Screening for breast cancer in the under 50s.
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Biomedical subjects
Publications and source records attributed to T Bates.
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The Qualitator is a daily diary card to measure Quality of Life, developed for use in chemotherapy trials for patients with advanced breast cancer. In a trial at King's College Hospital, 29 patients completed the Qualitator and their scores were compared with scores in the Linear Analogue Self-Assessment and Nottingham Health Profile taken four-weekly. In a separate study at Guy's Hospital, 31 patients completed the diary. The Qualitator offers accurate prognostic data regarding subsequent UICC response and survival and is simple to use.
Forty patients with advanced breast cancer, randomised to receive CMF or weekly low dose Epirubicin, were evaluated by UICC criteria of response and WHO toxicity criteria, in addition to three QoL instruments: the 'Qualitator' daily diary card, 4 weekly Nottingham Health Profile (NHP) and Linear Analogue Self-Assessment (LASA). Response rates were 58% for CMF and 29% for epirubicin (chi 2 = 3.51, 1 d.f., P > 0.05). Median time to treatment failure was 24 weeks for CMF, 7 weeks for epirubicin (P < 0.05) but survival was similar in both groups. Survival was better for responders than for non-responders (medians 87 and 30 weeks, P = 0.02). CMF caused more objective alopecia (P < 0.001), nausea and vomiting (P < 0.001) and haematological toxicity (P < 0.02). However, QoL measures only recorded a significant difference in energy and pain, influenced primarily by the non-responders in each treatment group but with no difference in overall global scores. Scores for responders, irrespective of treatment, were better to start with (LASA P = 0.001); at 12 weeks, scores had improved (Qualitator P < 0.05; NHP P < 0.05). Scores in non-responders showed no change. In this small study aggressive chemotherapy gave better response and similar survival without impairing Quality of life overall. Detailed QoL measurement should be integral to all cancer chemotherapy trials.
In a randomized trial of second line hormone therapy 56 postmenopausal women with advanced breast cancer received low dose aminoglutethimide (AGT) 125 mg twice daily without hydrocortisone (27 patients), or hydrocortisone (HC) 20 mg twice daily (29 patients). The two groups were well-matched for previous response to tamoxifen (TAM) therapy (AGT (35%) vs HC (32%)) and for relapse on adjuvant TAM. The mean age of the two groups was 69.2 years (AGT) and 63.2 years (HC). Liver metastases were present in 29% (AGT) and 33% (HC). The response rates were 11% (AGT) and 21% (HC). At 12 months the failure of treatment rate was 80% (AGT) and 70% (HC). Survival at 12 months was 50% for both groups. At 12 months 5/12 survivors were still on AGT and 8/12 on HC. These preliminary findings have so far failed to show any statistical difference in tumour response, time to treatment failure or survival between low-dose AGT and HC as second-line hormone treatment post-tamoxifen in advanced breast cancer.
Non-specific abdominal pain (NSAP) may have a detectable psychological component that could be used to predict outcome. To test this hypothesis, 131 patients aged 14-40 years admitted with acute abdominal pain were assessed using the General Health Questionnaire (GHQ) and Hospital Anxiety and Depression (HAD) scale, and a structured interview. Of 61 patients with NSAP, more had a psychosocial problem identified by the admitting registrar (P < 0.01) and marginally more had high questionnaire scores. The risk of having NSAP was high if an abnormality on interview accompanied high questionnaire scores (relative risk 1.93 (95 per cent confidence interval (c.i.) 1.35-2.77)) or if prodromal pain had lasted > 7 days (relative risk 2.13 (95 per cent c.i. 1.55-2.92)). After 2 years, patients with continuing pain had higher HAD and Spielberger Anxiety Trait scores (both P < 0.02); NSAP was associated with persisting pain (relative risk 2.22 (95 per cent c.i. 1.10-4.48)). Psychosocial factors are implicated in NSAP and in chronic pain, but the sensitivity and specificity of questionnaire assessment are too low to be useful in diagnosis.
Abdominal wound infection rates were significantly related to obesity, as measured by Body Mass Index, in two large clinical trials of prophylactic antibiotics in at-risk abdominal surgery. Obesity is a risk factor that should be taken into account in any study in which wound infection is an outcome measure.
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Local radiotherapy plays an important role in the management of bone metastases. Because it is given with palliative intent to patients with limited, if variable, life expectancy, radiotherapy schedules need to be identified which give maximum patient benefit (short and long term) with minimum associated morbidity and minimum disruption of the patients' remaining life. For localized bone pain, a single fraction of radiotherapy, repeated if necessary, appears to fulfill these criteria in patients with a short life expectancy. There are, however, unanswered questions regarding fraction size and the adequacy of one fraction for long-term control and for all pathological tumor types. Only randomized trials can answer these questions. Uncertainties also exist regarding the precise indications for radiotherapy to prevent and treat pathological fractures and the optimal dose schedule which will provide adequate local tumor control without inhibiting bone healing or interfering with bone integrity. Because of the many variables, guidelines on selection of cases of spinal cord compression for decompression by surgery or radiotherapy are likely to be of more value than randomized prospective studies in this condition. Experimental work and clinical experience to date suggest an advantage for a few large fractions of radiotherapy, at least initially, to achieve a rapid response, but this too needs confirmation. Treatment decisions based on past teaching and local custom rather than on valid clinical trial data have led to considerable differences in clinical practice among radiotherapists. Bone metastases are common and warrant a great deal more experimental and clinical study than they have received to date.
A prospective study of the prevalence of gall stone disease at necropsy in a stable population has been undertaken over a 10 year period up to June 1988. In women, the prevalence of gall stone disease remained static but in men aged 50-59 years it rose from 7% (n = 148) in the first three years to 18% (n = 138) in the last three years (p less than 0.01) and in men aged 60-69 it rose from 12% (n = 370) to 20% (n = 366, p less than 0.01). In the latter age group the female: male ratio fell from 2:1 to 0.8:1. The proportion of deaths from coronary heart disease in men fell slightly in those over 70 during the study period. There was a fall in deaths from coronary heart disease in all age groups in women. Men with gall stones were less likely to have had a cholecystectomy than women, and overall 88% of gall stones remained in situ. In a parallel clinical study, the number of cholecystectomies carried out in the same district fell by 18% over the 10 years without any apparent change in the provision of resources. Cholecystectomy remained almost three times more frequent in women. National data indicate that there have been major changes in the average diet before and during the period of study in favour of reducing coronary heart disease. There has been no change in mortality from coronary heart disease in young men but if the observed increase in the prevalence of gall stones in men and the decrease in deaths from coronary heart disease in women are real phenomena, it seems likely that they are diet related.
In a randomized prospective trial of prophylactic antibiotics in at-risk abdominal surgery, one dose of intravenous Augmentin (amoxycillin 250 mg and clavulanic acid 125 mg) on induction has been compared with three 8 hourly doses in 900 patients. Wound infection rates which included minor and delayed infections were very similar in those given one dose: 48/449 (10.7%) compared with those given three doses: 49/451 (10.9%) 95% confidence limits - 4.25% + 3.9%. There were more septic and sepsis-related deaths in those patients given one dose (14 deaths) than in those given three doses (7 deaths) P > 0.1 95% CL - 0.4% + 3.0%. However, there were more very elderly patients in the one dose group: 64% of the deaths were aged over 80 and all but one had an emergency operation. There was no difference in the other outcome measures studied which included non-fatal deep sepsis, length of postoperative hospital stay, duration of postoperative fever or the use of antibiotics for postoperative infection. One dose of a suitable intravenous antibiotic gives prophylaxis against wound infection in at-risk abdominal surgery which is at least as effective as multiple doses. However, there may be a risk of overwhelming systemic sepsis in very elderly patients having emergency surgery.
Fine needle aspiration cytology (FNAC) was introduced to a District General Hospital Breast Clinic in 1984 and since that time the rate of surgical excision biopsy for benign breast disease has halved. The rate of benign to malignant breast operations fell from 2.0 to 0.7 over a 7-year period from 1982 to 1988. During this period the diagnosis of breast cancer was made at the first clinic appointment in 85% of women. However, a delay in diagnosis of more than 50 days occurred in 33 patients (6.9%) and there was little difference in the annual rate of delayed diagnosis despite the addition of FNAC as an extra diagnostic tool in the later years of the study. Eighty-five per cent of patients with a delayed diagnosis were under the age of 55 (mean and median age 47) years. FNAC is a useful adjunct in the management of patients with diagnostic breast problems, but even in combination with mammography is not always sufficiently sensitive to exclude malignancy, particularly in young women.
The effectiveness of a pediatric pain management program was examined using a multiple case study design. This study examined both the children's pain experience during cancer treatment, as well as their parents' anxiety and behavioral stress. Fourteen children were videotaped while receiving lumbar punctures during an 8-12 month period. Baseline data were obtained at the first of three visits prior to the introduction of relaxation, imagery, and distraction exercises. Self-ratings of child fear and parent anxiety, videotaped observations of child and parent behavior, and child pain ratings were obtained at all three visits. The children's behavioral responses to the procedure varied considerably, but their fear scores were stable and their reports of pain decreased over time. Parents reported high-trait, low-state anxiety scores that were stable over time. They were observed to be very supportive during the procedures. Implications for further research in this area and recommendations for practice are presented.
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Three hundred and eighty-one women with operable breast cancer aged over 70 years were randomly allocated to 40 mg tamoxifen daily and optimal surgery or to tamoxifen alone. At a median follow-up of 34 months there was no demonstrable difference in survival rate or in quality of life between the two treatment groups. More patients treated with tamoxifen alone had a subsequent change of management and this was usually an operation for local treatment failure. This progression to surgery has not been shown to be disadvantageous and the study will continue. Informed consent for randomization was difficult to obtain, leading to the exclusion of eligible patients, and it is therefore proposed to include non-randomized patients in a total cohort study.
A group of 292 consecutive patients underwent cholecystectomy for gallstones with presumed biliary pain over a 4-year period and all completed a self-assessment questionnaire before operation. Over the following 2 years 18 patients died but no others were lost to follow-up. The remaining 274 patients completed a further questionnaire 1 and 2 years after operation. Demographic characteristics and abdominal symptoms have been compared with an age- and sex-matched control group using the same questionnaire. Before operation symptoms of flatulent dyspepsia were far more frequent in patients with gallstones but operation markedly reduced these symptoms to an incidence which almost matched that of the control group. However, 1 year after cholecystectomy 34 per cent of patients still suffered some abdominal pain and of 35 patients referred back to hospital for investigation none has been shown to have a retained bile duct stone at a minimum follow-up of 5 years. A multivariate analysis indicated that preoperative flatulence together with long duration of attacks of pain are risk factors for postoperative dissatisfaction as judged by a linear analogue scale. However, both these factors are common and neither is a good discriminator of a poor outcome. The prediction of a poor symptomatic outcome after cholecystectomy from preoperative symptoms or patient characteristics had only limited success and all patients should be warned of this risk.
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