N.H.S. numbers and cancer statistics.
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Biomedical subjects
Publications and source records attributed to R F Mould.
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The design of clinical trials in cancer is a subject which features reasonably often among FRCR (Part 1) examination questions, and as such should be of more than passing interest to oncologists. It is also a subject which is gaining in relevance since the number of trials is increasing annually due in part to the many chemotherapeutic regimes which are being proposed. This paper which is based on a lecture given in Cambridge at the Hospital Physicists' Association Annual Conference in September 1978, is intended to act as an introduction to clinical trial design. References for further reading are given and, in particular, the extensive report on randomised clinical trials to the Medical Research Council's Leukaemia Steering Committee (Peto et al., 1977, 1978) is recommended.
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A study of clotrimazole for the treatment of recurrent genital candidosis unexpectedly showed that symptoms and infection can be dissociated. The aim of the study was to see if intermittent antifungal treatment would reduce symptoms in women constantly distressed by recurrent genital candidosis. Forty women seriously affected by the condition were initially given oral and local antifungal treatment. When the patients were symptom-free and the vagina was free of yeasts, they were entered into a double-blind clinical trial and were treated prophylactically for four months with either intermittent clotrimazole pessaries and cream or a placebo. The prophylactic treatment kept symptoms below a critical level but did not affect the return of the yeasts to the vagina. This dissociation between symptoms and vaginal yeasts was unexpected. Rectal yeast carriage was unaffected by prophylactic vaginal treatment. Male contacts and patients both showed a high incidence of non-specific genital infection. This association has seldom been reported. A few patients cultured yeasts from their homes but this environment was not considered a major source of reinfection. The vaginal pH did not appear to be altered by the presence of yeasts. The results of the study suggested that symptoms in women with recurrent genital candidosis were not caused by yeasts alone, and possibly the reason for recurrences might lie not in constant reinfection by yeasts, but in failure to recognise and remove a primary underlying factor, perhaps infection with other sexually transmitted agents. The question of a synergistic action between yeasts and other organisms is discussed.
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The last few years have seen the introduction of medical statistics into the curriculum for MB, BS and for the FFR. Also, an increasing number of clinical trials have considered statistics at the planning stage of the trial, rather than only at the end point. However, there is one particular aspect of medical statistics which has consistently been neglected, namely, technique in calculating survival rates for cancer patients. All too often, a direct method of calculation, see section 3.1, is used when a life table method would provide a better estimate. The life table, or actuarial method, was first described in a medical context by Greenwood (1926), and later by Merrell and Shulman (1955) and Cutler and Ederer (1958). It has however, not been explained in detail in a British journal. The objective of the present paper is to remedy, this fact so that it can be used more widely in the future in preference to a direct method.
Fifty-six patients with disseminated malignant melanoma were randomly allocated to two treatment groups. The first group C received combination chemotherapy consisting of DTIC and ICRF 159. The second group (C+I) received the same chemotherapy but were also immunized with 2 X 10(7) irradiated allogeneic melanoma cells mixed with 50 mug of percutaneous BCG. The survival rates in both treatment groups C and (C+I) were not significantly different, and only minor enhancement of the chemotherapy was found in the (C+I) group. A similar pattern of tissue response was observed in both groups: lymph node, skin and, to some extent liver metastases, respond better than other sites.
The lognormal parametric statistical model can provide, for groups of carcinoma cervix patients, good estimates of long-term survival fractions several years earlier than would otherwise be possible. The present paper extends this model work to head and neck cancer by using a minimum chi-squared test for goodness of fit (P greater than 0-05), to study the distribution of survival times of patients who died with their cancer present. Some 12,000 case histories were available from 7 hospital registries, 4 regional cancer registries and one national registry (the OPCS). All histories were followed up for at least 10 years subsequent to treatment and could be grouped into one of 8 cancer sites: antrum, floor of mouth, larynx, nasopharynx, pyriform fossa, post cricoid, tonsil and tongue. The theoretical distributions investigated were the lognormal, negative exponential and skew exponential. The results showed that the lognormal provided the best overall fit to the data, although the range of optimum values for the lognormal parameter, S, differed with cancer site. The optimum range did, however, usually include the value S=0-45. These results will now permit the second stage of validation of the lognormal model to proceed for head and neck cancers.
A total of 4502 patients with carcinoma of the cervix was studied: in 113 patients 116 other primary neoplasms were found and tumours of lung, breast, colon and rectum occurred most frequently. Most of the patients in our series died with the other primary present. Treatment of the cancer of the cervix by radiotherapy seemed to play no role in the induction of anot;er primary cancer.