Background. The effectiveness of therapeutic interventions in psychosis is increasingly reported in terms of reductions in different symptom dimensions. It remains unclear, however, to what degree such symptomatic changes are accompanied by improvement in other measures such as service use, quality of life, and needs for care.

Methods. A sample of 708 patients with chronic psychotic illness was assessed on three occasions over 2 years (baseline, year 1 and year 2). A multilevel analysis was conducted to examine to what degree reduction in psychopathological scores derived from factor analysis of the Comprehensive Psychopathological Rating Scale (CPRS), was associated with improvement in service use, disability, subjective outcomes and measures of self-harm.

Results. Reduction in positive, negative, depressive and manic symptoms over the study period were all independently associated with lessening of social disability. Reduction in negative symptoms, and to a lesser extent in positive and manic symptoms, was associated with less time in hospital and more time living independently, whereas changes in positive and manic symptoms resulted in fewer admissions. Subjective outcomes such as improvement in quality of life, perceived needs for care and dissatisfaction with services showed the strongest associations with reduction in depressive symptoms. Reduction in positive symptoms was associated with decreased likelihood of parasuicide. Results did not differ according to diagnostic category.

Conclusion. The findings suggest that changes in distinct psychopathological dimensions independently and differentially influence outcome. Therapeutic interventions aimed at reducing symptoms of more than one dimension are likely to have more widespread effects.

Background. Typologies of anxiety, depression and somatization symptoms were investigated in individuals with no formal mental disorders, making no a priori assumptions about symptom distribution and inter-relationship.

Method. The subjects were 1617 adult primary care attenders from the WHO Collaborative Project on Psychological Problems in General Health Care, with at least three symptoms of anxiety, depression and/or somatization, but with no formal ICD-10 disorders. Analyses were based on the grade of membership model, a multivariate statistical procedure exploring indistinct boundaries between disease categories and preserving the heterogeneity of clinical picture within each category.

Results. Six prototype categories (or pure types) best described the structure of symptoms included in analyses. Pure type I included the full set of somatization symptoms. Pure type II was characterized by most anxiety and depression symptoms. Pure type III resembled generalized anxiety disorder. Pure type IV consisted of individuals reporting sporadic symptoms of anxiety, depression or somatization. Pure type V defined individuals with sleep problems. Finally, pure type VI was characterized by anxiety symptoms, including panic-like symptoms.

Conclusions. These findings provide support to the existence of a mixed anxiety–depression category crossing the diagnostic boundaries of current anxiety and depression disorders. Moreover, criteria of anxiety and somatization disorders may be re-examined to assess whether lower diagnostic thresholds can be identified that both preserve the symptom profile and clinical features of current diagnostic categories and allow for a better characterization of individuals with substantial psychopathology though not meeting the high symptom thresholds required for a diagnosis of formal mental disorders.

Background. Empirical data regarding prevalence of sexual and physical abuse histories in Japanese patients with eating disorders is lacking, in contrast to Western countries. This study investigated the prevalence of traumatic events in Japanese patients with eating disorders, and examined the relationship between such traumatic events and clinical features.

Methods. Subjects consisted of 33 patients with anorexia nervosa restricting type (RAN), 40 patients with anorexia nervosa binge eating/purging type (AN–BP), 63 patients with bulimia nervosa purging type (BN) and 99 healthy controls. All were female and diagnoses were based on DSM-IV. The Physical and Sexual Abuse Questionnaire (PSA), Eating Disorder Inventory (EDI) and Dissociation Experience Scale (DES) were administered to all of the subjects.

Results. Paradoxically, victims of minor sexual abuse committed by Chikan (a Japanese word indicating a person who commits minor sexual crimes) were more prevalent among controls than among patients with RAN, AN–BP or BN. However, physical punishment histories tended to be more prevalent among patients with AN–BP or BN than among RAN or controls. Only AN–BP and BN patients with physical punishment histories had twofold higher scores for DES and significantly more frequent histories of self-mutilation (67% v. 33%) compared with patients without such histories.

Conclusion. An abuse history is not essential or a prerequisite to developing an eating disorder in Japan.

Background. Recent literature has demonstrated that psychiatric patients, particularly those with a diagnosis of schizophrenia, may be at high risk for HIV infection. In fact, HIV-risk behaviour, such as intravenous drug with sharing needles, promiscuity associated with unprotected sex and high-risk sexual activity after using drugs has been reported by a substantial proportion of mentally ill patients.

Methods. In order to examine this problem in Italy, HIV-risk taking behaviour and knowledge about HIV/AIDS was investigated among 91 schizophrenic patients by using two self-report questionnaires (HIV-Risk Behaviour Questionnaire; AIDS-Risk Behaviour Knowledge Test).

Results. One-third of the patients reported having been tested for HIV infection and one tested seropositive (prevalence 3·4%). A high proportion of patients reported HIV-risk behaviour, such as injected drugs use (22·4%) and engaging in high risk sexual activity (e.g. multiple partners, 58%; prostitutes, 45%; occasional partners, 37%). Condoms were ‘never used’ by 41% of the patients and ‘almost never used’ by another 25%. In spite of these behaviours, 65% reported no concern of HIV infection. Knowledge about AIDS was lower among psychiatric patients than a healthy control group. Patients with long-lasting illness and numerous psychiatric admissions were less acknowledgeable about HIV infection. Certain misconceptions on HIV transmission were related to HIV risk behaviour.

Conclusions. These results indicate the urgent need for HIV educational programmes within mental health community-care settings.

Background. Numerous studies have shown that anxiety and depression are related to cognitive impairment, but the concomitant association between anxious symptoms, depressive symptoms and cognitive function has not been investigated, and, most studies have not considered psychotropic drug use as a possible confounding factor.

Methods. We assessed the independent association between depression, anxiety, psychotropic drug use and cognitive performance in 457 men and 659 women, aged 59–71 years living in the community. Data on demographic background, occupation, medical history, drug use and personal habits were obtained using a standardized questionnaire. The Spielberger Inventory Trait and the Center for Epidemiologic Study-Depression (CES-D) scales were used to evaluate anxious and depressive symptomatology respectively. Cognitive assessment included six traditional tests covering the main areas of cognitive functioning.

Results. In men, anxious and depressive symptomatologies had independent significant associations with most cognitive abilities, independent of psychotropic drug use. In women, the association between anxiety or depression and cognitive functioning was less strong and disappeared after adjustment for psychotropic drug use. Psychotropic drug use was associated with lower cognitive scores in both sexes. In men with high CES-D scores, we found positive correlations between anxiety level and cognitive scores.

Conclusions. The study showed that anxiety, depression and psychotropic drug use were significantly and independently associated with cognitive functioning in elderly men. The high prevalence of psychotropic drug use in women with or without psychological disorders may explain its major effect in women. Results suggested that anxiety may partly compensate for some negative effects of depression on cognitive functioning.

Background. Recent studies have suggested that major depressive disorders are associated with a breakdown in the organization of ultradian rhythm in sleep EEG. The present study used cross-spectral analysis of sleep EEG to confirm this finding, in a larger-scale study, evaluating the influence of gender and age on ultradian rhythms in depression.

Methods. Temporal coherence of ultradian (80–120 min) rhythms in beta, theta and delta, recorded from central and parietal sites, were compared in 120 symptomatic, unmedicated, depressed out-patients and 59 healthy normal controls.

Results. Few macro-architectural differences were noted between patients and controls. However, interhemispheric beta and theta coherence and intrahemispheric coherence between beta and delta rhythms were significantly lower in depressed patients. Coherence measures were lowest in women with depression and highest in men in the control group, but were not strongly influenced by age. Over 65% of depressed patients were [ges ]2 standard deviations below normal on at least one coherence measure, in sharp contrast to less than 10% of patients on macro-architectural variables.

Conclusions. It was concluded that dysregulation of ultradian rhythms characterizes the majority of depressed out-patients, primarily women, even when macro-architecture did not differentiate groups. The outcome of this study supports the view that the pathophysiology of depression is strongly influenced by gender. It was suggested that low temporal coherence in depression reflects a breakdown in the organization of sleep EEG rhythms within and between the two hemispheres.

Background. Higher level of urbanicity of place of birth and of place of residence at the time of illness onset has been shown to increase the risk for adult schizophrenia. However, because urban birth and urban residence are strongly correlated, no conclusions can be drawn about the timing of the risk-increasing effect. The current study discriminated between any effect of urbanization before and around the time of illness onset.

Methods. All individuals born between 1972 and 1978 were followed up through the Dutch National Psychiatric Case Register for first admission for schizophrenia until 1995 (maximum age 23 years). Exposure status was defined by a combination of place of birth and place of residence at the time of illness onset in the three most densely populated provinces of the Netherlands (the ‘Randstad’, exposed) or in all other areas (the ‘non-Randstad’, non-exposed). The risk for schizophrenia was examined in four different exposure groups: non-exposed born and non-exposed resident (NbNr, reference category), non-exposed born and exposed resident (NbEr), exposed born and non-exposed resident (EbNr) and exposed born and exposed resident (EbEr).

Results. The greatest risk for schizophrenia was found in the EbNR group, without evidence for any additive effect of urban residence (rate ratio (RR) for narrow schizophrenia in EbNr group, 2·05 (95% CI 1·18–3·57); in EbEr group, 1·96 (95% CI, 1·55–2·46)). Individuals who were not exposed at birth, but became so later in life, were not at increased risk of developing schizophrenia (RR for narrow schizophrenia in NbEr group, 0·79 (0·46–1·36)).

Conclusion. The results suggest that environmental factors associated with urbanization increase the risk for schizophrenia before rather than around the time of illness onset.

Background. There are considerable differences between and within countries in the involvement of general practitioners (GPs) in psychosocial care. This study aimed to describe the self-perceived role of GPs in 30 European countries as the first contacted professional for patients with psychosocial problems, and to examine the relationship with characteristics of the health care system, practice organization and doctors.

Methods. Data collected in the European Study of GP Task Profiles were analysed in relation to the self-perceived involvement of GPs in psychosocial care. In 30 countries 7233 GPs answered standardized questionnaires in their own languages about seven brief case scenarios. The questions focused on care given as the first health care professional contacted, and were answered in a scored scale (1–4) ranging from ‘never’ to ‘almost always’. Independent variables examined were both on a national level and on an individual level, including: listed practice population, referral system, employment status of GPs, workload, measures of practice organization, contacts with social workers and urbanization of practice area. Data were analysed using multi-level techniques.

Results. Self-perceived involvement in psychosocial care was much higher in Western than in Eastern Europe and also in countries with a referral system. Cooperation with social workers, rural practice, keeping medical records, presence of an appointment system and high workload were positively associated with this perceived involvement.

Conclusions. In countries with self-employed doctors and a referral system, GPs are in a better position to provide psychosocial care. GPs should be encouraged to cooperate with social workers and to keep medical records of their patient contacts routinely.

Background. Schizophrenia has a high natural mortality of a largely environmental aetiology. There is, however, little research about possible risk factors. This study measured the diet, cigarette and alcohol use, exercise and obesity of a cohort of people with schizophrenia and compared results to general population rates.

Methods. Semi-structured interview using validated research instruments on 102 middle-aged subjects with a diagnosis of schizophrenia, living in the community. Results were compared to general population norms using standard statistical tests.

Results. The subjects ate a diet higher in fat and lower in fibre than the general population. They took little exercise but were not significantly more obese. They smoked heavily but drank less alcohol. Most differences remained significant after controlling for social class.

Conclusions. People with schizophrenia have an unhealthy lifestyle, which probably contributes to the excess mortality of the disease. They are therefore an appropriate target group for health promotion interventions.

Background. Linkage and association studies have suggested genetic susceptibility to bipolar affective disorder in a region of chromosome 11 around the tyrosine hydroxylase locus. We attempted to test the hypothesis that there was allelic association between polymorphisms around the tyrosine hydroxylase locus and bipolar affective disorder.

Methods. A case–control association study was employed using four polymorphic markers, which span a region of approximately 2 cM across the tyrosine hydroxylase locus.

Results. No evidence for allelic association between bipolar affective disorder and any of these markers was found. However, linkage disequilibrium between the markers was detected.

Conclusions. This finding diminishes the probability that genes in this region influence susceptibility to bipolar affective disorder, at least in our sample.

Background. Current systems of describing personality pathology have significant shortcomings. A polydiagnostic approach is used to study the relationship between psychological, psychoanalytical and psychopathological models of personality.

Methods. The subjects were 256 patients enrolled in treatment studies of major depression and bulimia nervosa. Subjects were assessed using the Temperament and Character Inventory (TCI), the Defense Style Questionnaire (DSQ) and the Structured Clinical Interview for DMS-III-R personality disorders (SCID-II).

Results. Subjects had high rates of DSM-III-R personality disorders with 52% having at least one personality disorder. Cluster A personality disorders were correlated with low reward dependence, high harm avoidance and low self-directedness and cooperativeness. Cluster B personality disorders were related to high novelty seeking and low self-directedness and cooperativeness. Cluster C personality disorders were correlated with high harm avoidance and low novelty seeking and low self-directedness. Immature defences were related to DSM-III-R personality symptoms, but individual defences were not related to personality clusters in a predictable way. Immature defences were strongly related to low self-directedness and cooperativeness. Both TCI self-directedness scores and immature defence scores were moderately predictive of the presence and number of personality disorders.

Conclusion. A widely accepted clinical nosology (DSM-III-R personality disorders) rated using a clinical interview correlates reasonably predictably with two theoretical models derived from different paradigms and rated using self-reports. This might be seen as providing concurrent validity for all three models. However, serious methodological shortcomings confront studies of this type, including sample selection and measurement of personality dysfunction. One way to begin to resolve these problems is to study which personality measures are best related to treatment response and prognosis.

Background. The relationship between ethnicity and suicide risk is ill-understood. It is unclear whether, and if so, how, the ethnic mix of local areas affects risk in local individuals.

Methods. Coroners' records of 329 suicides were used to obtain ethnic (White, Afro-Caribbean, Asian) suicide rates in South London (population 902008) for 1991–3. Geographical variation and associations of ethnic suicide rates with small area (mean population 8274) ethnic densities (proportion of residents of given ethnic groups) and deprivation, were examined with random effects Poisson regression.

Results. Adjusted for deprivation, age and gender, suicide rates in wards with larger minority groups were higher among Whites (relative rate (RR) per standard deviation (S.D.) increase in minority density 1·18; 95% CI 1·02–1·37) but lower among minority groups (RR 0·75 (0·59–0·96)) (LR-test for interaction χ2=9·2 (df=1); P=0·003). Similar patterns were also apparent for Afro-Caribbeans and Asians separately. With White suicide rates as baseline, ethnic minority status is a risk factor for suicide in wards with small, but a protective factor in neighbourhoods with large minority populations. The RR of minority versus White suicide declines with a factor (relative RR) 0·67 (0·51–0·87) per S.D. increase in local minority density.

Conclusions. Minority suicide rates are higher in areas where minority groups are smaller. This effect is ethnic-specific and not due to confounding by gender, age, deprivation or unbalanced migration. Dependent on address, a suicide risk factor for a White individual may protect an ethnic minority individual and vice versa. This has implications for research and prevention.

Background. Temporal lobe atrophy on magnetic resonance imaging (MRI) has been suggested as a specific diagnostic marker for Alzheimer's disease (AD). No previous comparison with dementia with Lewy bodies (DLB) has been reported.

Method. T1-weighted MRI scans were performed on 11 subjects with AD (nine with NINCDS/ADRDA probable AD and two with neuropathologically proven AD) and nine subjects with DLB (four with probable DLB diagnosed by clinical criteria and five with neuropathologically proven DLB). Groups were matched for age, duration of illness and cognitive test score. Two raters, blind to diagnosis and neuropathological findings, measured the volumes of the frontal lobes, temporal lobes, hippocampi, parahippocampal gyri, amygdalae, and caudate nuclei using a computerized volumetric analysis system. Scans were also rated for medial temporal atrophy on a four-point scale by an experienced rater.

Results. AD subjects had significantly smaller left temporal lobes and parahippocampal gyri than those with DLB. Medial temporal atrophy was present in 9/11 AD cases (82%) and absent in 6/9 (67%) of DLB cases. Two neuropathologically confirmed cases of DLB had severe medial temporal atrophy; both had concurrent AD-type pathology in the temporal lobe (Braak stage 4).

Conclusions. This pilot study supports the hypothesis that a greater burden of pathology centres on the temporal lobes in AD compared with DLB, except in DLB cases with concurrent Alzheimer pathology. A larger study is needed to confirm these findings and to determine whether MRI has a role in assisting with the clinical differentiation between DLB and AD.

Background. The term frontotemporal dementia (FTD) covers both the temporal and frontal presentations of this condition. The frontal variant (fv) presents with insidious changes in personality and behaviour, with neuropsychological evidence of disproportionate frontal dysfunction. Although psychiatric features are well recognized, there is little systematic data examining the mental state using assessment instruments and no reported studies of the longitudinal progress and assessment.

Methods. Fifteen patients with a diagnosis of FTD(fv) were assessed using the Comprehensive Psychiatric Rating Scale (CPRS). A subgroup of five patients were reassessed annually using the same instrument, generating data over a 3-year period.

Results. At initial assessment a third of 15 patients had no psychiatric symptoms to report. Three patients reported symptoms of sadness, but only one patient met criteria for DSM-IV major depressive episode. One patient experienced symptoms of elation, but did not meet criteria for manic episode, while two patients had hypochondriacal complaints but did not meet DSM-IV criteria for hypochondriasis. One of these patients also experienced the compulsion to count but did not meet criteria for obsessive compulsive disorder. The objective mental state was, on the whole, not congruent with the reported symptoms. Five patients assessed over a 3-year period showed no progression of their subjectively reported symptoms.

Conclusions. Psychiatric symptoms although often present were characterized by their shallowness, lack of elaboration and non-development over time.

Background. In the assessment of stressful life events (SLEs), researchers have often tried to evaluate whether individual events are dependent or independent of the respondent's behaviour. We sought to validate this evaluation using a twin methodology. We predicted that dependent SLEs would be more heritable than independent SLEs.

Methods. We explored, by twin modelling, the resemblance in two pairs of past-year personal and network SLEs rated individually, by trained interviewers, on a four-point dependence–independence scale. We examined results from two waves of interviews with 785 female–female twin pairs ascertained from a population based registry.

Results. Twin model-fitting found no evidence for genetic effects on personal or network independent SLEs. However, familial–environmental factors played an important role in the aetiology of network independent SLEs. For personal and network dependent SLEs, by contrast, three of four analyses suggested a significant aetiological role for genetic factors with estimated heritabilities ranging from 19 to 51%.

Conclusions. Our results support the validity of interviewer assessments of dependence versus independence of SLEs. As predicted, these assessments were relatively successful at distinguishing SLEs that were influenced by genetic factors from those that were not.

Background. Schizophrenia has been defined in part by disturbances of thought and language. The non-schizophrenic relatives of patients also have been found to show subtle disturbances of language that may be associated with vulnerability. Investigators have hypothesized that these phenomena in patients and their relatives are, at least in part, the result of weaknesses in facets of attention and memory.

Methods. The present study assessed some neuropsychological process correlates of three different measures of thought and language symptoms in 55 stable out-patients, using tests of immediate auditory memory impairment and auditory distractability, and carefully controlling for generalized deficit effects. A parallel assessment was made of referential communication disturbances in 59 non-schizophrenic relatives of patients and 24 control subjects matched to the relatives.

Results. In patients, formal thought disorder, disorganization, and referential communication disturbances were all associated with each other and with auditory distractability. In addition, as expected, referential communication disturbances were associated with immediate auditory memory impairment. Referential disturbance ratings for relatives were similar in magnitude to those for the stable out-patients, and much higher than for controls. However, the relatives' language ratings were not associated specifically with weaknesses in attention or memory as measured.

Conclusions. Impairments in immediate auditory memory and attention are associated differentially with different types of communication disturbances in schizophrenia patients. The cognitive substrate for referential communication disturbances in relatives appears to differ qualitatively from that for patients.

Background. The success of large scale surveys depends on well designed questionnaires and the skills of lay interviewers. Discrepancies in prevalence rates between epidemiological surveys and poor agreement between survey interviewer and clinician diagnostic interviews are giving rise to increasing concern among researchers, public health planners and policy developers. New approaches to information collection are called for. The feasibility of training experienced survey interviewers in semi-structured, clinical, diagnostic interviewing has never been investigated systematically across the range of neurotic and psychotic disorders.

Methods. Eight experienced survey interviewers from the Office for National Statistics (ONS) were selected and underwent extended training in a Survey Form of SCAN (SCAN-SF). Sixty-four adults, including a majority of psychiatric in-patients were assessed by ONS interviewers and re-interviewed within a week by SCAN-trained clinicians. Feedback was sought from interviewers and trainers.

Results. Trainers found lay interviewers coped at least as well with psychotic as with neurotic symptoms. Concordance for any disorder was 0·74 (95% CI: 0·57 to 0·91); for any specific psychotic disorder 0·63 (0·40 to 0·86); for any specific neurotic disorder 0·63 (0·43 to 0·83). Sensitivity ranged from 0·6 to 0·9 and specificity from 0·8 to 0·9. There was no evidence of rater bias.

Conclusions. These preliminary findings are very promising. However, before the SCAN-SF, administered by carefully trained lay interviewers, can be recommended in large scale surveys, further evaluations of its feasibility and reliability in the general population are needed.

Background. Previous studies on male patients with sex chromosome abnormalities (SCA), namely XYY and XXY, suggest that such patients commit criminal acts more frequently than expected. Most of these studies are affected by ascertainment bias.

Methods. Using a population-based sample of men with SCA, identified by screening 34380 infants at birth between 1967 and 1979, comparison between 16 XYY men, 13 XXY men and 45 controls were made in terms of frequency of antisocial personality disorder (APD) using the Schedule for Affective Disorders and Schizophrenia lifetime version. Rates of criminal convictions were examined in 17 XYY men, 17 XXY men and 60 controls.

Results. XYY males showed a significantly higher frequency of antisocial behaviour in adolescence and adulthood and of criminal convictions than the controls, but multiple regression analysis showed this to be mediated mainly through lowered intelligence. Property offences constituted the majority of offences in all groups. The XXY men did not show an increased rate of criminal convictions. It is possible that this apparently negative result relates to the relatively small numbers of cases and hence low power of this study.

Conclusions. The findings of this study carry the advantage of not being affected by ascertainment bias and the disadvantage of having low power. It provides evidence for a slightly increased liability to antisocial behaviour in XYY men.

Background. Assessment of capacity plays a pivotal role in determining when decisions need to be made on behalf of an individual. It therefore has major clinical management implications for health care professionals and civil liberties implications for the person concerned. In many countries, there is a presumption that adults have the capacity to make health care decisions. However, in persons with a mental disability, capacity may be temporarily or permanently impaired.

Methods. A selective review is presented which considers: (i) the broad approaches taken to determining capacity; (ii) the abilities commonly assessed in determining capacity; and (iii) the principles underlying health care decision-making for adults who are without capacity.

Results. Capacity is a functional concept, determined by the person's ability to understand, retain, and weigh up information relevant to the decision in order to arrive at a choice, and then to communicate that choice. We have reviewed the studies that examined decision-making abilities in people with dementia, chronic mental illness or intellectual disabilities. Approaches to decision-making in adults who lack capacity include: anticipatory decisions made through advance health care statements or decisions by proxy based on ‘best interests’ or ‘substituted judgement’.

Conclusions. The understanding of clinical and legal aspects of capacity is still developing. This paper examines current concepts of capacity and decision-making on behalf of those without capacity. We propose a framework, in line with current ethical and legal guidelines, as an aid to clinicians when they are seeking consent for a health care intervention.

Objective. This study examined whether dementia patients with greater cognitive reserve had increased mortality rates, and whether this association was different across strata of cognition, functional ability and depression.

Methods. In the community-based Amsterdam Study of the Elderly, 261 non-institutionalized dementia patients, identified using the Geriatric Mental State Schedule (GMS), were followed for an average of 55·5 months after which mortality data were obtained. Cognitive reserve was indicated by years of education and pre-morbid intelligence (measured using the Dutch Adult Reading Test). Cognition, functional ability and depression were indicated by Mini-Mental State scores, ADL and IADL measurements and GMS depressive syndrome, respectively.

Results. During the follow-up 146 persons (55·9%) died. Cox regression analyses showed that more highly educated dementia patients had higher mortality rates, only if they had low MMSE scores or if they had a concurrent depression. Pre-morbid intelligence was associated with a higher mortality rate, independent of cognition, but this association was much stronger among patients with depression. The positive association between education or intelligence and mortality was not modified by functional disabilities.

Conclusions. The results suggest that dementia patients with greater cognitive reserve have increased mortality rates, only if the disease has progressed to such an extent that clinical symptoms are more severe. In this respect, the reserve hypothesis needs a modification. Depression in dementia patients with greater cognitive reserve may reflect a subgroup of patients with poor prognosis.