Linking Ambulance Trip and Emergency Department Surveillance Data on Opioid-Related Overdose, Massachusetts, 2017.

OBJECTIVES: Studies describing linkage of ambulance trips and emergency department (ED) visits of patients with opioid-related overdose (ORO) are limited. We linked records of patients experiencing ORO from ambulance trip and ED visit records in Massachusetts during April 1-June 30, 2017. METHODS: We estimated the positive predictive value of ORO-capturing definitions by examining the narratives and triage notes of a sample of OROs from each data source. Because of a lack of common unique identifiers, we deterministically linked OROs to records in the counter data set on date of birth, incident date, facility, and sex. To validate the linkage strategy, we compared ambulance trip narratives with ED triage notes and chief complaints for a sample of pairs. RESULTS: Of 3203 ambulance trips for ORO and 3046 ED visits for ORO, 82% and 63%, respectively, matched a record in the counter data set on date of birth, incident date, facility, and sex. In 200 randomly selected linked pairs from a final linked data set of 3006 paired records, only 5 (3%) appeared to be false matches. PRACTICE IMPLICATIONS: This exercise demonstrated the feasibility of linking ORO records between 2 data sets without a unique identifier. Future analyses of the linked data could produce insights not available from analyzing either data set alone. Linkage using 2 rapidly available data sets can actively inform the state's public health opioid overdose response and allow for de-duplicating counts of OROs treated by ambulance, in an ED, or both.

Posttraumatic stress disorder and mortality in VA patients with implantable cardioverter-defibrillators.

BACKGROUND: The association between posttraumatic stress disorder (PTSD) and mortality in patients undergoing implantable cardioverter-defibrillator (ICD) placement has not been evaluated in US veterans. HYPOTHESIS: PTSD in veterans with ICD is associated with increased mortality. METHODS: We studied a retrospective cohort of 25 678 veterans who underwent ICD implantation between September 30, 2002, and December 31, 2011. Of these subjects, 3280 carried the diagnosis of PTSD prior to ICD implantation. Primary outcome was all-cause mortality between date of ICD implantation and end of follow-up (September 30, 2013). We used Cox proportional hazard models to compute multivariable adjusted hazard ratios with corresponding 95% confidence intervals for the relation between PTSD diagnosis and death following ICD placement. RESULTS: During a mean follow-up of 4.21 ± 2.62 years, 11 015 deaths were reported. The crude incidence rate of death was 87.8 and 103.9/1000 person-years for people with and without PTSD, respectively. We did not find an association between presence of PTSD before or after ICD implantation and incident death when adjusted for multiple risk factors (hazard ratio: 1.003, 95% confidence interval: 0.948-1.061). In secondary analysis, no statistically significant association was found. CONCLUSIONS: In this retrospective cohort study among more than 25 000 veterans undergoing ICD implantation, almost 13% had a diagnosis of PTSD. Subjects with PTSD were significantly younger, yet they had a higher incidence of coronary heart disease, major cardiac comorbidities, cancer, and mental health conditions. We found no association between presence of PTSD before or after ICD implantation and incident death when adjusting for all covariates.

A Systematic Review of the Methods of Diagnostic Accuracy Studies of the Afirma Gene Expression Classifier.

BACKGROUND: The Afirma® Gene Expression Classifier (GEC) risk stratifies The Bethesda System for the Reporting of Thyroid Cytopathology class III/IV (indeterminate) thyroid nodules (ITNs) as suspicious for malignancy or benign. Several authors have published studies describing the diagnostic accuracy of the GEC. However, the quality of these methods has not been rigorously examined. SUMMARY: In this study, MEDLINE and EMBASE were searched for studies published between January 1, 2010, and June 30, 2016, examining the sensitivity, specificity, negative predictive value, and positive predictive value of the GEC. The Quality of Diagnostic Accuracy Studies 2 was customized to evaluate the methods of included studies in each of four domains: nodule selection, index test execution, reference standard assignment, and flow and timing. Signaling questions were used to identify sources of potential bias in calculation of diagnostic accuracy, and issues of applicability were assessed. Three panelists applied the Quality of Diagnostic Accuracy Studies 2 tool to each study included, and divergence was resolved in conference. In 12 studies evaluated, the most common methodologic flaw was lack of reference standard diagnosis assignment to un-excised GEC-benign ITNs. Exclusion of these ITNs from the analyses resulted in unreliable estimates of specificity and negative predictive value. Other flaws identified included restriction to ITNs that had already been selected for referral for thyroidectomy or lobectomy. CONCLUSIONS: Future studies should define and assign a "true negative" label to GEC-benign nodules that do not develop malignant signs or symptoms during a pre-specified period of follow-up, and these nodules should be included in calculations of diagnostic accuracy.

Aspirin use and risk of atrial fibrillation in the Physicians' Health Study.

BACKGROUND: Inflammatory processes have been associated with an increased risk of atrial fibrillation (AF), potentially allowing for preventive therapy by anti-inflammatory agents such as aspirin. However, the effect of chronic aspirin on the incidence of AF has not been evaluated in a prospective cohort followed for an extended period. METHODS AND RESULTS: This study was comprised of a prospective cohort of 23 480 male participants of the Physicians' Health Study. Aspirin intake and covariates were estimated using self-reported questionnaires. Incident AF was ascertained through yearly follow-up questionnaires. Cox's regression, with adjustment for multiple covariates, was used to estimate relative risk of AF. Average age at baseline was 65.1±8.9 years. During a mean follow-up of 10.0 years, 2820 cases of AF were reported. Age-standardized incidence rates were 12.6, 11.1, 12.7, 11.3, 15.8, and 13.8/1000 person-years for people reporting baseline aspirin intake of 0, <14 days per year, 14 to 30 days per year, 30 to 120 days per year, 121 to 180 days per year, and >180 days per year, respectively. Multivariable adjusted hazard ratios (95% confidence interval) for incident AF were 1.00 (reference), 0.88 (0.76 to 1.02), 0.93 (0.76 to 1.14), 0.96 (0.80 to 1.14), 1.07 (0.80 to 1.14), and 1.04 (0.94 to 1.15) across consecutive categories of aspirin intake. Analysis of the data using time-varying Cox's regression model to update aspirin intake over time showed similar results. CONCLUSIONS: In a large cohort of males followed for a long period, we did not find any association between aspirin use and incident AF.

Regular physical activity and risk of atrial fibrillation: a systematic review and meta-analysis.

BACKGROUND: Although previous studies have suggested that competitive athletes have a higher risk of atrial fibrillation than the general population, limited and inconsistent data are available on the association between regular physical activity and the risk of atrial fibrillation. METHODS AND RESULTS: A systematic, comprehensive literature search was performed using MEDLINE, EMBASE, and COCHRANE until 2011. Extracted data from the eligible studies were meta-analyzed using fixed effects model. Four studies, which included 95 526 subjects, were eligible for meta-analysis. For all of the studies included, the extreme groups (ie, maximum versus minimal amount of physical activity) were used for the current analyses. The total number of participants belonging to the extreme groups was 43 672. The pooled odds ratio (95% confidence interval) for atrial fibrillation among regular exercisers was 1.08 (0.97-1.21). CONCLUSIONS: Our data do not support a statistically significant association between regular physical activity and increased incidence of atrial fibrillation.

Pacing system malfunction is a rare cause of hospital admission for syncope in patients with a permanent pacemaker.

BACKGROUND: Few studies have examined the prevalence of permanent pacemaker (PPM) malfunction among patients with a previously implanted pacemaker admitted to the hospital with syncope. OBJECTIVE: This study sought to examine causes of syncope in patients with a previously implanted pacemaker admitted to our hospital with syncope. METHODS: We retrospectively reviewed our hospital admission database for patients who had both keywords "syncope" and "pacemaker" as their diagnoses from January 1, 1995 until June 1, 2012. One hundred and sixty-two patients who were admitted to the hospital because of syncope and had a PPM implanted prior to the index syncopal episode were included. All patients had pacemakers interrogated during the admission. Two independent physicians examined the discharge summary of each patient and determined the cause of syncope in each case. RESULTS: Of the 162 patients studied, eight (4.9%) were found to have pacemaker system malfunction as a cause of syncope. In 96 patients (59.2%), the cause of syncope could not be determined prior to hospital discharge. Among the identifiable causes of syncope, orthostatic hypotension was most prevalent (16%) followed by vasovagal (6%), severe aortic stenosis (4.3%), atrial arrhythmia (3.1%), acute and subacute infection (3.1%), and other less prevalent causes (3.1%). CONCLUSION: In this study, PPM system malfunction was rarely a cause of syncope in patients admitted to the hospital with a previously implanted device.

High-density lipoprotein and mortality before age 90 in male physicians.

BACKGROUND: In cross-sectional and some cohort studies with shorter follow-up, high-density lipoprotein cholesterol (HDL-C) has been associated with longer life. We sought to examine the relationship between HDL-C and death before age 90 in the Physicians' Health Study (PHS). METHODS AND RESULTS: Of PHS enrollees who had blood collected at PHS II baseline (approximately 1997), we selected 1351 men old enough to reach age 90 by March 4, 2009, and with complete data on HDL-C and total cholesterol, lifestyle factors, and comorbidities. We used Cox proportional hazards to determine the hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause, cardiovascular disease (CVD), and non-CVD mortality before age 90, adjusting for potential confounders. After a mean (SD) follow-up of 6.8 (3.2) years, 44.1% of men in the lowest baseline HDL-C quartile (<32.8 mg/dL) compared with 32.9% (11.2% absolute risk reduction) in the highest HDL-C quartile (≥ 54.1 mg/dL) died before age 90. In multivariable adjusted analyses, men in the highest HDL-C quartile had a 28% lower risk (HR, 0.72; 95% CI, 0.55 to 0.94) of death before age 90 compared with men in the lowest HDL-C quartile. In age-adjusted analyses, increasing baseline HDL-C was significantly associated with a lower risk of CVD death. No association was found between HDL-C and non-CVD mortality. CONCLUSION: In male physicians, higher baseline HDL-C levels were associated with a lower risk of all-cause and CVD mortality before age 90.

Lifestyle change and high-density lipoprotein change: the US Department of Veterans Affairs Normative Aging Study.

BACKGROUND: We sought to determine whether lifestyle modifications are associated with high-density lipoprotein cholesterol (HDL-C) change in a cohort with long-term follow-up. HYPOTHESIS: Changes in alcohol consumption, smoking, or body mass index (BMI) are associated with within-individual changes in HDL-C. METHODS: We selected 1420 men with ≥2 HDL-C measurements from the US Department of Veterans Affairs Normative Aging Study (NAS). Changes in HDL-C (in milligrams/deciliter) over a 3-year period were calculated for each pair of exams. For each interval of HDL-C change, lifestyle exposures were categorized: participants maintained a stable BMI >25 kg/m(2) (reference) or ≤25 kg/m(2) since the previous exam, or increased or decreased BMI; participants were actively smoking at both exams (reference), nonsmokers at both exams, quit, or initiated smoking between exams; and participants maintained alcohol intake of <2 (reference) or ≥2 drinks daily since the previous exam, or increased or decreased alcohol intake. Longitudinal analysis was used to examine the relationship between the lifestyle change categories and 3-year change in HDL-C for each interval, adjusting for comorbidities, lipids, and cholesterol medication. RESULTS: Participants were followed for approximately 14.3 years. Increases in HDL-C were associated with maintaining alcohol intake of ≥2 drinks daily (mean HDL-C increase, 0.86; P = 0.02), increasing alcohol intake from <2 to ≥2 drinks daily (mean, 2.53; P = 0.0003), and with maintaining a BMI of ≤25 kg/m(2) (mean, 0.71; P = 0.04). CONCLUSIONS: Increases in alcohol consumption, maintaining moderate alcohol intake, and maintaining BMI ≤25 kg/m(2) were associated with significant 3-year increases in HDL-C.

Benefits associated with achieving optimal risk factor levels for the primary prevention of cardiovascular disease in older men.

BACKGROUND: Most incident cardiovascular disease (CVD) occurs after patients reach the age of 65. The additive benefits of aggressive risk factor management with advancing age are not well established. OBJECTIVE: To evaluate the relationship between control of four modifiable risk factors (smoking, non-high density lipoprotein cholesterol, blood pressure, and aspirin use) and risk of CVD in a primary prevention population of older men. MATERIALS AND METHODS: U.S. male physicians from the Physicians' Health Study (n = 4182; an epidemiologic follow-up of a randomized trial of aspirin and beta-carotene) who in 1997 were ≥ 65 years, free of CVD and diabetes, and had a blood sample on file were studied. Cox proportional hazard models were adjusted for age and competing causes of death. The first of any CVD event, defined as cardiovascular death, nonfatal myocardial infarction, angina, coronary revascularization, nonfatal stroke, transient ischemic attack, carotid artery surgery, and other peripheral vascular disease surgery, was measured. RESULTS: Mean follow-up was 9.3 years, mean age was 73 years, and 96% were nonsmokers. Compared with when 4 of 4 risk factors were controlled (6.0% of participants), control of 0 of 4 risk factors almost quadrupled the risk of CVD (0.4% of participants; event rate 41.2%; hazard ratio [HR] 3.83, 95% confidence interval [95% CI] 1.72-8.55); control of 1 of 4 risk factors more than doubled the risk (14.2% of participants; HR 2.53, 95% CI 1.80-3.57); control of 2 of 4 risk factors almost doubled the risk (43.8% of participants; HR 1.94, 95% CI 1.41-2.69), and those with control of 3 of 4 risk factors also were at increased risk (35.6% of participants; HR 1.80, 95% CI 1.30-2.50). Control of each additional risk factor was associated with greater cardiovascular protection (P for trend P = .002). Depending on the number of risk factors controlled, the number-needed to control to prevent one CVD event ranged from 5 to 22. CONCLUSION: Control of 4 treatable risk factors (nonsmoking, control of non-high density lipoprotein cholesterol and blood pressure, and aspirin use) was associated with substantial protection against incident cardiovascular events in older men even after adjustment for competing causes of mortality.

Apolipoprotein ε4 polymorphism does not modify the association between body mass index and high-density lipoprotein cholesterol: a cross-sectional cohort study.

BACKGROUND: We sought to examine whether ε4 carrier status modifies the relation between body mass index (BMI) and HDL. The National Heart, Lung, and Blood Institute Family Heart Study included 657 families with high family risk scores for coronary heart disease and 588 randomly selected families of probands in the Framingham, Atherosclerosis Risk in Communities, and Utah Family Health Tree studies. We selected 1402 subjects who had ε4 carrier status available. We used generalized estimating equations to examine the interaction between BMI and ε4 allele carrier status on HDL after adjusting for age, gender, smoking, alcohol intake, mono- and poly-unsaturated fat intake, exercise, comorbidities, LDL, and family cluster. RESULTS: The mean (standard deviation) age of included subjects was 56.4(11.0) years and 47% were male. Adjusted means of HDL for normal, overweight, and obese BMI categories were 51.2(± 0.97), 45.0(± 0.75), and 41.6(± 0.93), respectively, among 397 ε4 carriers (p for trend < 0.0001) and 53.6(± 0.62), 51.3(± 0.49), and 45.0(± 0.62), respectively, among 1005 non-carriers of the ε4 allele (p-value for trend < 0.0001). There was no evidence for an interaction between BMI and ε4 status on HDL(p-value 0.39). CONCLUSION: Our findings do not support an interaction between ε4 allele status and BMI on HDL.

Lifestyle changes and 14-year change in high-density lipoprotein cholesterol in a cohort of male physicians.

BACKGROUND: Although cross-sectional studies have identified lifestyle factors associated with high-density lipoprotein cholesterol (HDL-C), no studies have examined the association between changes in lifestyle factors and long-term changes in HDL-C. METHODS: We examined the association between changes in lifestyle factors and changes in HDL-C over a 14-year period in a cohort of 4,168 US male physicians, followed up between 1982 and 1997 and with HDL-C measured at both time points. Using linear regression, we examined the association between HDL-C change and categorized changes in alcohol consumption, physical activity, body mass index (BMI), and smoking, adjusting for age, baseline HDL-C, and other covariates. RESULTS: Stable BMI of <25 kg/m(2) or BMI reduction from ≥25 to <25 kg/m(2) were associated with increases in HDL-C of 3.1 to 4.7 mg/dL over 14 years. Alcohol consumption of ≥1 drink daily or increase in alcohol consumption from <1 to ≥1 drink daily was associated with increases in HDL-C of 2.4 to 3.3 mg/dL over 14 years. Adopting a sedentary lifestyle was associated with decreases in 14-year decreases in HDL-C. CONCLUSION: These findings suggest that reductions in BMI and increases in alcohol consumption are associated with 14-year increases in HDL-C, whereas decreases in physical activity are associated with 14-year decreases in HDL-C.

Relation between high-density lipoprotein cholesterol and survival to age 85 years in men (from the VA normative aging study).

No previous researchers have sought to determine whether high-density lipoprotein (HDL) cholesterol levels are associated with survival to 85 years of age in a prospective cohort of aging men. We selected 652 men (mean age 65 years) enrolled in the VA Normative Aging Study who had ≥ 1 HDL cholesterol level documented during the study and who were old enough on the date of HDL cholesterol measurement to reach 85 years of age by the end of follow-up (July 1, 2008). We categorized initial HDL cholesterol into < 40 mg/dl (reference group), 40 to 49 mg/dl, or ≥ 50 mg/dl. Information on co-morbidities, lifestyle factors, measured lipid parameters, and medications were collected during triennial visits. We used proportional hazards to determine hazard ratios (HRs) for mortality before age 85 years for each category of initial HDL cholesterol compared to the reference adjusting for co-morbidities, calculated low-density lipoprotein cholesterol, medications, smoking, body mass index, and alcohol consumption. Treating HDL cholesterol as a continuous predictor, we also determined the HR for each 10-mg/dl increment in HDL cholesterol. Fully adjusted HR (95% confidence interval) for survival to 85 years of age for participants with an initial HDL cholesterol level ≥ 50 mg/dl compared to the reference was 0.72 (0.53 to 0.98). Each 10-mg/dl increment in HDL cholesterol was associated with a 14% (HR 0.86, 0.78 to 0.96) decrease in risk of mortality before 85 years of age. In conclusion, after adjusting for other factors associated with longevity, higher HDL cholesterol levels were significantly associated with survival to 85 years of age.

Cardiovascular benefit of magnitude of low-density lipoprotein cholesterol reduction: a comparison of subgroups by age.

BACKGROUND: We examined the effect of the magnitude of low-density lipoprotein cholesterol (LDL-C) reduction across subjects of various ages in a retrospective cohort study. METHODS AND RESULTS: We selected 20,132 male veterans at high risk for an acute cardiovascular event and who had 2 or more LDL-C measurements before their first documented acute myocardial infarction, revascularization, death, or censoring date. LDL-C reduction was categorized as no reduction (<10 mg/dL; reference), small reduction (between 10 and 40 mg/dL), moderate reduction (between 40 and 70 mg/dL), or large reduction (> or =70 mg/dL). The primary outcome was combined acute myocardial infarction or revascularization. The first and last LDL-C levels in the databases were used to calculate the LDL-C reduction in patients who experienced no outcome or who died. Within each age quartile and in a subgroup of patients > or =80 years of age, a Cox proportional hazards model was used to determine hazard ratios for each category of LDL-C reduction compared with the reference category, with adjustment for age, body mass index, current smoking status, medications, and comorbidities. In all age groups, the magnitude of LDL-C reduction was proportional to the magnitude of cardiovascular risk reduction. Risk reduction for the combined outcome in patients who achieved a large LDL-C reduction was similar in all age quartiles, with multivariate-adjusted hazard ratios of approximately 0.30. CONCLUSIONS: In a cohort of veterans at high risk for cardiovascular events, patients of all ages, including those 80 years or older, benefitted the most from large reductions in LDL-C.

Low-density lipoprotein reduction and magnitude of cardiovascular risk reduction.

The authors examined the relationship between the magnitude of low-density lipoprotein cholesterol (LDL-C) reduction and the magnitude of cardiovascular risk reduction. From the Veterans Integrated Service Network 1 databases, the authors selected 54,611 patients with prevalent ischemic heart disease, peripheral vascular disease or diabetes mellitus, and >or=2 documented LDL-C levels who were followed between 1997 and 2006. The outcome was defined as acute myocardial infarction or revascularization. Preoutcome LDL-C reduction was categorized as follows: <10 mg/dL, reference; >or=10 but <40 mg/dL, small reduction; >or=40 but <70 mg/dL, moderate reduction; >or=70 mg/dL, large reduction. Proportional hazards were used to determine the hazard ratio for the outcome for each LDL-C reduction category compared with the reference. Results revealed a graded relationship between the magnitude of reduction in LDL-C and cardiovascular risk reduction. Stratified analyses demonstrated these findings to be robust regardless of initial LDL-C levels or whether patients achieved "target" final LDL-C values of <100 mg/dL.

Change in high-density lipoprotein cholesterol and incident coronary heart disease in apparently healthy male physicians.

The association between change in high-density lipoprotein (HDL) cholesterol and risk of subsequent coronary heart disease (CHD) is unclear. Change in HDL cholesterol was calculated in a prospective cohort of 4,501 male physicians enrolled in the Physician's Health Study (PHS) I who had HDL cholesterol measured in 1982 and again approximately 14 years later. Subjects were divided into categories of those with a decrease (>or=-2.5 mg/dl), no change (change -2.5 to 2.5 mg/dl), a small increase of 2.5 to 12.5 mg/dl, or a large increase of >or=12.5 mg/dl. Cox proportional hazards was used to examine the association between change in HDL cholesterol and incident CHD (confirmed acute myocardial infarction or cardiac death). Hazard ratios (HRs) were adjusted for age, initial HDL cholesterol, diabetes mellitus, hypertension, non-HDL cholesterol, and history of cholesterol medication. Compared with subjects with a decrease in HDL cholesterol, multivariable-adjusted HRs for CHD were 0.66 (95% confidence interval [CI] 0.40 to 1.09) in subjects with no change, 0.56 (95% CI 0.35 to 0.89) for subjects with an increase of 2.5 to 12.5 mg/dl, and 0.43 (95% CI 0.23 to 0.83) for subjects with an HDL cholesterol increase >or=12.5 mg/dl. In conclusion, our findings were consistent with an inverse graded relation between 14-year increase in HDL cholesterol and risk of subsequent CHD.

Decision-making in percutaneous coronary intervention: a survey.

BACKGROUND: Few researchers have examined the perceptions of physicians referring cases for angiography regarding the degree to which collaboration occurs during percutaneous coronary intervention (PCI) decision-making. We sought to determine perceptions of physicians concerning their involvement in PCI decisions in cases they had referred to the cardiac catheterization laboratory at a major academic medical center. METHODS: An anonymous survey was mailed to internal medicine faculty members at a major academic medical center. The survey elicited whether responders perceived that they were included in decision-making regarding PCI, and whether they considered such collaboration to be the best process of decision-making. RESULTS: Of the 378 surveys mailed, 35% (133) were returned. Among responding non-cardiologists, 89% indicated that in most cases, PCI decisions were made solely by the interventionalist at the time of the angiogram. Among cardiologists, 92% indicated that they discussed the findings with the interventionalist prior to any PCI decisions. When asked what they considered the best process by which PCI decisions are made, 66% of non-cardiologists answered that they would prefer collaboration between either themselves or a non-interventional cardiologist and the interventionalist. Among cardiologists, 95% agreed that a collaborative approach is best. CONCLUSION: Both non-cardiologists and cardiologists felt that involving another decision-maker, either the referring physician or a non-interventional cardiologist, would be the best way to make PCI decisions. Among cardiologists, there was more concordance between what they believed was the best process for making decisions regarding PCI and what they perceived to be the actual process.