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Biomedical subjects

Peter Barker

Publications and source records attributed to Peter Barker.

10 recordsLinked to original sources

Quality of life of postmenopausal women in the ATAC ("Arimidex", tamoxifen, alone or in combination) trial after completion of 5 years' adjuvant treatment for early breast cancer.

The impact of treatment on health-related quality of life (HRQoL) is an important consideration in the adjuvant treatment of operable breast cancer. Here we report mature HRQoL outcomes from the ATAC trial, comparing anastrozole with tamoxifen as primary adjuvant therapy for postmenopausal women with localized breast cancer. Patients completed the Functional Assessment of Cancer Therapy-Breast (FACT-B) questionnaire plus endocrine subscale (ES) at baseline, 3 and 6 months, and every 6 months thereafter. Baseline characteristics in the HRQoL sub-protocol were well balanced between the anastrozole (n = 335) and tamoxifen (n = 347) groups in the primary analysis population. As with previously published results at 2 years, there was no statistically significant difference in the Trial Outcome Index of the FACT-B, the primary endpoint of the study, between treatments at 5 years. There were no statistically significant differences between treatment groups in ES total scores. Consistent with the 2-year analysis, there were differences between treatment groups in patient-reported side effects: diarrhea (anastrozole 3.1% vs. tamoxifen 1.3%), vaginal dryness (18.5% vs. 9.1%), diminished libido (34.0% vs. 26.1%), and dyspareunia (17.3% vs. 8.1%) were significantly more frequent with anastrozole compared to tamoxifen. Dizziness (3.1% vs. 5.4%) and vaginal discharge (1.2% vs. 5.2%) were significantly less frequent with anastrozole compared to tamoxifen. In this, the first report of HRQoL over 5 years of initial adjuvant therapy with an aromatase inhibitor, we conclude that anastrozole and tamoxifen had similar impacts on HRQoL, which was maintained or slightly improved during the treatment period for both groups.

Anastrozole↗

Patients with diffusion-perfusion mismatch on magnetic resonance imaging 48 hours or more after stroke symptom onset: clinical and imaging features.

BACKGROUND: Abnormalities in diffusion-weighted (DWI) and perfusion-weighted (PWI) magnetic resonance imaging (MRI) are thought to reflect the presence of brain tissue at risk for ischemic stroke. Many patients with acute ischemic stroke have a mismatch pattern in which the PWI volume is larger than the DWI lesion. This mismatch typically resolves over 24-48 hours. Little is known about the presence of DWI-PWI mismatch in later stages of stroke. METHODS: This is a retrospective study of 122 patients admitted with a diagnosis of acute ischemic stroke who had DWI and PWI abnormalities on studies performed within 7 days of onset of symptoms. Patients were divided into two groups: those with MRI performed <48 hours and those with MRI performed >or=48 hours from onset of symptoms. RESULTS: Among 42 patients with MRI performed >or=48 hours after onset of stroke symptoms, 15 of 42 (36%) showed a mismatch pattern, compared to 45 of 80 (56%) in the <48 hours group (P < 0.05). Most of the patients in the >or=48 hours group with mismatch had large artery occlusive disease and many had neurological fluctuations. A subset of these patients were treated with induced hypertension and showed clinical improvement. CONCLUSIONS: Some patients have persistent DWI-PWI mismatch up to several days after stroke onset. Further studies are needed to determine if these patients should be candidates for reperfusion therapy.

Brain↗

The roles of the "visual word form area" in reading.

Activation of the left midfusiform gyrus in response to reading words and pseudowords is such a reliable finding in functional imaging that this region has been called "the visual word form area" (VWFA). However, this label has recently been challenged, because activation in VWFA is also observed in other lexical tasks. We evaluated whether VWFA is necessary, sufficient, or specialized for reading by examining how frequently acute lesions in VWFA disrupt tasks that require access to written word forms versus other lexical tasks. We administered lexical tasks with spoken and written input and output, and identified damage or dysfunction of VWFA and other regions of interest (ROI) on diffusion- and perfusion-weighted imaging (DWI and PWI) in 80 patients within 24 h of onset of acute left ischemic stroke. Associations between abnormalities in each region of interest and impairment on lexical tasks were evaluated with chi-squared tests. Damage or dysfunction of VWFA was not significantly associated with impairment of written word comprehension or lexical decision, but was significantly associated with impairment on all tasks requiring lexical output: oral reading and oral naming (visual or tactile input), and written naming. We account for these results and results from functional imaging by proposing that the left midfusiform gyrus normally has two roles in reading: (1) computation of location- and modality-independent grapheme sequences from written word stimuli, and (2) a modality-independent stage of lexical processing that links modality-specific input and output representations. VWFA is not necessary for the former because the right homologue of VWFA can immediately assume this role.

Adult↗

Progressive cavitating leukoencephalopathy: a novel childhood disease.

We report 19 patients with a previously undelineated neurodegenerative syndrome characterized by episodic acute onset of irritability or neurological deficits between 2 months and 3.5 years of age, followed by steady or intermittent clinical deterioration. Seven children died between 11 months and 14 years of age. Cranial magnetic resonance imaging (MRI) shows patchy leukoencephalopathy with cavities, and vascular permeability, in actively affected regions. Early lesions affect corpus callosum and centrum semiovale, with or without cerebellar or cord involvement. After repeated episodes, areas of tissue loss coalesce with older lesions to become larger cystic regions in brain or spinal cord. Diffuse spasticity, dementia, vegetative state, or death ensues. Gray matter is spared until late in the course. In some, incomplete clinical or MRI recovery occurs after episodes. The clinical course varies from rapid deterioration to prolonged periods of stability that are unpredictable by clinical or MRI changes. Elevated levels of lactate in brain, blood, and cerebrospinal fluid, abnormal urine organic acids, and changes in muscle respiratory chain enzymes are present but inconsistent, without identifiable mitochondrial DNA mutations or deletions. Pathological studies show severe loss of myelin sparing U-fibers, axonal disruption, and cavitary lesions without inflammation. Familial occurrence and consanguinity suggest autosomal recessive inheritance of this distinct entity.

Adolescent↗

Small sample bias in the gamma frailty model for univariate survival.

The gamma frailty model is a natural extension of the Cox proportional hazards model in survival analysis. Because the frailties are unobserved, an E-M approach is often used for estimation. Such an approach is shown to lead to finite sample underestimation of the frailty variance, with the corresponding regression parameters also being underestimated as a result. For the univariate case, we investigate the source of the bias with simulation studies and a complete enumeration. The rank-based E-M approach, we note, only identifies frailty through the order in which failures occur; additional frailty which is evident in the survival times is ignored, and as a result the frailty variance is underestimated. An adaption of the standard E-M approach is suggested, whereby the non-parametric Breslow estimate is replaced by a local likelihood formulation for the baseline hazard which allows the survival times themselves to enter the model. Simulations demonstrate that this approach substantially reduces the bias, even at small sample sizes. The method developed is applied to survival data from the North West Regional Leukaemia Register.

Acute Disease↗

Modelling converging hazards in survival analysis.

The Cox proportional hazards model has become the standard model for survival analysis. It is often seen as the null model in that "... explicit excuses are now needed to use different models" (Keiding, Proceedings of the XIXth International Biometric Conference, Cape Town, 1998). However, converging hazards also occur frequently in survival analysis. The Burr model, which may be derived as the marginal from a gamma frailty model, is one commonly used tool to model converging hazards. We outline this approach and introduce a mixed model which extends the Burr model and allows for both proportional and converging hazards. Although a semi-parametric model in its own right, we demonstrate how the mixed model can be derived via a gamma frailty interpretation, suggesting an E-M fitting procedure. We illustrate the modelling techniques using data on survival of hospice patients.

Algorithms↗

Educational needs of rural and remote Australian non-specialist medical practitioners for obstetric ultrasound.

OBJECTIVE: To determine the educational needs of rural and remote non-specialist Australian doctors for obstetric ultrasound. DESIGN: Survey design. SETTING: The study surveyed rural and remote doctors practising in a variety of settings including general practice, rural hospitals, Aboriginal communities and flying doctor organisations throughout Australia. SUBJECTS: Subjects included 314 solo and group practice rural general practitioners, rural hospital medical superintendents, senior medical officers, Aboriginal community controlled health service doctors, flying doctors, rural locums, registrars and two rural obstetricians. A total of 55% of the subjects were general practitioners in group practice. Respondents included 68 (22%) women and 246 (78%) men. RESULTS: The response rate was 32%. The highest priority areas of need for education included detecting foetal abnormalities and anomalies (19.1%), basic routine ultrasonography (17.17%), placental position (17.17%), dating (17.17%), foetal viability (12.88%) and morphology scan (12.26%). The main areas where doctors stated they lacked confidence included detecting foetal abnormalities (29.09%), basic routine ultrasonography (including machine use), such as, carrying out and interpreting obstetric ultrasound scans (27.27%), morphology scans (16.36%) and placental position (14.54%). CONCLUSION: The study showed there was a large unmet need for education in obstetric ultrasound among rural and remote non-specialist doctors. Information from the needs assessment was used to develop the Australian College of Rural and Remote Medicine national obstetric ultrasound professional development program. WHAT IS ALREADY KNOWN: The authors could not find any published work on the educational needs of Australian non-specialist rural and remote doctors for obstetric ultrasound. There is research about the outcome of obstetric ultrasound education for urban family physicians in the USA, but no information about rural doctors' educational needs or education outcomes. The study needed to be done so that obstetric ultrasound professional development program of the Australian College of Rural and Remote Medicine could be based on the real needs of the target group. WHAT THIS PAPER ADDS: As a result of this research, there is now information on the educational needs of rural and remote Australian non-specialist medical practitioners that can be used by education providers to develop quality education programs in obstetric ultrasound.

Adult↗

Standard reference material for Her2 testing: report of a National Institute of Standards and Technology-sponsored Consensus Workshop.

A workshop was sponsored by the National Institute of Standards and Technology, the Cancer Diagnosis Program of the National Cancer Institute, the Food and Drug Administration, and the College of American Pathologists to address the need for a reference material for Her2 gene protein testing. It was agreed that such a standard was desirable and necessary to ensure the reliability of Her2 testing to qualify patients for trastuzumab therapy. Two standards consisting of well characterized cell lines will be produced, 1 that will be a National Institute of Standards and Technology-certifiable standard, and 1 that will be a commercially developed standard for use in all Her2 testing. It was also agreed that all Her2 testing must be performed on samples fixed only in 10% buffered formalin, as specified in the Food and Drug Administration-approved testing methods. Participants agreed to plan strategies to educate pathologists, clinicians, and laboratories about the need and use of such a standard. A National Committee for Clinical Laboratory Standards guideline for the use of the standard reference material will be created to facilitate this process.

Cell Line, Tumor↗