The neurobehavioral and pathologic features of Parkinson disease dementia (PDD) are virtually identical to those of dementia with Lewy bodies (DLB), suggesting that they represent different ...phenotypes of the same underlying disease. Both are characterized clinically by a "frontal-subcortical" dementia, fluctuating confusion, and, often, psychotic symptoms. Pathologically they are characterized by disseminated Lewy bodies and multiple transmitter deficits. These dementias with Lewy bodies constitute the second leading cause of dementia after Alzheimer disease (AD), and are thus an important treatment target. No drug has yet been approved for these indications, but treatment options are emerging. This paper addresses the conduct of clinical trials for this indication, including definition of target populations, screening metrics, outcome measures, and clinical trial designs. As the pathophysiology of these cognitive and behavioral changes becomes better understood, symptomatic as well as disease-modifying therapy may become possible, requiring an inclusive and consistent approach to clinical trials in this area.
The best way to initiate dopaminergic therapy for early Parkinson disease remains unclear.
To compare initial treatment with pramipexole vs levodopa in early Parkinson disease, followed by levodopa ...supplementation, with respect to the development of dopaminergic motor complications, other adverse events, and functional and quality-of-life outcomes.
Multicenter, parallel-group, double-blind, randomized controlled trial.
Academic movement disorders clinics at 22 sites in the United States and Canada.
Patients with early Parkinson disease (N = 301) who required dopaminergic therapy to treat emerging disability, enrolled between October 1996 and August 1997 and observed until August 2001.
Subjects were randomly assigned to receive 0.5 mg of pramipexole 3 times per day with levodopa placebo (n = 151) or 25/100 mg of carbidopa/levodopa 3 times per day with pramipexole placebo (n = 150). Dosage was escalated during the first 10 weeks for patients with ongoing disability. Thereafter, investigators were permitted to add open-label levodopa or other antiparkinsonian medications to treat ongoing or emerging disability.
Time to the first occurrence of dopaminergic complications: wearing off, dyskinesias, on-off fluctuations, and freezing; changes in the Unified Parkinson's Disease Rating Scale and quality-of-life scales; and adverse events.
Initial pramipexole treatment resulted in a significant reduction in the risk of developing dyskinesias (24.5% vs 54%; hazard ratio, 0.37; 95% confidence interval CI, 0.25-0.56; P<.001) and wearing off (47% vs 62.7%; hazard ratio, 0.68; 95% CI, 0.49-0.63; P =.02). Initial levodopa treatment resulted in a significant reduction in the risk of freezing (25.3% vs 37.1%; hazard ratio, 1.7; 95% CI, 1.11-2.59; P =.01). By 48 months, the occurrence of disabling dyskinesias was uncommon and did not significantly differ between the 2 groups. The mean improvement in the total Unified Parkinson's Disease Rating Scale score from baseline to 48 months was greater in the levodopa group than in the pramipexole group (2 +/- 15.4 points vs -3.2 +/- 17.3 points, P =.003). Somnolence (36% vs 21%, P =.005) and edema (42% vs 15%, P<.001) were more common in pramipexole-treated subjects than in levodopa-treated subjects. Mean changes in quality-of-life scores did not differ between the groups.
Initial treatment with pramipexole resulted in lower incidences of dyskinesias and wearing off compared with initial treatment with levodopa. Initial treatment with levodopa resulted in lower incidences of freezing, somnolence, and edema and provided for better symptomatic control, as measured by the Unified Parkinson's Disease Rating Scale, compared with initial treatment with pramipexole. Both options resulted in similar quality of life. Levodopa and pramipexole both appear to be reasonable options as initial dopaminergic therapy for Parkinson disease, but they are associated with different efficacy and adverse-effect profiles.
Birth models that work Davis-Floyd, Robbie; Barclay, Lesley; Tritten, Jan ...
2009., 20090307, 2009, 2009-04-06
eBook
This groundbreaking book takes us around the world in search of birth models that work in order to improve the standard of care for mothers and families everywhere. The contributors describe examples ...of maternity services from both developing countries and wealthy industrialized societies that apply the latest scientific evidence to support and facilitate normal physiological birth; deal appropriately with complications; and generate excellent birth outcomes—including psychological satisfaction for the mother. The book concludes with a description of the ideology that underlies all these working models—known internationally as the midwifery model of care.
COMT inhibitors in Parkinson's disease Rivest, J; Barclay, C L; Suchowersky, O
Canadian journal of neurological sciences,
08/1999, Letnik:
26 Suppl 2
Journal Article
Recenzirano
Odprti dostop
The COMT inhibitors, tolcapone and entacapone, are a new class of Parkinson's medications. By inhibiting the enzyme catechol-o-methyl-transferase (COMT), they prevent peripheral degradation of ...levodopa, allowing a higher concentration to cross the blood-brain barrier. Pharmacokinetic studies have shown that both tolcapone and entacapone significantly prolong the elimination half life, and increase the area under the curve of levodopa without increasing C max. Clinical studies with COMT inhibitors have shown benefit in both stable and fluctuating PD patients with improvement in motor function with lower levodopa doses. Fluctuating patients also had increased "on" time and reduced "wearing off". Side effects were most commonly related to increased dopaminergic stimulation. Specific side effects included diarrhea and elevated liver enzymes. The recent reports of three cases of fulminant hepatitis with the use of tolcapone has led many countries to remove this compound from their market. Concerns about a possible class effect should impose close monitoring of liver function tests with the use of any of the nitrocatechols.
Men on trial Barclay, Katie
2018, 20190102, 2019, 2018-11-12
eBook
Men on trial explores how the Irish perform 'the self' within the early nineteenth-century courtroom and its implications for law, society and nation. Drawing on new methodologies from the history of ...emotion, as well as theories of performativity and performative space, it emphasises that manliness was not simply a cultural ideal, but something practised, felt and embodied.Men on trial explores how gender could be a creative dynamic in productions of power. Targeted at scholars in Irish history, law and gender studies, this book argues that justice was not simply determined through weighing evidence, but through weighing men, their bodies, behaviours, and emotions. Moreover, in a context where the processes of justice were publicised in the press for the nation and the world, manliness and its role in the creation of justice became implicated in the making of national identity.Men on trial explores how the Irish perform 'the self' within the early nineteenth-century courtroom and its implications for law, society and nation. Drawing on new methodologies from the history of emotion, as well as theories of performativity and performative space, it emphasises that manliness was not simply a cultural ideal, but something practised, felt and embodied. Men on trial explores how gender could be a creative dynamic in productions of power. Targeted at scholars in Irish history, law and gender studies, this book argues that justice was not simply determined through weighing evidence, but through weighing men, their bodies, behaviours, and emotions. Moreover, in a context where the processes of justice were publicised in the press for the nation and the world, manliness and its role in the creation of justice became implicated in the making of national identity.
Much of the variation in inherited risk of colorectal cancer (CRC) is probably due to combinations of common low risk variants. We conducted a genome-wide association study of 550,000 tag SNPs in 930 ...familial colorectal tumor cases and 960 controls. The most strongly associated SNP (P = 1.72 × 10−7, allelic test) was rs6983267 at 8q24.21. To validate this finding, we genotyped rs6983267 in three additional CRC case-control series (4,361 affected individuals and 3,752 controls; 1,901 affected individuals and 1,079 controls; 1,072 affected individuals and 415 controls) and replicated the association, providing P = 1.27 × 10−14 (allelic test) overall, with odds ratios (ORs) of 1.27 (95% confidence interval (c.i.): 1.16-1.39) and 1.47 (95% c.i.: 1.34-1.62) for heterozygotes and rare homozygotes, respectively. Analyses based on 1,477 individuals with colorectal adenoma and 2,136 controls suggest that susceptibility to CRC is mediated through development of adenomas (OR = 1.21, 95% c.i.: 1.10-1.34; P = 6.89 × 10−5). These data show that common, low-penetrance susceptibility alleles predispose to colorectal neoplasia.
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