Comparative Effectiveness of Aspirin Dosing in Cardiovascular Disease and Diabetes Mellitus: A Subgroup Analysis of the ADAPTABLE Trial.

OBJECTIVE: Patients with diabetes mellitus (DM) and concomitant atherosclerotic cardiovascular disease (ASCVD) must be on the most effective dose of aspirin to mitigate risk of future adverse cardiovascular events. RESEARCH DESIGN AND METHODS: ADAPTABLE, an open-label, pragmatic study, randomized patients with stable, chronic ASCVD to 81 mg or 325 mg of daily aspirin. The effects of aspirin dosing was assessed on the primary effectiveness outcome, a composite of all-cause death, hospitalization for myocardial infarction, or hospitalization for stroke, and the primary safety outcome of hospitalization for major bleeding. In this prespecified analysis, we used Cox proportional hazards models to compare aspirin dosing in patients with and without DM for the primary effectiveness and safety outcome. RESULTS: Of 15,076 patients, 5,676 (39%) had DM of whom 2,820 (49.7%) were assigned to 81 mg aspirin and 2,856 (50.3%) to 325 mg aspirin. Patients with versus without DM had higher rates of the composite cardiovascular outcome (9.6% vs. 5.9%; P < 0.001) and bleeding events (0.78% vs. 0.50%; P < 0.001). When comparing 81 mg vs. 325 mg of aspirin, patients with DM had no difference in the primary effectiveness outcome (9.3% vs. 10.0%; hazard ratio [HR] 0.98 [95% CI 0.83-1.16]; P = 0.265) or safety outcome (0.87% vs. 0.69%; subdistribution HR 1.25 [95% CI 0.72-2.16]; P = 0.772). CONCLUSIONS: This study confirms the inherently higher risk of patients with DM irrespective of aspirin dosing. Our findings suggest that a higher dose of aspirin yields no added clinical benefit, even in a more vulnerable population.

[A Structural Equation Model on Social Re-Adjustment of Stroke Patients: Based on Roy's Adaptation Model].

PURPOSE: This study aimed to develop and test a structural equation model on social re-adjustment of individuals with stroke based on a literature review and Roy's adaptation model. METHODS: This study involved 321 participants who had a stroke and visited the outpatient department after discharge. The hypothetical model was developed based on Roy's adaptation model and a comprehensive review of previous literature on the topic. The model comprised four exogenous variables (neurological damage, gender [man], age, and social support) and five endogenous variables (activities of daily living, acceptance of disability, depression, rehabilitation motivation, and social re-adjustment). The data were analyzed using SPSS Windows software version 22.0 and AMOS 23.0. RESULTS: Out of 28 research hypotheses, 18 were supported, and they indicated approximately 64% probability of social re-adjustment. Social re-adjustment is directly and significantly affected by age, social support, activities of daily living, and depression. Social re-adjustment is indirectly affected by neurological impairment, gender (men), age, social support, and rehabilitation motivation. CONCLUSION: Continuous assistance and care should be provided for individuals with disabilities caused by sudden neurological damage to facilitate gradual improvement in their social re-adjustment. To enhance social re-adjustment, especially among older adults, newly developed interventions should focus on improving their activities of daily living, preventing depression, and enhancing support from family and healthcare personnel.

Comparison of the effectiveness and safety of 2 aspirin doses in secondary prevention of cardiovascular outcomes in patients with chronic kidney disease: A subgroup analysis of ADAPTABLE.

BACKGROUND: Among patients with established cardiovascular disease, the ADAPTABLE trial found no significant differences in cardiovascular events and bleeding rates between 81 mg and 325 mg of aspirin (ASA) daily. In this secondary analysis from the ADAPTABLE trial, we studied the effectiveness and safety of ASA dosing in patients with a history of chronic kidney disease (CKD). METHODS: ADAPTABLE participants were stratified based on the presence or absence of CKD, defined using ICD-9/10-CM codes. Within the CKD group, we compared outcomes between patients taking ASA 81 mg and 325 mg. The primary effectiveness outcome was defined as a composite of all cause death, myocardial infarction, or stroke and the primary safety outcome was hospitalization for major bleeding. Adjusted Cox proportional hazard models were utilized to report differences between the groups. RESULTS: After excluding 414 (2.7%) patients due to missing medical history, a total of 14,662 patients were included from the ADAPTABLE cohort, of whom 2,648 (18%) patients had CKD. Patients with CKD were older (median age 69.4 vs 67.1 years; P < .0001) and less likely to be white (71.5% vs 81.7%; P < .0001) when compared to those without CKD. At a median follow-up of 26.2 months, CKD was associated with an increased risk of both the primary effectiveness outcome (adjusted HR 1.79 [1.57, 2.05] P < .001 and the primary safety outcome (adjusted HR 4.64 (2.98, 7.21), P < .001 and P < .05, respectively) regardless of ASA dose. There was no significant difference in effectiveness (adjusted HR 1.01 95% CI 0.82, 1.23; P = .95) or safety (adjusted HR 0.93; 95% CI 0.52, 1.64; P = .79) between ASA groups. CONCLUSIONS: Patients with CKD were more likely than those without CKD to have adverse cardiovascular events or death and were also more likely to have major bleeding requiring hospitalization. However, there was no association between ASA dose and study outcomes among these patients with CKD.

Test-to-Stay in Kindergarten Through 12th Grade Schools After Household Exposure to Severe Acute Respiratory Syndrome Coronavirus 2.

BACKGROUND: Test-to-stay (TTS) is a strategy to limit school exclusion following an exposure to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the use of TTS within universally masked kindergarten through 12th grade (K-12) school settings following household SARS-CoV-2 exposure. METHODS: Three hundred twenty-two participants were enrolled. Serial rapid antigen testing was performed up to 15 days post-exposure. Analysis-eligible participants completed the 15-day testing protocol, tested positive any time during the testing window, or received a negative test on or after day 9. Primary outcomes included within-school tertiary attack rate (TAR) (test positivity among close contacts of positive TTS participants), and school days saved among TTS participants. RESULTS: Seventy-three of 265 analysis-eligible participants tested positive for SARS-CoV-2 (secondary attack rate of 28% [95% CI: 16-63%]). Among 77 within-school close contacts, 2 were positive (TAR = 3% [95% CI: 1-5%]). Participant absences were limited to 338 days, resulting in 82% of 1849 school days saved. IMPLICATIONS FOR SCHOOL HEALTH POLICY, PRACTICE, AND EQUITY: TTS facilitates continued in-person learning and can greatly reduce the number of missed school days. CONCLUSIONS: Within universally masked K-12 schools, TTS is a safe alternative to school exclusion following household SARS-CoV-2 exposure.

Predictors of health-related quality of life after coronary artery bypass graft surgery.

Health-related quality of life (HRQOL) is a multifactorial concept in assessing physical and mental health. This study was performed to evaluate the HRQOL of patients undergoing coronary artery bypass graft (CABG) surgery and the predictors of HRQOL in patients until 1 year after surgery. This cross-sectional study included 110 consecutive patients who underwent elective CABG in a medical center in South Korea. The Short-Form Health Survey, cardiac symptom survey, cardiac self-efficacy, and the Interpersonal Support Evaluation List-12 were used to measure the HRQOL, symptom experience, self-efficacy, and social support, respectively. The regression model explained 42% of the variance in the participants' physical HRQOL. The predictors of the physical HRQOL include the presence of a spouse, post-CABG duration, symptom experience, and self-efficacy. The regression model explained 36% of the variance in the participants' mental HRQOL. The predictors of the mental HRQOL included perceived health status, self-efficacy, and social support. The predictive factors for HRQOL after CABG were the presence of a spouse, post-CABG duration, symptom experience, self-efficacy, and social support. Furthermore, a suitable program and nursing interventions could be implemented to improve the HRQOL of post-CABG patients.

Test-to-Stay After SARS-CoV-2 Exposure: A Mitigation Strategy for Optionally Masked K-12 Schools.

OBJECTIVES: We evaluated the impact of a test-to-stay (TTS) program on within-school transmission and missed school days in optionally masked kindergarten through 12th grade schools during a period of high community severe acute respiratory syndrome coronavirus 2 transmission. METHODS: Close contacts of those with confirmed severe acute respiratory syndrome coronavirus 2 infection were eligible for enrollment in the TTS program if exposure to a nonhousehold contact occurred between November 11, 2021 and January 28, 2022. Consented participants avoided school exclusion if they remained asymptomatic and rapid antigen testing at prespecified intervals remained negative. Primary outcomes included within-school tertiary attack rate (test positivity among close contacts of positive TTS participants) and school days saved among TTS participants. We estimated the number of additional school-acquired cases resulting from TTS and eliminating school exclusion. RESULTS: A total of 1675 participants tested positive or received at least 1 negative test between days 5 and 7 and completed follow-up; 92% were students and 91% were exposed to an unmasked primary case. We identified 201 positive cases. We observed a tertiary attack rate of 10% (95% confidence interval: 6%-19%), and 7272 (89%) of potentially missed days were saved through TTS implementation. We estimated 1 additional school-acquired case for every 21 TTS participants remaining in school buildings during the entire study period. CONCLUSIONS: Even in the setting of high community transmission, a TTS strategy resulted in substantial reduction in missed school days in optionally masked schools.

The trial to assess chelation therapy 2 (TACT2): Rationale and design.

BACKGROUND: Intravenous edetate disodium-based infusions reduced cardiovascular events in a prior clinical trial. The Trial to Assess Chelation Therapy 2 (TACT2) will replicate the initial study design. METHODS: TACT2 is an NIH-sponsored, randomized, 2x2 factorial, double masked, placebo-controlled, multicenter clinical trial testing 40 weekly infusions of a multi-component edetate disodium (disodium ethylenediamine tetra-acetic acid, or Na2EDTA)-based chelation solution and twice daily oral, high-dose multivitamin and mineral supplements in patients with diabetes and a prior myocardial infarction (MI). TACT2 completed enrollment of 1000 subjects in December 2020, and infusions in December 2021. Subjects are followed for 2.5 to 5 years. The primary endpoint is time to first occurrence of all-cause mortality, MI, stroke, coronary revascularization, or hospitalization for unstable angina. The trial has >;85% power to detect a 30% relative reduction in the primary endpoint. TACT2 also includes a Trace Metals and Biorepository Core Lab, to test whether benefits of treatment, if present, are due to chelation of lead and cadmium from patients. Design features of TACT2 were chosen to replicate selected features of the first TACT, which demonstrated a significant reduction in cardiovascular outcomes in the EDTA chelation arm compared with placebo among patients with a prior MI, with the largest effect in patients with diabetes. RESULTS: Results are expected in 2024. CONCLUSION: TACT2 may provide definitive evidence of the benefit of edetate disodiumbased chelation on cardiovascular outcomes, as well as the clinical importance of longitudinal changes in toxic metal levels of participants.

Test-to-Stay After Exposure to SARS-CoV-2 in K-12 Schools.

OBJECTIVES: We evaluated the safety and efficacy of a test-to-stay program for unvaccinated students and staff who experienced an unmasked, in-school exposure to someone with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Serial testing instead of quarantine was offered to asymptomatic contacts. We measured secondary and tertiary transmission rates within participating schools and in-school days preserved for participants. METHODS: Participating staff or students from universally masked districts in North Carolina underwent rapid antigen testing at set intervals up to 7 days after known exposure. Collected data included location or setting of exposure, participant symptoms, and school absences up to 14 days after enrollment. Outcomes included tertiary transmission, secondary transmission, and school days saved among test-to-stay participants. A prespecified interim safety analysis occurred after 1 month of enrollment. RESULTS: We enrolled 367 participants and completed 14-day follow-up on all participants for this analysis. Nearly all (215 of 238, 90%) exposure encounters involved an unmasked index case and an unmasked close contact, with most (353 of 366, 96%) occurring indoors, during lunch (137 of 357, 39%) or athletics (45 of 357, 13%). Secondary attack rate was 1.7% (95% confidence interval: 0.6%-4.7%) based on 883 SARS-CoV-2 serial rapid antigen tests with results from 357 participants; no tertiary cases were identified, and 1628 (92%) school days were saved through test-to-stay program implementation out of 1764 days potentially missed. CONCLUSION: After unmasked in-school exposure to SARS-CoV-2, even in a mostly unvaccinated population, a test-to-stay strategy is a safe alternative to quarantine.

Supportive Care Needs and Health-Related Quality of Life of Esophageal Cancer Survivors.

OBJECTIVE: The aim of this study is (1) to describe the prevalence and correlates of unmet needs among esophageal cancer survivors (ECS) in Korea and (2) to identify the association between unmet needs and health-related quality of life (HRQOL). METHODS: We used a cross-sectional descriptive study design. Participants were 118 ECS from a hospital in Korea who received surgery at least 12 months before participating. We collected data including the Supportive Care Needs Survey-short form 34 and to measure HRQOL, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 with a self-report questionnaire. RESULTS: Participants' mean age was 65.2 years, and 92.4% were male. Among five domains of supportive care needs, unmet need prevalence ranged from 0.8% to 50%. The most commonly reported domains of unmet needs were Health System and Information and Physical and Daily Living. Participants with unmet needs in Psychological Needs, Physical and Daily Living Needs, and Patient Care and Support Needs demonstrated significantly poorer HRQOL in almost all measured domains. CONCLUSIONS: Our finding suggests that Korean ECS had substantial unmet needs, especially in the Health System and Information domain. Psychological, Patient Care and Support, and Physical and Daily Living Needs were related to HRQOL. The study can advance understanding of priority issues in ECS.

Genetic correlations between traits associated with hyperuricemia, gout, and comorbidities.

Hypertension, obesity, chronic kidney disease and type 2 diabetes are comorbidities that have very high prevalence among persons with hyperuricemia (serum urate > 6.8 mg/dL) and gout. Here we use multivariate genetic models to test the hypothesis that the co-association of traits representing hyperuricemia and its comorbidities is genetically based. Using Bayesian whole-genome regression models, we estimated the genetic marker-based variance and the covariance between serum urate, serum creatinine, systolic blood pressure (SBP), blood glucose and body mass index (BMI) from two independent family-based studies: The Framingham Heart Study-FHS and the Hypertension Genetic Epidemiology Network study-HyperGEN. The main genetic findings that replicated in both FHS and HyperGEN, were (1) creatinine was genetically correlated only with urate and (2) BMI was genetically correlated with urate, SBP, and glucose. The environmental covariance among the traits was generally highest for trait pairs involving BMI. The genetic overlap of traits representing the comorbidities of hyperuricemia and gout appears to cluster in two separate axes of genetic covariance. Because creatinine is genetically correlated with urate but not with metabolic traits, this suggests there is one genetic module of shared loci associated with hyperuricemia and chronic kidney disease. Another module of shared loci may account for the association of hyperuricemia and metabolic syndrome. This study provides a clear quantitative genetic basis for the clustering of comorbidities with hyperuricemia.

Rationale and design of PROACT Xa: A randomized, multicenter, open-label, clinical trial to evaluate the efficacy and safety of apixaban versus warfarin in patients with a mechanical On-X Aortic Heart Valve.

Vitamin K antagonists are the only approved oral anticoagulants for long-term prophylaxis against valve thrombosis and thromboembolism in patients with a mechanical heart valve. Despite the proven efficacy and safety of anticoagulation with the oral direct factor Xa inhibitor apixaban compared with warfarin in high-risk populations including subjects with atrial fibrillation or with venous thromboembolism, it remains unknown whether patients with a mechanical heart valve can be safely managed with apixaban. The On-X Aortic Heart Valve and On-X Ascending Aortic Prosthesis with the Vascutek Gelweave Valsalva Graft may have lower rates of valve thrombosis and thromboembolism than conventional bileaflet and tilting disc valves due its unique pyrolytic carbon composition and flared inlet design. DESIGN: PROACT Xa is a randomized, multicenter, open-label, active-controlled trial comparing apixaban with warfarin in patients with an On-X Aortic Heart Valve or On-X Ascending Aortic Prosthesis with the Vascutek Gelweave Valsalva Graft. The study will randomize approximately 1,000 patients from approximately 60 sites in North America who underwent aortic valve replacement at least 3 months prior. Patients will be randomized 1:1 to receiving apixaban 5 mg twice daily or warfarin with a target international normalized ratio of 2.0-3.0. The last randomized participant will be followed for at least 2 years. The primary efficacy outcome is the composite of valve thrombosis and valve-related thromboembolism, and the primary safety outcome is major bleeding. Assuming the primary outcome occurs in warfarin-anticoagulated patients at a rate of 1.75%/patient-year, the study has more than 90% power to assess noninferiority of apixaban treatment with an absolute noninferiority margin of 1.75%/patient-year. A second co-primary analysis is to compare the hazard rate for the apixaban arm to twice the objective performance criterion for thromboembolism and valve thrombosis, that is, 3.4%/patient-year. SUMMARY: PROACT Xa will determine whether patients with an On-X Aortic Heart Valve can be anticoagulated with apixaban as an alternative to warfarin.

Possible differential benefits of edetate disodium in post-myocardial infarction patients with diabetes treated with different hypoglycemic strategies in the Trial to Assess Chelation Therapy (TACT).

BACKGROUND: The NIH-funded Trial to Assess Chelation Therapy (TACT) randomized 1708 stable patients age ≥50 who were ≥6 months post myocardial infarction to 40 infusions of an edetate disodium-based regimen or placebo. In 633 patients with diabetes, edetate disodium significantly reduced the primary composite endpoint of mortality, recurrent myocardial infarction, stroke, coronary revascularization, or hospitalization for angina (hazard ratio [HR] 0.59, 95% confidence interval [CI] 0.44-0.79, p < 0.001). The principal secondary endpoint of a composite of cardiovascular death, myocardial infarction, or stroke was also reduced (HR 0.60, 95% CI 0.39-0.91, p = 0.017). It is unknown if the treatment effect differs by diabetes therapy. METHODS: We grouped the subset of 633 patients with diabetes according to glucose-lowering therapy at time of randomization. The log-rank test was used to compare active therapy versus placebo. All treatment comparisons were performed using 2-sided significance tests at the significance level of 0.05 and were as randomized. Relative risks were expressed as HR with associated 95% CI, calculated using the Cox proportional hazards model. RESULTS: There were 162 (25.7%) patients treated with insulin; 301 (47.5%) with oral hypoglycemics only; and 170 (26.8%) receiving no pharmacologic treatment for diabetes. Patients on insulin reached the primary endpoint more frequently than patients on no pharmacologic treatment [61 (38%) vs 49 (29%) (HR 1.56, 95% CI 1.07-2.27, p = 0.022)] or oral hypoglycemics [61 (38%) vs 87 (29%) (HR 1.46, 1.05-2.03, p = 0.024)]. The primary endpoint occurred less frequently with edetate disodium based therapy versus placebo in patients on insulin [19 (26%) vs 42 (48%) (HR 0.42, 95% CI 0.25-0.74, log-rank p = 0.002)], marginally in patients on oral hypoglycemics [38 (25%) vs 49 (34%) (HR 0.66, 95% CI 0.43-1.01, log-rank p = 0.041)], and no significant difference in patients not treated with a pharmacologic therapy [23 (25%) vs 26 (34%) (HR 0.69, 95% CI 0.39-1.20, log-rank p = 0.225)]. The interaction between randomized intravenous treatment and type of diabetes therapy was not statistically significant (p = 0.203). CONCLUSIONS: Edetate disodium treatment in stable, post-myocardial infarction patients with diabetes suggests that patients on insulin therapy at baseline may accrue the greatest benefit. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov identifier: http://clinicaltrials.gov/ct2/show/NCT00044213?term=TACT&rank=7 identifier Trial to Assess Chelation Therapy (TACT), NCT00044213.

The mediating and moderating effects of meaning in life on the relationship between depression and quality of life in patients with dysphagia.

AIMS AND OBJECTIVES: To identify whether meaning in life has moderating and mediating effects on the relationship between depression and quality of life in patients with dysphagia. BACKGROUND: Dysphagic patients typically have multidimensional problems, such as depression, which can negatively influence their quality of life. Meaning in life, therefore, can be used as a psychological resource that may enhance quality of life for these patients. DESIGN: A descriptive cross-sectional research design was used. METHODS: Ninety patients with dysphagia were recruited for a survey from eight general and rehabilitation hospitals in Korea. The questionnaires, which included the Korean version of the Swallowing Quality of Life scale developed by Cha, the Center for Epidemiological Studies-Depression Scale developed by Radloff, and the Purpose in Life test developed by Crumbaugh and Maholick, were used for data collection. Descriptive statistics, Hayes' PROCESS macro and Cronbach's alpha were used for data analyses. RESULTS: Meaning in life was found to mediate the relationship between depression and quality of life in patients with dysphagia. However, the index of moderation was not statistically significant, which mean that meaning in life did not moderate the relationship between the patients' depression and quality of life. CONCLUSIONS: Meaning in life had a mediating effect on the relationship between depression and quality of life in patients with dysphagia. Thus, to improve the quality of life of patients with dysphagia, nurses should apply interventions to help them find meaning in life. RELEVANCE TO CLINICAL PRACTICE: Meaning in life can be used as a nursing intervention strategy to improve the quality of life for patients living with dysphagia and depression.

The effect of EDTA-based chelation on patients with diabetes and peripheral artery disease in the Trial to Assess Chelation Therapy (TACT).

OBJECTIVE: Approximately 1 in 7 US adults have diabetes; and over 60% of deaths in patients with diabetes have cardiac disease as a principal or contributing cause. Both coronary and peripheral artery disease (PAD) identify high-risk cohorts among patients with diabetes. We have previously demonstrated improved cardiovascular outcomes with edetate disodium-based chelation in post-MI patients with diabetes, enrolled in the Trial to Assess Chelation Therapy (TACT). In these analyses we further studied the effect size of patients with diabetes and severe disease in 2 vascular beds; coronaries, and lower extremity arteries. We questioned whether greater atherosclerotic burden would attenuate the observed beneficial effect of edetate disodium infusions. RESEARCH DESIGN AND METHODS: The multicenter TACT used a double blind, placebo controlled, 2 × 2 factorial design with 1708 participants, randomly assigned to receive edetate disodium-based chelation, or placebo and high dose oral vitamins or placebo. There were 162 (9.5% of 1708) post-MI patients with a diagnosis of diabetes mellitus and PAD for this post hoc analysis. Patients received up to 40 double-blind intravenous infusions of edetate disodium-based chelation, or placebo. The composite primary endpoint of TACT consisted of death from any cause, myocardial infarction, stroke, coronary revascularization and hospitalization for angina. RESULTS: The median age was 66 years, 15% female, 5% non-Caucasian, and BMI was 31. Insulin was used by 32% of patients. Active infusions significantly reduced the primary endpoint compared with placebo infusions (HR, 0.52; 95% CI, 0.30-0.92; P = 0.0069), with a 30% absolute risk reduction in the primary endpoint. There was a marked reduction in total mortality from 24% to 11%, although of borderline significance (P = 0.052). CONCLUSION: Atherosclerotic disease in multiple vascular beds did not attenuate the beneficial effect of edetate disodium infusions in post MI patients with diabetes. Studies now in progress will prospectively test this post hoc finding.

Understanding and Preventing Loss to Follow-up: Experiences From the Spinal Cord Injury Model Systems.

Background: One of the most critical threats to the validity of any longitudinal research is the bias caused by study attrition. Prevention efforts should be focused on those individuals at high risk of non-participation to improve the generalizability of study findings. Objective: To identify demographic and clinical factors associated with loss to follow-up (FU) at post-injury years 1 to 35 among 25,871 people with spinal cord injury (SCI) enrolled in the National Spinal Cord Injury Database. Methods: Loss to FU was defined as no research information obtained from participants who were eligible for the planned data collection. Generalized linear mixed models were used for analysis of factors at each post-injury year. Results: The loss to FU rates were 23.1% and 32.9% for post-injury years 1 and 5, respectively, and remained >40% between post-injury years 20 and 35. The FU rate varied by study sites and was improved in recent injury cohorts. People who were more seriously injured and those who attained higher levels of education were more likely to return for FU than their counterparts. People who were at risk of being marginalized in society (non-whites, those with less education, the unemployed, victims of violence, and those with no health insurance) had the highest odds of being lost to FU across all post-injury years. Conclusion: These findings can be used to identify individuals who are less likely to participate in follow-up, which may allow targeted attention to improve their response rate.

Will Big Data Close the Missing Heritability Gap?

Despite the important discoveries reported by genome-wide association (GWA) studies, for most traits and diseases the prediction R-squared (R-sq.) achieved with genetic scores remains considerably lower than the trait heritability. Modern biobanks will soon deliver unprecedentedly large biomedical data sets: Will the advent of big data close the gap between the trait heritability and the proportion of variance that can be explained by a genomic predictor? We addressed this question using Bayesian methods and a data analysis approach that produces a surface response relating prediction R-sq. with sample size and model complexity (e.g., number of SNPs). We applied the methodology to data from the interim release of the UK Biobank. Focusing on human height as a model trait and using 80,000 records for model training, we achieved a prediction R-sq. in testing (n = 22,221) of 0.24 (95% C.I.: 0.23-0.25). Our estimates show that prediction R-sq. increases with sample size, reaching an estimated plateau at values that ranged from 0.1 to 0.37 for models using 500 and 50,000 (GWA-selected) SNPs, respectively. Soon much larger data sets will become available. Using the estimated surface response, we forecast that larger sample sizes will lead to further improvements in prediction R-sq. We conclude that big data will lead to a substantial reduction of the gap between trait heritability and the proportion of interindividual differences that can be explained with a genomic predictor. However, even with the power of big data, for complex traits we anticipate that the gap between prediction R-sq. and trait heritability will not be fully closed.

Prospective Endoscopic Ultrasound-Based Approach to the Evaluation of Idiopathic Pancreatitis: Causes, Response to Therapy, and Long-term Outcome.

OBJECTIVES: Although idiopathic pancreatitis is common, the natural history is not well studied, and the best diagnostic approach to both single and multiple attacks remains undefined. METHODS: We prospectively evaluated patients with idiopathic pancreatitis over a 10-year period, and clinical information for each episode was reviewed. Endoscopic ultrasound (EUS) was performed in all patients. Patients with microlithiasis or bile duct stones were referred for cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP), respectively. For those with a single attack, if EUS was normal or chronic pancreatitis or pancreas divisum was diagnosed, the patient was followed up for recurrence. For those with multiple attacks and a negative EUS, ERCP and sphincter of Oddi manometry with endoscopic therapy as appropriate were recommended. All patients were followed up in the long term to evaluate for recurrent pancreatitis, the primary study end point. RESULTS: Over the study period, 201 patients were identified (80 single attack, 121 multiple attacks; mean age 53 years, range 17-95 years, s.d. 16.3 years; and 53% female). After EUS, 54% of patients with a single attack were categorized as idiopathic, and for multiple attacks sphincter of Oddi dysfunction (SOD) was the most common diagnosis (41%). Long-term follow-up (median 37 months; interquartile range 19-70 months) documented recurrence of pancreatitis in 15 (24%; 95% confidence interval (CI), 15-38%) patients with a single attack and in 48 (49%; 95% CI, 38-62%) patients with multiple attacks. Despite endoscopic therapy, patients with pancreas divisum and SOD had relapse rates of 50% (95% CI, 35 to 68%) and 55% (95% CI, 31 to 82%), respectively. CONCLUSIONS: Following a single idiopathic attack of pancreatitis and a negative EUS examination, relapse was infrequent. Despite endoscopic therapy, patients with multiple attacks, especially those attributed to pancreas divisum and SOD, had high rates of recurrence. EUS may be a useful, minimally invasive tool for the diagnostic evaluation of idiopathic pancreatitis. The study was listed in Clinicaltrials.gov NCT00609726.

Prospective Evaluation of the Clinical Features of Choledocholithiasis: Focus on Abdominal Pain.

OBJECTIVES: Although abdominal pain is a cardinal feature of choledocholithiasis, there has been little formal study of the features of pain in this condition. The objective of this study was to prospectively evaluate the clinical, laboratory, and radiological features of common bile duct stones, focusing on the characteristics of abdominal pain. METHODS: All of the patients evaluated for choledocholithiasis at the time of endoscopic cholangiopancreatography during a 3.5-year period were prospectively interviewed and evaluated. Specific features of abdominal pain were recorded, including pertinent radiographic and laboratory data and endoscopic cholangiopancreatography findings. RESULTS: During the 42-month study period, 61 patients (mean age 55.3 years; 42.6% men) were identified; 31 patients (50.8%) had undergone cholecystectomy. Of the 52 patients who reported pain, abdominal pain was most commonly described as constant (100%), located in the epigastrium alone (65%) or both the epigastrium and the right upper quadrant (25%), occurring at night (44.3%), and radiating to the back (59.6%) with the number of distinct pain episodes before diagnosis ranging from 1 to 20. The median duration of pain was 3 hours and ranged from 20 minutes to 2 days. Associated symptoms of nausea (69.2%) and vomiting (30.7%) were common. No differences in pain characteristics were detected between those with or without a prior cholecystectomy. Liver tests were abnormal in all patients, with serum transaminase values being most elevated. CONCLUSIONS: In our study, choledocholithiasis had a characteristic pattern of constant epigastric pain radiating to the back that was associated with nausea. A prior episode was common. The most common laboratory abnormality was transaminase elevation, and the most common imaging finding was common bile duct dilatation.

Performance characteristic of endoscopic ultrasound-guided fine needle aspiration is unaffected by pancreatic mass size.

BACKGROUND AND STUDY AIMS: Despite a well-established tool for diagnosis of pancreatic masses, endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) studies have shown suboptimal diagnostic performance at divergent mass sizes. Since the impact of gold standard follow-up and presence of on-site evaluation on this observation is unknown, we aimed to study the performance characteristics of EUS-FNA under these strict conditions. PATIENTS AND METHODS: EUS-FNA results from pancreatic mass lesions performed between July 2000 and March 2013 were evaluated. All patients with histological follow-up were then stratified into four groups: Group A ( ≤ 10 mm), Group B (11 - 20 mm), Group C (21 - 40 mm), and Group D (> 40 mm). Sensitivity and diagnostic accuracy were calculated for each group and compared. RESULTS: A total of 612 /3832 (16 %) patients with pancreatic masses who underwent EUS-FNA had histology confirmation. Of these, 81 were excluded due to unavailable lesion size, while the rest formed the study cohort. Mean age (SD) was 65.8 years (9.3) with 51.2 % female. The mean number of passes for the entire cohort was 2.9 (SD 1.9; range 1 - 12); patients in group D had a significantly higher number of passes for on-site diagnosis (P = 0.0124). There was no significant difference between the groups for sensitivity (P = 0.1134) or diagnostic accuracy (P = 0.2111). Proportional trend analysis revealed no significant correlation between size and sensitivity (P = 0.6192). The size of lesion measured by EUS was not associated with sensitivity or specificity after adjusting for age, sex, and pancreatic location. CONCLUSION: In the presence of rapid on-site cytopathology and when final histology is taken as the gold standard, pancreatic mass size does not affect the performance characteristics of EUS-FNA.

Clinical Alarms in Intensive Care Units: Perceived Obstacles of Alarm Management and Alarm Fatigue in Nurses.

OBJECTIVES: The purpose of this descriptive study was to investigate the current situation of clinical alarms in intensive care unit (ICU), nurses' recognition of and fatigue in relation to clinical alarms, and obstacles in alarm management. METHODS: Subjects were ICU nurses and devices from 48 critically ill patient cases. Data were collected through direct observation of alarm occurrence and questionnaires that were completed by the ICU nurses. The observation time unit was one hour block. One bed out of 56 ICU beds was randomly assigned to each observation time unit. RESULTS: Overall 2,184 clinical alarms were counted for 48 hours of observation, and 45.5 clinical alarms occurred per hour per subject. Of these, 1,394 alarms (63.8%) were categorized as false alarms. The alarm fatigue score was 24.3 ± 4.0 out of 35. The highest scoring item was "always get bothered due to clinical alarms". The highest scoring item in obstacles was "frequent false alarms, which lead to reduced attention or response to alarms". CONCLUSIONS: Nurses reported that they felt some fatigue due to clinical alarms, and false alarms were also obstacles to proper management. An appropriate hospital policy should be developed to reduce false alarms and nurses' alarm fatigue.