bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence and correlates of personality disorders in a community sample
Authors: Samuels Jack , Eaton William W. , Bienvenu O. Joseph , Brown Clayton H. , Costa Paul T. , Nestadt Gerald
Published: August 2002

Background

Knowledge of the prevalence and correlates of personality disorders in the community is important for identifying treatment needs and for provision of psychiatric services.

Aims

To estimate the prevalence of personality disorders in a community sample and to identify demographic subgroups with especially high prevalence.

Method

Clinical psychologists used the International Personality Disorder Examination to assess DSM-IV and ICD-10 personality disorders in a sample of 742 subjects, ages 34–94 years, residing in Baltimore, Maryland. Logistic regression was used to evaluate the association between demographic characteristics and DSM - IV personality disorder clusters.

Results

The estimated overall prevalence of DSM - IV personality disorders was 9%. Cluster A disorders were most prevalent in men who had never married. Cluster B disorders were most prevalent in young men without a high school degree, and cluster C disorders in high school graduates who had never married.

Conclusions

Approximately 9% of this community sample has a DSM-IV personality disorder. Personality disorders are over-represented in certain demographic subgroups of the community
Validity of the diagnosis of personality disorder in adults with learning disability and severe behavioural problems
Authors: Flynn Andrew , Matthews Helen , Hollins Sheila
Published: August 2002

Background

Personality disorder in people with learning disability has received little research attention, with only a handful of cross-sectional surveys of prevalence available. As yet, there have been no studies to include an examination of validity.

Aims

To investigate the prevalence of personality disorder in adults with learning disability who are in specialist challenging behaviour in-patient services and to examine the validity of the diagnosis of personality disorder in this group in terms of its association with abusive experience in early life.

Method

The Standardised Assessment of Personality (SAP) was used to diagnose personality disorder in 36 individuals with mild/moderate learning disability Case notes were reviewed for details of clinical diagnosis and early psychosocial history.

Results

Thirty-nine per cent of the sample met the criteria for severe personality disorder. This diagnosis showed a significant association with early traumatic experience.

Conclusions

Severe personality disorder is a common diagnosis in this group. There is preliminary evidence that the diagnosis is associated with abuse in childhood.
Assessing the evidence on case management
Authors: Ziguras S. J. , Stuart G. W. , Jackson A. C.
Published: August 2002

Background

Evidence on the impact of case management is contradictory.

Aims

To discuss two different systematic reviews (one conducted by the authors and one conducted through the Cochrane collaboration) that came to contradictory conclusions about the impact of case management in mental health services.

Method

We summarised the findings of the two reviews with respect to case management effectiveness, examined key methodological differences between the two approaches and discuss the impact of these on the validity of the results.

Results

The differences in conclusions between the two reviews result from the differences in inclusion criteria, namely non-randomised trials, data from unpublished scales and data from variables with skewed distributions. The theoretical and empirical effects of these are discussed.

Conclusions

Systematic reviewers may face a trade-off between the application of strict criteria for the inclusion of studies and the amount of data available for analysis and hence statistical power. The available research suggests that case management is generally effective.
Influence of supplementary vitamins, minerals and essential fatty acids on the antisocial behaviour of young adult prisoners
Authors: Gesch C. Bernard , Hammond Sean M. , Hampson Sarah E. , Eves Anita , Crowder Martin J.
Published: August 2002

Background

There is evidence that offenders consume diets lacking in essential nutrients and this could adversely affect their behaviour.

Aims

To test empirically if physiologically adequate intakes of vitamins, minerals and essential fatty acids cause a reduction in antisocial behaviour.

Method

Experimental, double-blind, placebo-controlled, randomised trial of nutritional supplements on 231 young adult prisoners, comparing disciplinary offences before and during supplementation.

Results

Compared with placebos, those receiving the active capsules committed an average of 26.3% (95% CI 8.3-44.33%) fewer offences (P=0.03, two-tailed). Compared to baseline, the effect on those taking active supplements for a minimum of 2 weeks (n=172) was an average 35.1% (95% CI 16.3-53.9%) reduction of offences (P < 0.001, two-tailed), whereas placebos remained within standard error.

Conclusions

Antisocial behaviour in prisons, including violence, are reduced by vitamins, minerals and essential fatty acids with similar implications for those eating poor diets in the community.
Efficacy of Citalopram in the prevention of recurrent depression in elderly patients: Placebo-controlled study of maintenance therapy
Authors: Klysner René , Bent-Hansen Jesper , Hansen Hanne L. , Lunde Marianne , Pleidrup Elisabeth , Poulsen Dorte Loldrup , Andersen Marc , Petersen Hans Erik Høpfner
Published: August 2002

Background

The highly recurrent nature of major depression in the young and the elderly warrants long-term antidepressant treatment.

Aims

To compare the prophylactic efficacy of citalopram and placebo in elderly patients; to evaluate long-term tolerability of citalopram.

Method

Out-patients, ⩾65 years, with unipolar major depression (DSM – IV: 296.2 x or 296.3 x) and Montgomery – Åsberg Depression Rating Scale score ⩾22 were treated with citalopram 20–40 mg for 8 weeks. Responders continued on their final fixed dose of citalopram for 16 weeks before randomisation to double-blind treatment with citalopram or placebo for at least 48 weeks.

Results

Nineteen of the 60 patients using citalopram v. 41 of the 61 patients using placebo had recurrence. Time to recurrence was significantly different between citalopram— and placebo-patients, in favour of citalopram (log-rank test, P < 0.0001). Long-term treatment was well tolerated.

Conclusions

Long-term treatment with citalopram is effective in preventing recurrence of depression in the elderly and is well tolerated.
Estimating the relationship between disease progression and cost of care in dementia
Authors: Wolstenholme Jane L. , Fenn Paul , Gray Alastair M. , Keene Janet , Jacoby Robin , HOPE TONY
Published: August 2002

Background

Previous studies have shown a positive relationship between disease severity and cost.

Aims

To explore the factors affecting time to institutionalisation and estimate the relationship between the costs of care and disease progression.

Method

Retrospective analysis of a longitudinal data-set for a cohort of 100 patients diagnosed with Alzheimer's disease or vascular dementia.

Results

Changes in both Mini-Mental State Examination (MMSE) and Barthel scores have independent and significant marginal effects on costs. Each one-point decline in the MMSE score is associated with a £56 increase in the four-monthly costs, whereas each one-point fall in the Barthel index is associated with a £586 increase in costs.

Conclusions

It may be inappropriate for economic models of disease progression in dementia to be based solely on measures of cognitive change. MMSE and the Barthel index are independent significant predictors of time to institutionalisation and cost of care, but changes in the Barthel index are particularly important in predicting costs outside institutional care.
Pathways to care in children at risk of attention-deficit hyperactivity disorder
Authors: Sayal Kapil , Taylor Eric , Beecham Jennifer , Byrne Patrick
Published: August 2002

Background

There is underdiagnosis of and low use of specialist services for attention-deficit hyperactivity disorder (ADHD).

Aims

To quantify the filters in the help-seeking pathway through primary care and to investigate factors influencing progress for children at risk of ADHD.

Method

A total of 127 children (5–11 years old) with pervasive hyperactivity who passed each filter (primary care attendance and general practitioner (GP) recognition of disorder) were compared with those who had not.

Results

Primary care attendance was only associated with parental perception of the behaviour as problematic (OR 2.11; 95% CI 1.11-4.03). However, GP recognition was related to both parent and child factors – parental request for referral (OR 20.83; 95% CI 3.05-142.08) and conduct problems (OR 1.48; 95% CI 1.04-2.12). GP non-recognition was the main barrier in the pathway to care; following recognition, most children were referred.

Conclusions

Parents can be regarded as the main gatekeepers for access to specialist services.
Sexual dysfunction in patients taking conventional antipsychotic medication
Authors: Smith Shubulade , O'Keane Veronica , Murray Robin
Published: August 2002

Background

Antipsychotic drugs are associated with sexual dysfunction but the mechanisms are poorly understood.

Aims

To ascertain the frequency of sexual dysfunction in patients taking conventional antipsychotics and to determine the possible underlying mechanisms.

Method

Sexual dysfunction was assessed in 101 patients receiving conventional antipsychotic medication, 57 normal controls and 55 controls attending a sexual dysfunction clinic.

Results

Sexual dysfunction occurred in 45% of patients taking antipsychotic medication, 17% of normal controls and 61% of controls attending a sexual dysfunction clinic. Sexual dysfunction was associated with autonomic side-effects in normoprolactinaemic males, but the presence of hyperprolactinaemia overrode other causes of sexual dysfunction. For women, hyperprolactinaemia was the main cause of sexual dysfunction.

Conclusions

Conventional antipsychotic medications cause significant levels of sexual dysfunction. Clinicians should routinely enquire about sexual symptoms prior to the prescription of antipsychotics and on follow-up.
Neurasthenia: Prevalence, disability and health care characteristics in the Australian community
Authors: Hickie Ian , Davenport Tracey , Issakidis Cathy , Andrews Gavin
Published: August 2002

Background

Neurasthenia imposes a high burden on primary medical health care systems in all societies.

Aims

To determine the prevalence of ICD-10 neurasthenia and associated comorbidity, disability and health care utilisation.

Method

Utilisation of a national sample of Australian households previously surveyed using the Composite International Diagnostic Interview and other measures.

Results

Prolonged and excessive fatigue was reported by 1465 people (13.29% of the sample). Of these, one in nine people meet current ICD-10 criteria for neurasthenia. Comorbidity was associated with affective, anxiety and physical disorders. People with neurasthenia alone (< 0.5% of the population) were less disabled and used less services than those with comorbid disorders.

Conclusions

Fatigue is frequent in the Australian community and is common in people attending general practice. Neurasthenia is disabling and demanding of services largely because of its comorbidity with other mental and physical disorders. Until a remedy for persistent fatigue is provided, doctors should take an active psychological approach to treatment.
Economic impact of personality disorders in UK primary care attenders
Authors: Rendu Alison , Moran Paul , Patel Anita , Knapp Martin , Mann Anthony
Published: August 2002

Background

The economic impact of personality disorders on UK health services is unknown.

Aims

To test the hypothesis that people with personality disorders have higher mean health and non-health costs compared with those without personality disorders.

Method

Prospective cohort study design. A total of 303 general practice attenders were followed-up 1 year after they had been assessed for the presence of personality disorders. Costs were estimated in £ sterling at 1999 price levels.

Results

The mean total cost for patients with personality disorders was £3094 (s.d.=5324) compared with £1633 (s.d.=3779) for those without personality disorders. Personality disorders were not independently associated with increased costs. Multivariate analyses identified the presence of a significant interaction between personality disorders and common mental disorders and increased total costs (coefficient=499, 95% CI 180.1-626.2, P=0.002).

Conclusions

Personality disorders are not independently associated with increased costs. An interaction between personality disorders and common mental disorders significantly predicts increased total costs.
Behavioural symptoms among people with severe and profound intellectual disabilities: A 26-year follow-up study
Authors: Thompson Christina L. , Reid Andrew
Published: August 2002

Background

Very little is known about the natural history of challenging behaviour and psychiatric disorder in people with severe and profound degrees of intellectual disability.

Aims

To clarify the natural history of challenging behaviour and psychiatric disorder in this population through a long-term prospective cohort study over a 26-year period.

Method

One hundred individuals with severe or profound intellectual disability were randomly selected in 1975. Their behaviour was recorded through carer and psychiatrist ratings using the Modified Manifest Abnormality Scale of the Clinical Interview Schedule. The presence and severity of psychiatric disorder were also recorded. The study was repeated in 1981/82 and 1992/93. We repeated the study again in 2001, supplementing the original observational data with the Checklist of Challenging Behaviour.

Results

Behavioural symptomatology is remarkably persistent, particularly stereotypy, emotional abnormalities, eye avoidance and overactivity although the severity of overall psychiatric disorder does show some abatement through time.

Conclusions

These findings influence the prospects of success in relocating adults with severe and profound degrees of intellectual disability back into the community.
Sudden death and suicide: A comparison of brain weight
Authors: Hamilton S. J. , McMahon R. F. T.
Published: August 2002

Background

Recent evidence suggests that the brain weight of individuals over the age of 60 who commit suicide is significantly higher than in those who die of natural causes.

Aims

To ascertain whether brain weight is different in people of a younger age who commit suicide than in those who die accidentally.

Method

A retrospective review of post-mortem reports collecting height, weight and brain weight in 100 suicide victims (87 males, mean age 38.5 years) and 100 age/gender-matched controls who died accidentally or of natural causes (87 males, mean age 38.7 years). Comparison by t-test was made of brain weight in isolation as well as brain weight corrected for height, weight and body mass index.

Results

These results reveal no significant difference in brain weight in suicide cases compared to the general population (P > 0.05). The brain weight of those who died by hanging was significantly higher than of those who died by overdose.

Conclusions

Whatever the significant neuropsychiatric elements are that influence suicidal behaviour, they do not consistently affect brain weight in the population studied.
Outcomes research in mental health
Authors: Gilbody Simon M. , House Allan O. , Sheldon Trevor A.
Published: August 2002

Background

Outcomes research involves the secondary analysis of data collected routinely by clinical services, in order to judge the effectiveness of interventions and policy initiatives. It permits the study of large databases of patients who are representative of ‘real world’ practice. However, there are potential problems with this observational design.

Aims

To establish the strengths and limitations of outcomes research when applied in mental health.

Method

A systematic review was made of the application of outcomes research in mental health services research.

Results

Nine examples of outcomes research in mental health services were found. Those that used insurance claims data have information on large numbers of patients but use surrogate outcomes that are of questionable value to clinicians and patients. Problems arise when attempting to adjust for important confounding variables using routinely collected claims data, making results difficult to interpret.

Conclusions

Outcomes research is unlikely to be a quick or cheap means of establishing evidence for the effectiveness of mental health practice and policy.
Prevalence of psychiatric disorder and the need for psychiatric care in Northern Ireland
Authors: Mcconnell Pamela , Bebbington Paul , Mcclelland Roy , Gillespie Kate , Houghton Sharon
Published: August 2002

Background

This is the first report on the epidemiology of psychiatric disorders and needs for psychiatric treatment in the District of Derry, Northern Ireland.

Aims

To assess the prevalence of psychiatric disorder and the needs for treatment in the general population of Derry.

Method

The sample was drawn at random with a two-phase design using the General Health Questionnaire (GHQ–28) during the first phase, and the Schedules for Clinical Assessment in Neuropsychiatry (SCAN) with the Needs for Care Assessment (NFCAS–C) in the second phase.

Results

The second phase (n=307) gave a weighted 1-month prevalence of hierarchically ordered ICD–10 psychiatric disorders of 7.5% and a 1-year prevalence of 12.2%. The equivalent prevalences for depressive disorders were 2.4% and 6.0%, respectively, and those for anxiety states were 3.5% and 3.7%. Only a quarter of needs for treatment were met, with the situation being better for depression than for anxiety.

Conclusions

The rates of psychiatric disorder in Derry were even higher than those reported by a similar survey in inner London. This almost certainly reflects the very high levels of social deprivation in the District. Needs for treatment were often unmet.
Suicide among the elderly: The long-term impact of a telephone support and assessment intervention in northern Italy
Authors: De Leo Diego , Buono Marirosa Dello , Dwyer Jonathan
Published: August 2002

Background

Previous short-term work reported fewer suicides among elderly users of a telephone helpline and emergency response service (the Tele Help–Tele Check Service).

Aims

To examine long-term effects of the service on suicide in an elderly population of northern Italy.

Method

The service provided twice-weekly support and needs assessment telephone calls and a 24 h emergency alarm service. Data from 1988 to 1998 allowed comparison of 18 641 service users with a comparable general population group of the Veneto region in Italy.

Results

Significantly fewer suicide deaths (nOBSERVED=6) occurred among elderly service users (standardised mortality ratio (SMR) 28.8%) than expected (nEXPECTED=20.86; χ2=10.58, d.f.=1, P < 0.001) despite an assumed overrepresentation of persons at increased risk. The service performed well for elderly females (nOBSERVED=2, SMR=16.6%, nEXPECTED=12.03; χ2=8.36, d.f.=1, P < 0.001).

Conclusions

The study confirms the initial promise of the Tele Help–Tele Check service over a much longer time period. Further research will clarify the apparent lack of benefit for elderly males.
Exposure to case management: Relationships to patient characteristics and outcome
Authors: Burns Tom , White Ian , Byford Sarah , Fiander Matthew , Creed Francis , Fahy Tom
Published: August 2002

Background

Trials in community psychiatry must balance rigour with generalisability. The UK700 trial failed to find a significant effect on hospitalisation, but its sample population contained significant heterogeneity of exposure to case management in the two groups.

Aims

To test whether patients successfully exposed to a minimum of 12 months' intensive case management over the 2-year follow-up period achieved reduced hospitalisation.

Method

Of 679 participants with hospitalisation data, 84 were identified as having < 12 months' exposure owing to prolonged hospitalisation, imprisonment or a combination of the two. These patients were excluded and outcomes tested for the remaining 595 patients.

Results

Overall reduced case-load size did not reduce hospitalisation or treatment costs over 2 years despite elimination of outliers. Age, previous hospitalisation and source of recruitment to the study all correlated with outcome.

Conclusions

Case-load reduction is not in itself enough to reduce the need for hospital care in psychosis. Baseline patient characteristics (in particular length of previous hospitalisation and recruitment from in-patient care) have a significant influence and should be allowed for in power calculations. Identifying the optimal clinical profile for patients likely to benefit from intensive case management remains a pressing need for further studies.
Neuroticism as a predictor of mood change: The effects of tryptophan depletion
Authors: Stewart Mary E. , Deary I.J. , Ebmeier K. P.
Published: August 2002

Background

Acute tryptophan depletion (ATD) results in a transient lowering of mood in patients recovered from depression and in healthy volunteers with a family history of affective disorders. The personality trait of neuroticism is strongly associated with depression.

Aims

To assess whether neuroticism predicts mood change in response to ATD in healthy volunteers.

Method

Healthy volunteers who scored at the top and bottom fifth percentiles of neuroticism scores (17 and 15 respectively) were selected. In a double-blind, crossover study they received a tryptophan-free or a control drink. Mood and cognition were assessed.

Results

Neuroticism did not predict the amount of mood change following ATD but did moderate performance on the verbal fluency test. A family history of affective disorder (n=5) predicted mood change but not cognitive function following ATD.

Conclusions

Neuroticism moderates aspects of cognitive function, but in this study it was not strongly related with mood change via serotonin.
Predictors of response to treatment for chronic fatigue syndrome
Authors: Bentall Richard P. , Powell Pauline , Nye Fred J. , Edwards Richard H. T.
Published: August 2002

Background

Controlled trials have shown that psychological interventions designed to encourage graded exercise can facilitate recovery from chronic fatigue syndrome.

Aims

To identify predictors of response to psychological treatment for chronic fatigue syndrome.

Method

Of 114 patients assigned to equally effective treatment conditions in a randomised, controlled trial, 95 completed follow-up assessments. Relationships between variables measured prior to randomisation and changes in physical functioning and subjective handicap at 1 year were evaluated by multiple regression.

Results

Poor outcome was predicted by membership of a self-help group, being in receipt of sickness benefit at the start of treatment, and dysphoria as measured by the Hospital Anxiety and Depression scale. Severity of symptoms and duration of illness were not predictors of response.

Conclusions

Poor outcome in the psychological treatment of chronic fatigue syndrome is predicted by variables that indicate resistance to accepting the therapeutic rationale, poor motivation to treatment adherence or secondary gains from illness.
Ten books
Authors: Persaud Raj
Published: August 2002

Choosing ten books you would take to a desert island as your sole companions is not that difficult a task for a consultant psychiatrist working in the National Health Service. This is because current working conditions remarkably resemble eking out an existence in a desolate place. You have to make do with whatever detritus you find washed up on the shore as resources, and after a long while, you might find a footprint in the sand indicating that a manager once passed by. This discovery produces a mixture of emotions, including fear, because you aren't sure if you ever meet whether you will be able to communicate, and also whether you might not be eaten alive.
Explaining Interindividual Variability of Docetaxel Pharmacokinetics and Pharmacodynamics in Asians Through Phenotyping and Genotyping Strategies
Authors: Goh Boon-Cher , Lee Soo-Chin , Wang Ling-Zhi , Fan Lu , Guo Jia-Yi , Lamba Jatinder , Schuetz Erin , Lim Robert , Lim Hong-Liang , Ong Ai-Bee , Lee How-Sung
Published: August 2002

PURPOSE: To explain the variability of docetaxel pharmacokinetics through study of CYP3A phenotype and genotype, and MDR1 genotype.

PATIENTS AND METHODS: We studied the pharmacokinetics and pharmacodynamics of docetaxel in patients in whom it was indicated and who had not received known CYP3A4 substrates. Midazolam was administered intravenously to these patients at least 2 days before docetaxel treatment, and systemic clearances of both drugs were correlated. Patients were characterized for polymorphisms in the CYP3A4 promoter region, CYP3A5, and the C3435T polymorphism of MDR1.

RESULTS: Thirty-two patients were enrolled, of whom 31 had full pharmacokinetic data sets. Docetaxel clearance correlated with midazolam clearance, body-surface area, serum albumin, and performance status. Docetaxel and midazolam clearances were normally distributed. In multiple linear regression analyses, midazolam clearance and performance status were the only significant covariates of docetaxel clearance, and the area under the curve of docetaxel, serum levels of alpha-1-acid glycoprotein, and ALT were significant predictors of nadir neutrophil count. No polymorphisms were detected in the 5′ regulatory region of CYP3A4. Nine patients of 25 studied were homozygous for the CYP3A5*3 genotype, and had lower mean clearance of midazolam but not docetaxel. The T/T genotype at the C3435T of MDR1, which is associated with reduced P-glycoprotein function, was found in eight of 27 patients.

CONCLUSION: Midazolam may be used as a probe drug for CYP3A activity to predict docetaxel clearances, hence reducing interindividual variability. Homozygotes for CYP3A5*3 and C3435T of MDR1 are common in our population, and their effects on pharmacokinetics of relevant substrates should be studied further.
Molecular Targeting of Platelet-Derived Growth Factor B by Imatinib Mesylate in a Patient With Metastatic Dermatofibrosarcoma Protuberans
Authors: Rubin Brian P. , Schuetze Scott M. , Eary Janet F. , Norwood Thomas H. , Mirza Sohail , Conrad Ernest U. , Bruckner James D.
Published: August 2002

PURPOSE: Dermatofibrosarcoma protuberans is caused by activation of the platelet-derived growth factor B (PDGFB) receptor, a transmembrane tyrosine kinase. We investigated the response of dermatofibrosarcoma protuberans to the tyrosine kinase inhibitor imatinib mesylate.

PATIENTS AND METHODS: A patient with unresectable, metastatic dermatofibrosarcoma protuberans received imatinib mesylate (400 mg bid). Response to therapy was assessed by [18F]fluorodeoxyglucose (FDG) positron emission tomography, magnetic resonance imaging, and histopathologic and immunohistochemical evaluation.

RESULTS: The patient was treated for 4 months with imatinib mesylate. The hypermetabolic uptake of FDG fell to background levels within 2 weeks of treatment, and the tumor volume shrank by over 75% during the 4 months of therapy, allowing for resection of the mass. There was no residual viable tumor in the resected specimen, indicating a complete histologic response to treatment with imatinib mesylate.

CONCLUSION: Imatinib mesylate is highly active in dermatofibrosarcoma protuberans. The dramatic response seen in this patient demonstrates that inhibition of PDGFB receptor tyrosine kinase activity can significantly impact viability of at least one type of solid tumor.
Revision of the American Joint Committee on Cancer Staging System for Breast Cancer
Authors: Singletary S. Eva , Allred Craig , Ashley Pandora , Bassett Lawrence W. , Berry Donald , Bland Kirby I. , Borgen Patrick I. , Clark Gary , Edge Stephen B. , Hayes Daniel F. , Hughes Lorie L. , Hutter Robert V.P. , Morrow Monica , Page David L. , Recht Abram , Theriault Richard L. , Thor Ann , Weaver Donald L. , Wieand H. Samuel , Greene Frederick L.
Published: August 2002

PURPOSE: To revise the American Joint Committee on Cancer staging system for breast carcinoma.

MATERIALS AND METHODS: A Breast Task Force submitted recommended changes and additions to the existing staging system that were (1) evidence-based and/or consistent with widespread clinical consensus about appropriate diagnostic and treatment standards and (2) useful for the uniform accrual of outcome information in national databases.

RESULTS: Major changes included the following: size-based discrimination between micrometastases and isolated tumor cells; identifiers to indicate usage of innovative technical approaches; classification of lymph node status by number of involved axillary lymph nodes; and new classifications for metastasis to the infraclavicular, internal mammary, and supraclavicular lymph nodes.

CONCLUSION: This revised staging system will be officially adopted for use in tumor registries in January 2003.
Lack of Effect of a Low-Fat, High-Fruit, -Vegetable, and -Fiber Diet on Serum Prostate-Specific Antigen of Men Without Prostate Cancer: Results From a Randomized Trial
Authors: Shike Moshe , Latkany Lianne , Riedel Elyn , Fleisher Martin , Schatzkin Arthur , Lanza Elaine , Corle Donald , Begg Colin B. ,   the Polyp Prevention Trial Study Group
Published: August 2002

PURPOSE: To determine whether a diet low in fat and high in fruits, vegetables, and fiber may be protective against prostate cancer by having an impact on serial levels of serum prostate-specific antigen (PSA).

METHODS: Six hundred eighty-nine men were randomized to the intervention arm and 661 to the control arm. The intervention group received intensive counseling to consume a diet low in fat and high in fiber, fruits, and vegetables. The control group received a standard brochure on a healthy diet. PSA in serum was measured at baseline and annually thereafter for 4 years, and newly diagnosed prostate cancers were recorded.

RESULTS: The individual PSA slope for each participant was calculated, and the distributions of slopes were compared between the two groups. There was no significant difference in distributions of the slopes (P = .99). The two groups were identical in the proportions of participants with elevated PSA at each time point. There was no difference in the PSA slopes between the two groups (P = .34) and in the frequencies of elevated PSA values for those with elevated PSA at baseline. Incidence of prostate cancer during the 4 years was similar in the two groups (19 and 22 in the control and intervention arms, respectively).

CONCLUSION: Dietary intervention over a 4-year period with reduced fat and increased consumption of fruits, vegetables, and fiber has no impact on serum PSA levels in men. The study also offers no evidence that this dietary intervention over a 4-year period affects the incidence of prostate cancer during the 4 years.
Mechanisms and Management of Toxicities Associated With High-Dose Interferon Alfa-2b Therapy
Authors: Kirkwood John M. , Bender Catherine , Agarwala Sanjiv , Tarhini Ahmad , Shipe-Spotloe Janice , Smelko Barbara , Donnelly Sandra , Stover Lori
Published: August 2002

PURPOSE: The toxicity associated with adjuvant high-dose interferon-alfa-2b therapy (HDI) for high-risk melanoma can lead to premature discontinuation. It is important to understand the expected adverse events and their underlying mechanisms and to anticipate and aggressively manage toxicity during treatment in order to ensure that patients receive the maximum therapeutic benefit.

METHODS: The toxicity profile of HDI was reviewed by examining data from the United States cooperative group trials. Available published data related to the potential mechanisms responsible for the observed adverse events are discussed, and comprehensive recommendations for managing side effects are presented.

RESULTS: The HDI regimen is associated with acute constitutional symptoms, chronic fatigue, myelosuppression, elevated liver enzyme levels, and neurologic symptoms. The majority of patients tolerate 1 year of therapy with an understanding of the anticipated toxicities in conjunction with appropriate dose modifications and supportive care. Ongoing monitoring for liver dysfunction and hematologic toxicity is critical to ensure safety. Many of the toxicities associated with interferon-alfa (IFN-α) seem to be the result of endogenous cytokines and their effects on the neuroendocrine system. Recent data have also demonstrated that IFN-α suppresses the activity of specific CYP450 isoenzymes and that this correlates with discrete toxicities. Pharmacologic interventions are under study for fatigue and depression. An increased understanding of the mechanisms of IFN-α–associated toxicity will lead to more rational and effective supportive care and improved quality of life.

CONCLUSION: Continued research in this area should lead to improvements in the safety and tolerability of adjuvant therapy for melanoma.
Multicenter Phase III Study of Uracil/Tegafur and Oral Leucovorin Versus Fluorouracil and Leucovorin in Patients With Previously Untreated Metastatic Colorectal Cancer
Authors: Douillard Jean-Yves , Hoff Paulo M. , Skillings Jamey R. , Eisenberg Peter , Davidson Neville , Harper Peter , Vincent Mark D. , Lembersky Barry C. , Thompson Seth , Maniero Antonella , Benner Steven E.
Published: August 2002

PURPOSE: This phase III study was designed to demonstrate equivalence in survival of oral uracil/tegafur (UFT) and oral leucovorin (LV) to conventional intravenous (IV) fluorouracil (5-FU) and LV in previously untreated metastatic colorectal carcinoma. Safety was also compared.

PATIENTS AND METHODS: Eight hundred sixteen patients were randomized to receive either UFT (300 mg/m2/d) and LV (75 or 90 mg/d) for 28 days every 35 days or IV bolus 5-FU (425 mg/m2/d) and LV (20 mg/m2/d) for 5 days every 28 days.

RESULTS: UFT/LV produced survival comparable to the IV 5-FU/LV regimen. Median survival was 12.4 months (95% confidence interval [CI], 11.2 to 13.6 months) with UFT/LV and 13.4 months (95% CI, 11.6 to 15.4 months) with 5-FU/LV (P = .630). The hazard ratio for survival was 0.964 (95.6% CI, 0.826 to 1.125), supporting equivalent survival. The overall response rate did not differ between treatment arms (UFT/LV, 11.7%; 5-FU/LV, 14.5%; P = .232). Median time to progression favored 5-FU/LV (UFT/LV, 3.5 months; 5-FU/LV, 3.8 months; P = .011), but tumor assessment schedules differed between arms. UFT/LV significantly improved safety compared with 5-FU/LV. Diarrhea, nausea and vomiting, and stomatitis and mucositis were significantly less frequent with UFT/LV, as was myelosuppression. Patients treated with UFT/LV had fewer episodes of febrile neutropenia (P < .001) and documented infections (P < .05). Increased bilirubin, without other liver function abnormalities, was observed more often with UFT/LV (P < .001). Concomitant medications were more frequent with 5-FU/LV, including use of antibiotics, growth factors, and antiemetics.

CONCLUSION: UFT/LV provided a safer, more convenient oral alternative to a standard bolus IV 5-FU/LV regimen for metastatic colorectal cancer while producing equivalent survival.
Phase II Randomized Trial of Temozolomide and Concurrent Radiotherapy in Patients With Brain Metastases
Authors: Antonadou D. , Paraskevaidis M. , Sarris G. , Coliarakis N. , Economou I. , Karageorgis P. , Throuvalas N.
Published: August 2002

PURPOSE: To determine the efficacy, tolerability, and safety of concurrent temozolomide and radiotherapy in patients with previously untreated brain metastases.

PATIENTS AND METHODS: Fifty-two patients with brain metastases from solid tumors were randomized to oral temozolomide (75 mg/m2/d) concurrent with 40-Gy fractionated conventional external-beam radiotherapy (2 Gy, 5 d/wk) for 4 weeks versus 40-Gy radiotherapy alone. The group receiving temozolomide and radiotherapy continued temozolomide therapy (200 mg/m2/d) for 5 days every 28 days for an additional six cycles. The primary end points were radiologic response and neurologic symptom evaluation.

RESULTS: The objective response rate was significantly (P = .017) improved in patients receiving temozolomide and radiotherapy versus radiotherapy alone. Among 24 patients assessable for response in the temozolomide group, 23 (96%) of 24 responded, including nine (38%) patients with a complete response and 14 (58%) patients with a partial response. With radiotherapy alone, 14 (67%) of 21 assessable patients responded, including seven (33%) complete responses and seven (33%) partial responses. There was marked neurologic improvement in the group receiving temozolomide, and the proportion of patients requiring corticosteroids 2 months after treatment was lower in the temozolomide group compared with radiotherapy alone (67% v 91%, respectively). Daily temozolomide concurrent with radiotherapy was generally well tolerated; however, grade ≥ 2 nausea (48% v 13%, P = .13) and vomiting (32% v 0%, P = .004) were significantly increased in the temozolomide group. Hematologic toxicity was predictable and reversible.

CONCLUSION: Temozolomide is safe, and a significant improvement in response rate was observed when administered in combination with radiotherapy in patients with previously untreated brain metastases. A larger randomized trial is warranted to verify these results.
Prospective Exploratory Analysis of the Association Between Tumor Response, Quality of Life, and Expenditures Among Patients Receiving Paclitaxel Monotherapy for Refractory Metastatic Breast Cancer
Authors: Modi Shanu , Panageas Katherine S. , Duck Elaine T. , Bach Ariadne , Weinstock Nancy , Dougherty James , Cramer Laura , Hudis Clifford , Norton Larry , Seidman Andrew
Published: August 2002

PURPOSE: To prospectively evaluate the association between tumor response, change in quality of life (QoL), and hospital expenditures in patients with metastatic breast cancer (MBC) receiving single-agent paclitaxel.

PATIENTS AND METHODS: Eligible patients had bidimensionally measurable MBC and any number of previous therapies, excluding taxane chemotherapy. Paclitaxel was administered by various different infusion schedules. QoL measures were evaluated for each patient at baseline and serially using the Memorial Symptom Assessment Scale (MSAS)-Global Distress Index (GDI) and Functional Assessment of Cancer Therapy–Breast (FACT-B) instruments. Patients were assessed for early (first 6 weeks) and ever changes in QoL parameters. Charges were monitored through the hospital’s centralized computer billing system and converted to cost ratios for the analysis. Correlations between response and improvement in QoL were assessed by Fisher’s exact test statistic. Associations between improvements in QoL with cost ratios were assessed by logistic regression and likewise between response and cost ratios.

RESULTS: Of the 59 patients treated, 50 had sufficient data for comparative analyses. The overall response rate was 24% (all partial responses). Minor responses were observed in 17% of patients, 25% had stable disease, and 29% had progression. Responding patients had significant improvement in QoL as assessed by MSAS-GDI (P = .004) and FACT-B (P = .028). The mean total cost/month ratios for patients experiencing improved GDI QoL scores was 1.31 versus 1.56 for those without QoL benefit (P = .52) and 1.05 versus 1.76 for responders versus nonresponders, respectively (P = .07).

CONCLUSION: Patients with evidence of tumor response on paclitaxel had a QoL benefit not observed in nonresponders, and this response was associated with a trend for lower overall costs.
Correlation of Smoking History and Other Patient Characteristics With Major Complications of Pelvic Radiation Therapy for Cervical Cancer
Authors: Eifel Patricia J. , Jhingran Anuja , Bodurka Diane C. , Levenback Charles , Thames Howard
Published: August 2002

PURPOSE: The purpose of this study was to identify patient-related factors that influence the risk of serious late complications of pelvic radiation therapy.

PATIENTS AND METHODS: The records of 3,489 patients treated with radiation therapy for International Federation of Gynecology and Obstetrics stage I or II carcinoma of the cervix were reviewed for information about patient characteristics, treatment details, and outcomes. Any complication occurring or persisting more than 3 months after treatment that required hospitalization, transfusion, or an operation or caused severe symptoms or the patient’s death was considered a major late complication. Complication rates were calculated actuarially. The median duration of follow-up was 85 months, and 99% of patients were followed for at least 3 years or until they died.

RESULTS: Heavy smoking was the strongest independent predictor of overall complications (multivariate hazard ratio, 2.30; 95% confidence interval [CI], 1.84 to 2.87). The most striking influence of smoking was on the incidence of small bowel complications (hazard ratio for smokers of one or more packs per day, 3.25; 95% CI, 2.21 to 4.78). Hispanics had a significantly lower rate of small bowel complications than whites, and blacks had higher rates of bladder and rectal complications than whites. Thin women had an increased risk of gastrointestinal complications, and obese women were more likely to have serious bladder complications.

CONCLUSION: Complications of pelvic radiation therapy are strongly correlated with smoking, race, and other patient characteristics. These factors should be considered before the results of clinical studies are generalized to different cultural and racial groups.
Randomized Comparative Study of Tegafur/Uracil and Oral Leucovorin Versus Parenteral Fluorouracil and Leucovorin in Patients With Previously Untreated Metastatic Colorectal Cancer
Authors: Carmichael James , Popiela Tadeusz , Radstone David , Falk Stephen , Borner Markus , Oza Amit , Skovsgaard Torben , Munier Stephane , Martin Christophe
Published: August 2002

Purpose: This phase III study compared the time to progression (TTP) of an oral regimen of dihydropyrimidine dehydrogenase inhibitory fluoropyrimidine composed of a fixed combination of tegafur and uracil in a 1:4 molar ratio (UFT) and leucovorin (LV) to intravenous (IV) fluorouracil (5-FU) and LV in previously untreated metastatic colorectal carcinoma (CRC) patients. Secondary end points were survival, tumor response, safety, and quality of life.

Patients and Methods: Between May 1996 and July 1997, 380 patients were randomized to receive either UFT (300 mg/m2/d) and LV (90 mg/d), administered for 28 days every 35 days, or 5-FU (425 mg/m2/d) and LV (20 mg/m2/d), given IV for 5 days every 35 days.

Results: No statistically significant difference in TTP was observed between treatments. With 320 events assessed, the median TTP was 3.4 months (95% Confidence interval [CI], 2.6 to 3.8) on UFT/LV and 3.3 months (95% CI, 2.5 to 3.7) on 5-FU/LV (P = .591, stratified log-rank test). There were no statistically significant differences in survival, tumor response, duration of response, and time to response. Substantial safety benefits were observed in patients treated with UFT/LV. They experienced significantly less stomatitis/mucositis (P < .001) and myelosuppression, resulting in fewer episodes of febrile neutropenia (P < .001) and less documented infection (P = .04). Concomitant medication usage was significantly greater on 5-FU/LV (P = .010). With respect to quality of life, after correcting for baseline imbalances, there were no significant differences between treatments for any scale, except diarrhea.

Conclusion: The oral UFT/LV regimen failed to achieve improved TTP; however, the study confirms significant safety improvements compared with bolus IV 5-FU/LV for the first-line treatment of metastatic CRC.
Communication in End-of-Life Cancer Care: A Comparison of Team Assessments in Three European Countries
Authors: Higginson Irene J. , Costantini Massimo
Published: August 2002

PURPOSE: To compare team assessments of end-of-life communication in three European countries, and to identify factors associated with problematic communication.

PATIENTS AND METHODS: Three prospective cohort studies used similar standardized procedures, and included patients referred to palliative care services in the United Kingdom, Ireland, and Italy. Palliative team care staff assessed three components of communication in the last week of the patient’s life—between the patient and family (or those close to them), between professionals and patient and family, and between professionals—using a validated measure. Univariate and multivariate analyses explored the data and tested for relationships between possible explanatory variables and communication.

RESULTS: Data were collected on 1,326 patients, 416 in the United Kingdom, 411 in Ireland, and 499 in Italy. Mean age was 68 years (range, 19 to 95 years), 55% were male, and almost two thirds were married. Team members assessed that communication between patient and family was a moderate or severe problem in the last week of life for 30% to 40% of patients; 10% to 20% had moderate or severe problems recorded for the other two communication items. Problematic communication was associated with respiratory and breast cancers, a shorter time in care, and hospice death. It was also associated with greater spiritual need, need for care planning, and poorer patient and family insight (Spearman’s ρ > 0.4), but not especially with pain and symptom control, in both univariate and multivariate analyses, both within countries and for all data combined.

CONCLUSION: Severe communication problems were reported by team assessments in up to 40% of patients at the end of life. A multiprofessional approach is needed to recognize and improve this.
Racial Variation in CAG Repeat Lengths Within the Androgen Receptor Gene Among Prostate Cancer Patients of Lower Socioeconomic Status
Authors: Bennett Charles L. , Price Douglas K. , Kim Simon , Liu Dachao , Jovanovic Borko D. , Nathan Derek , Johnson Margaret E. , Montgomery Jeffrey S. , Cude Kelly , Brockbank Justin C. , Sartor Oliver , Figg William D.
Published: August 2002

PURPOSE: To evaluate (1) whether there were racial differences in the androgen receptor gene CAG repeat length and in clinical or laboratory attributes of prostate cancer at the time of diagnosis; (2) whether there were differences in race, Gleason score, prostate-specific antigen (PSA) level, and stage at diagnosis by androgen receptor gene CAG repeat length; and (3) whether sociodemographic, clinical, and laboratory based factors might be associated with advanced-stage prostate cancer. To our knowledge, our study is the first to report on CAG repeat lengths in a cohort of prostate cancer patients, which includes large numbers of African-American men.

METHODS: CAG repeat lengths on the androgen receptor gene were evaluated for 151 African-American and 168 white veterans with prostate cancer. The χ2 test, t test, and logistic regression analyses were used to evaluate the associations between CAG repeat lengths and race, stage, histologic grade, and PSA levels at diagnosis.

RESULTS: The mean age of the cohort at the time of diagnosis was 68.7 years. At presentation, 42.0% had stage D prostate cancer, 26.5% had Gleason scores of 8 to 10, and 53.0% had PSA levels ≥ 10 ng/dL. Mean androgen receptor gene CAG repeat length for white veterans was 21.9 (SD, 3.5) versus 19.8 (SD, 3.2) for African-American veterans (P = .001). Men with shorter CAG repeats were more likely to have stage D prostate cancer (P = .09) but were not more likely to have a higher PSA concentration or Gleason score.

CONCLUSION: In this cohort of men with prostate cancer, short CAG repeat length on the androgen receptor gene was associated with African-American race and possibly with higher stage but not with other clinical or pathologic findings.