Sunnybrook Health Sciences Centre

About: Sunnybrook Health Sciences Centre is a healthcare organization based out in Toronto, Ontario, Canada. It is known for research contribution in the topics: Population & Medicine. The organization has 7689 authors who have published 15236 publications receiving 523019 citations. The organization is also known as: Sunnybrook.

Clinical, imaging, and pathological heterogeneity of the Alzheimer's disease syndrome

Abstract: With increasing knowledge of clinical in vivo biomarkers and the pathological intricacies of Alzheimer's disease (AD), nosology is evolving. Harmonized consensus criteria that emphasize prototypic illness continue to develop to achieve diagnostic clarity for treatment decisions and clinical trials. However, it is clear that AD is clinically heterogeneous in presentation and progression, demonstrating variable topographic distributions of atrophy and hypometabolism/hypoperfusion. AD furthermore often keeps company with other conditions that may further nuance clinical expression, such as synucleinopathy exacerbating executive and visuospatial dysfunction and vascular pathologies (particularly small vessel disease that is increasingly ubiquitous with human aging) accentuating frontal-dysexecutive symptomatology. That some of these atypical clinical patterns recur may imply the existence of distinct AD variants. For example, focal temporal lobe dysfunction is associated with a pure amnestic syndrome, very slow decline, with atrophy and neurofibrillary tangles limited largely to the medial temporal region including the entorhinal cortex. Left parietal atrophy and/or hypometabolism/hypoperfusion are associated with language symptoms, younger age of onset, and faster rate of decline - a potential 'language variant' of AD. Conversely, the same pattern but predominantly affecting the right parietal lobe is associated with a similar syndrome but with visuospatial symptoms replacing impaired language function. Finally, the extremely rare frontal variant is associated with executive dysfunction out of keeping with degree of memory decline and may have prominent behavioural symptoms. Genotypic differences may underlie some of these subtypes; for example, absence of apolipoprotein E e4 is often associated with atypicality in younger onset AD. Understanding the mechanisms behind this variability merits further investigation, informed by recent advances in imaging techniques, biomarker assays, and quantitative pathological methods, in conjunction with standardized clinical, functional, neuropsychological and neurobehavioral evaluations. Such an understanding is needed to facilitate 'personalized AD medicine', and eventually allow for clinical trials targeting specific AD subtypes. Although the focus legitimately remains on prototypic illness, continuing efforts to develop disease-modifying therapies should not exclude the rarer AD subtypes and common comorbid presentations, as is currently often the case. Only by treating them as well can we address the full burden of this devastating dementia syndrome.

Clinical Utility of an Instrument Assessing Migraine Disability: The Migraine Disability Assessment (MIDAS) Questionnaire

Abstract: Objective.—We evaluated the agreement between Migraine Disability Assessment (MIDAS) scores and independent physician judgments about pain, disability, and treatment needs based on patient medical histories. Background.—The MIDAS questionnaire measures headache-related disability as lost time due to headache from paid work or school, household work, and nonwork activities. Methods.—Twelve histories from patients with migraine were presented to 49 primary and specialty care physicians unaware of the MIDAS scores. Physicians graded each patient for pain level (mild, moderate, or severe), level of disability (none, mild, moderate, or severe), and need for medical care (from 0 [lowest] to 100 [highest]). Physicians also identified MIDAS scores they associated with different degrees of disability and with the urgency to prescribe an effective treatment during the first consultation. Results.—The physicians' perceptions of the need for medical care based on medical histories correlated with the MIDAS score (r = .69). Estimates of pain and disability by physicians were directly correlated with increasing MIDAS scores. Using the physicians' clinical judgments, the overall MIDAS score was categorized into four grades of increasing severity. Conclusions.—Scores on the MIDAS are highly correlated with physician judgments regarding patients' pain, disability, and need for medical care. These findings support the potential utility of the MIDAS questionnaire in clinical practice.

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With >= 2 HER2-Directed Regimens: Phase III NALA Trial

Abstract: PURPOSENALA (ClinicalTrials.gov identifier: NCT01808573) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capec...