Survival analysis: the importance of censored observations.

We have considered the issue of predicting from diagnosis of a condition such as malignant melanoma survival past an often arbitrarily chosen fixed time-point, such as 5 years. Prediction of survival past any time-point becomes rather complicated due to the presence of 'censored observations', and these observations are often ignored in any analysis. Censored observations are subjects who either die of causes other than the disease of interest or are lost to follow-up. The aim of this paper is to show that the result of ignoring these 'censored observations' is an underestimation of the probability of survival beyond the fixed time-point. Ignoring these censored observations results in potentially valuable information on survival being thrown away. This underestimation will often prove to be of considerable magnitude and dependent on the proportion of censored observations present in the data. It is therefore essential to carry out a full actuarial survival analysis which will incorporate all the information contained in these censored observations.

Prognostic trees to aid prognosis in patients with cutaneous malignant melanoma. Scottish Melanoma Group.

OBJECTIVES: To design user friendly guides to prognosis for patients who have had invasive primary cutaneous malignant melanomas surgically excised. DESIGN: Adaptation of the classification tree method was used to derive prognostic trees for four different subgroups of malignant melanoma patients in whom known and possible prognostic variables interacted in different ways. SETTING: Scotland. SUBJECTS: Statistical modelling for prognostic trees was based on 1978 patients whose primary malignant melanoma was first diagnosed in 1979-86 for whom five year follow up and all relevant clinical pathological data were available. The resultant model was validated with 300 patients first diagnosed in 1987 for whom the same information was available. MAIN OUTCOME MEASURES: Actual and predicted rate of survival after diagnosis of primary cutaneous malignant melanoma. RESULTS: The four subgroups of patients were men and women with ulcerated and non-ulcerated cutaneous primary melanomas. Validation of the model showed excellent agreement between actual status of patients in the relevant subgroups and their status as predicted by the model. CONCLUSIONS: The prognostic trees are simple to use and give more accurate prognosis for individual patients than is currently available from tumour thickness alone.

Prognostic models for subgroups of melanoma patients from the Scottish Melanoma Group database 1979-86, and their subsequent validation.

For the past 20 years thickness of the primary tumour has been accepted as the most important guide to prognosis for patients with primary cutaneous malignant melanoma. The changing epidemiology of melanoma with an increasing number of patients with thin tumours has necessitated a reappraisal of this, with particular reference to interactions among tumour thickness, the patients' sex and the presence or absence of ulceration of the primary tumour. All primary cutaneous malignant melanomas diagnosed in Scotland between 1979 and 1986 were used as the test group (1978 patients). The proportional hazards model was used on all potential risk factors in the database and their two-way interactions, and the resulting models based on stepwise procedures were subsequently validated on 289 melanoma patients first diagnosed in 1987 in the same geographic area. Four distinct subgroups of males and females with ulcerated or non-ulcerated lesions were identified. For females with ulcerated lesions, tumour thickness, mitotic count and anatomical site of primary all gave valuable prognostic information, whereas for females with non-ulcerated lesions only tumour thickness was of prognostic value. For males with ulcerated lesions, level of invasion was the only prognostic guide, while for males with non-ulcerated lesions both tumour thickness and level of invasion contributed significantly to prediction of prognosis. Prognosis markedly different across subgroups of the melanoma population, even to the extent that essential prognostic factors are not the same in the distinct subgroups. Verification of these prognostic guides derived from 1979-86 patients has been achieved for all patients diagnosed with melanoma in 1987 from the same geographic area. These data will therefore be useful aids for clinicians managing patients.

Plantar malignant melanoma in a white Caucasian population.

Fifty-one white Caucasian patients from the west of Scotland, with stage I primary malignant melanoma arising on the plantar surface were studied. Subungual lesions were excluded from the study. Clinical and pathological features were related to survival, and compared with a group of 239 cases of clinical stage 1 melanoma of the lower limb, excluding the foot, collected in the same geographical area over the same period of time (1979-84). The average age of patients with plantar melanoma was 67 years and was significantly older than those with leg melanomas, in whom the mean age was 53 years. Twenty patients with plantar lesions had superficial spreading melanomas, 27 had acral lentiginous melanomas, and four had nodular lesions. The female:male ratio was 3:2 which was significantly different from the 7:1 female:male ratio for leg lesions. Plantar melanomas were more commonly ulcerated (57%) than were melanomas on the leg (29%) [P < 0.001]. There was no significant difference between the mean thickness of melanomas on the plantar surface and those on the leg. Nine (17%) of the patients with plantar melanomas gave a clinical history of pre-existing naevus and in 27% there was pathological evidence of a pre-existing naevus. Disease-free survival at 5 years for the population with plantar melanomas was 82, 51 and 0%, respectively, for melanomas 0-1.49, 1.5-3.49 and over 3.5 mm in thickness. This compares with 95, 71 and 46%, respectively, for leg lesions. In each thickness category patients with leg melanomas have a significantly better survival.(ABSTRACT TRUNCATED AT 250 WORDS)

A clinico-genetic study of psychiatric disorder in Huntington's chorea.

The introduction in 1985 of a genetic linkage test programme to identify asymptomatic heterozygotes among subjects at 50% initial risk for Huntington's chorea required a review of all cases of Huntington's chorea and their families referred to the Department of Medical Genetics of the Oxford Regional Health Area (population 2.5 million). From a representative sample of these subjects, psychiatric data were collected to estimate the frequency and time of onset of functional psychiatric illness and behaviour disorder. The rationale and method of the linkage test is described. The frequency of functional psychiatric disorder found was compared with that reported for the general population and for Alzheimer's disease. The role in relation to the aetiology of functional psychiatric disorder (1) of the Huntington's chorea gene and (2) of the family disturbance produced, was investigated by comparison between the frequency of functional psychiatric disorder in populations containing different proportions of heterozygotes as shown by (a) the manifestation of Huntington's chorea, and (b) the result of the genetic linkage analysis. In order to investigate the influence of the onset of Huntington's chorea on the production of functional psychiatric disorder the time of onset of the various functional psychiatric disorders was compared between asymptomatic subjects at 50% risk for Huntington's chorea and their cohabiting spouses who were assumed to be at zero risk and who shared their environment. It is concluded that possessing the Huntington's chorea gene: (1) has no influence on the production of functional psychiatric disorder in asymptomatic subjects at risk for Huntington's chorea; and (2) increases the tendency to major depressive disorder in subjects already affected with physical signs of Huntington's chorea.

Stage II melanoma in the west of Scotland, 1976-1985: prognostic factors for survival.

The outcome of 142 patients undergoing therapeutic lymphadenectomy for clinical stage II malignant melanoma was retrospectively assessed. 5 year survival was 26%, and survival was not altered in the 25 patients who received two courses of adjuvant combination chemotherapy after lymphadenectomy. On univariate analysis, the most significant determinants of survival were the number of malignant nodes removed at lymphadenectomy (P = 0.00004), the age of the patient (P = 0.009) and the disease-free interval between primary and stage II disease (P = 0.01). The following features were not significantly related to survival: sex, site, histogenetic type of primary tumour, tumour thickness and level of invasion. The number of malignant lymph-nodes was confirmed on multivariate analysis as the single most useful and significant predictor of survival, with the patient's age providing an additional significant contribution. In future adjuvant trials in stage II melanoma after therapeutic lymphadenectomy, patients should be stratified for both age and number of malignant nodes.

A study of genetic linkage in schizophrenia.

Families with more than one member affected by schizophrenia were identified and their members were interviewed. Four standardized diagnostic definitions (PSE, DSM-III, ICD-9, Feighner) were applied to all subjects who were classified as schizophrenic or not schizophrenic according to each definition. Non-schizophrenic psychiatric disorders which have been shown to be familially associated with schizophrenia were also identified. Twenty blood markers were ascertained for all subjects and evidence of co-segregation with schizophrenia was sought. No selective segregation was found and therefore there was no evidence suggesting linkage or supporting a monogenic theory of transmission of susceptibility to schizophrenia.

Platelet monoamine oxidase: specific activity and turnover number in schizophrenics and their families.

Monoamine oxidase specific activities and molecular turnover numbers have been measured in families with at least two schizophrenic members. Neither measure of monoamine oxidase was different in schizophrenics compared with their first degree relatives. Molecular turnover number was remarkably similar in males and females and when the group was considered by age, diagnosis, drug status and family membership. Neither specific activity nor turnover number could be used in risk estimation for the development of schizophrenia in members of these families.

Hypercalcemia in the etiology of puerperal psychosis.

The serum calcium of 53 recently delivered mothers hospitalized for severe puerperal psychiatric illness, which represented the whole intake from a defined catchment area, was compared with that of 35 female psychiatric patients and that of 49 normal postnatal women. The mean corrected and ionized serum calcium values of the puerperal psychiatric patients with no personal or family history of psychiatric disorder were markedly above the normal range. They were also significantly higher than those of the puerperal psychiatric patients with a personal or family history of psychiatric illness and those of the two control groups. There was a modest positive correlation between the degree of hypercalcemia and the severity of the psychiatric illness. The follow-up of 16 puerperal psychiatric patients indicated that the fall in ionized serum calcium levels correlated positively and significantly with the improvement in rated symptomatology. Patients with severe puerperal psychiatric disorder can be divided etiologically into two groups. The larger proportion is psychiatrically vulnerable, but in the remainder (about a third of the total number), the psychiatric illness appears to be related to a disorder of calcium homeostasis in the puerperium.

The natural history of schizophrenia: a 5-year prospective follow-up of a representative sample of schizophrenics by means of a standardized clinical and social assessment.

A comprehensive, representative cohort of 121 schizophrenics from a delimited catchment area, hospitalized in the course of 20 months (1973--4) and who met PSE criteria, was collected for a therapeutic trial (1976--6) in which, during the year after discharge, standardized clinical and social assessments has been made by personal interview at home. Standardized observations were repeated 4 years later. Follow-up was 99% complete. 48% of the cohort and 58% of the first admissions had a good outcome. Females fared significantly better than males.