is needed now on how to correct these deficiencies. In particular, the place of trauma centres must be considered.

Low birth weight and hypertension.

Abstract: species. While the incubation period for all the slow spongiform viral encephalopathies is long, making an epidemiological study of the extent of bovine spongiform encephalopathy time consuming and expensive, use could be made of an antiserum developed to the so called \"prion protein\" (PrP 27-30) which has been used successfully to identify these abnormal extracellular filaments which are found in scrapie and Creutzfeldt-Jakob disease.5 The appearance of bovine spongiform encephalopathy has given an urgent impetus to the intellectual challenge of finding the infectious agent. Current evidence favours the \"virino\" (RNA containing subviral particle) theory.6