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Träfflista för sökning "WFRF:(O''Brien John) srt2:(2005-2009)"

Sökning: WFRF:(O''Brien John) > (2005-2009)

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  • Druker, Brian J., et al. (författare)
  • Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia
  • 2006
  • Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 355:23, s. 2408-2417
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The cause of chronic myeloid leukemia (CML) is a constitutively active BCR-ABL tyrosine kinase. Imatinib inhibits this kinase, and in a short-term study was superior to interferon alfa plus cytarabine for newly diagnosed CML in the chronic phase. For 5 years, we followed patients with CML who received imatinib as initial therapy. METHODS: We randomly assigned 553 patients to receive imatinib and 553 to receive interferon alfa plus cytarabine and then evaluated them for overall and event-free survival; progression to accelerated-phase CML or blast crisis; hematologic, cytogenetic, and molecular responses; and adverse events. RESULTS: The median follow-up was 60 months. Kaplan-Meier estimates of cumulative best rates of complete cytogenetic response among patients receiving imatinib were 69% by 12 months and 87% by 60 months. An estimated 7% of patients progressed to accelerated-phase CML or blast crisis, and the estimated overall survival of patients who received imatinib as initial therapy was 89% at 60 months. Patients who had a complete cytogenetic response or in whom levels of BCR-ABL transcripts had fallen by at least 3 log had a significantly lower risk of disease progression than did patients without a complete cytogenetic response (P<0.001). Grade 3 or 4 adverse events diminished over time, and there was no clinically significant change in the profile of adverse events. CONCLUSIONS: After 5 years of follow-up, continuous treatment of chronic-phase CML with imatinib as initial therapy was found to induce durable responses in a high proportion of patients. (ClinicalTrials.gov number, NCT00006343 [ClinicalTrials.gov].)
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  • Firbank, Michael J, et al. (författare)
  • White matter hyperintensities and depression--preliminary results from the LADIS study.
  • 2005
  • Ingår i: International journal of geriatric psychiatry. - 0885-6230. ; 20:7, s. 674-9
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: White matter hyperintensities have been associated with the development of depression in older subjects, though the details of this relationship are not fully understood. METHODS: In a pan-European multicentre study of 629 older subjects, we examined the relationship between MRI white matter hyperintensities (WMH), depressive symptoms and self perceived health quality of life (QOL). WMH were rated using a three-point scale. RESULTS: We found depressive symptoms as assessed by the geriatric depression 15-item scale to be associated with WMH rating (Spearman's rho 0.11, p = 0.008) and also with the Euro-QOL health score (Spearman's rho -0.5, p < 0.001). In a ordinal logistic regression model, QOL was found to strongly predict GDS score (p < 0.001) and severe vs mild WMH were associated with increased depression (p = 0.028). The relationship between history of severe depression and WMH score was examined, but there were no differences either between those with and without a history of severe depression, or those with an early vs late onset of depression. CONCLUSIONS: The results suggest that WMH play a role in increasing depressive symptoms, even when perceived quality of life is controlled for as a possible mediating factor.
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  • Jokinen, Hanna, et al. (författare)
  • Longitudinal cognitive decline in subcortical ischemic vascular disease--the LADIS Study.
  • 2009
  • Ingår i: Cerebrovascular diseases (Basel, Switzerland). - 1421-9786. ; 27:4, s. 384-91
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Cross-sectional studies have indicated that subcortical ischemic vascular disease (SIVD), as defined according to imaging criteria, is associated with a specific clinical and cognitive profile. Much less is known about the long-term cognitive consequences of SIVD. The aim of the study was to investigate the longitudinal cognitive performance and incident dementia in subjects with and without SIVD in a sample of older adults with white matter lesions. METHODS: In the Leukoaraiosis and Disability (LADIS) study, 639 participants were examined with annual clinical and neuropsychological evaluations for 3 years. The subjects meeting the MRI criteria of SIVD at baseline were compared to the other subjects of the sample with linear mixed models. RESULTS: The overall level of cognitive performance over the follow-up period was inferior in multiple cognitive domains in SIVD subjects as compared to the reference group. The subjects with SIVD presented significantly steeper decline of performance in the Stroop test (parts I and II), Trail Making A test, Verbal fluency test, and Mini-Mental State Examination. They also had a threefold risk of developing dementia during follow-up independently of age, sex, education and medial temporal lobe atrophy. CONCLUSIONS: SIVD, as a manifestation of cerebral small vessel disease, is related to progressive cognitive impairment and a considerable risk of developing dementia. SIVD seems to specifically contribute to the deterioration of psychomotor speed, executive control, and global cognitive function.
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  • Jokinen, Hanna, et al. (författare)
  • MRI-defined subcortical ischemic vascular disease: baseline clinical and neuropsychological findings. The LADIS Study.
  • 2009
  • Ingår i: Cerebrovascular diseases (Basel, Switzerland). - 1421-9786. ; 27:4, s. 336-44
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Subcortical ischemic vascular disease (SIVD) is a common, but often overlooked cause of vascular cognitive impairment. Diagnostic research criteria for SIVD are based on magnetic resonance imaging (MRI) findings including substantial white matter lesions (WML) and multiple lacunar infarcts. Empirical studies validating these imaging criteria are still few. The purpose of the study was to describe the clinical and cognitive characteristics of the MRI-defined SIVD in a mixed sample of functionally independent elderly subjects with WML. METHODS: The subjects of the Leukoaraiosis and Disability (LADIS) study, aged 65-84 years, underwent comprehensive clinical and neuropsychological examinations, and brain MRI at the baseline assessment. The subjects meeting the SIVD imaging criteria (n = 89) were compared to the other subjects of the sample (n = 524). RESULTS: SIVD was associated with lower education, hypertension and, independently, with obesity. The subjects with SIVD had more often motor impairment, a history of falls, and subtle impairment in activities of daily living, but they did not differ for depressive symptoms. SIVD subjects performed significantly inferiorly in tests of global cognitive function, psychomotor speed, attention and executive functions, verbal fluency, and working memory. CONCLUSION: In this population of nondisabled older adults with WML, SIVD was related to specific clinical and functional characteristics. Neuropsychological features included psychomotor slowing as well as deficits in attention and executive functions.
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