Quantifying risk of advanced proximal colorectal neoplasia might allow tailoring of colorectal cancer screening, with colonoscopy for those at high risk, and less invasive screening for very low-risk persons.
We analyzed findings from 10,124 consecutive adults age ≥ 50 years who underwent screening colonoscopy to the cecum between September 1995 and August 2008. We quantified the risk of advanced neoplasia (tubular adenoma ≥ 1 cm; a polyp with villous histology or high-grade dysplasia; or adenocarcinoma) both proximally (cecum to splenic flexure) and distally (descending colon to anus). Prevalence of advanced proximal neoplasia was quantified by age, gender and distal findings.
Mean (s.d.) age was 57.5 (6.0) years; 44% were women; 7835 (77%) had no neoplasia, and 1856 (18%) had one or more non-advanced adenomas. Overall, 433 subjects (4.3%) had advanced neoplasia (267 distally; 196 proximally; 30 both), 33 (0.33%) of which were adenocarcinoma (18 distal, 15 proximal). Risk of advanced proximal neoplasia increased with age decade (1.13%, 2.00%, and 5.26%, respectively; P=0.001) and was higher in men (relative risk [RR] =1.91; CI, 1.32–2.77). In women younger than 70 years, risk was 1.1% overall (vs. 2.2% in men; RR=1.98; CI, 1.42–2.76) and was 0.86% in those with no distal neoplasia (vs. 1.54% in men; RR=1.81; CI, 1.20–2.74).
Risk of advanced proximal neoplasia is a function of age and gender. Women younger than age 70 have a very low risk, particularly those with no distal adenoma. Sigmoidoscopy with or without occult blood testing may be sufficient and even preferable for screening these subgroups.
Cancer screening; colonoscopy; colorectal cancer; colorectal neoplasm
Quinolone antibiotics are associated with increased risk of tendinopathy. Identifying at-risk individuals has important clinical implications. We examined whether age, sex, glucocorticoid use, obesity, diabetes, and renal failure/dialysis predispose individuals to the adverse effects of quinolones.
Among 6.4 million patients in The Health Improvement Network (THIN) database, 28,907 cases of Achilles tendonitis and 7,685 cases of tendon rupture were identified in a case-crossover study. For each participant, we ascertained whether there was a prescription of a quinolone and comparison antibiotic within 30 days prior to diagnosis of tendon disorder (case period) as well as prescription of the same medications within 30 days one year prior to disease diagnosis (control period).
Use of quinolones was strongly associated with an increased risk of Achilles tendonitis (OR=4.3, 95% CI: 3.2–5.7) and tendon rupture (OR=2.0, 95% CI: 1.2–3.3). No association was found between the use of other antibiotics and either outcome. The association with Achilles tendonitis was stronger among participants who were older than 60 years (OR 8.3 vs. 1.6), non-obese (OR 7.7 vs. 2.4), and who used oral glucocorticoids (GC; OR 9.1 vs. 3.2) and nonsignificantly stronger in women (OR 5.0 vs. 3.6), diabetics (OR 7.0 vs. 4.1), and renal failure/dialysis (OR 20.0 vs. 3.9). The effect for tendon rupture was stronger in women, with borderline-significance in glucocorticoid users and non-obese.
Quinolone-associated tendinopathy is more pronounced among elderly, non-obese persons, and individuals with concurrent use of glucocorticoids.
quinolone; fluoroquinolone; tendon rupture; tendonitis
Acute kidney injury is a frequent postoperative complication that confers increased mortality, morbidity, and costs. The purpose of this study was to evaluate whether preoperative statin use is associated with a decreased risk of postoperative acute kidney injury.
We assembled a retrospective cohort of 98,939 patients who underwent a major open abdominal, cardiac, thoracic, or vascular procedure between 2000 and 2010. Statin users were pair-matched to nonusers on the basis of surgery type, baseline kidney function, days from admission until surgery, and propensity score based on demographics, comorbid conditions, and concomitant medications. Acute kidney injury was defined based on changes in serum creatinine measurements applying Acute Kidney Injury Network and Risk-Injury-Failure staging systems, and on the need for renal replacement therapy. Associations between statin use and acute kidney injury were estimated by conditional logistic regression.
Across various acute kidney injury definitions, statin use was consistently associated with a decreased risk: adjusted odds ratios (95% confidence intervals) varied from 0.74 (0.58–0.95) to 0.80 (0.71–0.90). Associations were similar among diabetics and nondiabetics, and across strata of baseline kidney function. The protective association of statins was most pronounced among patients undergoing vascular surgery and least among patients undergoing cardiac surgery.
Preoperative statin use is associated with a decreased risk of postoperative acute kidney injury. Future randomized clinical trials are needed to determine causality.
Acute kidney injury; Acute renal failure; 3-Hydroxy-3-glutaryl Co-A reductase inhibitors; Perioperative complications; Statins; Surgery
Over the last 15 years, substantial advances have been made in the treatment of chronic obstructive pulmonary disease (COPD). Little information is available, however, on whether these treatments have resulted in reduced rates of hospitalization and acute exacerbations among COPD patients. This retrospective cohort study examined changes in hospitalization rates among Medicare beneficiaries with COPD from 1999 to 2008.
We analyzed data from 424,418 fee-for-service Medicare beneficiaries enrolled between 1999 and 2008 who were diagnosed with COPD. We examined temporal changes in the frequency of hospitalization and acute exacerbations among Medicare beneficiaries with COPD.
Over the 10-year study period, the hospitalization rates for COPD patients—adjusted for age, sex, race, socioeconomic status, region, and number of comorbidities—decreased: from 131 to 107 per 100 person-years for all causes (P < .001); from 58 to 44 per 100 person-years for all respiratory causes (P < .001); and from 73 to 63 per 100 person-years for nonrespiratory causes (P < .001). There was no change in prevalence of COPD in the Medicare population over this time. Additionally, the percentage of COPD patients hospitalized with 2 or more acute exacerbations decreased from 5.5% to 4.3% over the 10-year study period (P < .001).
Between 1999 and 2008, hospitalization rates decreased substantially among Medicare beneficiaries diagnosed with COPD.
COPD; Hospitalization; Older adults
consultation quality; peer evaluation; practice-based learning
Previous studies suggest that obesity is associated with higher prostate cancer progression and mortality despite an association with lower prostate cancer incidence. This study aims to better understand these apparently inconsistent relationships among obese men, by combining evidence from three nationally representative cross-sectional surveys.
We evaluated relationships between obesity and (1) testosterone concentrations in the Third National Health and Nutrition Examination Survey (NHANES III; n=845), (2) prostate-specific antigen (PSA) in NHANES 2001–2004 (n=2,458) and (3) prostate biopsy rates in the National Health Interview Survey (NHIS 2000; n=4,789) population. Mean testosterone, PSA concentrations and biopsy rates were computed for body mass index (BMI) categories.
Testosterone concentrations were inversely associated with obesity (p-trend<0.0001) in NHANES III. In NHANES 2001–2004 obese (BMI >35) versus lean (BMI <25) men were less likely to have PSA concentrations that reached the biopsy threshold of >4 ng/ml (3% versus 8%; p<0.0001). Among NHIS participants all BMI groups had similar rates of PSA testing (p=0.24). However, among men who had PSA tests, 11% of men with BMI >30 versus 16% with BMI <25, achieved a PSA threshold of 4 ng/ml; p=0.01. Furthermore, biopsy rates were lower among men with BMI >30 versus BMI <25 in NHIS participants (4.6% vs. 5.8%; p=0.05).
Obesity was associated with lower PSA-driven biopsy rates. These data support further studies to test the hypothesis that obesity affects prostate cancer detection independent of prostate cancer risk by decreasing the PSA-driven biopsy rates.
obesity; prostate cancer; prostate-specific antigen; biopsy
Atrial fibrillation is common among patients with cardiovascular disease and is a frequent complication of the acute coronary syndrome. Data are needed on recent trends in the magnitude, clinical features, treatment, and prognostic impact of pre-existing and new-onset atrial fibrillation in patients hospitalized with an acute coronary syndrome.
The study population consisted of 59,032 patients hospitalized with an acute coronary syndrome at 113 sites in the Global Registry of Acute Coronary Events Study between 2000 and 2007.
4,494 participants (7.6%) with acute coronary syndrome reported a history of atrial fibrillation and 3,112 (5.3%) developed new-onset atrial fibrillation during their hospitalization. Rates of new-onset atrial fibrillation (5.5% to 4.5%) and pre-existing atrial fibrillation (7.4% to 6.7%) declined during the study. Pre-existing atrial fibrillation was associated with older age and greater cardiovascular disease burden, whereas new-onset atrial fibrillation was closely related to the severity of the index acute coronary syndrome. Patients with atrial fibrillation were less likely than patients without atrial fibrillation to receive evidence-based therapies and were more likely to develop in-hospital complications, including heart failure. Overall hospital death rates in patients with new-onset and pre-existing atrial fibrillation were 14.5% and 8.9%, respectively, compared to 1.2% in those without atrial fibrillation. Short-term death rates in atrial fibrillation patients declined over the study period.
Despite a reduction in the rates of, and mortality from, atrial fibrillation, this arrhythmia exerts a significant adverse effect on survival among patients hospitalized with an acute coronary syndrome. Opportunities exist to improve the identification and treatment of acute coronary syndrome patients with, or at risk for, atrial fibrillation to reduce the incidence and resultant complications of this dysrhythmia.
atrial fibrillation; acute coronary syndrome; mortality
Conventional print materials for presenting risks and benefits of treatment are often difficult to understand. This study was undertaken to evaluate and compare subjects’ understanding and perceptions of risks and benefits presented using animated computerized text and graphics.
Adult subjects were randomized to receive identical risk/benefit information regarding taking statins that was presented on an iPad (Apple Corp, Cupertino, Calif) in 1 of 4 different animated formats: text/numbers, pie chart, bar graph, and pictograph. Subjects completed a questionnaire regarding their preferences and perceptions of the message delivery together with their understanding of the information. Health literacy, numeracy, and need for cognition were measured using validated instruments.
There were no differences in subject understanding based on the different formats. However, significantly more subjects preferred graphs (82.5%) compared with text (17.5%, P < .001). Specifically, subjects preferred pictographs (32.0%) and bar graphs (31.0%) over pie charts (19.5%) and text (17.5%). Subjects whose preference for message delivery matched their randomly assigned format (preference match) had significantly greater understanding and satisfaction compared with those assigned to something other than their preference.
Results showed that computer-animated depictions of risks and benefits offer an effective means to describe medical risk/benefit statistics. That understanding and satisfaction were significantly better when the format matched the individual’s preference for message delivery is important and reinforces the value of “tailoring” information to the individual’s needs and preferences.
Computer animation; Patient comprehension; Patient preferences; Risk/benefit statistics
Our aim was to compare clinical characteristics, prophylaxis, treatment, and outcomes of venous thromboembolism in patients with and without previously diagnosed chronic obstructive pulmonary disease.
We analyzed the population-based Worcester Venous Thromboembolism Study of 2,488 consecutive patients with validated venous thromboembolism to compare clinical characteristics, prophylaxis, treatment, and outcomes in patients with and without chronic obstructive pulmonary disease.
Of 2,488 venous thromboembolism patients, 484 (19.5%) had a history of clinical chronic obstructive pulmonary disease and 2,004 (80.5%) did not. Chronic obstructive pulmonary disease patients were older (mean age 68 years vs. 63 years) and had a higher frequency of heart failure (35.5% vs. 12.9%) and immobility (53.5% vs. 43.3%) than patients without chronic obstructive pulmonary disease (all p<0.0001). Chronic obstructive pulmonary disease patients were more likely to suffer in-hospital death (6.8% vs. 4%, p=0.01) and death within 30 days of venous thromboembolism diagnosis (12.6% vs. 6.5%, p<0.0001). Chronic obstructive pulmonary disease patients demonstrated increased mortality despite a higher frequency of venous thromboembolism prophylaxis. Immobility doubled the risk of in-hospital death (adjusted odds ratio 2.21; 95% confidence interval 1.35–3.62) and death within 30 days of venous thromboembolism diagnosis (adjusted odds ratio 2.04; 95% confidence interval 1.43–2.91).
Patients with chronic obstructive pulmonary disease have an increased risk of dying during hospitalization and within 30 days of venous thromboembolism diagnosis. Immobility in chronic obstructive pulmonary disease patients is an ominous risk factor for adverse outcomes.
chronic obstructive pulmonary disease; deep vein thrombosis; prophylaxis; pulmonary embolism; venous thromboembolism
Cardiac troponin levels help risk-stratify patients presenting with an acute coronary syndrome (ACS). Although they may be elevated in patients presenting with Non-ACS conditions, specific diagnoses and long-term outcomes within that cohort are unclear.
Methods and Results
Using the Veterans Affairs (VA) centralized databases, we identified all hospitalized patients in 2006 who had a troponin assay obtained during their initial reference hospitalization. Based on ICD-9 diagnostic codes, primary diagnoses were categorized as either ACS or Non-ACS conditions. Of a total of 21,668 patients with an elevated troponin level who were discharged from the hospital, 12,400 (57.2%) had a Non-ACS condition. Among that cohort, the most common diagnostic category involved the cardiovascular system and congestive heart failure (N=1661) and chronic coronary artery disease (N=1648) accounted for the major classifications. At one-year following hospital discharge, mortality in patients with a Non-ACS condition was 22.8% and was higher than the ACS cohort (Odds Ratio=1.39; 95%CI: 1.30–1.49). Despite the high prevalence of cardiovascular diseases in patients with a Non-ACS diagnosis, utilization of cardiac imaging within 90 days of hospitalization was low compared with ACS patients (Odds Ratio=0.25; 95%CI: 0.23–0.27).
Hospitalized patients with an elevated troponin level most often have a primary diagnosis that is not an acute coronary syndrome. Their long-term survival is poor and justifies novel diagnostic or therapeutic strategy-based studies to target the highest risk subsets prior to hospital discharge.
outcomes; troponins; non-ACS diagnosis; cardiac imaging; coronary artery disease
Adherence to evidence-based medications after myocardial infarction is associated with improved outcomes. However, long-term data on factors affecting medication adherence after myocardial infarction are lacking.
Olmsted County residents hospitalized with myocardial infarction from 1997-2006 were identified. Adherence to HMG-CoA reductase inhibitors (statins), beta blockers, angiotensin-converting enzyme inhibitors (ACE Inhibitors), and angiotensin II receptor blockers (ARB), were examined. Cox proportional hazard regression was used to determine the factors associated with medication adherence over time.
Among 292 persons with incident myocardial infarction (63% men, mean age 65 years), patients were followed for an average of 52±31 months. Adherence to guideline-recommended medications declined over time, with 3-year medication continuation rates of 44%, 48%, and 43% for statins, beta blockers, and ACE Inhibitors/ARB, respectively. Enrollment in a cardiac rehabilitation program was associated with an improved likelihood of continuing medications, with adjusted hazard ratio (95% confidence interval) for discontinuation of statins and beta blockers among cardiac rehabilitation participants of 0.66 (0.45-0.92) and 0.70 (0.49-0.98), respectively. Smoking at the time of myocardial infarction was associated with a decreased likelihood of continuing medications, though results did not reach statistical significance. There were no observed associations between demographic characteristics, clinical characteristics of the myocardial infarction and medication adherence.
After myocardial infarction, a large proportion of patients discontinue use of medications over time. Enrollment in cardiac rehabilitation after myocardial infarction is associated with improved medication adherence.
Myocardial infarction; drugs; adherence; cardiac rehabilitation
Dietary sodium indiscretion frequently contributes to hospitalizations in elderly heart failure patients. Animal models suggest an important role for dietary sodium intake in the pathophysiology of heart failure with preserved systolic function. The documentation and effects of hospital discharge recommendations, particularly for sodium-restricted diet, have not been extensively investigated in heart failure with preserved systolic function.
We analyzed 1700 heart failure admissions to Michigan community hospitals. We compared documentation of guideline-based discharge recommendations between preserved systolic function and systolic heart failure patients with chi-squared testing, and used logistic regression to identify predictors of 30-day death and hospital readmission in a prespecified follow-up cohort of 443 patients with preserved systolic function. We hypothesized that patients who received a documented discharge recommendation for sodium-restricted diet would have lower 30-day adverse event rates.
Heart failure patients with preserved systolic function were significantly less likely than systolic heart failure patients to receive discharge recommendations for weight monitoring (33% vs 43%) and sodium-restricted diet (42% vs 53%). Upon propensity score-adjusted multivariable analysis, patients with preserved systolic function who received a documented sodium-restricted diet recommendation had decreased odds of 30-day combined death and readmission (odds ratio 0.43, 95% confidence interval, 0.24–0.79; P = .007). No other discharge recommendations predicted 30-day outcomes.
Clinicians document appropriate discharge instructions less frequently in heart failure with preserved systolic function than systolic heart failure. Selected heart failure patients with preserved systolic function who receive advice for sodium-restricted diet may have improved short-term outcomes after hospital discharge.
Diastolic heart failure; Dietary salt; Discharge recommendations; Normal ejection fraction; Outcomes; Performance measures
Most patient chronic disease self-management interventions target single disease outcomes. We evaluated the effect of a tailored hypertension self-management intervention on the unintended targets of glycosylated hemoglobin (Hb A1c) and LDL cholesterol (LDL-C).
We examined 588 patients from the Veterans Study to Improve the Control of Hypertension (V-STITCH), a two year randomized controlled trial. Patients received either a hypertension self-management intervention delivered by a nurse over the telephone or usual care. Although the study focused on hypertension self-management, we compared changes in Hb A1c among a subgroup of 216 patients with diabetes and LDL-C among 528 patients with measurements during the study period. Changes in these lab values over time were compared between the two treatment groups using linear mixed-effects models.
For the patients with diabetes, the hypertension self-management intervention resulted in a 0.46% reduction in Hb A1c over two years compared to usual care (95% CI: 0.04% to 0.89%; p=0.03). For LDL-C, the self-management intervention arm resulted in a reduction of 0.9mg/dl over two years compared to usual care (95% CI: -7.3mg/dl to 5.6mg/dl; p=0.79).
There was no evidence of a hypertension self-management intervention effect on LDL-C, but there was a modest effect of the intervention on the unintended target of Hb A1c. This effect was similar to that seen in self-management interventions specifically targeting diabetes management. Chronic disease self-management interventions may spill over into patients’ co-morbid diagnoses.
Self-management; telemedicine; chronic disease; randomized controlled trial
We sought to examine how expansions in insurance coverage of nonbiologic and biologic disease modifying anti-rheumatic drugs (DMARDs) impacted the access, costs and health status of older patients with rheumatoid arthritis.
We identified a nationally-representative sample of older adults with rheumatoid arthritis in the 2000–2006 Medicare Current Beneficiary Survey (unweighted n=1051). We examined changes in DMARD use, self-reported health status, functional status (activities of daily living [ADL]), and total costs and out-of-pocket costs for medical care and prescription drugs. Tests for time trends were conducted using weighted regressions.
Between 2000 and 2006, the proportion of older adults with rheumatoid arthritis who received biologics tripled (4.6% vs. 13.2%, p=0.01), while the proportion of people that used a nonbiologic did not change. During the same period, the proportion of older rheumatoid arthritis patients rating their health as excellent/good significantly increased (43.0% in 2000 to 55.6% in 2006; p=0.015). Significant improvements occurred in activities of daily living measures of functional status. Total prescription drug costs (in 2006 US dollars) increased from $2645 in 2000 to $4685 in 2006, p=0.0001, while out-of-pocket prescription costs remained constant ($842 in 2000 vs. $832 in 2006; p=0.68). Total medical costs did not significantly increase ($16563 in 2000 vs. $19510 in 2006; p=0.07).
Receipt of biologics in older adults with rheumatoid arthritis increased over a period of time where insurance coverage was expanded without increasing patients’ out-of-pocket costs. During this time period concurrent improvements in self-reported health status and functional status suggest improved arthritis care.
Rheumatoid Arthritis; Disease Modifying Anti-Rheumatic Drugs (DMARD); Biologic Response Modifiers; Medication; Costs
Financial reinforcement interventions based on behavioral economic principles are being increasingly applied in health care settings, and this study examined the use of financial reinforcers for enhancing adherence to medications.
Electronic databases and bibliographies of relevant references were searched, and a meta-analysis of identified trials was conducted. The variability in effect size and the impact of potential moderators (study design, duration of intervention, magnitude of reinforcement, and frequency of reinforcement) on effect size were examined.
Fifteen randomized studies and 6 non-randomized studies examined the efficacy of financial reinforcement interventions for medication adherence. Financial reinforcers were applied for adherence to medications for tuberculosis, substance abuse, HIV, hepatitis, schizophrenia, and stroke prevention. Reinforcement interventions significantly improved adherence relative to control conditions with an overall effect size of 0.77 (95% CI = 0.70–0.84), p < .001. Non-randomized studies had a larger average effect size than randomized studies, but the effect size of randomized studies remained significant at 0.44 (95% CI = 0.35–0.53), p < .001. Interventions that were longer in duration, provided average reinforcement of ≥$50/week, and reinforced patients at least weekly resulted in larger effect sizes than those that were shorter, provided lower reinforcers, and reinforced patients less frequently.
These results demonstrate the efficacy of medication adherence interventions and underscore principles that should be considered in designing future adherence interventions. Importantly, financial reinforcement interventions hold potential for improving medication adherence and may lead to benefits for both patients and society.
reinforcement; financial; medication adherence; meta-analysis; behavioral economics
Osteoarthritis is the most common form of arthritis, with knee osteoarthritis being the leading cause of lower extremity disability among older adults in the US. There are no treatments available to prevent the structural pathology of osteoarthritis. Because of vitamin K’s role in regulating skeletal mineralization, it has potential to be a preventative option for osteoarthritis. We therefore examined the relation of vitamin K to new-onset radiographic knee osteoarthritis and early osteoarthritis changes on magnetic resonance imaging (MRI).
Subjects from the Multicenter Osteoarthritis (MOST) Study had knee radiographs and MRI scans obtained at baseline and 30 months later, and plasma phylloquinone (vitamin K) measured at baseline. We examined the relationship of subclinical vitamin K deficiency to incident radiographic knee osteoarthritis and MRI-based cartilage lesions and osteophytes, respectively, using log binomial regression with generalized estimating equations, adjusting for potential confounders.
Among 1180 participants (62% women, mean age 62 ± 8 years, mean body mass index 30.1 ± 5.1 kg/m2), subclinical vitamin K deficiency was associated with incident radiographic knee osteoarthritis (risk ratio [RR] 1.56; 95% confidence interval [CI], 1.08–2.25) and cartilage lesions (RR 2.39; 95% CI, 1.05–5.40) compared with no deficiency, but not with osteophytes (RR 2.35; 95% CI, 0.54–10.13). Subclinically vitamin K-deficient subjects were more likely to develop osteoarthritis in one or both knees than neither knee (RR 1.33; 95% CI, 1.01–1.75 and RR 2.12; 95% CI, 1.06-4.24, respectively).
In the first such longitudinal study, subclinical vitamin K deficiency was associated with increased risk of developing radiographic knee osteoarthritis and MRI-based cartilage lesions. Further study of vitamin K is warranted given its therapeutic/prophylactic potential for osteoarthritis.
Incident knee osteoarthritis; MRI cartilage abnormalities; Vitamin K
Tumor-induced osteomalacia; hypophosphatemia; FGF-23
Coronary artery disease is a potentially treatable comorbidity observed frequently in both chronic obstructive pulmonary disease and interstitial lung disease. The prevalence of angiographically proven coronary artery disease in advanced lung disease is not well described. We sought to characterize the treatment patterns of coronary artery disease complicating advanced lung disease and to describe the frequency of occult coronary artery disease in this population.
We performed a 2-center, retrospective cross-sectional study of patients with either chronic obstructive pulmonary disease or interstitial lung disease evaluated for lung transplantation. Medications and diagnoses before the transplant evaluation were recorded in conjunction with left heart catheterization results.
Of 473 subjects, 351 had chronic obstructive pulmonary disease, and 122 had interstitial lung disease. In subjects diagnosed clinically with coronary artery disease, medical regimens included a statin in 78%, antiplatelet therapy in 62%, angiotensin-converting enzyme inhibitor or angiotensin receptor blocker in 42%, and a beta-blocker in 37%. Ten percent were on no medication from these 4 classes. Fifty-seven percent of these subjects were on an antiplatelet agent as well as a statin, and 13% were on neither. Beta-blockers were less frequently prescribed in chronic obstructive pulmonary disease than interstitial lung disease (23% vs 58%, P = .007). Coronary angiography was available in 322 subjects. It demonstrated coronary artery disease in 60% of subjects, and severe coronary artery disease in 16%. Occult coronary artery disease and severe occult coronary artery disease were found in 53% and 9%, respectively. There were no significant differences in angiographic results between chronic obstructive pulmonary disease and interstitial lung disease, despite imbalanced risk factors.
Coronary artery disease is common in patients with advanced lung disease attributable to chronic obstructive pulmonary disease or interstitial lung disease and is under-diagnosed. Guideline-recommended cardioprotective medications are suboptimally utilized in this population.
COPD; Coronary artery disease; Interstitial lung disease; Lung transplantation; Pulmonary fibrosis
Previous studies have described an “obesity paradox” with heart failure, whereby higher body mass index (BMI) is associated with lower mortality. However, little is known about the impact of obesity on survival after acute myocardial infarction.
Data from 2 registries of patients hospitalized in the United States with acute myocardial infarction between 2003–04 (PREMIER) and 2005–08 (TRIUMPH) were used to examine the association of BMI with mortality. Patients (n=6359) were categorized into BMI groups (kg/m2) using baseline measurements. Two sets of analyses were performed using Cox proportional hazards regression with fractional polynomials to model BMI as categorical and continuous variables. To assess the independent association of BMI with mortality, analyses were repeated adjusting for 7 domains of patient and clinical characteristics.
Median BMI was 28.6. BMI was inversely associated with crude 1-year mortality (normal, 9.2%; overweight, 6.1%; obese, 4.7%; morbidly obese; 4.6%; p<0.001), which persisted after multivariable adjustment. When BMI was examined as a continuous variable, the hazards curve declined with increasing BMI and then increased above a BMI of 40. Compared with patients with a BMI of 18.5, patients with higher BMIs had a 20% to 68% lower mortality at 1 year. No interactions between age (p=0.37), gender (p=0.87) or diabetes mellitus (p=0.55) were observed.
There appears to be an “obesity paradox” among acute myocardial infarction patients such that higher BMI is associated with lower mortality, an effect that was not modified by patient characteristics and was comparable across age, gender, and diabetes subgroups.
body mass index; mortality; myocardial infarction; fractional polynomials; obesity paradox
Analyses from double-blind randomized trials have reported lower mortality among participants who were more adherent to placebo compared with those who were less adherent. We explored this phenomenon by analyzing data from the placebo arm of the Heart and Estrogen/Progestin Replacement Study (HERS), a randomized, double-blind, placebo-controlled trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women.
Our primary aim was to measure and explain the association between adherence to placebo and total mortality among the placebo-allocated participants in the HERS trial. Secondary aims included assessment of the association between placebo adherence and cause-specific morbidity and mortality.
Participants with "higher placebo adherence" were defined as having taken at least 75% of their placebo study medication during each individual’s participation in the study, while those with “lower placebo adherence” took <75%. The primary outcome was in-study all-cause mortality.
More adherent participants had significantly lower total mortality compared to less-adherent participants (HR = 0.52, 95% Confidence Interval: 0.29–0.93). Adjusting for available confounders did not change the magnitude or significance of the estimates. Analyses revealed that the association of higher adherence and mortality might be explained, in part, by time-dependent confounding.
Analyses of the HERS trial data support a strong association between adherence to placebo study medication and mortality. While probably not due to simple confounding by healthy lifestyle factors, the underlying mechanism for the association remains unclear. Further analyses of this association are necessary to explain this observation.
Double-blind clinical trials; Placebo; Adherence
Antibiotic medications are associated with an increased risk of bleeding among patients receiving warfarin. The recent availability of data from the Medicare Part D prescription drug program provides an opportunity to assess the association of antibiotic medications and the risk of bleeding in a national population of older adults receiving warfarin.
We conducted a case-control study nested within a cohort of 38,762 patients aged 65 years and older who were continuous warfarin users, using enrollment and claims data for a 5% national sample of Medicare beneficiaries with Part D benefits. Cases were defined as persons hospitalized for a primary diagnosis of bleeding and were matched with three control subjects on age, race, gender, and indication for warfarin. Logistic regression analysis was used to calculate adjusted odds ratios (aORs) and 95% confidence intervals (CIs) for the risk of bleeding associated with prior exposure to antibiotic medications.
Exposure to any antibiotic agent within the 15 days of the event/index date was associated with an increased risk of bleeding (aOR 2.01; 95% CI, 1.62-2.50). All six specific antibiotic drug classes examined [azole antifungals (aOR, 4.57; 95% CI, 1.90-11.03), macrolides (aOR, 1.86; 95% CI, 1.08-3.21), quinolones (aOR, 1.69; 95% CI, 1.09-2.62), cotrimoxazole (aOR, 2.70; 95% CI, 1.46-5.05), penicillins (aOR, 1.92; 95% CI, 1.21-2.07) and cephalosporins (aOR, 2.45; 95% CI, 1.52-3.95) were associated with an increased risk of bleeding.
Among older continuous warfarin users, exposure to antibiotic agents—particularly azole antifungals—was associated with an increased risk of bleeding.
warfarin; antibiotics; patient safety; major bleeding; pharmacoepidemiology; older adults
We hypothesized that women with early- and mid-adult life obesity, as well as high mid-adult life waist-to-hip ratios, and high weight gain during adulthood, experience a greater incidence of gout.
We examined the incidence of gout in the Atherosclerosis Risk in Communities (ARIC) Study, a population-based biracial cohort comprised of individuals aged 45–65 years of age at baseline (1987–1989). A total of 6,263 women without prior history of gout were identified. We examined the association of BMI and obesity at cohort entry and at age 25 years, waist-to-hip ratio and weight change, with gout incidence (1996–1998).
Over 9 years of follow-up, 103 women developed gout. The cumulative incidence of gout, by age 70 years, according to BMI category at baseline of <25, 25–29.9, 30–34.9, and ≥ 35 kg/m2, was 1.9, 3.6, 7.9, and 11.8%, respectively (P <0.001). Obese women (BMI≥30) at baseline had an adjusted 2.4-fold greater risk of developing gout than non-obese women (95% confidence interval (CI) 1.53, 3.68). This association was attenuated after further adjustment for urate levels. Further, early adult obesity in women was associated with a 2.8-fold increased risk of gout compared to non-obese women (95% CI 1.33, 6.09), which remained statistically significant after baseline urate adjustment. There was a graded association between each anthropometric measure, including weight gain, with incident gout (each P for trend <0.001). The results were similar in black and white women.
In a large cohort of African American and Caucasian women, obesity in early and mid-adulthood, and weight gain during this interval, were each independent risk factors for incident gout in women.
Gout; Women; Obesity; Weight; Arthritis
Patients with chronic kidney disease are often reported to be unaware. We prospectively evaluated the association between awareness of kidney disease to end-stage renal disease and mortality.
We utilized 2000–2009 data from the National Kidney Foundation-Kidney Early Evaluation Program (KEEP™). Mortality was determined by cross reference to the Social Security Administration Death Master File, and development of end-stage by cross reference with the United States Renal Data System.
Of 109,285 participants, 28,244 (26%) had chronic kidney disease defined by albuminuria or eGFR <60ml/min/1.73m2. Only 9% (n=2660) reported being aware of kidney disease. Compared to those who were not aware, participants aware of chronic kidney disease had lower eGFR (49 vs 62ml/min/1.73m2) and a higher prevalence of albuminuria (52 vs 46%), diabetes (47 vs 42%), cardiovascular disease (43 vs 28%) and cancer (23 vs 14%). Over 8.5 years of follow-up, aware participants compared to those unaware had a lower rate of survival for end-stage (83% and 96%) and mortality (78 vs 81%), p<0.001 respectively. After adjustment for demographics, socioeconomic factors, comorbidity, and severity of kidney disease, aware participants continued to demonstrate an increased risk for end-stage renal disease [hazard ratio (95% CI) 1.37(1.07–1.75); p<0.0123] and mortality [1.27(1.07–1.52); p<0.0077] relative to unaware participants with chronic kidney disease.
Among persons identified as having chronic kidney disease at a health screening, only a small proportion had been made aware of their diagnosis previously by clinicians. This subgroup was at a disproportionately high risk for mortality and end-stage renal disease.
KEEP; CKD; awareness; ESRD; mortality