Lipid changes with statin treatments vary greatly between individuals for reasons which are largely unknown. This study was performed to examine the genetic determinants of lipid responses to ...rosuvastatin in Chinese patients. A total of 125 polymorphisms in 61 candidate genes from 386 Chinese patients were analyzed for association with the lipid responses to rosuvastatin 10 mg daily. The polymorphisms most highly associated with the low-density lipoprotein cholesterol (LDL-C) response were 421C>A in the ATP-binding cassette G2 gene (P=9.2×10), followed by 18281G>A (V257M) in the flavin-containing monooxygenase 3 gene (P=0.0002), 1421C>G in the lipoprotein lipase gene (P=0.002), and rs4420638 in the apolipoprotein E/C-I/C-IV/C-II gene cluster (P=0.004). Patients with familial hypercholesterolemia had 2.6% smaller reductions in LDL-C compared with patients without familial hypercholesterolemia. This study identified some genetic determinants of LDL-C response to rosuvastatin in Chinese patients, which need to be replicated in other populations.
The genetic bases of many common diseases have been identified through genome-wide association studies in the past decade. However, the application of this approach on public healthcare planning has ...not been well established. Using Macau with population of around 650,000 as a basis, we conducted a pilot study to evaluate the feasibility of population genomic research and its potential on public health decisions. By performing genome-wide SNP genotyping of over a thousand Macau individuals, we evaluated the population genetic risk profiles of 47 non-communicable diseases and traits, as well as two traits associated with influenza infection. We found that for most of the diseases, the genetic risks of Macau population were different from those of Caucasian, but with similar profile with mainland Chinese. We also identified a panel of diseases that Macau population may have a high or elevated genetic risks. This pilot study showed that (1) population genomic study is feasible in Asian regions like Macau; (2) Macau may have different profile of population-based genetic risks than Caucasians, (3) the different prevalence of genetic risk profile indicates the importance of Asian-specific studies for Asian populations; and (4) the results generated may have an impact for going forward healthcare planning.
The performance of a point-of-care device, the OratectXP Oral Fluid Drug Screen Device for Ketamine, was evaluated. The cutoff specification for the device was for ketamine at 15 ng/mL. A total of 72 ...authentic oral fluid samples were collected from volunteers at two local rehabilitation centers for clients with addiction to drugs of abuse. These samples were tested with the device for visual detection of ketamine and also measured by a liquid chromatography isotope-dilution tandem mass spectrometry method for ketamine, norketamine and dehydronorketamine concentrations. Sensitivity of the device was 87.5% when tested by 24 authentic oral fluid samples with ketamine concentrations ≥15 ng/mL. False positive rate of the device was 4.5%. Specificity of the device was 97.9% when tested by 48 authentic oral fluid samples with ketamine concentrations <15 ng/mL. False negative rate of the device was 6%. The overall efficiency of the device was 94%. According to the desirable acceptance criteria proposed by the "Driving Under the Influence of Drugs, Alcohol, and Medicines" project, the performance of the OratectXP was satisfactory and achieved the minimum standard for testing drivers under the influence of drugs. Furthermore, we propose the confirmation cutoff level for oral fluid ketamine to be at 25 ng/mL.
...she was prescribed thyroxine replacement and her TSH was normalised (3.28 mIU/L) by June 2014. ...testing in both patients for FDH targeting exon 7 of the ALB gene (OMIM *103600; Refseq ...NG_009291.1/NM_000477.6/NP_000468.1) showed heterozygous c.725Ggreater thanA p.(Arg242His), a reported pathogenic variant in Chinese.1 Discussion Familial dysalbuminaemic hyperthyroxinaemia is an autosomal dominant condition caused by variants of albumin, the gene product of ALB.2 The prevalence of FDH has been estimated to be 0.01% in Caucasian populations but much higher (1.0%-1.8%) in Hispanic populations.3 The prevalence is uncertain in East Asian populations. ...any previous thyroid function results should be reviewed. For FDH, it is important to note the assay platform used (hinted by the reference intervals provided), as a change of assay from one that is less affected by FDH to one that is prone to interference in FDH may give the clinician a false sense of an acquired condition. ...the TSH level in patien
Cadmium (Cd) and lead (Pb) are toxic elements in our environment. This study is to determine the reference intervals of Cd and Pb in blood and urine from Hong Kong school children and to identify ...their determinants.
A total of 2209 secondary school children and 893 preschool children were recruited. Cd and Pb in blood and urine were measured by inductively-coupled plasma mass spectrometry.
Blood Cd was affected by age, smoking and residential district, while urine Cd was influenced by age and blood Cd. Blood Cd was positively correlated with smoking as confirmed by urinary cotinine (rho=0.183, p<0.001, n=2074). Blood Pb was dependent on gender and residential district, while urinary Pb was dependent on gender and blood Pb. Students from schools of lower academic grading had higher blood Cd and Pb than those from higher academic grading schools (p<0.001, respectively). Urinary albumin was positively associated with urinary Cd and Pb.
Using a non-occupationallyexposed population, the reference ranges are: blood Cd <21.9nmol/L for smokers and <8.8nmol/L for non-smokers, and blood Pb <203.8 nmol/L. Reference intervals for urinary Cd and Pb are also reported.
Background
Parameter uncertainty in EQ-5D-5L value sets often exceeds the instrument’s minimum important difference, yet this is routinely ignored. Multiple imputation (MI) accounts for parameter ...uncertainty in the value set; however, no valuation study has implemented this methodology. Our objective was to create a Canadian MI value set for the EQ-5D-5L, thus enabling users to account for parameter uncertainty in the value set.
Methods
Using the Canadian EQ-5D-5L valuation study (N = 1,073), we first refit the original model followed by models with state-level misspecification. Models were compared based on the adequacy of 95% credible interval (CrI) coverage for out-of-sample predictions. Using the best-fitting model, we took 100 draws from the posterior distribution to create 100 imputed value sets. We examined how much the standard error of the estimated mean health utilities increased after accounting for parameter uncertainty in the value set by using the MI and original value sets to score 2 data sets: 1) a sample of 1,208 individuals from the Canadian general public and 2) a sample of 401 women with breast cancer.
Results
The selected model with state-level misspecification outperformed the original model (95% CrI coverage: 94.2% v. 11.6%). We observed wider standard errors for the estimated mean utilities on using the MI value set for both the Canadian general public (MI: 0.0091; original: 0.0035) and patients with breast cancer (MI: 0.0169; original: 0.0066).
Discussion and Conclusions
We provide 1) the first MI value sets for the EQ-5D-5L and 2) code to construct MI value sets while accounting for state-level model misspecification. Our study suggests that ignoring parameter uncertainty in value sets leads to falsely narrow SEs.
Highlights
Value sets for health state utility instruments are estimated subject to parameter uncertainty; this parameter uncertainty may exceed the minimum important difference of the instrument, yet it is not fully captured using current methods.
This study creates the first multiply imputed value set for a multiattribute utility instrument, the EQ-5D-5L, to fully capture this parameter uncertainty.
We apply the multiply imputed value set to 2 data sets from 1) the Canadian general public and 2) women with invasive breast cancer.
Scoring the EQ-5D-5L using a multiply imputed value set led to wider standard error estimates, suggesting that the current practice of ignoring parameter uncertainty in the value set leads to falsely low standard errors.
Our work will be of interest to methodologists and developers of the EQ-5D-5L and users of the EQ-5D-5L, such as health economists, researchers, and policy makers.
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