Assessing the preparedness and future-readiness of Malaysian community pharmacists in Klang Valley regarding the use of medical marijuana.

BACKGROUND: This study investigated community pharmacists' level of knowledge and attitude towards medical marijuana and its association with sociodemographic characteristics. METHODS: A cross-sectional study was conducted from 21 February 2022 to 15 November 2022. Community pharmacists working in Klang Valley were given a self-administered questionnaire. This survey instrument facilitated the collection of information about their sociodemographic attributes, training background, and knowledge and attitude concerning medical marijuana. Through rigorous analysis of the accumulated data, discernible factors correlating with the levels of knowledge and attitudes surrounding medical marijuana were identified. RESULTS: The majority (n=149, 53.8%) of participants had low knowledge of medical marijuana. Participants with lower knowledge of medical marijuana tend to have a negative attitude toward medical marijuana. Besides that, male participants showed higher knowledge of medical marijuana than female participants. Furthermore, it was found that atheists had the most negative attitude among other religions toward medical marijuana. CONCLUSION: Most community pharmacists in Malaysia lack sufficient knowledge about medical marijuana. This indicates that Malaysian pharmacists are not future-ready and need to equip themselves with adequate knowledge of the indications and adverse effects of medical marijuana if it is to be legalised one day. Thus, there is a need for improved training and education of pharmacists around cannabis-based medicines.

Case report: Aortoesophageal fistula-an extremely rare but life-threatening cardiovascular cause of hematemesis.

Aortoesophageal fistula (AEF) is an extremely rare cardiovascular etiology of hematemesis and upper gastrointestinal bleeding. As such, its recognition and diagnosis are challenging and may be delayed when such patients present to the emergency department (ED). Without timely surgical intervention, AEF is almost always fatal. Awareness of AEF as a possible diagnosis and consequently early identification of these patients presenting to the ED are therefore crucial in optimizing clinical outcomes. We report a 45-year-old male presenting to the ED with the classical triad of an AEF (Chiari's triad)-midthoracic pain or dysphagia, a sentinel episode of minor hematemesis, then massive hematemesis with risk of exsanguination. The case report highlights the importance of considering the differential diagnosis of AEF when evaluating patients presenting to the ED with hematemesis, especially if they have predisposing risk factors such as prior aortic or esophageal surgeries, aortic aneurysms, or thoracic malignancies. Patients suspected of having AEF should be prioritized for early computed tomography angiography to expedite diagnosis and treatment.

A robust association test with multiple genetic variants and covariates.

Due to the advancement of genome sequencing techniques, a great stride has been made in exome sequencing such that the association study between disease and genetic variants has become feasible. Some powerful and well-known association tests have been proposed to test the association between a group of genes and the disease of interest. However, some challenges still remain, in particular, many factors can affect the performance of testing power, e.g., the sample size, the number of causal and non-causal variants, and direction of the effect of causal variants. Recently, a powerful test, called TREM , is derived based on a random effects model. TREM has the advantages of being less sensitive to the inclusion of non-causal rare variants or low effect common variants or the presence of missing genotypes. However, the testing power of TREM can be low when a portion of causal variants has effects in opposite directions. To improve the drawback of TREM , we propose a novel test, called TROB , which keeps the advantages of TREM and is more robust than TREM in terms of having adequate power in the case of variants with opposite directions of effect. Simulation results show that TROB has a stable type I error rate and outperforms TREM when the proportion of risk variants decreases to a certain level and its advantage over TREM increases as the proportion decreases. Furthermore, TROB outperforms several other competing tests in most scenarios. The proposed methodology is illustrated using the Shanghai Breast Cancer Study.

Synthesis and Biological Evaluation of CF3 Se-Substituted α-Amino Acid Derivatives.

Several CF3 Se-substituted α-amino acid derivatives, such as (R)-2-amino-3-((trifluoromethyl)selanyl)propanoates (5 a/6 a), (S)-2-amino-4-((trifluoromethyl)selanyl)butanoates (5 b/6 b), (2R,3R)-2-amino-3-((trifluoromethyl)selanyl)butanoates (5 c/6 c), (R)-2-((S)-2-amino-3-phenylpropanamido)-3-((trifluoromethyl)selanyl)propanoates (11 a/12 a), and (R)-2-(2-aminoacetamido)-3-((trifluoromethyl)selanyl)propanoates (11 b/12 b), were readily synthesized from natural amino acids and [Me4 N][SeCF3 ]. The primary in vitro cytotoxicity assays revealed that compounds 6 a, 11 a and 12 a were more effective cell growth inhibitors than the other tested CF3 Se-substituted derivatives towards MCF-7, HCT116, and SK-OV-3 cells, with their IC50 values being less than 10 µM for MCF-7 and HCT116 cells. This study indicated the potentials of CF3 Se moiety as a pharmaceutically relevant group in the design and synthesis of novel biologically active molecules.

Left Ventricular Function and Myocardial Triglyceride Content on 3T Cardiac MR Predict Major Cardiovascular Adverse Events and Readmission in Patients Hospitalized with Acute Heart Failure.

BACKGROUND: This prospective study was designed to investigate whether myocardial triglyceride (TG) content from proton magnetic resonance spectroscopy (MRS) and left ventricular (LV) function parameters from cardiovascular magnetic resonance imaging (CMR) can serve as imaging biomarkers in predicting future major cardiovascular adverse events (MACE) and readmission in patients who had been hospitalized for acute heart failure (HF). METHODS: Patients who were discharged after hospitalization for acute HF were prospectively enrolled. On a 3.0 T MR scanner, myocardial TG contents were measured using MRS, and LV parameters (function and mass) were evaluated using cine. The occurrence of MACE and the HF-related readmission served as the endpoints. Independent predictors were identified using univariate and multivariable Cox proportional hazard regression analyses. RESULTS: A total of 133 patients (mean age, 52.4 years) were enrolled. The mean duration of follow-up in surviving patients was 775 days. Baseline LV functional parameters-including ejection fraction, LV end-diastolic volume, LV end-diastolic volume index (LVEDVI), and LV end-systolic volume (p < 0.0001 for all), and myocardial mass (p = 0.010)-were significantly associated with MACE. Multivariable analysis revealed that LVEDVI was the independent predictor for MACE, while myocardial mass was the independent predictor for 3- and 12-month readmission. Myocardial TG content (lipid resonances δ 1.6 ppm) was significantly associated with readmission in patients with ischemic heart disease. CONCLUSIONS: LVEDVI and myocardial mass are potential imaging biomarkers that independently predict MACE and readmission, respectively, in patients discharged after hospitalization for acute HF. Myocardial TG predicts readmission in patients with a history of ischemic heart disease.

Accuracy of neutrophil CD64 expression in diagnosing infection in patients with autoimmune diseases: a meta-analysis.

We aimed to systematically evaluate the accuracy of nCD64 in diagnosing infection in patients with autoimmune diseases. Studies were searched in PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Wanfang, and Chongqing VIP databases up to October 2018. There was no restriction for language and age. Prospective studies examining the accuracy of nCD64 in diagnosing infection in patients with autoimmune diseases were included. The Quality Assessment of Diagnostic Accuracy Studies-2 tool was used to assess the quality of eligible studies. Stata 15.1 and Meta-DiSc 1.4 software were used for data analysis. Eleven studies fulfilled the inclusion criteria (677 patients, 229 patients with bacterial infection, and 448 without infection). The pooled sensitivity and specificity of nCD64 were 89% (95% confidence interval (CI) 82-93) and 94% (95% CI 91-96), respectively. The pooled positive likelihood ratio and negative likelihood ratio were 14.9 (95% CI 9.3-23.8) and 0.12 (95% CI 0.07-0.20), respectively. The diagnostic odds ratio and area under the summary receiver operating characteristic curve were 123 (95% CI 53-283) and 0.97 (95% CI 0.95-0.98), respectively. The univariate meta-regression analysis showed that region, type of disease, antibiotic therapy, and presentation of nCD64 measurement results were responsible for the heterogeneity. The Deeks' funnel plot asymmetry test showed that there was no publication bias (p = 0.15). nCD64 has a good overall diagnostic performance for differentiating infection from disease flare in patients with autoimmune diseases. Further studies are needed to confirm the optimized cutoff value.

Risk of infection with different immunosuppressive drugs combined with glucocorticoids for the treatment of idiopathic membranous nephropathy: A pairwise and network meta-analysis.

INTRODUCTION: Idiopathic membranous nephropathy (IMN) is a common cause of nephrotic syndrome in adults and one of the leading causes of end-stage renal disease (ESRD). During recent years, the incidence of IMN has been increasing. The main treatment option for IMN is the use of immunosuppressive (IS) drugs combined with glucocorticoids (GC). However, the infection risk with different IS drug treatments has not been systematically compared. Therefore, a network meta-analysis was performed to compare the risk of infection of different IS drug treatments for IMN. METHODS: Randomized controlled trials (RCTs) that assessed the risk of infection in patients with IMN treated with different IS drugs combined with GC were included in the network meta-analysis. Risk ratios for dichotomous data with 95% confidence intervals (CI) were calculated and the data were pooled with a random-effects model. The surface under the cumulative ranking area (SUCRA) was calculated to rank the risk of infection with different interventions. RESULTS: A total of 38 RCTs with 2066 participants were included for comparison of nine interventions. Tacrolimus combined with GC (TAC + GC) was associated with a significantly lower risk of infection than that with intravenous cyclophosphamide (IVCTX) + GC with a risk ratio (95% CI) of 0.52 (0.34-0.79). IVCTX + GC was associated with a significantly higher risk of infection than that with TAC + GC, cyclosporin (CSA) + GC, and oral cyclophosphamide (POCTX) + GC. A sensitivity analysis, excluding studies with a very long follow-up period, revealed minimal differences in the estimates. The SUCRA showed that CSA + GC had the lowest risk of infection (SUCRA 86.0%), and the second best treatment was POCTX + GC (SUCRA 78.6%). Conversely, IVCTX + GC (SUCRA 16.2%) had a higher risk of infection than that with the other IS drugs. CONCLUSIONS: CSA + GC and POCTX+ GC were associated with a lower risk of infection than that with other IS drugs combined with GC for IMN. Combined with comparative efficacy data, these results can help patients make informed decisions about treatment options for IMN. PROSPERO registration: CRD42018104849.

Risk factors for 14-day rehospitalization following trauma with new traumatic spinal cord injury diagnosis: A 10-year nationwide study in Taiwan.

OBJECTIVES: Fourteen-day rehospitalization with new traumatic spinal cord injury (tSCI) diagnosis is used as an indicator for the diagnostic quality of the first hospitalization. In this nationwide population-based cohort study, we identified risk factors for this indicator. METHODS: We conducted a nested case-control study by using the data of patients who received a first hospitalization for trauma between 2001 and 2011. The data were retrieved from Taiwan's National Health Insurance Research Database. Variables including demographic and trauma characteristics were compared between patients diagnosed with tSCI at the first hospitalization and those receiving a 14-day rehospitalization with new tSCI diagnosis. RESULTS: Of the 23 617 tSCI patients, 997 had 14-day rehospitalization with new tSCI diagnosis (incidence rate, 4.22%). The risk of 14-day rehospitalization with new tSCI diagnosis was significantly lower in patients with severe (injury severity score [ISS] = 16-24; odds ratio [OR], 0.17; 95% confidence interval [CI], 0.13-0.21) and profound (ISS > 24; OR, 0.11; 95% CI, 0.07-0.18) injuries. Interhospital transfer (OR, 8.20; 95% CI, 6.48-10.38) was a significant risk factor, along with injuries at the thoracic (OR, 1.62; 95% CI, 1.21-2.18), lumbar (OR, 1.30; 95% CI, 1.02-1.65), and multiple (OR, 3.23; 95% CI, 1.86-5.61) levels. Brain (OR, 2.82), chest (OR, 2.99), and abdominal (OR, 2.74) injuries were also identified as risk factors. In addition, the risk was higher in patients treated at the orthopedic department (OR, 2.26; 95% CI, 1.78-2.87) and those of other surgical disciplines (OR, 1.89; 95% CI, 1.57-2.28) than in those treated at the neurosurgery department. CONCLUSIONS: Delayed tSCI diagnoses are not uncommon, particularly among trauma patients with ISSs < 16 or those who are transferred from lower-level hospitals. Further validation and implementation of evidence-based decision rules is essential for improving the diagnostic quality of traumatic thoracolumbar SCI.

Therapeutic effectiveness of percutaneous drainage and factors for performing an interval appendectomy in pediatric appendiceal abscess.

BACKGROUND: In this study, we studied the therapeutic effectiveness of percutaneous drainage with antibiotics and the need for an interval appendectomy for treating appendiceal abscess in children with a research-oriented dataset released by the Bureau of National Health Insurance in Taiwan through the Collaboration Center for Health Information Application (CCHIA). METHODS: We identified 1225 patients under 18 years of age who had non-surgical treatment for an appendiceal abscess between 2007 and 2012 in a Taiwan CCHIA dataset. The treatment included percutaneous drainage with antibiotics or antibiotics alone. We also analyzed data of patient's baseline characteristics, outcomes of percutaneous drainage, and indicating factors for performing an interval appendectomy. RESULTS: Totally, 6190 children had an appendiceal abscess, an 1225 patients received non-operative treatment. Of 1225 patients, 150 patients received treatment with percutaneous drainage and antibiotics, 78 had recurrent appendicitis, 185 went on to receive an interval appendectomy, and 10 had postoperative complications after the interval appendectomy. We found that patients treated with percutaneous drainage and antibiotics had a significantly lower rate of recurrent appendicitis (p < 0.05), a significantly smaller chance of receiving an interval appendectomy (p < 0.05), and significantly fewer postoperative complications after the interval appendectomy (p < 0.05) than those without percutaneous drainage treatment. Older children (13 ~ 18 years) patients were found to have a significantly smaller need to receive an interval appendectomy than those who were ≤ 6 years of age (odd ratio (OR) = 2.071, 95 % confidence interval (CI) = 1.34-3.19, p < 0.01), and those who were 7 ~ 12 years old (OR = 1.662, 95 % CI = 1.15-2.41, p < 0.01). In addition, those treated with percutaneous drainage were significantly less indicated to receive an interval appendectomy later (OR = 2.249, 95 % CI = 1.19 ~ 4.26, p < 0.05). In addition, those with recurrent appendicitis had a significantly increased incidence of receiving an interval appendectomy later (OR = 3.231, 95 % CI = 1.95 ~ 5.35, p < 0.001). CONCLUSIONS: In this study, we used nationwide data to demonstrate therapeutic effectiveness of percutaneous drainage and antibiotics was more beneficial than only antibiotics in treating patients with an appendiceal abscess. We also found three factors that were significantly associated with receiving an interval appendectomy: recurrent appendicitis, being aged ≤ 13 years, and treatment with antibiotics only.

National trends in therapeutic approaches and outcomes for pediatric appendicitis: a Taiwanese nationwide cohort study.

PURPOSE: To define the pattern of therapeutic approaches for pediatric appendicitis and compare their benefits in Taiwan, we analyzed a research-oriented dataset released by the Bureau of National Health Insurance in Taiwan through the Collaboration Center for Health Information Application (CCHIA) to document the impact of the rise of laparoscopic treatment on outcomes. METHODS: We identified 22,161 patients under 18 years who had been hospitalized with a diagnosis of acute appendicitis between 2007 and 2012 in the CCHIA. Statistical comparisons between the Laparoscopic appendectomy (LA) and open appendectomy (OA, control) groups were computed using a Chi squared test. The odds ratios (ORs) and 95% confidence intervals (CIs) of risk factors for intra-abdominal abscess (IAA) and postoperative bowel obstruction (PBO) were derived from multivariate logistic regression models. RESULTS: In each respective year, the incidence of LA increased from 29.17% in 2007 to 57.4% in 2012, while that of OA decreased from 70.83% in 2007 to 42.60% in 2012; incidences of non-perforated appendicitis and perforated appendicitis with LA or OA seemed similar. The length of hospitalization between an LA and OA for non-perforated appendicitis was the same, but that with an LA was shorter for perforated appendicitis. The adjusted ORs for IAA and PBO for those patients with perforated and non-perforated appendicitis were 6.30 (95% CI = 5.09-7.78; p < 0.001) and 6.49 (95% CI = 4.45-9.48; p < 0.001); while for those cases undergoing an LA and OA, they were 0.50 (95 % CI = 0.40-0.62; p < 0.001) and 2.07 (95% CI = 1.45-2.95; p < 0.001), respectively. The ORs of IAA and PBO for those patients ≤6 and 7-12 years of age were 1.67 (95% CI = 1.23-2.25; p = 0.001) and 1.20 (95% CI = 0.97-1.49; p = 0.095), and 1.88 (95% CI = 1.08-3.24; p = 0.025) and 1.47 (95% CI = 1.01-2.14; p = 0.043), respectively, compared to those aged 13-18 years. CONCLUSIONS: Our study demonstrated that young age and perforated appendicitis can affect postoperative IAA and PBO. LA appeared beneficial in reducing the length of hospitalization and postoperative IAA, but had an increasing risk of PBO. Although laparoscopic approach for pediatric appendectomy is increasing in our country, the different hospital levels and pediatric surgeon's laparoscopic experience must be evaluated in further study.

Geographical heterogeneity and influenza infection within households.

BACKGROUND: Although it has been suggested that schoolchildren vaccination reduces influenza morbidity and mortality in the community, it is unknown whether geographical heterogeneity would affect vaccine effectiveness. METHODS: A 3-year prospective, non-randomized sero-epidemiological study was conducted during 2008-2011 by recruiting schoolchildren from both urban and rural areas. Respective totals of 124, 206, and 176 households were recruited and their household contacts were followed. Serum samples were collected pre-vaccination, one-month post-vaccination and post-season from children and household contacts for hemagglutination inhibition (HI) assay. A multivariate logistic model implemented with generalized estimation equations (GEE) was fitted with morbidity or a four-fold increase in HI titer of the household contacts for two consecutive sera as the dependent variable; with geographical location, vaccination status of each household and previous vaccination history as predictor variables. RESULTS: Although our results show no significant reduction in the proportion of infection or clinical morbidity among household contacts, a higher risk of infection, indicated by odds ratio>1, was consistently observed among household children contacts from the un-vaccinated households after adjusting for confounding variables. Interestingly, a statistically significant lower risk of infection was observed among household adult contacts from rural area when compared to those from urban area (OR=0.89; 95% CI: 0.82-0.97 for Year 2 and OR=0.85; 95% CI: 0.75-0.96 for Year 3). CONCLUSIONS: A significant difference in the risk of influenza infection among household adults due to geographical heterogeneity, independent of schoolchildren vaccination status, was revealed in this study. Its impact on vaccine effectiveness requires further study.

A powerful and robust test in genetic association studies.

There are several well-known single SNP tests presented in the literature for detecting gene-disease association signals. Having in place an efficient and robust testing process across all genetic models would allow a more comprehensive approach to analysis. Although some studies have shown that it is possible to construct such a test when the variants are common and the genetic model satisfies certain conditions, the model conditions are too restrictive and in general difficult to verify. In this paper, we propose a powerful and robust test without assuming any model restrictions. Our test is based on the selected 2 × 2 tables derived from the usual 2 × 3 table. By signals from these tables, we show through simulations across a wide range of allele frequencies and genetic models that this approach may produce a test which is almost uniformly most powerful in the analysis of low- and high-frequency variants. Two cancer studies are used to demonstrate applications of the proposed test.

Asymptomatic ratio for seasonal H1N1 influenza infection among schoolchildren in Taiwan.

BACKGROUND: Studies indicate that asymptomatic infections do indeed occur frequently for both seasonal and pandemic influenza, accounting for about one-third of influenza infections. Studies carried out during the 2009 pH1N1 pandemic have found significant antibody response against seasonal H1N1 and H3N2 vaccine strains in schoolchildren receiving only pandemic H1N1 monovalent vaccine, yet reported either no symptoms or only mild symptoms. METHODS: Serum samples of 255 schoolchildren, who had not received vaccination and had pre-season HI Ab serotiters <40, were collected from urban, rural areas and an isolated island in Taiwan during the 2005-2006 influenza season. Their hemagglutination inhibition antibody (HI Ab) serotiters against the 2005 A/New Caledonia/20/99 (H1N1) vaccine strain at pre-season and post-season were measured to determine the symptoms with the highest correlation with infection, as defined by 4-fold rise in HI titer. We estimate the asymptomatic ratio, or the proportion of asymptomatic infections, for schoolchildren during the 2005-6 influenza season when this vaccine strain was found to be antigenically related to the circulating H1N1 strain. RESULTS: Fever has the highest correlation with the 2005-06 seasonal influenza A(H1N1) infection, followed by headache, cough, vomiting, and sore throat. Asymptomatic ratio for the schoolchildren is found to range between 55.6% (95% CI: 44.7-66.4)-77.9% (68.8-87.0) using different sets of predictive symptoms. Moreover, the asymptomatic ratio was 66.9% (56.6-77.2) when using US-CDC criterion of fever + (cough/sore throat), and 73.0 (63.3-82.8) when under Taiwan CDC definition of Fever + (cough or sore throat or nose) + ( headache or pain or fatigue). CONCLUSIONS: Asymptomatic ratio for children is found to be substantially higher than that of the general population in literature. In providing reasonable quantification of the asymptomatic infected children spreading pathogens to others in a seasonal epidemic or a pandemic, our estimates of symptomatic ratio of infected children has important clinical and public health implications.

Detecting rare variants in case-parents association studies.

Despite the success of genome-wide association studies (GWASs) in detecting common variants (minor allele frequency ≥0.05) many suggested that rare variants also contribute to the genetic architecture of diseases. Recently, researchers demonstrated that rare variants can show a strong stratification which may not be corrected by using existing methods. In this paper, we focus on a case-parents study and consider methods for testing group-wise association between multiple rare (and common) variants in a gene region and a disease. All tests depend on the numbers of transmitted mutant alleles from parents to their diseased children across variants and hence they are robust to the effect of population stratification. We use extensive simulation studies to compare the performance of four competing tests: the largest single-variant transmission disequilibrium test (TDT), multivariable test, combined TDT, and a likelihood ratio test based on a random-effects model. We find that the likelihood ratio test is most powerful in a wide range of settings and there is no negative impact to its power performance when common variants are also included in the analysis. If deleterious and protective variants are simultaneously analyzed, the likelihood ratio test was generally insensitive to the effect directionality, unless the effects are extremely inconsistent in one direction.

A method for analyzing clustered interval-censored data based on Cox's model.

Methods for analyzing interval-censored data are well established. Unfortunately, these methods are inappropriate for the studies with correlated data. In this paper, we focus on developing a method for analyzing clustered interval-censored data. Our method is based on Cox's proportional hazard model with piecewise-constant baseline hazard function. The correlation structure of the data can be modeled by using Clayton's copula or independence model with proper adjustment in the covariance estimation. We establish estimating equations for the regression parameters and baseline hazards (and a parameter in copula) simultaneously. Simulation results confirm that the point estimators follow a multivariate normal distribution, and our proposed variance estimations are reliable. In particular, we found that the approach with independence model worked well even when the true correlation model was derived from Clayton's copula. We applied our method to a family-based cohort study of pandemic H1N1 influenza in Taiwan during 2009-2010. Using the proposed method, we investigate the impact of vaccination and family contacts on the incidence of pH1N1 influenza.

Gout and subsequent increased risk of cardiovascular mortality in non-diabetics aged 50 and above: a population-based cohort study in Taiwan.

BACKGROUND: Limited data are available on the risk ratios for fatal cardiovascular disease (CVD) outcome from gout and chronic kidney disease (CKD) in non-diabetic individuals. METHODS: Nationwide population-based retrospective prospective study with a 5-year follow-up to investigate the association between physician-diagnosed gout and CKD in non-diabetics aged 50 and above who had no pre-existing serious CVD and the subsequent risk of death from CVD. Hazard ratios (HR) of CVD mortality were adjusted for gender, age, smoking- and alcoholism-related diagnoses, hypertension, hyperlipidemia, atrial fibrillation and Charlson's comorbidity index score. RESULTS: A case cohort (n=164,463) having gout and a control cohort (n=3,694,377) having no gout were formed. The prevalence of gout in this study was 4.26% whereas that of gout plus CKD was 8.17%. Male to female ratio among the individuals with gout was 3.2:1. The relative risk (RR) of subsequent cardiovascular mortality between the case and control cohort was 1.71 (95% confidence interval (CI), 1.66-1.75). The presence of CKD in nondiabetic subjects with no gout (control group) has a RR of CVD mortality at 3.05 (95% CI, 2.94-3.15). The presence of gout has protective effect on subjects with CKD with a RR of 1.84 (95% CI, 1.71-1.98). As compared with individuals with no gout, the adjusted HR (aHR) for CVD mortality among the individuals with gout was 1.10 (95% CI 1.07-1.13). In a Cox model, when compared with subjects having neither gout nor CKD, the aHR in subjects with no gout but with CKD is 1.76 (95% CI, 1.70-1.82); in subjects with gout but without CKD, 1.10 (1.07-1.13); interestingly, the aHR is attenuated in subjects with concomitant gout plus CKD which is 1.38 (1.29-1.48). CONCLUSIONS: Among non-diabetic individuals aged 50 years or above who had no preceding serious CVD, those with gout were 1.1 times more likely to die from CVD as were individuals without gout. The presence of gout appears to attenuate the risk of subsequent CV mortality in subjects with CKD. Further studies should focus on finding an explanation for the protective effect of gout on CV mortality in patients with CKD.

Assessment of performance of survival prediction models for cancer prognosis.

BACKGROUND: Cancer survival studies are commonly analyzed using survival-time prediction models for cancer prognosis. A number of different performance metrics are used to ascertain the concordance between the predicted risk score of each patient and the actual survival time, but these metrics can sometimes conflict. Alternatively, patients are sometimes divided into two classes according to a survival-time threshold, and binary classifiers are applied to predict each patient's class. Although this approach has several drawbacks, it does provide natural performance metrics such as positive and negative predictive values to enable unambiguous assessments. METHODS: We compare the survival-time prediction and survival-time threshold approaches to analyzing cancer survival studies. We review and compare common performance metrics for the two approaches. We present new randomization tests and cross-validation methods to enable unambiguous statistical inferences for several performance metrics used with the survival-time prediction approach. We consider five survival prediction models consisting of one clinical model, two gene expression models, and two models from combinations of clinical and gene expression models. RESULTS: A public breast cancer dataset was used to compare several performance metrics using five prediction models. 1) For some prediction models, the hazard ratio from fitting a Cox proportional hazards model was significant, but the two-group comparison was insignificant, and vice versa. 2) The randomization test and cross-validation were generally consistent with the p-values obtained from the standard performance metrics. 3) Binary classifiers highly depended on how the risk groups were defined; a slight change of the survival threshold for assignment of classes led to very different prediction results. CONCLUSIONS: 1) Different performance metrics for evaluation of a survival prediction model may give different conclusions in its discriminatory ability. 2) Evaluation using a high-risk versus low-risk group comparison depends on the selected risk-score threshold; a plot of p-values from all possible thresholds can show the sensitivity of the threshold selection. 3) A randomization test of the significance of Somers' rank correlation can be used for further evaluation of performance of a prediction model. 4) The cross-validated power of survival prediction models decreases as the training and test sets become less balanced.

Survival analysis of pediatric dialysis patients in Taiwan.

AIM: The long-term survival of Taiwanese children with end-stage renal disease (ESRD) has not been reported before. This study aimed to determine the long-term survival, mortality hazards and causes of death in paediatric patients receiving dialysis. METHODS: Paediatric patients (aged 19 years and younger) with incident ESRD who were reported to the Taiwan Renal Registry from 1995 to 2004 were included. A total of 319 haemodialysis (HD) and 156 peritoneal dialysis (PD) patients formed the database. After stratification by dialysis modality, multivariate Cox proportional-hazards model was constructed with age, sex and co-morbidity as predictive variables. RESULTS: The annual paediatric ESRD incidence rate was 8.12 per million of age-related populations. The overall 1-, 5-, and 10-year survival rates for PD patients were 98.1%, 88.0% and 68.4%, respectively, and were 96.9%, 87.3% and 78.5% for HD patients. The survival analysis showed no significant difference between HD and PD (P = 0.4878). Using '15-19 years' as a reference group, the relative risk (RR) of the youngest group (0-4 years) was 6.60 (95% CI: 2.50-17.38) for HD, and 5.03 (95% CI: 1.23-20.67) for PD. The death rate was 24.66 per 1000 dialysis patient-years. The three major causes of death were infection (23.4%), cardiovascular disease (13.0%) and cerebrovascular disease (10.4%). Hemorrhagic stroke (87.5%) was the main type of foetal cerebrovascular accident. CONCLUSION: We conclude that there was no significant difference of paediatric ESRD patient survival between HD and PD treatment in Taiwan. The older paediatric ESRD patients had better survival than younger patients.

Improved candidate biomarker detection based on mass spectrometry data using the Hilbert-Huang transform.

Mass spectrometry biomarker discovery may assist patient's diagnosis in time and realize the characteristics of new diseases. Our previous work built a preprocess method called HHTmass which is capable of removing noise, but HHTmass only a proof of principle to be peak detectable and did not tested for peak reappearance rate and used on medical data. We developed a modified version of biomarker discovery method called Enhance HHTMass (E-HHTMass) for MALDI-TOF and SELDI-TOF mass spectrometry data which improved old HHTMass method by removing the interpolation and the biomarker discovery process. E-HHTMass integrates the preprocessing and classification functions to identify significant peaks. The results show that most known biomarker can be found and high peak appearance rate achieved comparing to MSCAP and old HHTMass2. E-HHTMass is able to adapt to spectra with a small increasing interval. In addition, new peaks are detected which can be potential biomarker after further validation.

Brain cancer associated with environmental lead exposure: evidence from implementation of a National Petrol-Lead Phase-Out Program (PLPOP) in Taiwan between 1979 and 2007.

BACKGROUND AND OBJECTIVE: In 1981, a Petrol-Lead Phase-Out Program (PLPOP) was launched in Taiwan for the abatement of environmental lead emissions. The present study was intended to examine whether the high Petrol-Lead Emission Areas (PLEA) would result in an increase in the incidence rate of brain cancer based on a national data bank. METHODS: The national brain cancer incidence data was obtained from the Taiwan National Cancer Registry. Age standardized incidence rates were calculated based on the 2000 WHO world standard population, and gasoline consumption data was obtained from the Bureau of Energy. The differences in the trend tests for age-standardized incidence rates of brain cancer between high, median, low, and small PLEA were analyzed. RESULTS: A significant increase was found from small to high PLEA in age-standardized incidence rates of brain cancer. By taking six possible confounders into account, the age-standardized incidence rates for brain cancer were highly correlated with the median and high PLEA by reference to the small PLEA. CONCLUSION: After being adjusted for a number of relevant confounders, it could be concluded that high PLEA might result in an increase in the incidence rate of brain cancer resulting from high lead exposures.