Three-year Risk Research Articles

GLP1-RA versus DPP4 inhibitors on cardiovascular outcomes: A three-year real-world analysis

Abstract Background Cardiovascular outcome trials of GLP1-RAs have massively impacted the clinical practice in the management of patients with type 2 diabetes. The cardiovascular protective properties of GLP1-RA compared to DPP4 have been demonstrated in an observational setting before, however recent methodological developments have enabled clinically relevant effect estimation. Aim This study aimed to evaluate the real-world cardiovascular outcomes of GLP1-RA versus DPP4 inhibitors in patients with type 2 diabetes and high cardiovascular risk. Methods In this study, we utilized the Danish nationwide registers to identify new users of GLP1-RA or DPP4 therapies from 2012 to 2022. Participants were required to be either at least 50 years of age and have one or more of the following conditions: hypertension, chronic obstructive pulmonary disease, cardiovascular disease, or chronic renal disease or be at least 60 years of age and have hypertension. Additionally, their glycated hemoglobin (HbA1c) levels needed to be 53 mmol/mol or higher within the year preceding their first prescription date for these therapies. The index date was defined as the initial prescription date, and comorbidities and medicine use were evaluated up to 10 years prior to this date. Individuals who had filled prescriptions for SGLT2 inhibitors within six months prior to their index date were excluded from the study. The outcome of interest was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (MACE). Patients were followed for up to three years until MACE, all-cause mortality, emigration, or until the end of follow-up on December 31, 2022. To assess the three-year risk of MACE, the Aalen Johansson estimator was used. A casual inference framework was employed estimating the three-year average treatment effect using g-formula based on Cox regression with competing risk. Results A total of 26,190 individuals were included, with 19,494 initiating DPP4 inhibitor therapy and 6,696 initiating GLP1-RA therapy. The three-year risk of MACE was 8.56% (95% confidence interval [CI]: 8.11 to 9.00) for the DPP4 initiator group, compared to 4.76% (95% CI: 4.08 to 5.43) for the GLP1-RA initiator group. Emulating what would have happened had all included individuals initiated GLP1-RA treatment versus had all initiated treatment with DPP4, accounting for age, sex, income, education, degree of urbanization, diabetes duration, baseline hba1c level, co-medicine, and co-morbidities, we estimated an three-year average treatment effect of -2.05% (95% CI:-2.92;-1.18) , p-value<0.001) for GLP1-RA initiation versus DPP4 initiation for MACE. Conclusion Our findings suggest that GLP1-RA use is associated with a significantly lower risk of MACE compared to DPP4 inhibitors in a real-world population of patients with type 2 diabetes and high cardiovascular risk. This supports the cardiovascular protective role of GLP1-RA in clinical practice.

1327-P: Novel Subgroups of the Three-Year Risk of Incident Diabetes and Complications in Chinese Diabetes-Free Adults

1327-P: Novel Subgroups of the Three-Year Risk of Incident Diabetes and Complications in Chinese Diabetes-Free Adults

Data-driven clustering approach to identify novel clusters of high cognitive impairment risk among Chinese community-dwelling elderly people with normal cognition: A national cohort study.

Cognitive impairment is a highly heterogeneous disorder that necessitates further investigation into the distinct characteristics of populations at varying risk levels of cognitive impairment. Using a large-scale registry cohort of elderly individuals, we applied a data-driven approach to identify novel clusters based on diverse sociodemographic features. A prospective cohort of 6398 elderly people from the Chinese Longitudinal Healthy Longevity Survey, followed between 2008-14, was used to develop and validate the model. Participants were aged ≥60 years, community-dwelling, and the Chinese version of the Mini-Mental State Examination (MMSE) score ≥18 were included. Sixty-nine sociodemographic features were included in the analysis. The total population was divided into two-thirds for the derivation cohort (n = 4265) and one-third for the validation cohort (n = 2133). In the derivation cohort, an unsupervised Gaussian mixture model was applied to categorise participants into distinct clusters. A classifier was developed based on the most important 10 factors and was applied to categorise participants into their corresponding clusters in a validation cohort. The difference in the three-year risk of cognitive impairment was compared across the clusters. We identified four clusters with distinct features in the derivation cohort. Cluster 1 was associated with the worst life independence, longest sleep duration, and the oldest age. Cluster 2 demonstrated the highest loneliness, characterised by non-marital status and living alone. Cluster 3 was characterised by the lowest sense of loneliness and the highest proportions in marital status and family co-residence. Cluster 4 demonstrated heightened engagement in exercise and leisure activity, along with independent decision-making, hygiene, and a diverse diet. In comparison to Cluster 4, Cluster 1 exhibited the highest three-year cognitive impairment risk (adjusted odds ratio (aOR) = 3.31; 95% confidence interval (CI) = 1.81-6.05), followed by Cluster 2 and Cluster 3 after adjustment for baseline MMSE, residence, sex, age, years of education, drinking, smoking, hypertension, diabetes, heart disease and stroke or cardiovascular diseases. A data-driven approach can be instrumental in identifying individuals at high risk of cognitive impairment among cognitively normal elderly populations. Based on various sociodemographic features, these clusters can suggest individualised intervention plans.

391 Value estimation of the Diabetes Prevention Program: How well does clinical trial-based cost-effectiveness apply to the real world?

OBJECTIVES/GOALS: Many economic evaluations rely on clinical trial data that may not represent real world populations and intervention effectiveness. We compare risk and cost-effectiveness for the Diabetes Prevention Program (DPP) clinical trial cohort and a real world population eligible for the national DPP to assess the impact of using real world data. METHODS/STUDY POPULATION: To produce real world (US population) representative results, we identified National Health and Nutrition Examination Survey (NHANES) subjects eligible for the national DPP and adjusted projections using survey weights. We used clinical predictive models to estimate individual diabetes risk, and microsimulation to estimate lifetime costs, benefits, and net monetary benefits (NMB) for lifestyle intervention and metformin. We compared results across the DPP clinical trial and NHANES populations. RESULTS/ANTICIPATED RESULTS: Three-year risk of diabetes onset for the DPP trial population (mean of 19.7%, median of 10.3%) exceeded corresponding risk for the NHANES population (mean of 14.6%, median of 4.8%). The proportion of individuals with a three-year diabetes risk < 10% for the DPP trial population (49%) was less than the corresponding proportion for NHANES (67%). Mean NMB for metformin for the DPP trial population ($9,749) exceeded the corresponding value for NHANES ($5,391). The proportion of subjects with negative NMB was 49% for the DPP trial population and 67% for NHANES. Lifestyle intervention had a mean NMB of $34,889 for the DPP trial population and $28,652 for NHANES. Only 20% of the NHANES population eligible for national DPP met inclusion/exclusion criteria for the DPP trial. DISCUSSION/SIGNIFICANCE: Real world populations eligible for the national DPP include a greater proportion of low-risk individuals, and for these people, prevention programs may confer smaller benefits. Technology assessments based on clinical trial data should be revised using real world population and treatment effect data.

A Novel Model Using Serum Thymidine Kinase 1 and Low-dose Computed Tomography Parameters to Predict Three-year Lung Cancer Risk in People with Pulmonary Nodules: A Retrospective Study.

This study was designed to develop a model of serum thymidine kinase 1 protein (STK1p) concentration in combination with low-dose computed tomography (LDCT) to predict the risk of benign pulmonary nodules progressing into lung cancer within three years in a large screening population. The study included a retrospective cohort of 6,841 individuals aged > 30 years who had LDCT-detected pulmonary nodules, but no cancer history or baseline cancer. The outcome was a lung cancer diagnosis recorded within three years after the first detection of pulmonary nodules. The adaptive least absolute shrinkage and selection operator was used to select candidate predictors and fit a logistic model. The model was validated internally by examining discrimination (area under the receiver operating characteristic curve (AUC), calibration (calibration plot)) and net benefit. A web application was developed based on the model. The results showed that the proportion of incident lung cancer cases was 0.79% (n=52). Predictors selected for the model were STK1p and three LDCT parameters (nodule size, type, and count). The AUC of the model was 0.91 (95% confidence interval (CI): 0.86, 0.96). The model had satisfactory discrimination at internal validation (AUC: 0.90 (0.84, 0.96)) and in subgroups (AUC=0.69-0.93). The high-risk group identified by the model exhibited a significantly higher three-year lung cancer risk than the low-risk group (odds ratio (OR): 66.03 (95% CI: 30.49, 162.98)). We concluded that the novel model of STK1p and LDCT parameters together can be used to accurately predict the three-year risk of lung cancer in people with pulmonary nodules.

Age-Specific Cardiovascular Risk Factors for Major Adverse Cardiac Events in Patients Undergoing Myocardial Perfusion Imaging.

The prevalence of traditional cardiovascular risk factors shows different age-specific patterns. It is not known whether the prognostic impact of risk factors is similarly age-specific. We evaluated the profiles of cardiovascular risk factors and their prognostic impact on coronary artery disease (CAD) in relation to age. We included 3667 patients with suspected or known CAD undergoing stress myocardial perfusion imaging (MPI). We evaluated the risk for major adverse cardiac events (MACE) within three years from the index MPI in patients belonging to three groups according to age tertile distribution: <59, 59-68, and >68 years. Gender, body mass index, diabetes, hypertension, dyslipidemia, family history of CAD, smoking, angina, dyspnea, previous CAD, and MPI outcome were assessed as risk factors by a multivariable Cox's regression. The three-year risk of MACE increased progressively with age and was 9%, 13%, and 18% for each group, respectively (p < 0.0001). Dyspnea and abnormal MPI outcome were significant risk factors for all age groups. Diabetes and smoking were significant from the age of 59 onwards, while hypertension resulted significant for patients older than 68 years. The number of risk factors was significantly associated with the occurrence of MACE increase with age. It is noteworthy that a personal history of CAD was not useful for risk stratification, while MPI results were.

Single-Institution Prospective Evaluation of Moderately Hypofractionated Whole-Breast Radiation Therapy With Simultaneous Integrated Boost With or Without Lymphatic Drainage Irradiation After Breast-Conserving Surgery

We report treatment outcomes for patients who received adjuvant moderate hypofractionated whole-breast radiation therapy with simultaneous integrated boost (SIB-mhWBRT) after breast-conserving surgery. SIB-mhWBRT for patients with breast cancer was introduced in our department in July 2017. This prospective evaluation includes 424 consecutive patients treated with SIB-mhWBRT for stage I-III invasive breast cancer (n=391) and/or ductal carcinoma in situ (n=33) until December 2021. SIB-mhWBRT was applied with 40 Gy in 15 daily fractions over 3 weeks according to the START B trial, with an SIB dose to the tumor bed of 48 Gy according to Radiation Therapy Oncology Group 1005/UK-IMPORT-HIGH, delivered as 3-dinemsional conformal radiation therapy (RT; n=402), intensity modulated RT (n=4), or volumetric modulated arc therapy (n=18). The mean patient age was 60 years (range, 27-88). Since May 2018, patients with indications for lymphatic pathway RT were included (n=62). Baseline parameters and follow-up data were recorded and reported, including objective assessment of treatment-related outcomes and subjective patient-reported outcome measures (PROMs). Mean/median follow-up was 29/33 months (range, 2-60). Acute toxicity grade 0, 1, 2, and 3 was observed in 25.0%, 61.4%, 13.3%, and 0%, respectively, at the completion of RT. Data of 281, 266, 243, 172, and 58 patients were available for 6-month and 1-, 2-, 3-, and 4-year follow-up, respectively. Grade 2 late effects were identified in 8.5%, 6.0%, 4.9%, 2.2%, and 10.2% and grade 3 in 2.8%, 1.1%, 1.2%, 0%, and 0% of patients at 6-month and 1-, 2-, 3-, and 4-year follow-up, respectively. Medical treatment of breast edema was the only grade 3 late effect observed. PROM cosmesis results were evaluated as excellent-good, fair, and poor in 97.2%, 2.5%, and 0.4%; 96.5%, 3.1%, and 0.4%; 97.4%, 2.2%, and 0.4%; 97.5%, 2.5%, and 0%; and 96.5%, 3.5%, and 0.0% at 6 months and 1, 2, 3, and 4 years post-RT, respectively. For all patients, the 3-year overall, cancer-specific, and disease-free survival rates were 98.2%, 99.1%, and 95.9%, respectively. Three-year risk of any locoregional recurrence was 0.6%. No mortality or relapse was observed in patients with ductal carcinoma in situ. SIB-mhWBRT demonstrated very favorable side effect profiles and cosmesis/PROMs. Three-year results demonstrate excellent locoregional control. This short-term regimen offers substantial patient comfort and improves institutional efficacy.

МОДЕЛИ ПРОГНОЗА ПРОГРЕССИРУЮЩЕГО ТЕЧЕНИЯ ХРОНИЧЕСКИХ ГЛОМЕРУЛОПАТИЙ У ДЕТЕЙ

Background. The study of the rate of progression, the identification of the most significant risk factors for the unfavorable course of chronic glomerulopathies (GP) for the implementation of preventive measures is an important research area. Purpose of the study. Development of mathematical models for the short-term prognosis of the progression of primary and secondary chronic GP in children. Material and methods. A comprehensive examination was carried out of 88 patients with secondary, 188 with primary morphologically verified GP, who were under observation in the center of pediatric nephrology and renal replacement therapy "2nd Children’s Hospital" Minsk. Results. Anamnestic, clinical, laboratory, instrumental and morphological data were analyzed with the subsequent determination of the most significant factors associated with progression. Mathematical models have been developed for the short-term prognosis of the progressive course of primary and secondary GP in children. Conclusions. The most significant factors associated with a three-year risk of predicting the progression of primary (impaired renal function at the onset of the disease and glomerular filtration rate (GFR) &lt;87 ml/min/1.73 m2) and secondary (perinatal factors of kidney damage, recurrent course of the disease, persistent nephrotic proteinuria, decreased GFR at the onset of the disease) GP in children. With the help of prognostic models, threshold values were calculated and classification schemes were created, which enable to calculate the patient's belonging to the risk group of a progressive course based on the calculation of points for timely correction.

MP62-12 CONDITIONAL FREEDOM FROM PROGRESSION ON ACTIVE SURVEILLANCE OF PROSTATE CANCER STRATIFIED BY NCCN RISK

You have accessJournal of UrologyProstate Cancer: Localized: Active Surveillance II (MP62)1 Sep 2021MP62-12 CONDITIONAL FREEDOM FROM PROGRESSION ON ACTIVE SURVEILLANCE OF PROSTATE CANCER STRATIFIED BY NCCN RISK Joshua Harvey, Andrew Gusev, Florian Rumpf, Keyan Salari, Jeffrey Twum-Ampofo, Matthew Wszolek, Douglas Dahl, Michael Blute, and Adam Feldman Joshua HarveyJoshua Harvey More articles by this author , Andrew GusevAndrew Gusev More articles by this author , Florian RumpfFlorian Rumpf More articles by this author , Keyan SalariKeyan Salari More articles by this author , Jeffrey Twum-AmpofoJeffrey Twum-Ampofo More articles by this author , Matthew WszolekMatthew Wszolek More articles by this author , Douglas DahlDouglas Dahl More articles by this author , Michael BluteMichael Blute More articles by this author , and Adam FeldmanAdam Feldman More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000002102.12AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Active surveillance (AS) is an accepted strategy for men with very low, low, and select cases of favorable intermediate National Comprehensive Cancer Network (NCCN) risk prostate cancer (PCa). However it is not well defined how the risk of progression evolves during AS. Conditional survival measures the probability a patient will continue to survive some number of years, given that they have already survived a certain number without progression. We evaluated our AS cohort to investigate overall and conditional progression free survival on AS, stratified by the NCCN risk groups. METHODS: We reviewed our institutional database of 1252 men enrolled in AS for localized PCa from 1996-2016. Overall freedom from pathologic grade progression on follow-up biopsy and treatment free survival were estimated using the Kaplan-Meier method. Survival curves were compared pairwise using the Log-rank test and adjusted for false discovery rates with the Benjamini-Hochberg procedure. Three-year conditional survival estimates were derived for both outcomes from the Kaplan-Meier estimator. RESULTS: Of 1252 men, 521 (41.6%) met criteria for very low, 606 (48.4%) for low, and 125 (10.0%) for favorable intermediate NCCN risk at diagnosis. Median follow-up time was 6.5 years (IQR 4.1-9.4). Median pathologic grade progression free survival in years was significantly longer for very low risk (7.8, 95% CI 6.8-11.2) compared to low risk men (5.6, 95% CI 4.7-6.9), however neither was significantly different from favorable intermediate risk men (5.9). There was no significant difference in treatment free survival between the three risk groups. At diagnosis, the three-year risk for pathologic grade progression (24%, 95% CI 21-27%) and progression to treatment (22%, 95% CI 20-25%) were similar. However, with increasing time of event-free AS, the conditional probability of pathologic grade progression increased, while that of progression to treatment decreased. CONCLUSIONS: Our results demonstrate that despite a mild increase in pathologic progression free survival in very low risk men, there was no clear difference in overall treatment free survival between very low, low, and select favorable intermediate NCCN risk men. Further, with increased time spent on AS, despite elevated rates of pathologic progression, patient progression to treatment decreased. This trend may be indicative of changes in goals of care as men with PCa age and should be closely monitored during AS. Source of Funding: None © 2021 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 206Issue Supplement 3September 2021Page: e1096-e1097 Advertisement Copyright & Permissions© 2021 by American Urological Association Education and Research, Inc.MetricsAuthor Information Joshua Harvey More articles by this author Andrew Gusev More articles by this author Florian Rumpf More articles by this author Keyan Salari More articles by this author Jeffrey Twum-Ampofo More articles by this author Matthew Wszolek More articles by this author Douglas Dahl More articles by this author Michael Blute More articles by this author Adam Feldman More articles by this author Expand All Advertisement Loading ...

High-dose methotrexate is effective for prevention of isolated CNS relapse in diffuse large B cell lymphoma

The role of central nervous system (CNS) prophylaxis with high-dose methotrexate (HDMTX) in DLBCL is controversial. In this retrospective study, we evaluated the efficacy of prophylactic HDMTX on isolated CNS relapse, concomitant CNS and systemic relapse, systemic relapse, and survival outcomes in 226 patients with newly diagnosed DLBCL and high-risk CNS International Prognostic Index (CNS-IPI) score treated with RCHOP. The three-year risk of isolated CNS relapse was significantly lower in patients who received HDMTX, at 3.1% compared to 14.6% (P = 0.032) in those who did not. However, neither concomitant CNS-systemic relapse rates, systemic relapse rates, nor three-year PFS and OS were significantly different between treatment groups in multivariable analysis. Among propensity score-matched patients (N = 102), HDMTX was also associated with significantly lower isolated CNS relapse rates (HR 0.06, 95% CI 0.004–0.946, P = 0.046). HDMTX was well tolerated with manageable toxicities when given at a dose of 3 g/m2 by day 3 of RCHOP chemotherapy. Using propensity score matching and multivariable regression to yield treatment groups with well-balanced covariates, we showed that prophylactic HDMTX improved isolated CNS relapse rates but did not decrease concomitant CNS-systemic relapse rates, systemic relapse rates, or improve survival outcomes.

High risk of relapse with intermediate dose cytarabine for consolidation in young favourable‐risk acute myeloid leukaemia patients following induction with 7+3: a retrospective multicentre analysis and critical review of the literature

Following the 2017 European LeukemiaNet (ELN) guidelines, we changed our practice from using high-dose cytarabine (HIDAC-3 g/m2 q12h-D1,3,5) to intermediate-dose cytarabine (IDAC-1·5 g/m2 q12h-D1,3,5/D1-3) for consolidation in young(<60years) favourable-risk acute myeloid leukaemia (AML) patients. We assessed the clinical impact of this practice change. Of 80 patients, 51 received HIDAC prior to the protocol change, and subsequently, 29 received IDAC. The three-year risk of relapse was significantly higher with IDAC [61%; 95% confidence interval (CI) 40-82] compared with HIDAC (22%; 10-34), P<0·01. Our findings suggest HIDAC, rather than IDAC, is the preferred dose for single-agent cytarabine consolidation in young, favourable-risk AML following 7+3 induction.

Conditional progression-free survival in men on active surveillance for prostate cancer stratified by NCCN risk.

222 Background: Active surveillance (AS) is an accepted management strategy for men with very low, low, and select cases of favorable intermediate National Comprehensive Cancer Network (NCCN) risk prostate cancer (PCa). However, how patients’ risk of disease progression evolves over time during AS has not been well defined. Conditional survival measures the probability a patient will continue to survive some number of years, given that they have already survived a certain number without progression. We evaluated our AS cohort to investigate overall and conditional progression free survival on AS, stratified by the NCCN risk groups. Methods: We reviewed our institutional database of 1254 men enrolled in AS for localized PCa from 1996-2016. Our AS protocol includes prostate specific antigen (PSA) and digital rectal exam (DRE) every 4-6 months for 3 years, then annually. Mandatory confirmatory 12 core biopsy is done at 12-18 months. Multiparametric magnetic resonance imagining (mpMRI) or additional systematic or MRI-fusion biopsies are done at the discretion of physician and patient. Overall freedom from pathologic grade progression on follow-up biopsy and treatment free survival were estimated using the Kaplan-Meier method. Survival curves were compared pairwise using the Log-rank test and adjusted for false discovery rates with the Benjamini-Hochberg procedure. Three-year conditional survival estimates were derived for both outcomes from the Kaplan-Meier estimator. Results: Of 1254 men, 521 (41.6%) met criteria for very low, 606 (48.4%) for low, and 125 (10.0%) for favorable intermediate NCCN risk at diagnosis. Median follow-up time was 6.5 years (IQR 4.1-9.4). Median pathologic grade progression free survival in years was significantly longer for very low risk (7.8, 95% CI 6.8-11.2) compared to low risk men (5.6, 95% CI 4.7-6.9), however neither was significantly different from favorable intermediate risk men (5.9). There was no significant difference in treatment free survival between the three risk groups. At diagnosis, the three-year risk for pathologic grade progression (24%, 95% CI 21-27%) and progression to treatment (22%, 95% CI 20-25%) were similar. However, with increasing time of event-free AS, the conditional probability of pathologic grade progression increased, while that of progression to treatment decreased. Conclusions: Our results demonstrate that despite a mild increase in pathologic progression free survival in very low risk men, there was no clear difference in overall treatment free survival between very low, low, and select favorable intermediate NCCN risk men. Further, with increased time spent on AS, despite elevated rates of pathologic progression, patient progression to treatment decreased. This trend may be indicative of changes in goals of care as men with PCa age and should be closely monitored during AS.

Predicting adverse outcomes due to diabetes complications with machine learning using administrative health data

Across jurisdictions, government and health insurance providers hold a large amount of data from patient interactions with the healthcare system. We aimed to develop a machine learning-based model for predicting adverse outcomes due to diabetes complications using administrative health data from the single-payer health system in Ontario, Canada. A Gradient Boosting Decision Tree model was trained on data from 1,029,366 patients, validated on 272,864 patients, and tested on 265,406 patients. Discrimination was assessed using the AUC statistic and calibration was assessed visually using calibration plots overall and across population subgroups. Our model predicting three-year risk of adverse outcomes due to diabetes complications (hyper/hypoglycemia, tissue infection, retinopathy, cardiovascular events, amputation) included 700 features from multiple diverse data sources and had strong discrimination (average test AUC = 77.7, range 77.7–77.9). Through the design and validation of a high-performance model to predict diabetes complications adverse outcomes at the population level, we demonstrate the potential of machine learning and administrative health data to inform health planning and healthcare resource allocation for diabetes management.

Association of Glycated Hemoglobin Levels With Risk of Pancreatic Cancer

New-onset diabetes after the age of 50 years is a potential indicator of pancreatic cancer. Understanding the associations between hyperglycemia, diabetes, and pancreatic cancer, including pancreatic ductal adenocarcinoma, is key to developing an approach to early detection. To assess the association of elevation in glycated hemoglobin (HbA1c) with the risk of pancreatic cancer. This cohort study was conducted using data collected from an integrated health care system in California. A total of 851 402 patients aged 50 to 84 years who had HbA1c measurements taken between 2010 and 2014 were identified as the base cohort, with 12 contemporaneous cohorts created based on varying HbA1c thresholds (ie, 6.1%, 6.3%, 6.5%, and 6.7%) and prior diabetes status. Data analysis was conducted from August 2018 to September 2019. New cases of pancreatic cancer identified through cancer registry and California death files during a 3-year period. Three-year risk, incidence rate, sensitivity, number of patients needed to screen to detect 1 case, timing, and stage at diagnosis were determined. Among 851 402 patients in the base cohort, 447 502 (52.5%) were women, 255 441 (30.0%) were Hispanic participants, 383 685 (45.1%) were non-Hispanic white participants, 100 477 (11.8%) were Asian participants, and 88 969 (10.4%) were non-Hispanic black participants, with a median (interquartile range) age of 62 (56-69) years and a median (interquartile range) HbA1c level of 6.0% (5.7%-6.6%). The incidence rate of pancreatic cancer was 0.45 (95% CI, 0.43-0.49) per 1000 person-years. After excluding prior diabetes as well as confirmation of new-onset hyperglycemia based on an HbA1c level of 6.5%, a total of 20 012 patients remained, with 74 of 1041 pancreatic ductal adenocarcinoma cases (7.1%) from the base cohort included. The rate of pancreatic cancer was 0.72 (95% CI, 0.32-1.42) per 1000 person-years among Asian patients, 0.83 (95% CI, 0.35-1.71) per 1000 person-years among non-Hispanic black patients, 0.84 (95% CI, 0.48-1.37) per 1000 person-years among Hispanic patients, and 2.37 (95% CI, 1.75-3.14) per 1000 person-years among non-Hispanic white patients. Overall, 42 of 74 cancers (56.8%) were diagnosed within 1 year of the index laboratory test. Among 1041 total cases, 708 (68.0%) had staging information available, of whom 465 (65.7%) had stage III or IV disease at diagnosis. In the base cohort, the number needed to undergo evaluation to identify a single case of pancreatic ductal adenocarcinoma was 818 (95% CI, 770-869), with estimates ranging from 206 (95% CI, 160-264) to 600 (95% CI, 540-666) in the subcohorts. The findings of this study suggest that screening patients for pancreatic cancer based solely on elevation in HbA1c level is unlikely to represent an effective strategy. Future efforts to identify a high-risk population based on changes in glycemic parameters should account for racial/ethnic differences.

Brain deep medullary veins on 3-T MRI in a population-based cohort

Our aim is to investigate whether vascular risk factors are associated with cerebral deep medullary veins (DMVs) and whether DMVs are associated with MRI markers of cerebral small vessel disease (CSVD) or risk of stroke. In a community-based cohort of 1056 participants (mean age 55.7 years), DMVs were identified on susceptibility-weighted imaging (SWI) and counted in periventricular regions. Neuroimaging markers including lacunes, whiter matter hyperintensity (WMH), microbleeds, enlarged perivascular space, and brain atrophy were evaluated. The number of DMVs decreased with age (p = 0.007). After adjusting for age and sex, the number of DMVs was not associated with traditional vascular risk factors. Fewer DMVs was associated with increase of WMH and lacunes, but the association vanished after adjustment for vascular risk factors. However, fewer DMVs were independently associated with brain atrophy (p < 0.001). DMVs were not associated with three-year risk of stroke. Our results suggest that DMV is significantly different from other MRI markers of CSVD regarding risk factors, association with other CSVD markers, and risk of stroke. Nonetheless, the significant association between DMV and brain atrophy suggested the potential role of venules in age-related neurodegenerative process, which deserves further investigation.

Hypomagnesemia is not an independent risk factor for mortality in Japanese maintenance hemodialysis patients

PurposeIt is unclear whether hypomagnesemia is an independent risk factor or innocent bystander for mortality in maintenance hemodialysis (MHD) patients. Thus, we studied associations between hypomagnesemia and all-cause as well as cardiovascular (CV) mortality in MHD patients.MethodsBaseline clinical characteristics and coronary artery calcium score (CACS) of 353 Japanese MHD patients were reviewed. Three-year survival rate and mortality risk factors were assessed.ResultsMedian (interquartile range) age, dialysis vintage, serum magnesium (Mg), serum albumin and CACS of the subjects were 68 (60–78) years, 75 (32–151) months, 2.4 (2.2–2.7) mg/dl, 3.6 (3.3–3.8) g/dl, and 1181 (278–3190), respectively. During the 3-year period, 91 patients died. Kaplan–Meier overall 3-year survival rates were 59.0% in in patients with Mg < 2.4 mg/dl (n = 136) and 82.3% in patients with Mg ≥ 2.4 mg/dl (n = 217), (P < 0.0001). In Cox regression models not incorporating serum albumin, Mg < 2.4 mg/dl was significantly associated with 3-year all-cause death, independent of age, dialysis vintage, average ultrafiltration, Log (CACS + 1), warfarin use, serum potassium, high-sensitivity C-reactive protein (hsCRP), phosphate, uric acid, and intact parathyroid hormone [Hazard ratio (HR) 95% confidence interval (CI): 2.82 (1.31–6.29), P = 0.0078], and CV death, independent of age, dialysis vintage, Log (CACS + 1), warfarin use, serum hsCRP, and uric acid [HR (95% CI): 4.47 (1.45–16.76), P = 0.0086]. Nevertheless, associations of Mg < 2.4 mg/dl with all-cause and CV mortality were all absent in models that included serum albumin.ConclusionsHypomagnesemia is not an independent risk factor for mortality but is associated with malnutrition in MHD patients.

Depressive Symptoms Increase the Risk of Mortality for White but Not Black Older Adults.

Introduction. Long-term studies have shown that depressive symptoms predict the risk of mortality. However, it is unknown if this effect is present in shorter time intervals. In addition, recent research suggests that the salience of the negative affect on the risk of mortality is not similar across racial groups. The current study uses data from a national study of Black and White older adults to examine racial differences in the effect of baseline depressive symptoms on mortality risk over three years in the United States. Methods. This study used a longitudinal prospective design and followed 1493 older adults who were either White (n = 759) or Black (n = 734) for three years from 2001 to 2004. Depressive symptoms measured at baseline was the independent variable. Demographic factors, socio-economic characteristics (education, income, marital status), health behaviors (smoking and drinking), and health (self-rated health) measured at baseline in 2001 were covariates. The dependent variable was all-cause mortality between 2001 and 2004. Race was the moderator. Logistic regressions were used for data analysis. Results. In the pooled sample, high depressive symptoms at baseline were not associated with the three-year risk of mortality. In the pooled sample, we found a significant interaction between race and depressive symptoms on mortality, suggesting a stronger effect for Whites in comparison to Blacks. In race stratified models, depressive symptoms at baseline were predictive of mortality risk for Whites, but not Blacks. Conclusions. In the United States, Black-White differences exist in the effects of depressive symptoms on mortality risk in older adults. White older adults may be more vulnerable to the effects of depressive symptoms on mortality risk.

Long-term stroke and bleeding risk in patients with atrial fibrillation treated with oral anticoagulants in contemporary practice: Providing evidence for shared decision-making

BackgroundOral anticoagulation is recommended as a lifelong therapy for most patients with atrial fibrillation (AF). However, data on long-term outcomes in clinical practice on these drugs are scarce, particularly for the recently approved agents. We aimed to describe differences in characteristics between patients in everyday practice and those enrolled in the pivotal trials, and to report long-term outcomes on oral anticoagulation in practice. MethodsWe performed a retrospective cohort analysis using a large U.S. administrative database to identify patients with AF initiating oral anticoagulation and examine incident stroke (effectiveness endpoint, including ischemic stroke and systemic embolism) and major bleeding (safety endpoint). ResultsWe identified 107,373 patients with AF initiating anticoagulants 7/1/2006-6/30/2016. These patients were more likely to be elderly, female, or to have advanced kidney disease in comparison to those enrolled in the trials. The event rates for major bleeding (3.1%, 2.8%, 4.0% and 4.9%/year for in apixaban-, dabigatran-, rivaroxaban- and warfarin-treated patients, respectively) were higher than those observed in trials. The event rates for stroke 0.9%, 1.0%, 0.9% and 1.4%/year the four drug cohorts), were similar to the trials. The three-year risk of stroke was 2.3%, 2.1%, 2.3% and 3.5%, and the three year risk of major bleeding was 5.4%, 7.0%, 8.2%, and 11.7% in the four drug cohorts. ConclusionsClinical trials represent a narrow spectrum of the general AF population. The trials may underestimate the bleeding risk observed in practice. This study provides important data to help clinicians communicate expected outcomes to patient during shared decision-making.

Impact of diabetes duration on 3-year clinical outcomes following coronary revascularization.

The aim of this study was to evaluate the impact of diabetes duration on long-term clinical outcomes after drug-eluting stent (DES) implantation or coronary artery bypass grafting (CABG). A total of 820 diabetic patients treated with initial DES (n=451) or CABG (n=369) were consecutively enrolled in this single-center follow-up study. The main outcomes included major adverse cardiac events and major adverse cardiac or cerebrovascular events (MACCEs). Cox regression analysis with propensity adjustment was used for data analysis. Three-year risks of major adverse cardiac events were significantly higher in the DES group compared with the CABG group irrespective of whether the diabetes durations were less or more than 5 years [hazard ratio (HR) 2.27, 95% confidence interval (CI) 1.19-4.31, P=0.01; HR 3.73, 95% CI 2.72-10.12, P<0.01; P for interaction=0.28]. A similar trend was observed for repeat revascularization. However, CABG was associated with increased risk of stroke, especially in the patients with diabetes duration of at least 5 years (HR 0.02, 95% CI 0.002-0.12, P<0.01). Three-year risk of MACCEs was significantly higher in the DES group in patients with diabetes duration of at least 5 years (HR 2.13, 95% CI 1.34-3.39, P<0.01), but not for those less than 5 years (HR 1.03, 95% CI 0.65-1.63, P=0.91). A statistically significant interaction between diabetes duration and treatment strategy was found for MACCEs (P for interaction=0.04). Short diabetes duration (<5 years) was associated with equal risk of MACCEs among stable coronary artery disease patients with DES and CABG, emphasizing the need to consider the duration of diabetes when determining the best strategy for patients undergoing coronary revascularization.

Anti-Osteoporotic Therapy After Fragility Fracture Lowers Rate of Subsequent Fracture: Analysis of a Large Population Sample.

This investigation assessed the effectiveness of initiating anti-osteoporotic therapy after a fragility fracture in preventing subsequent fractures. The Truven Health MarketScan databases, which contain de-identified, integrated, person-specific claim data, were queried from 2003 to 2012. The study population included individuals fifty years of age or older who sustained a fragility fracture, defined as any fracture of the wrist, proximal part of the humerus, hip, or vertebra, and had three years of continuous enrollment following fracture. Patients were stratified into either an anti-osteoporotic therapy group or a no-treatment group. Subsequent fracture was defined as a fragility fracture occurring more than ninety days following the index fracture. Subjects were followed for three years. Unadjusted and age and sex-adjusted odds ratios for subsequent fracture were calculated for both groups. This investigation included 31,069 subjects, of whom 10.6% were treated with anti-osteoporotic therapy following the index fracture. The anti-osteoporotic therapy group was older and had a greater proportion of female patients compared with the no-treatment group. The three-year subsequent fracture rates were 7.5% in the anti-osteoporotic therapy group and 9.7% in the no-treatment group. Unadjusted odds ratios for subsequent fracture showed that the anti-osteoporotic therapy group experienced a risk reduction of 33% after an index wrist fracture, 48% after an index proximal humeral fracture, 28% after an index hip fracture, 20% after an index vertebral fracture, and 25% after all fractures combined. Age and sex-adjusted odds ratios showed that the anti-osteoporotic therapy group experienced a reduction in risk of 50% after an index wrist fracture, 52% after an index proximal humeral fracture, 34% after an index hip fracture, 43% after an index vertebral fracture, and 40% after all fractures combined. The number needed to treat to prevent a subsequent fragility fracture was twenty-eight after an index wrist fracture, twenty after an index proximal humeral fracture, twenty-six after an index hip fracture, twenty-five after an index vertebral fracture, and twenty-seven after all fractures combined. Treatment with anti-osteoporotic therapy after a fragility fracture leads to a 40% decrease in the three-year risk of subsequent fracture, when adjusted for age and sex. Initiation of anti-osteoporotic therapy following a fragility fracture can prevent a subsequent fracture over the following three years in approximately one of every twenty-seven patients treated.