Hypermethylation Loci of ZNF671, IRF8, and OTX1 as Potential Urine-Based Predictive Biomarkers for Bladder Cancer.

Bladder cancer (BCa) is a significant health issue and poses a healthcare burden on patients, highlighting the importance of an effective detection method. Here, we developed a urine DNA methylation diagnostic panel for distinguishing between BCa and non-BCa. In the discovery stage, an analysis of the TCGA database was conducted to identify BCa-specific DNA hypermethylation markers. In the validation phase, DNA methylation levels of urine samples were measured with real-time quantitative methylation-specific PCR (qMSP). Comparative analysis of the methylation levels between BCa and non-BCa, along with the receiver operating characteristic (ROC) analyses with machine learning algorithms (logistic regression and decision tree methods) were conducted to develop practical diagnostic panels. The performance evaluation of the panel shows that the individual biomarkers of ZNF671, OTX1, and IRF8 achieved AUCs of 0.86, 0.82, and 0.81, respectively, while the combined yielded an AUC of 0.91. The diagnostic panel using the decision tree algorithm attained an accuracy, sensitivity, and specificity of 82.6%, 75.0%, and 90.9%, respectively. Our results show that the urine-based DNA methylation diagnostic panel provides a sensitive and specific method for detecting and stratifying BCa, showing promise as a standard test that could enhance the diagnosis and prognosis of BCa in clinical settings.

Effects of a swallowing and oral-care program on resuming oral feeding and reducing pneumonia in patients following endotracheal extubation: a randomized, open-label, controlled trial.

BACKGROUND: The resumption of oral feeding and free from pneumonia are important therapeutic goals for critically ill patients who have been successfully extubated after prolonged (≥ 48 h) endotracheal intubation. We aimed to examine whether a swallowing and oral-care (SOC) program provided to critically ill patients extubated from prolonged mechanical ventilation improves their oral-feeding resumption and reduces 30-day pneumonia incidence. METHODS: In this randomized, open-label, controlled trial, participants were consecutively enrolled and randomized to receive the SOC program or usual care. The interventions comprised three protocols: oral-motor exercise, sensory stimulation and lubrication, and safe-swallowing education. Beginning on the day following patient extubation, an SOC nurse provided the three-protocol care for seven consecutive days or until death or hospital discharge. With independent outcome assessors, oral-feeding resumption (yes, no) corresponded to level 6 or level 7 on the Functional Oral Intake Scale (censored seven days postextubation) along with radiographically documented pneumonia (yes, no; censored 30 days postextubation), abstracted from participants' electronic medical records were coded. RESULTS: We analyzed 145 randomized participants (SOC group = 72, control group = 73). The SOC group received, on average, 6.2 days of intervention (14.8 min daily) with no reported adverse events. By day 7, 37/72 (51.4%) of the SOC participants had resumed oral feeding vs. 24/73 (32.9%) of the control participants. Pneumonia occurred in 11/72 (15.3%) of the SOC participants and in 26/73 (35.6%) of the control participants. Independent of age and intubation longer than 6 days, SOC participants were likelier than their control counterparts to resume oral feeding (adjusted hazard ratio, 2.35; 95% CI 1.38-4.01) and had lower odds of developing pneumonia (adjusted odds ratio, 0.28; 95% CI 0.12-0.65). CONCLUSIONS: The SOC program effectively improved patients' odds that oral feeding would resume and the 30-day pneumonia incidence would decline. The program might advance dysphagia care provided to critically ill patients extubated from prolonged mechanical ventilation. TRIAL REGISTRATION: NCT03284892, registered on September 15, 2017.

Predicting hospital mortality and length of stay: A prospective cohort study comparing the Intensive Care Delirium Screening Checklist versus Confusion Assessment Method for the Intensive Care Unit.

OBJECTIVE: The objective of this study was to compare two tools, the Intensive Care Delirium Screening Checklist (ICDSC) and Confusion Assessment Method for the intensive care unit (ICU) (CAM-ICU), for their predictive validity for outcomes related to delirium, hospital mortality, and length of stay (LOS). METHODS: The prospective study conducted in six medical ICUs at a tertiary care hospital in Taiwan enrolled consecutive patients (≥20 years) without delirium at ICU admission. Delirium was screened daily using the ICDSC and CAM-ICU in random order. Arousal was assessed by the Richmond Agitation-Sedation Scale (RASS). Participants with any one positive result were classified as ICDSC- or CAM-ICU-delirium groups. RESULTS: Delirium incidence evaluated by the ICDSC and CAM-ICU were 69.1% (67/97) and 50.5% (49/97), respectively. Although the ICDSC identified 18 more cases as delirious, substantial concordance (κ = 0.63; p < 0.001) was found between tools. Independent of age, Acute Physiology and Chronic Health Evaluation II score, and Charlson Comorbidity Index, both ICDSC- and CAM-ICU-rated delirium significantly predicted hospital mortality (adjusted odds ratio: 4.93; 95% confidence interval [CI]:1.56 to 15.63 vs. 2.79; 95% CI: 1.12 to 6.97, respectively), and only the ICDSC significantly predicted hospital LOS with a mean of 17.59 additional days compared with the no-delirium group. Irrespective of delirium status, a sensitivity analysis of normal-to-increased arousal (RASS≥0) test results did not alter the predictive ability of ICDSC- or CAM-ICU-delirium for hospital mortality (adjusted odds ratio: 2.97; 95% CI: 1.06 to 8.37 vs. 3.82; 95% CI: 1.35 to 10.82, respectively). With reduced arousal (RASS<0), neither tool significantly predicted mortality or LOS. CONCLUSIONS: The ICDSC identified more delirium cases and may have higher predictive validity for mortality and LOS than the CAM-ICU. However, arousal substantially affected performance. Future studies may want to consider patients' arousal when deciding which tool to use to maximise the effects of delirium identification on patient mortality.

Evaluating Sex Differences in the Effect of Increased Systolic Blood Pressure on the Risk of Cardiovascular Disease in Asian Populations: A Systematic Review and Meta-Analysis.

Background: Cardiovascular disease (CVD) is a serious health concern worldwide, and half of the cases of CVD occur in Asia. Because hypertension or high blood pressure has been confirmed to be an important risk factor for CVD, controlling blood pressure is helpful for CVD prevention. Although many studies have shown a sex difference in the impact of blood pressure on the risk of CVD, the risk threshold of blood pressure remained the same for both sexes in the latest global guidelines. Objective: The study aimed to evaluate sex differences in the effect of increased blood pressure on the risk of CVD in Asian populations. Methods: In this study, we performed a systematic review via PubMed, Embase, and MEDLINE to select studies conducted with Asian populations published before 30 June 2021. Results: Six female and eleven male effect sizes for CVD risk from six articles were identified. The unadjusted pooled effect size for CVD risk per 10-mmHg increase in systolic blood pressure was estimated to be 1.20 for females (95% confidence interval: [1.10, 1.32]) and 1.19 for males (95% confidence interval: [1.11, 1.27]). Furthermore, using meta-regression to adjust for the significant effect of smoking, we showed that the impact of a 10-mmHg systolic blood pressure increase on CVD risk among females was 1.232 times that among males, corresponding to a significant sex difference (95% confidence interval: [1.065, 1.426]; P = 0.02). In summary, the effect of an increased systolic blood pressure on the risk of CVD in females was significantly higher than that in males in the Asian population.

Association of Incident Delirium With Short-term Mortality in Adults With Critical Illness Receiving Mechanical Ventilation.

Importance: Intensive care unit (ICU)-acquired delirium and/or coma have consequences for patient outcomes. However, contradictory findings exist, especially when considering short-term (ie, in-hospital) mortality and length of stay (LOS). Objective: To assess whether incident delirium, days of delirium, days of coma, and delirium- and coma-free days (DCFDs) are associated with 14-day mortality, in-hospital mortality, and hospital LOS among patients with critical illness receiving mechanical ventilation. Design, Setting, and Participants: This single-center prospective cohort study was conducted in 6 ICUs of a university-affiliated tertiary hospital in Taiwan. A total of 267 delirium-free patients (aged ≥20 years) with critical illness receiving mechanical ventilation were consecutively enrolled from August 14, 2018, to October 1, 2020. Exposures: Participants were assessed daily for the development of delirium and coma status over 14 days (or until death or ICU discharge) using the Confusion Assessment Method for the Intensive Care Unit and the Richmond Agitation-Sedation Scale, respectively. Main Outcomes and Measures: Mortality rates (14-day and in-hospital) and hospital LOS using electronic health records. Results: Of 267 participants (median [IQR] age, 65.9 [57.4-75.1] years; 171 men [64.0%]; all of Taiwanese ethnicity), 149 patients (55.8%) developed delirium for a median (IQR) of 3.0 (1.0-5.0) days at some point during their first 14 days of ICU stay, and 105 patients (39.3%) had coma episodes also lasting for a median (IQR) of 3.0 (1.0-5.0) days. The 14-day and in-hospital mortality rates were 18.0% (48 patients) and 42.1% (112 of 266 patients [1 patient withdrew from the study]), respectively. The incidence and days of delirium were not associated with either 14-day mortality (incident delirium: adjusted hazard ratio [aHR], 1.37; 95% CI, 0.69-2.72; delirium by day: aHR, 1.00; 95% CI, 0.91-1.10) or in-hospital mortality (incident delirium: aHR, 1.00; 95% CI, 0.64-1.55; delirium by day: aHR, 1.02; 95% CI, 0.97-1.07), whereas days spent in coma were associated with an increased hazard of dying during a given 14-day period (aHR, 1.16; 95% CI, 1.10-1.22) and during hospitalization (aHR, 1.10; 95% CI, 1.06-1.14). The number of DCFDs was a protective factor; for each additional DCFD, the risk of dying during the 14-day period was reduced by 11% (aHR, 0.89; 95% CI, 0.84-0.94), and the risk of dying during hospitalization was reduced by 7% (aHR, 0.93; 95% CI, 0.90-0.97). Incident delirium was associated with longer hospital stays (adjusted ß = 10.80; 95% CI, 0.53-21.08) when compared with no incident delirium. Conclusions and Relevance: In this study, despite prolonged LOS, ICU delirium was not associated with short-term mortality. However, DCFDs were associated with a lower risk of dying, suggesting that future research and intervention implementation should refocus on maximizing DCFDs to potentially improve the survival of patients receiving mechanical ventilation.

A split-and-merge deep learning approach for phenotype prediction.

BACKGROUND: Phenotype prediction with genome-wide markers is a critical but difficult problem in biomedical research due to many issues such as nonlinearity of the underlying genetic mapping and high-dimensionality of marker data. When using the deep learning method in the small-n-large-p data, some serious issues occur such as over-fitting, over-parameterization, and biased prediction. METHODS: In this study, we propose a split-and-merge deep learning method, named SM-DL method, to learn a neural network on the dimension reduce data by using the split-and-merge technique. CONCLUSIONS: Numerically, the proposed method has significant performance in phenotype prediction for a simulated example. A real example is used to demonstrate how the proposed method can be applied in practice.

Predicting feeding-tube dependence in patients following endotracheal extubation: a two-item swallowing screen.

BACKGROUND: To meet the surging demands for intubation and invasive ventilation as more COVID-19 patients begin their recovery, clinicians are challenged to find an ultra-brief and minimally invasive screen for postextubation dysphagia predicting feeding-tube dependence persisting for 72 h after extubation. METHODS: This study examined the predictive validity of a two-item swallowing screen on feeding-tube dependence over 72 h in patients following endotracheal extubation. Intensive-care-unit (ICU) patients (≥ 20 years) successfully extubated after ≥ 48 h endotracheal intubation were screened by trained nurses using the swallowing screen (comprising oral stereognosis and cough-reflex tests) 24 h postextubation. Feeding-tube dependence persisting for 72 h postextubation was abstracted from the medical record by an independent rater. To verify the results and cross-check whether the screen predicted penetration and/or aspiration during fiberoptic endoscopic evaluation of swallowing (FEES), participants agreeing to receive FEES were analyzed within 30 min of screening. RESULTS: The results showed that 95/123 participants (77.2%) failed the screen, which predicted ICU patients' prolonged (> 72 h) feeding-tube dependence, yielding sensitivity of 0.83, specificity of 0.35, and accuracy of 0.68. Failed-screen participants had 2.96-fold higher odds of feeding-tube dependence (95% CI, 1.13-7.76). For the 38 participants receiving FEES, the swallowing screen had 0.89 sensitivity to detect feeding-tube dependence and 0.86 sensitivity to predict penetration/aspiration, although specificity had room for improvement (0.36 and 0.21, respectively). CONCLUSION: This ultra-brief swallowing screen is sufficiently sensitive to identify high-risk patients for feeding-tube dependence persisting over 72 h after extubation. Once identified, a further assessment and care are indicated to ensure the prompt return of patients' oral feeding. TRIAL REGISTRATION: NCT03284892, registered on September 15, 2017.

Surviving and Thriving 1 Year After Cardiac Surgery: Frailty and Delirium Matter.

BACKGROUND: We compared 1-year functional outcomes for 4 cardiac surgery patient groups: comparison (without preoperative frailty or postoperative delirium [POD]), frailty only (with preoperative frailty only), POD only (with POD only), and frailty-POD (combined frailty and POD). METHODS: Consecutive cardiac surgery patients (n = 298) at a university hospital were assessed for preoperative frailty using Fried's phenotype, and POD was assessed daily for 10 days after surgery using the Confusion Assessment Method. Functional outcomes (Barthel Index for activities of daily living [ADL]) and all-cause mortality were evaluated 1-year after surgery. RESULTS: Preoperative frailty presented in 85 of participants (28.5%) and POD in 38 (12.8%). Frail participants were at increased risk for POD (odds ratio = 4.9; P < .001). Overall, 1-year mortality was 4.0% (n = 12) and functional change was 0.4 ± 11.0 Barthel points. Controlling for age, cardiac risk, and baseline ADL, frailty-only and comparison participants had comparable 1-year functional outcomes. The POD-only group had greater mortality (adjusted hazard ratio = 23.9; P = .01), whereas the combined frailty-POD group had the greatest ADL decline (ß = -23.7; P = .01) and the highest mortality (adjusted hazard ratio = 30.2; P = .006) compared with the comparison group. CONCLUSIONS: Preoperative frailty alone did not negatively affect cardiac surgery patients' functional outcomes up to 1 year, but coexisting frailty and POD led to substantial loss of independence on 3 to 4 ADLs and a 30.2-fold higher likelihood of dying 1 year after surgery. Because frailty led to a 4.9-fold increase in POD risk, frailty may serve as a presurgical screen to identify patients who would likely benefit from delirium prevention and functional recovery programs to maximize 1-year postsurgical outcomes.

CONY: A Bayesian procedure for detecting copy number variations from sequencing read depths.

Copy number variations (CNVs) are genomic structural mutations consisting of abnormal numbers of fragment copies. Next-generation sequencing of read-depth signals mirrors these variants. Some tools used to predict CNVs by depth have been published, but most of these tools can be applied to only a specific data type due to modeling limitations. We develop a tool for copy number variation detection by a Bayesian procedure, i.e., CONY, that adopts a Bayesian hierarchical model and an efficient reversible-jump Markov chain Monte Carlo inference algorithm for whole genome sequencing of read-depth data. CONY can be applied not only to individual samples for estimating the absolute number of copies but also to case-control pairs for detecting patient-specific variations. We evaluate the performance of CONY and compare CONY with competing approaches through simulations and by using experimental data from the 1000 Genomes Project. CONY outperforms the other methods in terms of accuracy in both single-sample and paired-samples analyses. In addition, CONY performs well regardless of whether the data coverage is high or low. CONY is useful for detecting both absolute and relative CNVs from read-depth data sequences. The package is available at https://github.com/weiyuchung/CONY.

Risk of acute mesenteric ischemia in patients with diabetes: A population-based cohort study in Taiwan.

BACKGROUND AND AIMS: Diabetes is a common and complex endocrine disorder that often results in hyperglycemia, which has been strongly implicated in several cardiovascular and cerebrovascular events that cause disability. Acute mesenteric ischemia (AMI) is a vascular emergency with high mortality rates. We conducted a population-based cohort study that utilizes data from medical claims databases to investigate whether diabetes increases the risk of AMI. METHODS: Using claims data from Taiwan's National Health Insurance program, 66,624 diabetic patients were enrolled from 1998 to 2009, and a comparison group of 266,496 individually matched subjects without diabetes was selected. The two groups were followed up until diagnosis of AMI, death, or the end of 2011. Incidence rates of AMI were assessed in both groups. Cox proportional hazards models were used to estimate the hazard ratios of diabetes for AMI. RESULTS: The diabetes cohort had a higher incidence rate than the comparison cohort for AMI (0.56 vs. 0.29 per 1,000 person-years). After adjusting for sex, age, comorbidity, and health system utilization, the adjusted hazard ratio of diabetes was 1.32 (95% confidence interval 1.11-1.56) for AMI. The risk of AMI associated with diabetes was greater in men (adjusted hazard ratio = 1.48, 95% confidence interval 1.17-1.87) than in women (adjusted hazard ratio = 1.17, 95% confidence interval 0.92-1.49). CONCLUSIONS: There was an increased risk of AMI in patients with diabetes. However, further research is required to understand whether this association is causal or due to a common set of risk factors.

Effects of a swallowing and oral care intervention for patients following endotracheal extubation: a pre- and post-intervention study.

BACKGROUND: For patients who survive a critical illness and have their oral endotracheal tube removed, dysphagia is highly prevalent, and without intervention, it may persist far beyond hospital discharge. This pre- and post-intervention study with historical controls tested the effects of a swallowing and oral care (SOC) intervention on patients' time to resume oral intake and salivary flow following endotracheal extubation. METHODS: The sample comprised intensive care unit patients (≥ 50 years) successfully extubated after ≥ 48 h endotracheal intubation. Participants who received usual care (controls, n = 117) were recruited before 2015, and those who received usual care plus the intervention (n = 54) were enrolled after 2015. After extubation, all participants were assessed by a blinded nurse for daily intake status (21 days) and whole-mouth unstimulated salivary flow (2, 7, 14 days). The intervention group received the nurse-administered SOC intervention, comprising toothbrushing/salivary gland massage, oral motor exercise, and safe-swallowing education daily for 14 days or until hospital discharge. RESULTS: The intervention group received 8.3 ± 4.2 days of SOC intervention, taking 15.4 min daily with no reported adverse event (coughing, wet voice, or decreased oxygen saturation) during and immediately after intervention. Participants who received the intervention were significantly more likely than controls to resume total oral intake after extubation (aHR 1.77, 95% CI 1.08-2.91). Stratified by age group, older participants (≥ 65 years) in the SOC group were 2.47-fold more likely than their younger counterparts to resume total oral intake (aHR 2.47, 95% CI 1.31-4.67). The SOC group also had significantly higher salivary flows 14 days following extubation (ß = 0.67, 95% CI 0.29-1.06). CONCLUSIONS: The nurse-administered SOC is safe and effective, with greater odds of patients' resuming total oral intake and increased salivary flows 14 days following endotracheal extubation. Age matters with SOC; it more effectively helped participants ≥ 65 years old resume total oral intake postextubation. TRIAL REGISTRATION: NCT02334774, registered on January 08, 2015.

Effects of sarcopenia on functional improvement over the first year after cardiac surgery: a cohort study.

BACKGROUND: Sarcopenia is linked with poor postoperative outcomes. AIMS: To evaluate the effects of sarcopenia on first-year functional changes after cardiac surgery. METHODS: In this prospective cohort study, functional changes (physical activity levels in metabolic equivalent hours/week, 6-minute walking distance in metres, and grip strength in kg) from preoperative baseline to 1, 3, 6 and 12 months postoperatively were compared in adult patients with and without sarcopenia undergoing cardiac surgery at a tertiary medical centre. Presurgical sarcopenia was defined as low muscle mass plus either low strength or poor physical performance (i.e. reduced gait speed). Secondary outcomes (length of hospital stay and 1-year mortality) were compared between sarcopenia and non-sarcopenia groups. RESULTS: Sarcopenia presented in 27.7% ( n=67) of 242 participants. Participants with sarcopenia were significantly older, predominantly women, and had lower body mass index and higher cardiac surgery risk (measured by the EuroSCORE II) than those without sarcopenia. For both groups, physical activity levels, walking distance and grip strength steadily improved over the year following cardiac surgery. Independent of EuroSCORE II, changes in physical activity levels, walking distance and grip strength did not differ significantly between the sarcopenia and non-sarcopenia groups 1, 3, 6 and 12 months after surgery. Nevertheless, the sarcopenia group had a significantly longer length of hospital stay than the non-sarcopenia group (19.4 vs. 15.3 days; ß=2.9, P=0.02) but 1-year mortality (3.4 vs. 3.9% for non-sarcopenia group) was comparable. CONCLUSIONS: Despite a longer length of hospital stay for the sarcopenia group, sarcopenia was not a restriction for cardiac surgery given their comparable functional improvement and mortality 1 year following surgery.

Assessing Sex Differences in the Risk of Cardiovascular Disease and Mortality per Increment in Systolic Blood Pressure: A Systematic Review and Meta-Analysis of Follow-Up Studies in the United States.

In the United States (US), cardiovascular (CV) disease accounts for nearly 20% of national health care expenses. Since costs are expected to increase with the aging population, informative research is necessary to address the growing burden of CV disease and sex-related differences in diagnosis, treatment, and outcomes. Hypertension is a major risk factor for CV disease and mortality. To evaluate whether there are sex-related differences in the effect of systolic blood pressure (SBP) on the risk of CV disease and mortality, we performed a systematic review and meta-analysis. We conducted a comprehensive search using PubMed and Google Scholar to identify US-based studies published prior to 31 December, 2015. We identified eight publications for CV disease risk, which provided 9 female and 8 male effect size (ES) observations. We also identified twelve publications for CV mortality, which provided 10 female and 18 male ES estimates. Our meta-analysis estimated that the pooled ES for increased risk of CV disease per 10 mmHg increment in SBP was 25% for women (95% Confidence Interval (CI): 1.18, 1.32) and 15% for men (95% CI: 1.11, 1.19). The pooled increase in CV mortality per 10 mm Hg SBP increment was similar for both women and men (Women: 1.16; 95% CI: 1.10, 1.23; Men: 1.17; 95% CI: 1.12, 1.22). After adjusting for age and baseline SBP, the results demonstrated that the risk of CV disease per 10 mm Hg SBP increment for women was 1.1-fold higher than men (P<0.01; 95% CI: 1.04, 1.17). Heterogeneity was moderate but significant. There was no significant sex difference in CV mortality.

Trajectories of caregiver depressive symptoms while providing end-of-life care.

OBJECTIVE: The course of caregivers' depressive symptoms may not be homogenous. This study identified trajectories of depressive symptoms among caregivers providing end-of-life care to cancer patients and profiled the unique characteristics of caregivers within each trajectory. METHODS: Trajectories of depressive symptoms were explored in 447 caregivers who completed the Center for Epidemiological Studies Depression Scale over four periods close to the patient's death (1-30, 31-90, 91-180, and >180 days). Distinct trajectories were identified by latent class analysis. RESULTS: Four trajectories were identified as endurance, resilience, moderately symptomatic, and chronically distressed and contained 32.0%, 11.4%, 36.9%, and 19.7% of the sample, respectively. Caregivers in the endurance trajectory were relatively well-adjusted individuals with less education, adequate financial support, and ample psychological resources but provided care to older patients with greater symptom distress. They perceived less subjective caregiving burden than caregivers with moderate or chronic depressive symptoms. Caregivers in the resilience trajectory were in a more vulnerable position than those in other trajectories when they first transitioned into the caregiving role because they were more likely to be the patient's spouse, have greater educational attainment and insufficient finances, provide higher intensity assistance to a younger relative, and have weaker psychological resources. However, they were older, reported greater confidence in caregiving, and perceived less caregiving burden than caregivers in other trajectories. The moderately symptomatic and chronically distressed trajectories were differentiated only by the strength of psychological resources. CONCLUSIONS: Caregivers of terminally ill cancer patients follow distinct depressive-symptom trajectories while providing end-of-life care.

A simple Bayesian mixture model with a hybrid procedure for genome-wide association studies.

Genome-wide association studies often face the undesirable result of either failing to detect any influential markers at all because of a stringent level for testing error corrections or encountering difficulty in quantifying the importance of markers by their P-values. Advocates of estimation procedures prefer to estimate the proportion of association rather than test significance to avoid overinterpretation. Here, we adopt a Bayesian hierarchical mixture model to estimate directly the proportion of influential markers, and then proceed to a selection procedure based on the Bayes factor (BF). This mixture model is able to accommodate different sources of dependence in the data through only a few parameters. Specifically, we focus on a standardized risk measure of unit variance so that fewer parameters are involved in inference. The expected value of this measure follows a mixture distribution with a mixing probability of association, and it is robust to minor allele frequencies. Furthermore, to select promising markers, we use the magnitude of the BF to represent the strength of evidence in support of the association between markers and disease. We demonstrate this procedure both with simulations and with SNP data from studies on rheumatoid arthritis, coronary artery disease, and Crohn's disease obtained from the Wellcome Trust Case-Control Consortium. This Bayesian procedure outperforms other existing methods in terms of accuracy, power, and computational efficiency. The R code that implements this method is available at http://homepage.ntu.edu.tw/~ckhsiao/Bmix/Bmix.htm.