The role of occupational and environmental exposures in the aetiology of acquired severe aplastic anaemia: a case control investigation.

Aplastic anaemia is a rare but serious disorder with a high morbidity and mortality rate. The causes of aplastic anaemia are, for the most part, unknown. We report on the hypothesis that aplastic anaemia may be caused by occupational and/or environmental exposures to certain chemicals. The UK Aplastic Anaemia Study was an interview-based case-control study covering the whole of Great Britain. Those patients diagnosed between 1 July 1993 and 20 October 1997, aged < or =75 years and born and diagnosed in the UK were eligible for the study. Two hundred eligible cases of aplastic anaemia were compared with 387 age- and sex-matched controls. A number of occupational exposures showed increases in risk. In a multivariate model of these exposures the odds ratios (ORs) for solvents/degreasing agents, pesticides and radiation were >2 and statistically significant. Reported chemical treatment of houses within 5 years of diagnosis had a significantly raised risk for adults [OR = 2.51, 95% confidence interval (CI) 1.02-12.01], particularly for woodworm treatment (OR = 5.1, 95% CI 1.5-17.4). This study identified significant risks associated with self-reported exposure to solvents, radiation and pesticides in the workplace. Self-reported chemical treatment of houses was also associated with an increased risk of developing aplastic anaemia, in keeping with previous literature.

Exposure to power frequency electric fields and the risk of childhood cancer in the UK.

The United Kingdom Childhood Cancer Study, a population-based case-control study covering the whole of Great Britain, incorporated a pilot study measuring electric fields. Measurements were made in the homes of 473 children who were diagnosed with a malignant neoplasm between 1992 and 1996 and who were aged 0-14 at diagnosis, together with 453 controls matched on age, sex and geographical location. Exposure assessments comprised resultant spot measurements in the child's bedroom and the family living-room. Temporal stability of bedroom fields was investigated through continuous logging of the 48-h vertical component at the child's bedside supported by repeat spot measurements. The principal exposure metric used was the mean of the pillow and bed centre measurements. For the 273 cases and 276 controls with fully validated measures, comparing those with a measured electric field exposure >/=20 V m(-1) to those in a reference category of exposure <10 V m(-1), odds ratios of 1.31 (95% confidence interval 0.68-2.54) for acute lymphoblastic leukaemia, 1.32 (95% confidence interval 0.73-2.39) for total leukaemia, 2.12 (95% confidence interval 0.78-5.78) for central nervous system cancers and 1.26 (95% confidence interval 0.77-2.07) for all malignancies were obtained. When considering the 426 cases and 419 controls with no invalid measures, the corresponding odds ratios were 0.86 (95% confidence interval 0.49-1.51) for acute lymphoblastic leukaemia, 0.93 (95% confidence interval 0.56-1.54) for total leukaemia, 1.43 (95% confidence interval 0.68-3.02) for central nervous system cancers and 0.90 (95% confidence interval 0.59-1.35) for all malignancies. With exposure modelled as a continuous variable, odds ratios for an increase in the principal metric of 10 V m(-1) were close to unity for all disease categories, never differing significantly from one.

Risk factors for squamous cell carcinoma of the oesophagus in women: a case-control study.

Oesophageal cancer rates in women in the UK are more than 3 times higher than in most other European populations. A population-based matched case-control study of histologically confirmed squamous cell carcinoma of the oesophagus in women was carried out in 4 regions in England and Scotland. Interviews were carried out in hospital or at home and topics included: smoking; alcohol; tea and coffee consumption; medical and obstetric history; and diet. Response rates were 62% for cases and 65% for first-chosen controls. There were 159 case-control pairs. Significant results were found for: eating salads (odds ratio (OR) 0.42, 95% CI 0.20-0.92 in the highest quartile of consumption) and a light (as distinct from no) breakfast (OR 0.18, 95% CI 0.07 - 0.48) were protective; quantity of tea was a risk factor and there was a significant positive trend with temperature at which hot drinks were consumed (P = 0.03). Alcohol consumption was unrelated to risk, but there was a significant trend with years of smoking (P = 0.015). A protective effect of aspirin consumption was confined to the English centres (OR 0.08, 95% CI 0.01-0.56). Comparison with a parallel study of adenocarcinoma indicated a common protective effect of a healthy diet but otherwise distinct risk factors.

Reproductive, menstrual and menopausal factors: which are associated with bone mineral density in early postmenopausal women?

The associations between a number of reproductive and menopausal factors and bone mineral density (BMD) were studied in a sample of early postmenopausal women. The study included 580 women aged 45-61 years who completed a risk factor questionnaire containing sections on obstetric and menstrual history. BMD measurements were taken at the anteroposterior (AP) spine, greater trochanter, femoral neck, total radius and whole body, along with whole body bone mineral content (BMC). In analyses adjusting for key confounders, number of pregnancies was more strongly associated with increased BMD than number of live births at all sites (p<0.05 at femoral neck and total radius), and menstrual years was more strongly associated with increased BMD than years since menopause (p<0.05 at all sites). Hysterectomized women had a significantly higher adjusted mean BMD than non-hysterectomized women at all sites (AP spine: 0.999 g/cm2 vs 0.941 g/cm2, p<0.001), although there were no significant differences in BMD between hysterectomized women who had a bilateral oophorectomy and those whose ovaries were preserved. Negative associations between the duration of hot flushes and BMD were statistically significant (p<0.05) at the three non-hip sites. In multiple regression analyses containing all reproductive terms, duration of hormone replacement therapy (HRT) use, menstrual years and hysterectomy status were significantly associated with BMD at all five sites, whilst oral contraceptive use before the age of 23 years was significantly associated with increased BMD at all sites except the total radius. Breastfeeding duration, the duration of oral contraceptive use and premenopausal amenorrhea were found to have no association with BMD. Results for whole body BMC were consistent with those for the five BMD sites, across all the variables considered here. These findings confirm the importance of HRT use and duration of menses as predictors of BMD, whilst the results for hysterectomy status and early oral contraceptive use require further consideration.

Attitudes and impressions of participants in a study of the causes of childhood cancer.

Researchers and ethics committees are increasingly concerned about the perceived emotional impact on individuals following participation in epidemiologic studies. This attitudinal survey was designed to investigate this issue among 751 of the parents who had already given an interview in the UK Childhood Cancer Study (UKCCS), one of the largest case-control studies ever undertaken to investigate the aetiology of cancer in children. Information was collected by postal questionnaire on their reasons for agreeing to take part in the UKCCS, on whether questions had caused distress or difficulty and what their feelings were immediately after the interview and at the time of this survey. Parents were asked if they felt they had benefited in any way by taking part and control parents were asked if they would have taken part without prior consent of their doctor. 90% of both cases and controls felt glad to have taken part immediately after the interview and few reported any anxiety at having done so; 95% of both cases and controls felt satisfied that they had made a worthwhile contribution. Although 18% of cases felt tense and 14% felt unhappy after the interview, over 90% of them felt glad that they had taken part a few weeks later. Of particular interest is that 38% of cases and 24% of controls said they had positively benefited from taking part in the UKCCS and 96% of control mothers did not mind their family doctor giving permission for them to be contacted.

Occupational activity and bone mineral density in postmenopausal women in England.

Few studies have assessed the relationship between occupational activity and bone mineral density (BMD), although two case-control studies have reported a protective effect of occupational activity on hip fracture. In the present study 580 postmenopausal women aged 45-61 years completed a risk factor questionnaire including a detailed occupational history. For each job, hours spent sitting, standing, walking, lifting and carrying were recorded; these measures, evaluated at ages 20, 30, 40 years, in the current job and over the working lifetime, were used in the analysis. BMD was measured with dual-energy X-ray absorptiometry, and measurements at five sites were used in a multiple regression analysis adjusting for potential confounding variables. There was a significant negative association between sitting at age 20 years and BMD at the radius (p = 0.037), with negative relationships of borderline significance at the anteroposterior spine (p = 0.091) and whole body (p = 0.078). There were significant positive associations between standing at age 30 years and BMD at all five sites (p < 0.05), but no significant linear associations for standing at ages 20 and 40 years. No significant associations were found for lifetime or current occupational measures of sitting, standing, walking and lifting or carrying. The lack of consistency of these significant findings suggests that they may have occurred by chance, and that occupational activity has little if any effect on BMD in postmenopausal women.

A case-control study of oesophageal adenocarcinoma in women: a preventable disease.

The incidence of adenocarcinoma of the oesophagus in British women is among the highest in the world. To investigate its aetiology, we conducted a multi-centre, population based case-control study in four regions in England and Scotland. We included 74 incident cases in women with histologically confirmed diagnoses of adenocarcinoma of the oesophagus, and 74 female controls matched by age and general practice. High body mass index (BMI) around the age of 20 years (highest vs lowest quartile, adjusted odds ratio (OR) = 6.04, 95% confidence interval (CI) 1.28-28.52) and low consumption of fruit (highest vs lowest quartile, adjusted OR = 0.08, 95% CI 0.01-0.49) were associated with increases in risk. Breastfeeding by women was associated with reduced risk of their subsequently developing this cancer (ever vs never, adjusted OR = 0.41, 95% CI 0.20-0.82) and there was a significant dose-response effect with total duration of breastfeeding. The summary population attributable risk from these three factors was 96% (90% if breastfeeding is excluded). We conclude that high BMI in early adulthood and low consumption of fruit are important risk factors for adenocarcinoma of the oesophagus. Breastfeeding may confer a protective effect but this needs confirmation. This cancer is a largely preventable disease in women.

Risk factors for testicular germ cell tumours by histological tumour type. United Kingdom Testicular Cancer Study Group.

There are two main histological groups of testicular germ cell tumours, which may have different risk factors. Some authors have analysed potential risk factors by histological group but few consistent differences have been identified. In this paper we examine risk factors for pure seminoma and other tumours using data from the United Kingdom case control study of testicular cancer. Seven hundred and ninety-four cases were included in the study, each with a matched control; 400 cases had pure seminoma tumours, and 394 had other testicular tumours. The risk of seminoma associated with undescended testis was slightly higher than that for other tumours (odds ratio of 5.3 compared with 3.0). When split at the median age at diagnosis, this difference was greater in men aged 32 and over (odds ratio of 11.9 compared with 5.1) than in the younger men (3.0 compared with 2.5). Risks associated with testicular or groin injuries were higher in the non-seminoma group, as was the risk for a history of sexually transmitted disease. The protective effect of a late puberty was more marked for tumours of other histologies. Some differences were also detected for participation in sports. Whilst some of the differences detected may have arisen by chance, the stronger association between undescended testis and pure seminoma has been identified by a number of other studies and may reflect a genuine difference in aetiology.

Association between a family history of fractures and bone mineral density in early postmenopausal women.

The aim of this analysis was to measure the strength of the association between a family history of fractures and bone mineral density (BMD), and to determine what definition of family fracture history best predicts BMD. Five hundred and eighty postmenopausal women aged 45-59 at recruitment completed a risk factor questionnaire. Women were asked to recall details of fractures sustained by any female relative. BMD measurements taken at five sites were used. The data were analysed using linear regression, adjusting for age. Two hundred and ninety-seven (52.8%) women reported a family history of fractures, and they had a significantly lower BMD at two of the sites measured (p < 0.05). The associations with BMD were most significant when only counting fractures that occurred in the subject's mother or a sister as a result of low trauma, with no restrictions made on age at the time of fracture and site of fracture (p < 0.01 at three sites; 0.01 < p < 0.05 at two sites). Women with a family history according to this definition had a 4.6% reduction in BMD at the femoral neck. When T scores were used to categorize women as either osteopenic/osteoporotic (T < -1) or normal at the femoral neck, the sensitivity of using this definition was 39% and the specificity was 74%. The small group of women that reported a low-trauma hip fracture in a mother or sister (n = 23) had a mean femoral neck BMD which was 8.9% lower than that of the remainder of the sample, although this difference was less statistically significant than when low trauma fractures at any site were counted. Of these 23 women, 70% were osteopenic or osteoporotic, compared with 57% of those reporting a low-trauma fracture at any site and 47% of the sample as a whole. The sensitivity of this definition, however, was low (6%). From these analyses it can be concluded that the definition of family fracture history that best predicts BMD in postmenopausal women is a fracture at any age in a mother or sister resulting from low trauma, although the sensitivity and specificity of using a family history of fractures by itself to screen for low BMD were poor.

Habitual physical activity and bone mineral density in postmenopausal women in England.

BACKGROUND: Reduced levels of physical activity have been found to be associated with an increased risk of osteoporotic fracture in a number of epidemiological studies, and intervention studies have shown beneficial effects of exercise regimes on bone mineral density. It is not yet established, however, which specific forms of customary physical activity are most strongly associated with bone mineral density in postmenopausal women. METHODS: A cross-sectional study was conducted in 580 postmenopausal women, aged 45-61 years, resident in Nottingham, England. The participants completed a detailed interviewer-administered activity questionnaire. Physical activity was assessed as total hours of participation per week in activities including housework, walking, gardening and sports. Stair-climbing and self-reported walking pace were also reported. Bone mineral density measurements were made using dual energy x-ray absorptiometry, measurements at five sites were used in analysis. RESULTS: The strongest associations between the activity measures and bone mineral density were for stair-climbing and walking pace, which both gave statistically significant positive associations at the trochanter hip site and the whole body. In women reporting a fairly brisk or fast walking pace, bone mineral density at the proximal femur was also significantly and positively associated with the frequency of walking at least a mile. There were no significant associations with aggregate measures of total customary physical activity. CONCLUSIONS: This study has identified two forms of physical activity, namely stair-climbing and brisk walking which are associated with increased bone mineral density at the hip and whole body in postmenopausal women. Both are feasible forms of activity for promoting to middle-aged women.

Tooth counts do not predict bone mineral density in early postmenopausal Caucasian women. EPIC study group.

BACKGROUND: It has been suggested that poor dental status may be a suitable criterion for bone densitometry referral in early postmenopausal women. We evaluated this hypothesis in a cohort of 1365 Caucasian women aged between 45 and 59 years, who were enrolled into an international multi-centre trial. METHODS: Subjects were recruited at four study centres, using population-based techniques. Bone mineral density (BMD) at the lumbar spine and proximal femur was measured by dual energy x-ray absorptiometry (DXA) (Hologic QDR 2000). A full physical examination was performed including a tooth count. RESULTS: Baseline tooth counts ranged from 0 to 32 (median 26): 84 (6%) subjects were edentulous. When classified according to the WHO criteria 445 (33%) of the subjects were osteoporotic at one or more of the skeletal sites analysed; 694 (51%) were osteopenic, and 226 (16%) were normal. Adjusting for confounding variables, there was no significant correlation between tooth count and BMD at any skeletal site. Subjects were divided into tertiles of tooth count, and chi2 tests used to compare the two 'extreme' groups against the WHO criteria for BMD. At each of the six BMD regions the proportion of subjects with normal, osteopenic or osteoporotic BMD was similar for both tertiles. CONCLUSIONS: We found no relationship between tooth count and BMD in early postmenopausal women. This may be because in younger women dental status is a reflection more of dietary habits and past dental surgery than of age-related bone loss. Tooth counts therefore cannot be used to identify individuals at risk of osteoporosis.

Prevention of bone loss with alendronate in postmenopausal women under 60 years of age. Early Postmenopausal Intervention Cohort Study Group.

BACKGROUND: Estrogen-replacement therapy prevents osteoporosis in postmenopausal women by inhibiting bone resorption, but the balance between its long-term risks and benefits remains unclear. Whether other antiresorptive therapies can prevent osteoporosis in these women is also not clear. METHODS: We studied the effect of 2.5 mg or 5 mg of alendronate per day or placebo on bone mineral density in 1174 postmenopausal women under 60 years of age. An additional 435 women who were prepared to receive a combination of estrogen and progestin were randomly assigned to one of the above treatments or open-label estrogen-progestin. The main outcome measure was the change in bone mineral density of the lumbar spine, hip, distal forearm, and total body measured annually for two years by dual-energy x-ray absorptiometry. RESULTS: The women who received placebo lost bone mineral density at all measured sites, whereas the women treated with 5 mg of alendronate daily had a mean (+/-SE) increase in bone mineral density of 3.5+/-0.2 percent at the lumbar spine, 1.9+/-0.1 percent at the hip, and 0.7+/-0.1 percent for the total body (all P<0.001). Women treated with 2.5 mg of alendronate daily had smaller increases in bone mineral density. Alendronate did not increase bone mineral density of the forearm, but it slowed the loss. The responses to estrogen-progestin were 1 to 2 percentage points greater than those to the 5-mg dose of alendronate. Alendronate was well tolerated, with a safety profile similar to that of placebo or estrogen-progestin. CONCLUSIONS: Alendronate prevents bone loss in postmenopausal women under 60 years of age to nearly the same extent as estrogen-progestin.

Cigarette smoking, alcohol and caffeine consumption, and bone mineral density in postmenopausal women. The Nottingham EPIC Study Group.

The aim of this analysis was to compare the effects of different measures of cigarette, alcohol and caffeine consumption upon bone mineral density (BMD). Five hundred and eighty postmenopausal women aged 45-59 years at recruitment completed a risk factor questionnaire that contained detailed sections on cigarette, alcohol and caffeine consumption. BMD was measured using dual-energy X-ray absorptiometry. Measurements taken at five bone sites were used: anterior-posterior spine, femoral neck, greater trochanter, radius/ulna and whole body. The data were analyzed using multiple linear regression, adjusting for a number of established BMD risk factors. BMD was more strongly related to the number of months spent smoking than to pack-years of smoking at all five sites (p < 0.05 at four of the five sites). There were significant reductions in BMD when comparing smokers with non-smokers at ages 20, 30 and 40 years, but not for current smoking. Lifetime alcohol consumption and current alcohol consumption did not have an independent association with BMD. However, the heaviest beer drinkers in the sample had a particularly low bone density. Caffeine consumption at various ages was not associated with BMD. The results of these analyses suggest that for predicting BMD a simple history of smoking duration is as good as trying to obtain more detailed smoking information, but that only 25% of the variation in BMD is explained by personal characteristics, family history and lifestyle factors.

The contribution of bone densitometry to the diagnosis and treatment of osteoporosis.

OBJECTIVE: It has recently been proposed that a specialist osteoporosis service, including bone densitometry, should be made available to those most at risk in the UK population. The aim of this study was to evaluate such a service, and in particular the role of bone densitometry, in terms of its effect on the diagnosis of osteoporosis and clinical management of the disease. METHODS: A retrospective data abstraction study was performed to investigate the diagnosis and management of patients referred to the Metabolic Clinic, City Hospital Nottingham, with a potential diagnosis of osteoporosis. Hospital records were available for 117 patients, aged between 45 and 59, who had attended the Clinic in a given time period and undergone bone mineral density measurement. RESULTS: Forty-eight patients (41.0%) had osteoporosis of the lumbar spine. The final diagnosis of osteoporosis after attending the clinic was different from that on referral in a substantial proportion (62.6%) of cases. Only 48.9% of patients with spinal osteoporosis were identified by their referring doctor. The percentage of patients receiving treatment for osteoporosis increased from 34.2% to 72.6% after attending the clinic. CONCLUSIONS: Measurement of bone mineral density identifies cases of osteoporosis who would not otherwise be detected and as a consequence contributes to the proportion of patients receiving treatment after referral. The osteoporosis service provided by the Metabolic Clinic including measurement of bone mineral density was thus found to have a considerable impact on the diagnosis and treatment of patients with osteoporosis.

Continued inadequacies in data sources for the evaluation of cancer services.

There is a need to evaluate cancer services and provide a baseline on current treatment success and organization. This study shows that this process may be severely hindered by case note destruction or inaccessibility and incomplete information. This is an ongoing problem that needs to be addressed now.

Depot medroxyprogesterone acetate and breast cancer. A review of current knowledge.

Depot medroxyprogesterone acetate (DMPA) has been used worldwide since 1964 as a contraceptive and by 1993 was in use in more than 90 countries. It was licensed for contraceptive use in the US in 1992. One of the reasons for this delay in licensing in the US was the possibility of an increased risk of breast cancer associated with its use. A pooled analysis has recently been published, which brings together the data from 2 large studies of breast cancer risk associated with DMPA use. The overall results are reassuring, but there is some evidence of an increased risk of breast cancer associated with recent use of DMPA. There are substantial difficulties in interpreting this increase in risk. It is certainly possible that it may be the result of surveillance bias, although it could be a short term increase in risk that is not in fact sustained. The conclusion that DMPA should not be restricted as a contraceptive, provided that appropriate advice is given before use, is well-founded. However, further epidemiological work is needed on the long term effects of DMPA.

PIP: Although further epidemiological studies of the long-term effects of depot medroxyprogesterone acetate (DMPA) on breast cancer risk are needed, preliminary research results are reassuring. Pooled analysis of the results of two large case-control studies--the World Health Organization Study (involving women newly diagnosed with breast cancer in 1979-88 in Thailand, Kenya, and Mexico) and the New Zealand Study (comprised of women with breast cancer diagnosed in 1983-87)--has facilitated assessment of this association. Overall, 219 of the 1768 breast cancer cases and 1725 of the 13,905 controls had ever used DMPA (odds ratio, 1.1; 95% confidence interval, 0.97-1.4), with no increase in risk with increasing duration of use. Women under 35 years of age at diagnosis and those initiating DMPA use before 25 years of age had marginally statistically significant increases in breast cancer risk. The highest risks were recorded among women who had initiated DMPA use within 5 years of diagnosis. Risks declined with time since first use in all age categories. After 5 years since last use, DMPA use for more than 2 years was associated with a decreased risk of breast cancer. The raised relative risks in certain subgroups are difficult to interpret and may reflect surveillance bias. Enhanced understanding of the biology of breast cancer will aid interpretation of these results.

Mortality pattern among biological research laboratory workers.

A cohort study was conducted to investigate the mortality of individuals employed by biological research institutes in the UK. The inclusion criteria were met by 12,703 individuals, of whom 95% were traced (11,502 alive, 395 deaths, 246 embarkations). All-cause mortality was significantly reduced in men (standardised) mortality ratio (SMR) 55 and women (SMR 52). Mortality was also significantly reduced for circulatory and respiratory diseases, and overall there was low mortality from malignant neoplasms. SMRs exceeded 100, but were not statistically significant, for infective and parasitic diseases. There were no statistically significant raised SMRs for any cancer site. Workers were categorised as ever worked in a laboratory (laboratory workers) and never worked in a laboratory (non-laboratory workers). The all-cause SMR was significantly reduced in both groups, as was mortality from circulatory and respiratory diseases. The SMR for malignant neoplams was also significantly reduced in laboratory workers. On the basis of follow-up to 31 December 1994, there is no evidence of any overall increased risk of mortality in biological research laboratory workers. However, the power of the analysis is limited by the young age of many cohort members and short duration of follow-up. Follow-up is continuing and the data will be reanalysed once more deaths have accumulated.

A case-control study of cryptorchidism and maternal hormone concentrations in early pregnancy.

Serum samples taken between 6 and 20 weeks of gestation were obtained from 28 mothers who gave birth to cryptorchid sons (cases) and from 108 control mothers. In comparison with controls the cases had 10% higher geometric mean oestradiol (95% CI -13% to +39%: P=0.42) and 10% lower geometric mean testosterone (95% CI -27% to +10%: P=0.30). Among the samples collected between 6 and 14 weeks of gestation geometric mean concentrations of oestradiol and testosterone were 5% lower (95% CI -32% to +31%: P=0.74) and 25% lower (95% CI -45% to +1%: P=0.06) respectively in cases than in controls. Among the samples collected between 15 and 20 weeks of gestation geometric mean concentrations of oestradiol and testosterone were 29% higher (95% CI -8% to +79%: P=0.14) and 21% higher (95% CI -8% to +60%: P=0.18) respectively in cases than in controls. The results do not support the hypothesis that cryptorchidism may be caused by high concentrations of oestradiol in the maternal blood during the first phase of testicular descent, but suggest that the possible association of cryptorchidism with low maternal testosterone during early gestation should be further investigated.

Adjuvant cyclophosphamide, methotrexate, and fluorouracil versus fluorouracil, epirubicin, and cyclophosphamide chemotherapy in premenopausal women with axillary node-positive operable breast cancer: results of a randomized trial. The International Collaborative Cancer Group.

PURPOSE: To determine whether a combination chemotherapy regimen that contains epirubicin (fluorouracil, epirubicin, and cyclophosphamide [FEC]) is superior to the standard cyclophosphamide, methotrexate, and fluorouracil (CMF) combination in premenopausal women with axillary node-positive operable breast cancer. PATIENTS AND METHODS: The International Collaborative Cancer Group (ICCG) conducted a large randomized trial in which two alternative schedules were used according to participating center: CMF1 versus FEC1 and CMF2 versus FEC2. RESULTS: Seven hundred fifty-nine patients were entered onto the trial. At a median follow-up time of 4.5 years, no significant benefit for the anthracycline-containing regimen was observed in terms of relapse-free (P = .61) or overall survival (P = .13). FEC1 and CMF1 appear to be of similar efficacy, but there is a suggestion that FEC2 may be superior to CMF2, since patients who received FEC2 had improved overall (P = .02) and relapse-free survival (P = .03) rates. Nausea and vomiting and alopecia were more common in the epirubicin-containing regimen (P = .001). CONCLUSION: We conclude that the FEC2 regimen, in which epirubicin replaced the methotrexate in CMF, is the preferable adjuvant chemotherapy regimen for premenopausal patients with operable axillary node-positive breast cancer.

The effect of social deprivation on birthweight, excluding physiological and pathological effects.

OBJECTIVE: To study the effect of social deprivation on birthweight, excluding the effect of known physiological factors and exploring the effect of possible pathological factors. DESIGN: Retrospective analysis of computerised obstetric database. SETTING: Two teaching hospitals and an associated district general hospital which provided a defined catchment area in the East Midlands. SUBJECTS: The final analysis included 7493 women with complete datasets and gestations of between 259 and 300 days at delivery, dated by ultrasound scan. MAIN OUTCOME MEASURES: Smoking habit, alcohol consumption, weight gain during pregnancy, systolic and diastolic blood pressures at booking, bleeding during pregnancy and Jarman score; also, the effect of these variables on birthweight, adjusted for the effects of physiological factors using the individualised birthweight ratio. RESULTS: Smoking during pregnancy reduced birthweight but the effect is not linear, becoming less marked as the number of cigarettes smoked increases. Alcohol intake, diastolic and systolic blood pressures at the booking visit and vaginal bleeding during early pregnancy were not significantly related to birthweight. Pregnancy weight gain was significantly positively related to birthweight especially in the normal weight range (60-99 kg). A multivariate analysis including physiological and pathological factors found increasing Jarman score to be negatively related to birthweight. CONCLUSIONS: In this central British population social deprivation is correlated negatively with birthweight: the most socially deprived mothers have the smallest babies. This association cannot be explained in terms of physiological differences in the population nor in a higher prevalence of known pathological factors.