bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

BackgroundVery little is known about the natural history of challenging behaviour and psychiatric disorder in people with severe and profound degrees of intellectual disability.AimsTo 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.MethodOne 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.ResultsBehavioural 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.ConclusionsThese 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

BackgroundRecent 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.AimsTo ascertain whether brain weight is different in people of a younger age who commit suicide than in those who die accidentally.MethodA 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.ResultsThese 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.ConclusionsWhatever 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

BackgroundOutcomes 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.AimsTo establish the strengths and limitations of outcomes research when applied in mental health.MethodA systematic review was made of the application of outcomes research in mental health services research.ResultsNine 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.ConclusionsOutcomes 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

BackgroundThis is the first report on the epidemiology of psychiatric disorders and needs for psychiatric treatment in the District of Derry, Northern Ireland.AimsTo assess the prevalence of psychiatric disorder and the needs for treatment in the general population of Derry.MethodThe 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.ResultsThe 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.ConclusionsThe 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

BackgroundPrevious short-term work reported fewer suicides among elderly users of a telephone helpline and emergency response service (the Tele Help–Tele Check Service).AimsTo examine long-term effects of the service on suicide in an elderly population of northern Italy.MethodThe 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.ResultsSignificantly 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).ConclusionsThe 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

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

BackgroundAcute 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.AimsTo assess whether neuroticism predicts mood change in response to ATD in healthy volunteers.MethodHealthy 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.ResultsNeuroticism 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.ConclusionsNeuroticism 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

BackgroundControlled trials have shown that psychological interventions designed to encourage graded exercise can facilitate recovery from chronic fatigue syndrome.AimsTo identify predictors of response to psychological treatment for chronic fatigue syndrome.MethodOf 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.ResultsPoor 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.ConclusionsPoor 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.
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.