Management strategies for CLN2 disease Williams, Ruth E., DM, FRCPCH; Adams, Heather R., PhD; Blohm, Martin, MD ...
Pediatric neurology,
04/2017, Letnik:
69
Journal Article
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Abstract CLN2 disease (neuronal ceroid lipofuscinosis type 2) is a rare, autosomal recessive, pediatric-onset, rapidly progressive neurodegenerative lysosomal storage disorder caused by TPP1 enzyme ...deficiency, and is characterized by language delay, seizures, rapid cognitive and motor decline, blindness and early death. No management guidelines exist and there is a paucity of published disease-specific evidence to inform clinical practice, which currently draws upon experience from the field of childhood neurodisability. Twenty-four disease experts were surveyed on CLN2 disease management and a subset met to discuss current practice. Management goals and strategies are consistent among experts globally, and are guided by the principles of pediatric palliative care. Goals and interventions evolve as the disease progresses, with a shift in focus from maintenance of function early in the disease to maintenance of quality of life. A multidisciplinary approach is critical for optimal patient care. This work represents an initial step towards development of consensus-based management guidelines for CLN2 disease.
Background Evidence from existing cohort studies support the prediction of incident coronary heart disease and stroke using 10-year cardiovascular disease (CVD) risk scores and the American Heart ...Association/American Stroke Association’s cardiovascular health (CVH) metric. Methods We included all Jackson Heart Study participants with complete scoring information at the baseline study visit (2000–2004) who had no history of stroke (n=4,140). We used Kaplan-Meier methods to calculate the cumulative incidence of stroke, and used Cox models to estimate hazard ratios and 95% confidence intervals for stroke according to CVD risk and CVH score. We compared the discrimination of the two models according to the Harrell c-index, and plotted predicted versus observed stroke risk calibration plots for each of the two models. Results The median age of the African-American participants was 54.5 years, and 65% were female. The cumulative incidence of stroke increased across worsening categories of CVD risk and CVH. A one-unit increase in CVD risk increased the hazard of stroke (1.07, 1.06-1.08), while each one-unit increase in CVH corresponded to a decreased hazard of stroke (0.76, 0.69-0.83). As evidenced by the c-statistics, the CVH model was less discriminating than the CVD risk model (0.59, 0.55-0.64 versus 0.79, 0.76-0.83). Conclusions Both scores were associated with incident stroke in a dose–response fashion; however, the CVD risk model was more discriminating than the CVH model. The CVH score may still be preferable for its simplicity in application to broad patient populations and public health efforts.
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