Predictive value of functional disability scales among stroke survivors: A long-term mortality evaluation in a Brazilian stroke cohort.

OBJECTIVE: To assess the influence of two functional scales- Modified Rankin Scale (m-RS) and Modified Katz Index (m-Katz Index) on long-term mortality in a stroke cohort. MATERIAL AND METHODS: Among 760 stroke survivors (median age: 66 (IQR:56-75), 56.4 % women) m-Katz Index and m-RS scales applied at 1 and 6 months after stroke, were investigated in relation to 12-years of all-cause mortality. Kaplan-Meier survival curves were computed, and time-varying covariate Cox regression models were fitted to calculate hazard ratios (HRs) with 95 % confidence intervals (CIs) in all sample and by sex. The prognostic ability of the fitted models was computed for each model by six different measures. RESULTS: After 12 years of follow-up (median survival time: 7.3 years), 311 participants died. Overall survival curves show lower survival rates among those with the highest levels of disability/dependence (all log-rank p-values <0.0001). These findings were confirmed in all regression models for both sexes, particularly in men who had higher levels of dependence on Activities of Daily Living (ADLs) by m-Katz Index and severe disability by m-RS and presented the highest HR of dying (HR: 3.34 (95 %CI: 2.27-4.92) and HR: 4.94 (95 % CI: 3.15-7.75), respectively). CONCLUSIONS: Both the m-Katz Index and the m-RS scale were good predictors of long-term mortality, which is of importance for guiding the functional rehabilitation of stroke patients. Besides, high levels of disability and dependence were implicated with high mortality risks, regardless of sex.

Association between serum alkaline phosphatase and C-reactive protein in the United States National Health and Nutrition Examination Survey 2005-2006.

BACKGROUND: Alkaline phosphatase (ALP) is a widely used marker for skeletal and hepatobiliary disorders, but its activity is also increased in atherosclerosis and peripheral vascular disease. It is an inflammatory marker like C-reactive protein (CRP). We therefore analyzed its relationship with CRP in the United States National Health and Nutrition Examination Survey (NHANES) 2005-2006. METHODS: The analysis included 4155 men and non-pregnant women over the age of 20 years. The relationship between log-transformed ALP and plasma CRP was analyzed using univariate and multivariate models. RESULTS: ALP activity was significantly correlated with age, waist circumference, body mass index, blood pressure, exercise, alcohol, triglycerides, and other liver enzymes after adjusting for age, gender and ethnicity (p<0.001). ALP was significantly associated with a higher frequency of cardiovascular disease (p=0.02), hypertension (p=0.01) hypercholesterolemia (p=0.04), and diabetes (p=0.02). Compared to the lowest quartile of ALP, the adjusted odds ratio (OR) associated with the highest quartile were 1.9 [95% confidence intervals (CI) 1.1-3.5], 1.6 (95% CI 1.0-2.5), 1.5 (95% CI 1.1-2.1) and 1.7 (95% CI 1.0-2.4) for cardiovascular disease, hypertension, hypercholesterolemia, and diabetes, respectively. In multivariate analysis, log ALP was an independent predictor of log CRP (p=1.0x10(-6)). A multivariate model that included log ALP, ethnicity, glycohemoglobin, waist circumference, albumin, apolipoprotein B, gamma-glutamyltransferase and uric acid explained 40% of the variance in log CRP. CONCLUSIONS: ALP is a marker of cardiometabolic risk, but it needs to be tested as part of a multivariate model in prospective studies.

Pharmacokinetic profile of the somatostatin analogue lanreotide in individuals with chronic hepatic insufficiency.

BACKGROUND AND OBJECTIVES: The somatostatin analogue lanreotide is indicated for the treatment of acromegaly and to relieve the symptoms of neuroendocrine tumours. The objective of the present study was to compare the pharmacokinetic profile and safety of intravenous lanreotide in healthy volunteers and individuals with hepatic impairment. METHODS: Immediate-release lanreotide was administered at 7 microg/kg during a 20-minute intravenous infusion. Blood samples were collected over 24 hours and lanreotide serum levels determined by radioimmunoassay. Pharmacokinetic parameters were estimated by non-compartmental analyses. RESULTS: Two study centres recruited 53 individuals. Study A comprised 10 individuals with hepatic insufficiency Child-Pugh grade A (mild), 7 with grade B (moderate) and 12 healthy volunteers - all Caucasian. Study B comprised 4 individuals with hepatic insufficiency Child-Pugh grade A, 6 with grade B, 2 with grade C (severe) and 12 healthy volunteers - all Chinese. All participants were included in the safety analysis. The pharmacokinetic analysis included all participants from study B, but only 12 with hepatic impairment and 11 healthy volunteers from study A. Combined analysis of both studies showed an increased serum elimination half-life (57%; p < or = 0.001), mean residence time (53%; p < or = 0.001) and volume of distribution (at steady state, 57%; at terminal disposition phase, 64%; both p < or = 0.001) in individuals with mild hepatic insufficiency compared with healthy volunteers. These differences were more pronounced in individuals with moderate-to-severe hepatic insufficiency compared with healthy volunteers; additionally, the area under the serum concentration-time curve from time zero to infinity (AUC(infinity)) was increased (23%; p < or = 0.05) and clearance (CL) decreased (19%; p < or = 0.05) compared with healthy volunteers. The peak serum concentration of lanreotide tended to be lower in individuals with hepatic insufficiency than in healthy volunteers (statistically non-significant). There were no pharmacokinetic differences between the two groups of healthy volunteers. Lanreotide was well tolerated with only two mild adverse events that were considered to be possibly related to treatment (both nausea and headache with either vomiting or dizziness). There were no clinically relevant changes in laboratory parameters or vital signs during the study. CONCLUSION: The pharmacokinetic profile of lanreotide depends on the severity of hepatic insufficiency with CL and AUC(infinity), which are only slightly altered with moderate-to-severe insufficiency. The changes in exposure do not, however, require dosage adjustment. Moreover, lanreotide is usually given as a prolonged-release microparticle or Autogel formulation, and terminal half-life and serum concentrations depend on the release properties of the formulation. Dosing is also adapted for each patient, based on therapeutic response. Thus, hepatic insufficiency does not require additional dosage adjustments.

A genome-wide linkage and association scan reveals novel loci for hypertension and blood pressure traits.

Hypertension is caused by the interaction of environmental and genetic factors. The condition which is very common, with about 18% of the adult Hong Kong Chinese population and over 50% of older individuals affected, is responsible for considerable morbidity and mortality. To identify genes influencing hypertension and blood pressure, we conducted a combined linkage and association study using over 500,000 single nucleotide polymorphisms (SNPs) genotyped in 328 individuals comprising 111 hypertensive probands and their siblings. Using a family-based association test, we found an association with SNPs on chromosome 5q31.1 (rs6596140; P<9 × 10(-8)) for hypertension. One candidate gene, PDC, was replicated, with rs3817586 on 1q31.1 attaining P = 2.5 × 10(-4) and 2.9 × 10(-5) in the within-family tests for DBP and MAP, respectively. We also identified regions of significant linkage for systolic and diastolic blood pressure on chromosomes 2q22 and 5p13, respectively. Further family-based association analysis of the linkage peak on chromosome 5 yielded a significant association (rs1605685, P<7 × 10(-5)) for DBP. This is the first combined linkage and association study of hypertension and its related quantitative traits with Chinese ancestry. The associations reported here account for the action of common variants whereas the discovery of linkage regions may point to novel targets for rare variant screening.

The use of waist-to-stature ratio to identify underweight and overweight in adolescents.

OBJECTIVES: To examine the percentile distribution of waist-to-stature ratio (WSR) and derive WSR cut-offs for underweight, normal weight, and overweight based on the International Obesity Task Force (IOTF) and local weight-for-height standards in Hong Kong Chinese adolescents. METHODS: In the Hong Kong Student Obesity Surveillance project in 2006-2007, height, weight and waist circumference of 13 568 (40.3% boys) Chinese adolescents aged 12-18 were measured. Smoothed percentile distributions of WSR by age and sex were examined using Lambda-Mu-Sigma (LMS) regression. The sex- and age-specific WSR values corresponding to underweight and overweight, as defined by the IOTF and local weight-for-height standards, were determined using receiver operating characteristic curves. RESULTS: The percentile values of WSR were stable across age in both sexes. In general, WSR values of 0.40 and 0.46 corresponded to underweight and overweight, respectively, as defined by both IOTF and local weight-for-height standards. As a reference for normal weight status, the median weight-for-height values corresponded to a WSR value of 0.42 in most sex-age subgroups. CONCLUSION: Sex and age independent WSR cut-off values for underweight, median weight and overweight in Hong Kong adolescents were identified. WSR is potentially a practical indicator for adolescents to monitor their weight status.