Cannabis use and acute postoperative pain outcomes in older adults: a propensity matched retrospective cohort study.

INTRODUCTION: Cannabis use is increasing among older adults, but its impact on postoperative pain outcomes remains unclear in this population. We examined the association between cannabis use and postoperative pain levels and opioid doses within 24 hours of surgery. METHODS: We conducted a propensity score-matched retrospective cohort study using electronic health records data of 22 476 older surgical patients with at least 24-hour hospital stays at University of Florida Health between 2018 and 2020. Of the original cohort, 2577 patients were eligible for propensity-score matching (1:3 cannabis user: non-user). Cannabis use status was determined via natural language processing of clinical notes within 60 days of surgery and structured data. The primary outcomes were average Defense and Veterans Pain Rating Scale (DVPRS) score and total oral morphine equivalents (OME) within 24 hours of surgery. RESULTS: 504 patients were included (126 cannabis users and 378 non-users). The median (IQR) age was 69 (65-72) years; 295 (58.53%) were male, and 442 (87.70%) were non-Hispanic white. Baseline characteristics were well balanced. Cannabis users had significantly higher average DVPRS scores (median (IQR): 4.68 (2.71-5.96) vs 3.88 (2.33, 5.17); difference=0.80; 95% confidence limit (CL), 0.19 to 1.36; p=0.01) and total OME (median (IQR): 42.50 (15.00-60.00) mg vs 30.00 (7.50-60.00) mg; difference=12.5 mg; 95% CL, 3.80 mg to 21.20 mg; p=0.02) than non-users within 24 hours of surgery. DISCUSSION: This study showed that cannabis use in older adults was associated with increased postoperative pain levels and opioid doses.

Cannabis Use and Inhalational Anesthesia Administration in Older Adults: A Propensity Matched Retrospective Cohort Study.

BACKGROUND: Cannabis use is associated with higher intravenous anesthetic administration. Similar data regarding inhalational anesthetics are limited. With rising cannabis use prevalence, understanding any potential relationship with inhalational anesthetic dosing is crucial. We compared average intraoperative isoflurane/sevoflurane minimum alveolar concentration equivalents between older adults with and without cannabis use. METHODS: The electronic health records of 22,476 surgical patients ≥65 years old at the University of Florida Health System between 2018-2020 were reviewed. The primary exposure was cannabis use within 60 days of surgery, determined via i) a previously published natural language processing algorithm applied to unstructured notes and ii) structured data, including International Classification of Disease codes for cannabis use disorders and poisoning by cannabis, laboratory cannabinoids screening results, and RxNorm codes. The primary outcome was the intraoperative time-weighted average of isoflurane/sevoflurane minimum alveolar concentration equivalents at one-minute resolution. No a priori minimally clinically important difference was established. Patients demonstrating cannabis use were matched 4:1 to non-cannabis use controls using a propensity score. RESULTS: Among 5,118 meeting inclusion criteria, 1,340 patients (268 cannabis users and 1,072 nonusers) remained after propensity score matching. The median and interquartile range (IQR) age was 69 (67, 73) years; 872 (65.0%) were male, and 1,143 (85.3%) were non-Hispanic White. The median (IQR) anesthesia duration was 175 (118, 268) minutes. After matching, all baseline characteristics were well-balanced by exposure. Cannabis users had statistically significantly higher average minimum alveolar concentrations than nonusers [mean±SD: 0.58±0.23 versus 0.54±0.22, respectively; mean difference=0.04; 95% confidence limits, 0.01 to 0.06; p=0.020]. CONCLUSION: Cannabis use was associated with administering statistically significantly higher inhalational anesthetic minimum alveolar concentration equivalents in older adults, but the clinical significance of this difference is unclear. These data do not support the hypothesis that cannabis users require clinically meaningfully higher inhalational anesthetics doses.

Lipid Testing among Youth in Medicaid: The Role of Social Determinants of Health and Providers.

OBJECTIVES: To assess recent temporal trends in guideline-compliant pediatric lipid testing, and to examine the influence of social determinants of health (SDoH) and provider characteristics on the likelihood of testing in youth. STUDY DESIGN: In this observational, multi-year cross-sectional study, we calculated lipid testing prevalence by year among 268,627 12-year-olds from 2015 through 2019 who were enrolled in Florida Medicaid and eligible for universal lipid screening during age 9 to 11, and 11,437 22-year-olds (2017-2019) who were eligible for screening during age 17-21. We compared trends in testing prevalence by SDoH and health risk factors at two recommended ages and modeled the associations between patient characteristics and provider type on lipid testing using generalized estimating equations. RESULTS: Testing among 12-year-olds remained low between 2015 through 2019 with the highest prevalence in 2015 (8.0%) and lowest in 2017 (6.7%). Screening compliance among 22-year-olds was highest in 2017 (21.1%) and fell to 17.8% in 2019. Hispanics and non-Hispanic Blacks in both age groups had about 2-3% lower testing prevalence than non-Hispanic Whites. Testing in 12-year-olds was 12.3% versus 7.7% with and without obesity, and 14.4% versus 7.6% with and without antipsychotic use. Participants who saw providers who were more likely to prescribe lipid testing were more likely to receive testing (odds ratio=2.3, 95% CI 2.0-2.8, P<.001). CONCLUSIONS: Although lipid testing prevalence was greatest among high-risk children, overall prevalence of lipid testing in youth remains very low. Provider specialty and choices by individual providers play important roles in improving guideline-compliant pediatric lipid testing.

The Science of Precision Prevention: Research Opportunities and Clinical Applications to Reduce Cardiovascular Health Disparities.

Precision prevention embraces personalized prevention but includes broader factors such as social determinants of health to improve cardiovascular health. The quality, quantity, precision, and diversity of data relatable to individuals and communities continue to expand. New analytical methods can be applied to these data to create tools to attribute risk, which may allow a better understanding of cardiovascular health disparities. Interventions using these analytic tools should be evaluated to establish feasibility and efficacy for addressing cardiovascular disease disparities in diverse individuals and communities. Training in these approaches is important to create the next generation of scientists and practitioners in precision prevention. This state-of-the-art review is based on a workshop convened to identify current gaps in knowledge and methods used in precision prevention intervention research, discuss opportunities to expand trials of implementation science to close the health equity gaps, and expand the education and training of a diverse precision prevention workforce.

Developing and validating a natural language processing algorithm to extract preoperative cannabis use status documentation from unstructured narrative clinical notes.

OBJECTIVE: This study aimed to develop a natural language processing algorithm (NLP) using machine learning (ML) techniques to identify and classify documentation of preoperative cannabis use status. MATERIALS AND METHODS: We developed and applied a keyword search strategy to identify documentation of preoperative cannabis use status in clinical documentation within 60 days of surgery. We manually reviewed matching notes to classify each documentation into 8 different categories based on context, time, and certainty of cannabis use documentation. We applied 2 conventional ML and 3 deep learning models against manual annotation. We externally validated our model using the MIMIC-III dataset. RESULTS: The tested classifiers achieved classification results close to human performance with up to 93% and 94% precision and 95% recall of preoperative cannabis use status documentation. External validation showed consistent results with up to 94% precision and recall. DISCUSSION: Our NLP model successfully replicated human annotation of preoperative cannabis use documentation, providing a baseline framework for identifying and classifying documentation of cannabis use. We add to NLP methods applied in healthcare for clinical concept extraction and classification, mainly concerning social determinants of health and substance use. Our systematically developed lexicon provides a comprehensive knowledge-based resource covering a wide range of cannabis-related concepts for future NLP applications. CONCLUSION: We demonstrated that documentation of preoperative cannabis use status could be accurately identified using an NLP algorithm. This approach can be employed to identify comparison groups based on cannabis exposure for growing research efforts aiming to guide cannabis-related clinical practices and policies.

Deaf Weight Wise: A novel randomized clinical trial with Deaf sign language users.

OBJECTIVE: The goal of this study was to address the absence of evidence-based weight-control programs developed for use with Deaf people. METHODS: Community-based participatory research informed the design of the Deaf Weight Wise (DWW) trial and intervention. DWW focuses primarily on healthy lifestyle and weight through change in diet and exercise. The study enrolled 104 Deaf adults aged 40 to 70 years with BMI of 25 to 45 from community settings in Rochester, New York, and randomized participants to immediate intervention (n = 48) or 1-year delayed intervention (n = 56). The delayed intervention serves as a no-intervention comparison until the trial midpoint. The study collected data five times (every 6 months) from baseline to 24 months. All DWW intervention leaders and participants are Deaf people who use American Sign Language (ASL). RESULTS: At 6 months, the difference in mean weight change for the immediate-intervention arm versus the delayed-intervention arm (no intervention yet) was -3.4 kg (multiplicity-adjusted p = 0.0424; 95% CI: -6.1 to -0.8 kg). Most (61.6%) in the immediate arm lost ≥5% of baseline weight versus 18.1% in the no-intervention-yet arm (p < 0.001). Participant engagement indicators include mean attendance of 11/16 sessions (69%), and 92% completed 24-month data collection. CONCLUSION: DWW, a community-engaged, culturally appropriate, and language-accessible behavioral weight loss intervention, was successful with Deaf ASL users.

Emergency department condition acuity, length of stay, and revisits among deaf and hard-of-hearing patients: A retrospective chart review.

OBJECTIVE: Deaf and hard-of-hearing (DHH) patients are understudied in emergency medicine health services research. Theory and limited evidence suggest that DHH patients are at higher risk of emergency department (ED) utilization and poorer quality of care. This study assessed ED condition acuity, length of stay (LOS), and acute ED revisits among DHH patients. We hypothesized that DHH patients would experience poorer ED care outcomes. METHODS: We conducted a retrospective chart review of a single health care system using data from a large academic medical center in the southeast United States. Data were received from the medical center's data office, and we sampled patients and encounters from between June 2011 and April 2020. We compared DHH American Sign Language (ASL) users (n = 108), DHH English speakers (n = 358), and non-DHH English speakers (n = 302). We used multilevel modeling to assess the differences among patient segments in outcomes related to ED use and care. RESULTS: As hypothesized, DHH ASL users had longer ED LOS than non-DHH English speakers, on average 30 min longer. Differences in ED condition acuity, measured through Emergency Severity Index and triage pain scale, were not statistically significant. DHH English speakers represented a majority (61%) of acute ED revisit encounters. CONCLUSIONS: Our study identified that DHH ASL users have longer ED LOS than non-DHH English speakers. Additional research is needed to further explain the association between DHH status and ED care outcomes (including ED LOS and acute revisit), which may be used to identify intervention targets to improve health equity.

Emergency department utilization among deaf and hard-of-hearing patients: A retrospective chart review.

BACKGROUND: Deaf and hard-of-hearing (DHH) patients are an underserved priority population. Existing, although contextually limited, findings indicate that DHH patients are more likely to use the emergency department (ED) than non-DHH patients. However, little attention has been given to the differences in ED utilization by patients' language modalities. OBJECTIVE: We hypothesized that DHH ASL-users and DHH English speakers would have higher rates of ED utilization in the past 36 months than non-DHH English speakers. METHODS: We used a retrospective chart review design using data from a large academic medical center in the southeastern United States. In total, 277 DHH ASL-users, 1000 DHH English speakers, and 1000 non-DHH English speakers were included. We used logistic regression and zero-inflated modeling to assess relations between patient segment and ED utilization in the past 12- and 36-months. We describe primary ED visit diagnosis codes using AHRQ Clinical Classifications Software. RESULTS: DHH ASL users and DHH English speakers had higher adjusted odds ratios of using the ED in the past 36-months than non-DHH English speakers (aORs = 1.790 and 1.644, respectively). Both DHH ASL users and DHH English speakers had a higher frequency of ED visits among patients who used the ED in the past 36-months (61.0% and 70.1%, respectively). The most common principal diagnosis code was for abdominal pain, with DHH English speakers making up over half of all abdominal pain encounters. CONCLUSIONS: DHH ASL users and DHH English speakers are at higher risk of using the ED compared to non-DHH English speakers. We call for additional attention on DHH patients in health services and ED utilization research.

Conceptual Model of Emergency Department Utilization among Deaf and Hard-of-Hearing Patients: A Critical Review.

Deaf and hard-of-hearing (DHH) populations are understudied in health services research and underserved in healthcare systems. Existing data indicate that adult DHH patients are more likely to use the emergency department (ED) for less emergent conditions than non-DHH patients. However, the lack of research focused on this population's ED utilization impedes the development of health promotion and quality improvement interventions to improve patient health and quality outcomes. The purpose of this study was to develop a conceptual model describing patient and non-patient (e.g., community, health system, provider) factors influencing ED utilization and ED care processes among DHH people. We conducted a critical review and used Andersen's Behavioral Model of Health Services Use and the PRECEDE-PROCEED Model to classify factors based on their theoretical and/or empirically described role. The resulting Conceptual Model of Emergency Department Utilization Among Deaf and Hard-of-Hearing Patients provides predisposing, enabling, and reinforcing factors influencing DHH patient ED care seeking and ED care processes. The model highlights the abundance of DHH patient and non-DHH patient enabling factors. This model may be used in quality improvement interventions, health services research, or in organizational planning and policymaking to improve health outcomes for DHH patients.

Aspirin in Primary Prevention: What Changed? A Critical Appraisal of Current Evidence.

Aspirin has been the mainstay of both secondary and primary prevention of cardiovascular disease for half a century. In 2018, 3 trials showed a modest reduction in cardiovascular outcomes that appeared counterbalanced by the risk of clinically significant bleeding. The latest ACC/AHA primary prevention guidelines downgraded their recommendation for aspirin use in primary prevention to that of physician preference. Despite the consistent and robust evidence previously supporting the use of aspirin in cardiovascular disease prevention, little discussion has been given to mechanisms or analytic explanations for this revision of recommendations. In this review, we explore 3 possible mechanisms that may have contributed to the alteration of our perception of aspirin's role in primary prevention. These include changes in the population potentially using aspirin in primary prevention, changes in cardiovascular disease and its presentation, and changes in aspirin itself. Here we present a translational look at knowledge gaps that should be addressed to better guide contemporary aspirin use in primary prevention. In conclusion, based on these considerations, the current recommendations might be improved by recalibration of the cardiovascular risk threshold above which aspirin should be recommended for primary prevention, including the incorporation of newer risk assessment modalities such as calcium scoring. A second enhancement would be developing a bleeding risk calculator to support clinicians' assessment of risk vs benefit. The use of enteric-coated aspirin vs noncoated aspirin should also be reassessed.

Precision Health Analytics With Predictive Analytics and Implementation Research: JACC State-of-the-Art Review.

Emerging data science techniques of predictive analytics expand the quality and quantity of complex data relevant to human health and provide opportunities for understanding and control of conditions such as heart, lung, blood, and sleep disorders. To realize these opportunities, the information sources, the data science tools that use the information, and the application of resulting analytics to health and health care issues will require implementation research methods to define benefits, harms, reach, and sustainability; and to understand related resource utilization implications to inform policymakers. This JACC State-of-the-Art Review is based on a workshop convened by the National Heart, Lung, and Blood Institute to explore predictive analytics in the context of implementation science. It highlights precision medicine and precision public health as complementary and compelling applications of predictive analytics, and addresses future research and training endeavors that might further foster the application of predictive analytics in clinical medicine and public health.

The Type and Amount of Dietary Fat Affect Plasma Factor VIIc, Fibrinogen, and PAI-1 in Healthy Individuals and Individuals at High Cardiovascular Disease Risk: 2 Randomized Controlled Trials.

BACKGROUND: Factor VIIc, fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) are cardiovascular disease (CVD) risk factors and are modulated, in part, by fat type and amount. OBJECTIVE: We evaluated fat type and amount on the primary outcomes: factor VIIc, fibrinogen, and PAI-1. METHODS: In the Dietary Effects on Lipoproteins and Thrombogenic Activity (DELTA) Trial, 2 controlled crossover feeding studies evaluated substituting carbohydrate or MUFAs for SFAs. Study 1: healthy participants (n = 103) were provided with (8 wk) an average American diet [AAD; designed to provide 37% of energy (%E) as fat, 16% SFA], a Step 1 diet (30%E fat, 9% SFA), and a diet low in SFA (Low-Sat; 26%E fat, 5% SFA). Study 2: participants (n = 85) at risk for CVD and metabolic syndrome (MetSyn) were provided with (7 wk) an AAD, a step 1 diet, and a high-MUFA diet (designed to provide 37%E fat, 8% SFA, 22% MUFA). RESULTS: Study 1: compared with AAD, the Step 1 and Low-Sat diets decreased mean factor VIIc by 1.8% and 2.6% (overall P = 0.0001), increased mean fibrinogen by 1.2% and 2.8% (P = 0.0141), and increased mean square root PAI-1 by 0.0% and 6.0% (P = 0.0037), respectively. Study 2: compared with AAD, the Step 1 and high-MUFA diets decreased mean factor VIIc by 4.1% and 3.2% (overall P < 0.0001), increased mean fibrinogen by 3.9% and 1.5% (P = 0.0083), and increased mean square-root PAI-1 by 2.0% and 5.8% (P = 0.1319), respectively. CONCLUSIONS: Replacing SFA with carbohydrate decreased factor VIIc and increased fibrinogen in healthy and metabolically unhealthy individuals and also increased PAI-1 in healthy subjects. Replacing SFA with MUFA decreased factor VIIc and increased fibrinogen but less than carbohydrate. Our results indicate an uncertain effect of replacing SFA with carbohydrate or MUFA on cardiometabolic risk because of small changes in hemostatic factors and directionally different responses to decreasing SFA. This trial was registered at https://clinicaltrials.gov/ct2/show/NCT00000538?term=NCT00000538&rank=1 as NCT00000538.

An external exposome-wide association study of hypertensive disorders of pregnancy.

It is widely recognized that exogenous factors play an important role in the development of hypertensive disorders of pregnancy (HDP). However, only a few external environmental factors have been studied, often separately, with no attempt to examine the totality of the external environment, or the external exposome. We conducted an external exposome-wide association study (ExWAS) using the Florida Vital Statistics Birth Records including 819,399 women with live births in 2010-2013. A total of 5784 factors characterizing women's surrounding natural, built, and social environment during pregnancy from 10 data sources were collected, harmonized, integrated, and spatiotemporally linked to the women based on pregnancy periods using 250 m buffers around their geocoded residential addresses. A random 50:50 split divided the data into discovery and replication sets, and a 3-phase procedure was used. In phase 1, associations between HDP and individual factors were examined, and Bonferroni adjustment was performed. In phase 2, an elastic net model was used to perform variable selection among significant variables from phase 1. In phase 3, a multivariable logistic regression model including all variables selected by the elastic net model was fitted. Variables that were significant in both the discovery and replication sets were retained. Among the 528 and 490 variables identified in Phase 1, 232 and 224 were selected by the elastic net model in Phase 2, and 67 and 48 variables remained statistically significant in Phase 3 in the discovery and replication sets, respectively. A total of 12 variables were significant in both the discovery and replication sets, including air toxicants (e.g., 2,2,4-trimethylpentane), meteorological factors (e.g., omega or vertical velocity at 125mb pressure level), neighborhood crime and safety (e.g., burglary rate), and neighborhood sociodemographic status (e.g., urbanization). This is the first large external exposome study of HDP. It confirmed some of the previously reported associations and generated unexpected predictors within the environment that may warrant more focused evaluation.

Assessment of Mortality and Smoking Rates Before and After Reduction in Community-wide Prevention Programs in Rural Maine.

Importance: It is unclear whether effective population-wide interventions that reduce risk factors and improve health result in sustained benefits to a community's health. If benefits do persist after a program is ended, interventions could be brief rather than maintained long term. Objective: To measure mortality and smoking rates in a rural community over decades before, during, and after prevention program reductions. Design, Setting, and Participants: This cross-sectional study compared smoking and mortality rates in a rural Maine county with other Maine counties over time by 5-year intervals. Multiple changes occurred between 2001 and 2015 in the physiological and behavioral risk factor reduction programs offered in the county. They included reductions in leadership, staff, institutional resources, data monitoring, and the programs themselves. Data were analyzed from May 2018 to March 2019. Intervention: Previous multifaceted interventions and outcome monitoring were withdrawn or diminished in the past decade. Main Outcomes and Measures: Smoking and age-adjusted mortality rates vs household income. Results: Reduced mortality rates in Franklin County in 1986 to 2005 reverted to those predicted by household incomes, relative to other Maine counties, by 2006 to 2015 (1986-1990 T score = -2.86 [P = .01] and 2001-2005 T score = -3.00 [P = .01] to 2006 to 2010 T score = -0.43 [P = .67] and 2011-2015 T score = -0.72 [P = .48]). Analysis of County Health Rankings data from 2010 to 2018 also showed that Franklin County's outcomes have reverted to no better than predicted by socioeconomic status. The county's T scores increased from -3.62 (P = .003) in 2010 to -0.41 (P = .69) in 2015 to 0.13 (P = .90) in 2018. Statewide association of income with mortality by analyses of variance showed that the R2 values have increased from the decades preceding 2000 (1976-1980, R2 = 0.21; P = .08; 1986-1990, R2 = 0.32; P = .02) to 2006 to 2010 (R2 = 0.73; P < .001) and 2011 to 2015 (R2 = 0.70; P < .001). Conclusions and Relevance: This study suggests that gains associated with population health interventions may be lost when the interventions are reduced. Adjusting outcome measures for socioeconomic status may allow quicker and more sensitive monitoring of intervention adequacy and success. The increasing trend of age-adjusted mortality in Maine and nationally to correlate inversely with incomes may warrant further community interventions, especially for poorer populations.

Risk of Coronary Events 55 Years after Thymic Irradiation in the Hempelmann Cohort.

BACKGROUND: Studies of cancer survivors treated with older radiotherapy (RT) techniques (pre-1990s) strongly suggest that ionizing radiation to the chest increases the risk of coronary heart disease (CHD). Our goal was to evaluate the impact of more modern cardiac shielding techniques of RT on the magnitude and timing of CHD risk by studying a cohort exposed to similar levels of cardiac irradiation years ago. METHODS: Between 2004 and 2008, we re-established a population-based, longitudinal cohort of 2,657 subjects exposed to irradiation for an enlarged thymus during infancy between 1926 and 1957 and 4,388 of their non-irradiated siblings. CHD events were assessed using a mailed survey and from causes of death listed in the National Death Index. We used Poisson regression methods to compare incidence rates by irradiation status and cardiac radiation dose. Results were adjusted for the CHD risk factors of attained-age, sex, diabetes, dyslipidemia hypertension and smoking. RESULTS: Median age at time of follow-up was 57.5 years (range 41.2 - 88.8 yrs) for irradiated and non-irradiated siblings. The mean estimated cardiac dose amongst the irradiated was 1.45 Gray (range 0.17 - 20.20 Gy), with 91% receiving <3.00 Gy. During a combined 339,924 person-years of follow-up, 213 myocardial infarctions (MI) and 350 CHD events (MI, bypass surgery and angioplasty) occurred. After adjustment for attained age, gender, and other CHD risk factors, the rate ratio for MI incidence in the irradiated group was 0.98 (95%CI, 0.74 - 1.30), and for any CHD event was 1.07 (95%CI, 0.86 - 1.32). Higher radiation doses were not associated with more MIs or CHD events in this dose range, in either the crude or the adjusted analyses. CONCLUSIONS: Radiation to the heart during childhood of <3 Gy, the exposure in most of our cohort, does not increase the lifelong risk of CHD. Reducing cardiac radiation to this amount without increasing other cardiotoxic therapies may eliminate the increased CHD risk associated with radiotherapy for childhood cancer. By extension there is unlikely to be increased CHD risk from relatively higher dose imaging techniques, such as CT, because such techniques use much smaller radiation doses than received by our cohort.

Assessing Baseline and Temporal Changes in Cardiometabolic Risk Using Metabolic Syndrome Severity and Common Risk Scores.

Background Type 2 diabetes mellitus (T2 DM ) is considered a cardiovascular disease ( CVD ) risk equivalent, thereby linking assessment of cardiometabolic risk with that of CVD risk over time. Our goal was to determine how commonly used CVD risk scores and metabolic syndrome (MetS) severity performed in predicting T2 DM with and without ultimate CVD . Methods and Results We assessed data from 8273 participants of the ARIC (Atherosclerosis Risk in Communities) Study, using the pooled cohort atherosclerotic CVD risk score, the Framingham Risk Score, and a MetS severity Z score to assess their association with future risk for CVD alone, T2 DM alone, or both over 20 years of follow-up. Baseline levels of all scores were significantly associated with isolated incident T2 DM (odds ratios [ OR s] for each 1- SD increase: atherosclerotic CVD =1.7, Framingham risk score=1.7, MetS Z score=5.1). All 3 baseline scores were also significantly associated with isolated incident CVD (atherosclerotic CVD OR =2.4, Framingham risk score OR =2.3, MetS Z-score OR =1.8), with the 2 CVD scores remaining significant independent of MetS severity. MetS severity was strongly associated with future T2 DM leading to CVD (MetS Z-score OR =7.0, atherosclerotic CVD OR =3.9, Framingham risk score OR =3.5). Furthermore, changes in MetS severity were independently associated with future T2 DM - CVD progression. Conclusions CVD risk scores are associated with risk for future isolated T2 DM in addition to isolated CVD . However, MetS severity (both baseline and changes over time) was more strongly associated with T2 DM , including T2 DM ultimately leading to CVD . Following MetS severity within patients over time may identify those at greatest risk of combined cardiometabolic disease.

Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: The use of aspirin in the primary prevention of cardiovascular events remains controversial. We aimed to assess the efficacy and safety of aspirin versus placebo in patients with a moderate estimated risk of a first cardiovascular event. METHODS: ARRIVE is a randomised, double-blind, placebo-controlled, multicentre study done in seven countries. Eligible patients were aged 55 years (men) or 60 years (women) and older and had an average cardiovascular risk, deemed to be moderate on the basis of the number of specific risk factors. We excluded patients at high risk of gastrointestinal bleeding or other bleeding, or diabetes. Patients were randomly assigned (1:1) with a computer-generated randomisation code to receive enteric-coated aspirin tablets (100 mg) or placebo tablets, once daily. Patients, investigators, and others involved in treatment or data analysis were masked to treatment allocation. The primary efficacy endpoint was a composite outcome of time to first occurrence of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischaemic attack. Safety endpoints were haemorrhagic events and incidence of other adverse events, and were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00501059. FINDINGS: Between July 5, 2007, and Nov 15, 2016, 12 546 patients were enrolled and randomly assigned to receive aspirin (n=6270) or placebo (n=6276) at 501 study sites. Median follow-up was 60 months. In the intention-to-treat analysis, the primary endpoint occurred in 269 (4·29%) patients in the aspirin group versus 281 (4·48%) patients in the placebo group (hazard ratio [HR] 0·96; 95% CI 0·81-1·13; p=0·6038). Gastrointestinal bleeding events (mostly mild) occurred in 61 (0·97%) patients in the aspirin group versus 29 (0·46%) in the placebo group (HR 2·11; 95% CI 1·36-3·28; p=0·0007). The overall incidence rate of serious adverse events was similar in both treatment groups (n=1266 [20·19%] in the aspirin group vs n=1311 [20·89%] in the placebo group. The overall incidence of adverse events was similar in both treatment groups (n=5142 [82·01%] vs n=5129 [81·72%] in the placebo group). The overall incidence of treatment-related adverse events was low (n=1050 [16·75%] vs n=850 [13·54%] in the placebo group; p<0·0001). There were 321 documented deaths in the intention-to-treat population (n=160 [2·55%] vs n=161 [2·57%] of 6276 patients in the placebo group). INTERPRETATION: The event rate was much lower than expected, which is probably reflective of contemporary risk management strategies, making the study more representative of a low-risk population. The role of aspirin in primary prevention among patients at moderate risk could therefore not be addressed. Nonetheless, the findings with respect to aspirin's effects are consistent with those observed in the previously published low-risk primary prevention studies. FUNDING: Bayer.

Differing Effects of Parathyroid Hormone, Alendronate, and Odanacatib on Bone Formation and on the Mineralization Process in Intracortical and Endocortical Bone of Ovariectomized Rabbits.

Bone is formed by deposition of a collagen-containing matrix (osteoid) that hardens over time as mineral crystals accrue and are modified; this continues until bone remodeling renews that site. Pharmacological agents for osteoporosis differ in their effects on bone remodeling, and we hypothesized that they may differently modify bone mineral accrual. We, therefore, assessed newly formed bone in mature ovariectomized rabbits treated with the anti-resorptive bisphosphonate alendronate (ALN-100µ g/kg/2×/week), the anabolic parathyroid hormone (PTH (1-34)-15µ g/kg/5×/week), or the experimental anti-resorptive odanacatib (ODN 7.5 µM/day), which suppresses bone resorption without suppressing bone formation. Treatments were administered for 10 months commencing 6 months after ovariectomy (OVX). Strength testing, histomorphometry, and synchrotron Fourier-transform infrared microspectroscopy were used to measure bone strength, bone formation, and mineral accrual, respectively, in newly formed endocortical and intracortical bone. In Sham and OVX endocortical and intracortical bone, three modifications occurred as the bone matrix aged: mineral accrual (increase in mineral:matrix ratio), carbonate substitution (increase in carbonate:mineral ratio), and collagen molecular compaction (decrease in amide I:II ratio). ALN suppressed bone formation but mineral accrued normally at those sites where bone formation occurred. PTH stimulated bone formation on endocortical, periosteal, and intracortical bone surfaces, but mineral accrual and carbonate substitution were suppressed, particularly in intracortical bone. ODN treatment did not suppress bone formation, but newly deposited endocortical bone matured more slowly with ODN, and ODN-treated intracortical bone had less carbonate substitution than controls. In conclusion, these agents differ in their effects on the bone matrix. While ALN suppresses bone formation, it does not modify bone mineral accrual in endocortical or intracortical bone. While ODN does not suppress bone formation, it slows matrix maturation. PTH stimulates modelling-based bone formation not only on endocortical and trabecular surfaces, but may also do so in intracortical bone; at this site, new bone deposited contains less mineral than normal.