Analysis of response to enteral infusion of levodopa in patients with Parkinson's disease

Objective: We present a new evaluation of levodopa plasma concentrations and clinical effects during duodenal infusion of a levodopa/carbidopa gel (Duodopa ) in 12 patients with advanced Parkinson s disease (PD), from a study reported previously (Nyholm et al, Clin Neuropharmacol 2003; 26(3): 156-163). One objective was to investigate in what state of PD we can see the greatest benefits with infusion compared with corresponding oral treatment (Sinemet CR). Another objective was to identify fluctuating response to levodopa and correlate to variables related to disease progression. Methods: We have computed mean absolute error (MAE) and mean squared error (MSE) for the clinical rating from -3 (severe parkinsonism) to +3 (severe dyskinesia) as measures of the clinical state over the treatment periods of the study. Standard deviation (SD) of the rating was used as a measure of response fluctuations. Linear regression and visual inspection of graphs were used to estimate relationships between these measures and variables related to disease progression such as years on levodopa (YLD) or unified PD rating scale part II (UPDRS II).Results: We found that MAE for infusion had a strong linear correlation to YLD (r2=0.80) while the corresponding relation for oral treatment looked more sigmoid, particularly for the more advanced patients (YLD>18).

Response process and test-retest reliability of the Context Assessment for Community Health tool in Vietnam

BACKGROUND: The recently developed Context Assessment for Community Health (COACH) tool aims to measure aspects of the local healthcare context perceived to influence knowledge translation in low- and middle-income countries. The tool measures eight dimensions (organizational resources, community engagement, monitoring services for action, sources of knowledge, commitment to work, work culture, leadership, and informal payment) through 49 items. OBJECTIVE: The study aimed to explore the understanding and stability of the COACH tool among health providers in Vietnam. DESIGNS: To investigate the response process, think-aloud interviews were undertaken with five community health workers, six nurses and midwives, and five physicians. Identified problems were classified according to Conrad and Blair's taxonomy and grouped according to an estimation of the magnitude of the problem's effect on the response data. Further, the stability of the tool was examined using a test-retest survey among 77 respondents. The reliability was analyzed for items (intraclass correlation coefficient (ICC) and percent agreement) and dimensions (ICC and Bland-Altman plots). RESULTS: In general, the think-aloud interviews revealed that the COACH tool was perceived as clear, well organized, and easy to answer. Most items were understood as intended. However, seven prominent problems in the items were identified and the content of three dimensions was perceived to be of a sensitive nature. In the test-retest survey, two-thirds of the items and seven of eight dimensions were found to have an ICC agreement ranging from moderate to substantial (0.5-0.7), demonstrating that the instrument has an acceptable level of stability. CONCLUSIONS: This study provides evidence that the Vietnamese translation of the COACH tool is generally perceived to be clear and easy to understand and has acceptable stability. There is, however, a need to rephrase and add generic examples to clarify some items and to further review items with low ICC.

Perfectionist Philosophy as a (an Untaken) Way of Life

I am honored to respond to Paul Guyer’s elaboration on the role of examples of perfectionism in Cavell’s and Kant’s philosophies. Guyer’s appeal to Kant’s notion of freedom opens the way for suggestive readings of Cavell’s work on moral perfectionism but also, as I will show, for controversy. There are salient aspects of both Kant’s and Cavell’s philosophy that are crucial to understanding perfectionism and, let me call it, perfectionist education, that I wish to emphasize in response to Guyer. In responding to Guyer’s text, I shall do three things. First, I shall explain why I think it is misleading to speak of Cavell’s view that moral perfectionism is involved in a struggle to make oneself intelligible to oneself and others in terms of necessary and sufficient conditions for moral perfection. Rather, I will suggest that the constant work on oneself that is at the core of Cavell’s moral perfectionism is a constant work for intelligibility. Second, I shall recall a feature of Cavell’s perfectionism that Guyer does not explicitly speak of: the idea that perfectionism is a theme, “outlook or dimension of thought embodied and developed in a set of texts.” Or, as Cavell goes on to say, “there is a place in mind where good books are in conversation. … [W]hat they often talk about … is how they can be, or sound, so much better than the people that compose them.” This involves what I would call a perfectionist conception of the history of philosophy and the kinds of texts we take to belong to such history. Third, I shall sketch out how the struggle for intelligibility and a perfectionist view of engagement with texts and philosophy can lead to a view of philosophy as a form of education in itself. In concluding these three “criticisms,” I reach a position that I think is quite close to Guyer’s, but with a slightly shifted emphasis on what it means to read Kant and Cavell from a perfectionist point of view.