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1.  [No title available] 
PMCID: PMC3932622  PMID: 24067296
2.  Long-term Adherence to Healthy Dietary Guidelines and Chronic Inflammation in the Prospective Whitehall II Study☆ 
The American Journal of Medicine  2015;128(2):152-160.e4.
Background
Inflammation plays an important role in the cause of cardiovascular diseases and may contribute to the association linking an unhealthy diet to chronic age-related diseases. However, to date the long-term associations between diet and inflammation have been poorly described. Our aim was to assess the extent to which adherence to a healthy diet and dietary improvements over a 6-year exposure period prevented subsequent chronic inflammation over a 5-year follow-up in a large British population of men and women.
Methods
Data were drawn from 4600 adults (mean ± standard deviation, age 49.6 ± 6.1 years, 28% were women) from the prospective Whitehall cohort II study. Adherence to a healthy diet was measured using Alternative Healthy Eating Index (AHEI) scores in 1991-1993 (50.7 ± 11.9 points) and 1997-1999 (51.6 ± 12.4 points). Chronic inflammation, defined as average levels of serum interleukin-6 from 2 measures 5 years apart, was assessed in 1997-1999 and 2002-2004.
Results
After adjustment for sociodemographic factors, health behaviors, and health status, participants who maintained a high AHEI score (ie, a healthy diet, n = 1736, 37.7%) and those who improved this score over time (n = 681, 14.8%) showed significantly lower mean levels of interleukin-6 (1.84 pg/mL, 95% confidence interval [CI], 1.71-1.98 and 1.84 pg/mL, 95% CI, 1.70-1.99, respectively) than those who had a low AHEI score (n = 1594, 34.6%) over the 6-year exposure period (2.01 pg/mL, 95% CI, 1.87-2.17).
Conclusions
These data suggest that maintaining and improving adherence to healthy dietary recommendations may reduce the risk of long-term inflammation.
doi:10.1016/j.amjmed.2014.10.002
PMCID: PMC4315808  PMID: 25305231
Alternative Healthy Eating Index; Diet quality indices; Inflammatory marker; Interleukin-6; Middle-aged population; Nutritional Epidemiology; Prospective cohort
3.  Improving the Quality of Pneumonia Care that Patients Experience 
The American journal of medicine  2002;113(5):379-383.
PURPOSE
Although many hospitals have reported attempts to reduce length of stay for patients hospitalized with community-acquired pneumonia, few have included efforts to educate patients to prepare them for earlier discharges. We aimed to improve patients’ knowledge about pneumonia and their experiences with inpatient care as part of a multifaceted intervention that included attempts to reduce unnecessary time on intravenous antibiotics and length of hospital stay.
METHODS
We developed guidelines for the appropriate duration of intravenous antibiotics in patients with community-acquired pneumonia and collected baseline data retrospectively on patients discharged from October 1996 through April 1997. We surveyed these patients to assess knowledge and experience with care. Beginning in July 1997, we conducted a series of physician and nurse educational interventions (lectures, feedback of performance data, one-on-one education by peers). Patients received education about pneumonia from their nurses and a specially developed educational brochure. Following the interventions, we collected clinical and survey data on patients with pneumonia discharged from October 1997 through April 1998.
RESULTS
Among patients who responded to the survey (163 in the preintervention period; 114 in the postintervention period), fewer reported that no one went out of the way to help them (preintervention, 37% [n = 60]; postintervention, 6% [n = 7]; P =0.001), more reported that they received all the information they needed to recover (75% [n =122] vs. 94% [n =107], P = 0.02), and more reported that they were told about danger signals of relapse (46% [n =75] vs. 60% [n =68], P =0.03). Mean (± SD) time on intravenous antibiotics decreased from 5.0 ± 3.7 days to 4.3 ± 3.3 days (P = 0.04).
CONCLUSION
The interventions improved patients’ knowledge and experiences with care, while decreasing time on intravenous antibiotics.
PMCID: PMC4304662  PMID: 12401532
4.  Risk of Suicide after Long Term Follow-up from Bariatric Surgery 
The American journal of medicine  2010;123(11):1036-1042.
Purpose
Bariatric surgery is recognized as the treatment of choice for class III obesity (body mass index >= 40) and has been increasingly recommended for obese patients. Prior research has suggested an excess of deaths due to suicide following bariatric surgery but few large long term follow up studies exist. We examined post-bariatric surgery suicides by time since operation, sex, age, and suicide death rates as compared to US suicide rates.
Methods
Medical data following bariatric operations performed on Pennsylvania residents between 01/01/1995 and 12/31/2004 were obtained from the Pennsylvania Health Care Cost and Containment Council. Matching mortality data from suicides between 09/1/1996 and 12/28/2006 were obtained from the Division of Vital Records, Pennsylvania State Department of Health.
Results
There were 31 suicides (16,683 operations), for an overall rate of 6.6/10,000, 13.7 per 10,000 among men and 5.2 per 10,000 among women. About 30% of suicides occurred within the first two years following surgery, with almost 70% occurring within three years. For every age category except the youngest, suicide rates were higher among men vs. women. Age and sex-matched suicide rates in the US population (ages 35–64) were 2.4/10,000 (men) and 0.7/10,000 (women).
Conclusions
Compared to age and sex-matched suicide rates in the U.S., there was a substantial excess of suicides among all patients who had bariatric surgery in Pennsylvania during a ten-year period. These data document a need to develop more comprehensive longer-term surveillance and follow-up methods in order to evaluate factors associated with post-bariatric surgery suicide.
doi:10.1016/j.amjmed.2010.06.016
PMCID: PMC4296730  PMID: 20843498
bariatric surgery; suicides; public health
5.  Comparison of 24-hour Holter Monitoring with 14-day Novel Adhesive Patch Electrocardiographic Monitoring 
The American journal of medicine  2013;127(1):10.1016/j.amjmed.2013.10.003.
BACKGROUND
Cardiac arrhythmias are remarkably common and routinely go undiagnosed because they are often transient and asymptomatic. Effective diagnosis and treatment can substantially reduce the morbidity and mortality associated with cardiac arrhythmias. The Zio Patch (iRhythm Technologies, Inc, San Francisco, Calif) is a novel, single-lead electrocardiographic (ECG), lightweight, Food and Drug Administration–cleared, continuously recording ambulatory adhesive patch monitor suitable for detecting cardiac arrhythmias in patients referred for ambulatory ECG monitoring.
METHODS
A total of 146 patients referred for evaluation of cardiac arrhythmia underwent simultaneous ambulatory ECG recording with a conventional 24-hour Holter monitor and a 14-day adhesive patch monitor. The primary outcome of the study was to compare the detection arrhythmia events over total wear time for both devices. Arrhythmia events were defined as detection of any 1 of 6 arrhythmias, including supraventricular tachycardia, atrial fibrillation/flutter, pause greater than 3 seconds, atrioventricular block, ventricular tachycardia, or polymorphic ventricular tachycardia/ventricular fibrillation. McNemar’s tests were used to compare the matched pairs of data from the Holter and the adhesive patch monitor.
RESULTS
Over the total wear time of both devices, the adhesive patch monitor detected 96 arrhythmia events compared with 61 arrhythmia events by the Holter monitor (P < .001).
CONCLUSIONS
Over the total wear time of both devices, the adhesive patch monitor detected more events than the Holter monitor. Prolonged duration monitoring for detection of arrhythmia events using single-lead, less-obtrusive, adhesive-patch monitoring platforms could replace conventional Holter monitoring in patients referred for ambulatory ECG monitoring.
doi:10.1016/j.amjmed.2013.10.003
PMCID: PMC3882198  PMID: 24384108
Atrial fibrillation; Cardiac arrhythmias; Electrocardiographic; Holter monitor; iRhythm; Zio Patch
6.  Pulmonary Emphysema Subtypes on Computed Tomography in Smokers 
The American journal of medicine  2013;127(1):10.1016/j.amjmed.2013.09.020.
Background
Pulmonary emphysema is divided into three major subtypes at autopsy: centrilobular, paraseptal and panlobular emphysema. These subtypes can be defined by visual assessment on computed tomography (CT); however, clinical characteristics of emphysema subtypes on CT are not well-defined. We developed a reliable approach to visual assessment of emphysema subtypes on CT and examined if emphysema subtypes have distinct characteristics.
Methods
The Multi-Ethnic Study of Atherosclerosis COPD Study recruited smokers with COPD and controls age 50–79 years with ≥10 pack-years. Participants underwent CT following a standardized protocol. Definitions of centrilobular, paraseptal and panlobular emphysema were obtained by literature review. Six-minute walk distance and pulmonary function were performed following guidelines.
Results
Twenty-seven percent of 318 smokers had emphysema on CT. Inter-rater reliability of emphysema subtype was substantial (K:0.70). Compared to participants without emphysema, individuals with centrilobular or panlobular emphysema had greater dyspnea, reduced walk distance, greater hyperinflation, and lower diffusing capacity. In contrast, individuals with PSE were similar to controls, except for male predominance. Centrilobular but not panlobular or paraseptal emphysema was associated with greater smoking history (+21 pack-years P<0.001). Panlobular but not other types of emphysema was associated with reduced body mass index (−5 kg/m2;P=0.01). Other than for dyspnea, these findings were independent of the forced expiratory volume in one second. Seventeen percent of smokers without COPD on spirometry had emphysema, which was independently associated with reduced walk distance.
Conclusions
Emphysema subtypes on CT are common in smokers with and without COPD. Centrilobular and panlobular emphysema but not paraseptal emphysema have considerable symptomatic and physiological consequences.
doi:10.1016/j.amjmed.2013.09.020
PMCID: PMC3882898  PMID: 24384106
Emphysema; computed tomography; centrilobular; paraseptal; panlobular
7.  Digoxin Use and Lower 30-Day All-Cause Readmission for Medicare Beneficiaries Hospitalized for Heart Failure 
The American journal of medicine  2013;127(1):61-70.
BACKGROUND
Heart failure is the leading cause for hospital readmission, the reduction of which is a priority under the Affordable Care Act. Digoxin reduces 30-day all-cause hospital admission in chronic systolic heart failure. Whether digoxin is effective in reducing readmission after hospitalization for acute decompensation remains unknown.
METHODS
Of the 5153 Medicare beneficiaries hospitalized for acute heart failure and not receiving digoxin, 1054 (20%) received new discharge prescriptions for digoxin. Propensity scores for digoxin use, estimated for each of the 5153 patients, were used to assemble a matched cohort of 1842 (921 pairs) patients (mean age, 76 years; 56% women; 25% African American) receiving and not receiving digoxin, who were balanced on 55 baseline characteristics.
RESULTS
30-day all-cause readmission occurred in 17% and 22% of matched patients receiving and not receiving digoxin, respectively (hazard ratio {HR} for digoxin, 0.77; 95% confidence interval {CI}, 0.63–0.95). This beneficial association was observed only in those with ejection fraction <45% (HR, 0.63; 95% CI, 0.47–0.83), but not in those with ejection fraction ≥45% (HR, 0.91; 95% CI, 0.60–1.37; p for interaction, 0.145), a difference that persisted throughout first 12-month post-discharge (p for interaction, 0.019). HRs (95% CIs) for 12-month heart failure readmission and all-cause mortality were 0.72 (0.61–0.86) and 0.83 (0.70–0.98), respectively.
CONCLUSIONS
In Medicare beneficiaries with systolic heart failure, a discharge prescription of digoxin was associated with lower 30-day all-cause hospital readmission, which was maintained at 12 months, and was not at the expense of higher mortality. Future randomized controlled trials are needed to confirm these findings.
doi:10.1016/j.amjmed.2013.08.027
PMCID: PMC3929967  PMID: 24257326
Digoxin; heart failure; hospital readmission
8.  Increased Risk of Recurrent Gout Attacks with Hospitalization 
The American journal of medicine  2013;126(12):10.1016/j.amjmed.2013.06.026.
Background
While anecdotal evidence suggests that risk of recurrent gout attack increases with hospitalization, no study has formally tested this hypothesis.
Methods
We conducted an online case-crossover study of individuals with gout. We obtained information on gout attacks over a one-year period, including: onset date, symptoms and signs, medications, and exposure to potential risk factors, including hospitalization, during the 2-day hazard period prior to each gout attack. The same exposure information was also obtained over 2-day intercritical gout control periods. We performed conditional logistic regression to examine the relationship of hospitalization with recurrent gout attacks and whether such a relationship was modified by concomitant use of anti-gout medications.
Results
Of 724 participants (mean age 54.5 years, 78.5% male), 35 hospitalizations occurred during either a hazard or control period. The adjusted odds of gout attacks was increased 4-fold with hospitalization (OR 4.05, 95% confidence interval: 1.78–9.19) compared with no hospitalization. The effect of hospitalization tended to attenuate with use of allopurinol, colchicine, or NSAIDs, but not statistically significantly.
Conclusions
Our study confirmed that the risk of gout attacks increases among gout patients during hospitalization. Appropriate measures should be considered for prevention of gout attacks during hospitalization for patients with pre-existing gout.
doi:10.1016/j.amjmed.2013.06.026
PMCID: PMC3838663  PMID: 24054179
9.  Body Mass Index, Waist Circumference, Physical Activity and Risk of Hearing Loss in Women 
The American journal of medicine  2013;126(12):10.1016/j.amjmed.2013.04.026.
BACKGROUND
Acquired hearing loss is highly prevalent, but prospective data on potentially modifiable risk factors are limited. In cross-sectional studies, higher body mass index (BMI), larger waist circumference, and lower physical activity have been associated with poorer hearing, but these have not been examined prospectively.
METHODS
We examined the independent associations between BMI, waist circumference and physical activity and self-reported hearing loss in 68,421 women in the Nurses’ Health Study II from 1989 to 2009. Baseline and updated information on BMI, waist circumference and physical activity was obtained from biennial questionnaires.
RESULTS
After more than 1.1 million person-years of follow-up, 11,286 cases of hearing loss were reported to have occurred. Higher BMI and larger waist circumference were associated with increased risk of hearing loss. Compared with women with BMI <25 kg/m2, the multivariate-adjusted relative risk (RR) for women with BMI ≥ 40 was 1.25 (95% CI 1.14,1.37). Compared with women with waist circumference <71 cm, the multivariate-adjusted RR for waist circumference >88 cm was 1.27 (95% CI 1.17, 1.38). Higher physical activity was inversely related to risk; compared with women in the lowest quintile of physical activity, the multivariate-adjusted RR for women in the highest quintile was 0.83 (95% CI 0.78,0.88). Walking 2 hours per week or more was inversely associated with risk. Simultaneous adjustment for BMI, waist circumference and physical activity slightly attenuated the associations but they remained statistically significant.
CONCLUSIONS
Higher BMI and larger waist circumference are associated with increased risk and higher physical activity is associated with reduced risk of hearing loss in women. These findings provide evidence that maintaining healthy weight and staying physically active, potentially modifiable lifestyle factors, may help reduce the risk of hearing loss.
doi:10.1016/j.amjmed.2013.04.026
PMCID: PMC3848606  PMID: 24125639
hearing loss; prospective study; body mass index; waist circumference; physical activity; epidemiology
10.  Dietary Fiber Intake and Cardiometabolic Risks among US Adults, NHANES 1999–2010 
The American journal of medicine  2013;126(12):10.1016/j.amjmed.2013.07.023.
Background
Dietary fiber may decrease the risk of cardiovascular disease and associated risk factors. We examined trends in dietary fiber intake among diverse US adults between 1999 and 2010, and investigated associations between dietary fiber intake and cardiometabolic risks including metabolic syndrome, cardiovascular inflammation, and obesity.
Methods
Our cross-sectional analysis included 23,168 men and non-pregnant women aged 20+ years from 1999–2010 National Health and Nutrition Examination Survey. We used weighted multivariable logistic regression models to estimate predicted marginal risk ratios and 95% confidence intervals (CIs) for the risks of having the metabolic syndrome, inflammation, and obesity associated with quintiles of dietary fiber intake.
Results
Dietary fiber intake remained consistently below recommended adequate intake levels for total fiber defined by the Institute of Medicine. Mean dietary fiber intake averaged 15.7g–17.0g. Mexican-Americans (18.8 g) consumed more fiber than non-Hispanic Whites (16.3 g) and non-Hispanic Blacks (13.1 g). Comparing the highest to lowest quintiles of dietary fiber intake, adjusted predicted marginal risk ratios (95% CI) for the metabolic syndrome, inflammation, and obesity were 0.78 (0.69–0.88), 0.66 (0.61–0.72), and 0.77 (0.71–0.84), respectively. Dietary fiber was associated with lower levels of inflammation within each racial and ethnic group, though statistically significant associations between dietary fiber and either obesity or metabolic syndrome were seen only among whites.
Conclusions
Low dietary fiber intake from 1999–2010 in the US, and associations between higher dietary fiber and a lower prevalence of cardiometabolic risks suggest the need to develop new strategies and policies to increase dietary fiber intake.
doi:10.1016/j.amjmed.2013.07.023
PMCID: PMC3865784  PMID: 24135514
Dietary fiber; disparities; metabolic diseases; NHANES
11.  Does CHA2DS2-VASc Improve Stroke Risk Stratification in Postmenopausal Women with Atrial Fibrillation? 
The American journal of medicine  2013;126(12):10.1016/j.amjmed.2013.05.023.
Background
Risk stratification of atrial fibrillation patients with a CHADS2 score of < 2 remains imprecise, particularly in women. Our objectives were to validate the CHADS2 and CHA2DS2-VASc stroke risk scores in a healthy cohort of American women with atrial fibrillation and to determine whether CHA2DS2-VASc further risk stratifies individuals with a CHADS2 score of < 2.
Methods
We identified a cohort of 5,981 women with atrial fibrillation not on warfarin at baseline (mean age 65.9±7.2 years) enrolled in the Women's Health Initiative and followed for a median of 11.8 years. Univariate and multivariate proportional hazards analyses were used to examine these two risk scores with main outcome measures being annualized event rates of ischemic stroke or transient ischemic attack stratified by risk score.
Results
Annualized stroke/ transient ischemic attack rates ranged from 0.36-2.43% with increasing CHADS2 score (0-4+) (hazard ratio (HR) 1.57, 95% confidence interval (CI) 1.45-1.71 for each 1 point increase) and 0.20-2.02% with increasing CHA2DS2-VASc score (1-6+) (HR 1.50, 95% CI 1.41-1.60 for each 1 point increase). CHA2DS2-VASc had a higher c statistic than CHADS2: 0.67 (95% CI 0.65-0.69) vs. 0.65 (95% CI 0.62-0.67), p < 0.01. For CHADS2 scores < 2, stroke risk almost doubled with every additional CHA2DS2-VASc point.
Conclusions
Although both CHADS2, and CHA2DS2-VASc are predictive of stroke risk in post-menopausal women with atrial fibrillation, CHA2DS2-VASc further risk-stratifies patients with a CHADS2 score < 2.
doi:10.1016/j.amjmed.2013.05.023
PMCID: PMC3883047  PMID: 24139523
atrial fibrillation; CHADS2; CHA2DS2-VASc; stroke; women
12.  Anxiety, Anger, and Mortality Risk Among Survivors of Myocardial Infarction 
The American journal of medicine  2013;126(12):1107-1113.
Background
Although there is evidence that anxiety and anger are associated with a higher risk of cardiovascular events, studies examining the relationship between these stressors and prognosis following myocardial infarction have been mixed.
Methods
We conducted a prospective cohort study of 1968 participants (average age 60.2, 30.6% women) in the Determinants of Myocardial Infarction Onset Study recruited at the time of admission for myocardial infarction between 1989-1996. We used the state anxiety and anger subscales of the State-Trait Personality Inventory. Participants were followed for all-cause mortality through December 31, 2007 using the National Death Index. We constructed multivariable Cox proportional hazards models adjusted for demographic, behavioral, and clinical confounders and calculated hazard ratios and 95% confidence intervals to examine the relationship between high levels of anxiety and anger and all-cause mortality.
Results
Over 10 years of follow-up, 525 participants died. Compared to those scoring lower, an anxiety score >90th percentile was associated with a 1.31-times (95% CI 0.93-1.84) higher mortality rate. The association was apparent in the first 3 years (HR=1.78; 95% CI 1.08-2.93) but not thereafter. Likewise, an anger score >90th percentile was associated with a 1.25-times (95% CI 0.87-1.80) higher mortality rate. The association was higher in the first 3 years (HR=1.58; 95% CI 0.91-2.74) than in subsequent years, but it was not statistically significant during either follow-up period.
Conclusions
In this study of myocardial infarction survivors, a high level of anxiety was associated with all-cause mortality, with the strongest association in the first 3 years of follow-up.
doi:10.1016/j.amjmed.2013.07.022
PMCID: PMC3933314  PMID: 24083642
Anxiety; Anger; Myocardial Infarction; All-cause mortality
13.  Prevalence of hyponatremia and association with mortality: Results from NHANES 
The American journal of medicine  2013;126(12):1127-37.e1.
Background
Hyponatremia is the most common electrolyte abnormality in hospitalized patients and is associated with adverse outcomes, but its prevalence and significance in the general U.S. population is unknown. Our aims were to determine the prevalence of hyponatremia and its association with mortality in the population.
Methods
We performed a population-based cross-sectional study of 14,697 adults aged ≥ 18 years who participated in the nationally representative National Health and Nutrition Examination Survey for 1999 – 2004. Using measurements of serum sodium corrected for dilutional effect of hyperglycemia, we determined the association of hyponatremia with patient characteristics, comorbidities, and prescription medications, and performed unadjusted and adjusted Cox proportional hazards regression to find the association of hyponatremia with all-cause mortality.
Results
We provide the first estimate of the prevalence of hyponatremia in the U.S. population, which in our weighted analysis was 1.72%. Prevalence of hyponatremia was significantly higher in females (2.09%, p=0.004) and increased with age. Hyponatremia was more common in subjects with hypertension, diabetes, coronary artery disease, stroke, chronic obstructive pulmonary disease, cancer, and psychiatric disorders, and less common with those with no comorbidities (1.04%, p<0.001). There was a significant risk of death associated with hyponatremia in unadjusted (HR 3.61, p<0.001) and adjusted Cox models controlling for demographics, smoking, comorbidities and insurance status (HR 2.43, p<0.001). There was a U-shaped relationship between serum sodium and hazard ratio for mortality.
Conclusions
Our findings suggest that hyponatremia is a predictor of mortality in the general population independent of age, gender, and comorbid conditions.
doi:10.1016/j.amjmed.2013.07.021
PMCID: PMC3933395  PMID: 24262726
hyponatremia; mortality; Epidemiology and outcomes; electrolytes; NHANES; medications; comorbidity; outpatient; general population
14.  Racial and Ethnic Disparities in Disease Activity in Rheumatoid Arthritis Patients 
The American journal of medicine  2013;126(12):1089-1098.
Background
Observational studies of patients with rheumatoid arthritis have suggested that racial and ethnic disparities exist for minority populations. We compared disease activity and clinical outcomes across racial and ethnic groups using data from a large, contemporary United States registry.
Methods
We analyzed data from two time periods (2005-2007 and 2010-2012). The Clinical Disease Activity Index was examined as both a continuous measure and as dichotomous measures of disease activity states. Outcomes were compared in unadjusted and a series of cross-sectional and longitudinal multivariable regression models.
Results
For 2005-2007, significant differences of mean disease activity level (p<0.001) were observed across racial and ethnic groups. Over the five-year period, modest improvements in disease activity were observed across all groups, including whites [3.7 (95% CI 3.2 - 4.1) compared with African Americans [4.3 (95% CI 2.7 – 5.8)] and Hispanics [2.7 (95% CI 1.2 – 4.3)]. For 2010-2012, significant differences of mean disease activity level persisted (p<0.046) across racial and ethnic groups, ranging from 11.6 (95% CI 10.4-12.8) in Hispanics to 10.7 (95% CI 9.6-11.7) in whites. Remission rates remained significantly different across racial/ethnic groups across all models for 2010-2012, ranging from 22.7 (95% CI 19.5-25.8) in African Americans to 27.4 (95% CI 24.9-29.8) in whites.
Conclusions
Despite improvements in disease activity across racial and ethnic groups over a 5-year period, disparities persist in disease activity and clinical outcomes for minority groups versus white patients.
doi:10.1016/j.amjmed.2013.09.002
PMCID: PMC4006346  PMID: 24262723
Rheumatoid Arthritis; Disparities; Disease activity
15.  Avoidable Antibiotic Exposure for Uncomplicated Skin and Soft Tissue Infections in the Ambulatory Care Setting 
The American journal of medicine  2013;126(12):1099-1106.
Background
Uncomplicated skin and soft tissue infections are among the most frequent indications for outpatient antibiotics. A detailed understanding of current prescribing practices is necessary to optimize antibiotic use for these conditions.
Methods
This was a retrospective cohort study of children and adults treated in the ambulatory care setting for uncomplicated cellulitis, wound infection, or cutaneous abscess between March 1, 2010 and February 28, 2011. We assessed the frequency of avoidable antibiotic exposure, defined as: use of antibiotics with broad gram-negative activity, combination antibiotic therapy, or treatment for 10 or more days. Total antibiotic-days prescribed for the cohort were compared to antibiotic-days in four hypothetical short-course (5 – 7 days), single-antibiotic treatment models consistent with national guidelines.
Results
364 cases were included for analysis (155 cellulitis, 41 wound infection, and 168 abscess). Antibiotics active against methicillin-resistant Staphylococcus aureus were prescribed in 61% of cases of cellulitis. Of 139 cases of abscess where drainage was performed, antibiotics were prescribed in 80% for a median of 10 (interquartile range 7 – 10) days. Of 292 total cases where complete prescribing data were available, avoidable antibiotic exposure occurred in 46%. This included use of antibiotics with broad gram-negative activity in 4%, combination therapy in 12%, and treatment for 10 or more days in 42%. Use of the short-course, single-antibiotic treatment strategies would have reduced prescribed antibiotic-days by 19 – 55%.
Conclusions
Nearly half of uncomplicated skin infections involved avoidable antibiotic exposure. Antibiotic use could be reduced through treatment approaches utilizing short courses of a single antibiotic.
doi:10.1016/j.amjmed.2013.08.016
PMCID: PMC4075054  PMID: 24262724
skin and soft tissue infection; cellulitis; abscess; uncomplicated skin and soft tissue infection; antimicrobial stewardship
16.  Promotion of Cardiovascular Health in Preschool Children: 36-Month Cohort Follow-up 
The American journal of medicine  2013;126(12):1122-1126.
BACKGROUND
Educational interventions in preschool children could improve dietary behavior and physical activity, and prevent unhealthy body weights in low- and middle-income countries. Previously, we have reported the beneficial impact of an educational intervention in preschoolers in a 6-month trial. We now report extended results after 36 months.
METHODS
Evaluating the cohort of previously intervened children, baseline measurements were made in May 2009 in 14 preschool facilities in Usaquén (Bogotá, Colombia). Follow-up measurements were performed at 18 and 36 months. The primary outcome was the mean change in children’s knowledge and attitudes scores regarding healthy eating and living an active lifestyle, including habits scores related to physical activity. Secondary outcomes were the change over time of children’s nutritional status and the mean change in parent’s knowledge, attitudes, and habits.
RESULTS
We included 1216 children, 3–5 years of age, and 928 parents. After adjusting by sex and age of children, socioeconomic status, age of parents, and age and education level of teachers, we found a significant increase in mean knowledge, attitudes, and habits scores at 36 months, compared with baseline: 87.94 vs 76.15 (P <.001); 86.39 vs 57.03 (P <.001); and 66.29 vs 48.72 (P <.001), respectively. We observed a similar increase in knowledge and attitude scores in parents: 73.45 vs 70.01 (P <.001); and 78.08 vs 74.65 (P <.001). The proportion of eutrophic children increased from 62.1% at baseline to 75.0% at 36 months (P <.0001).
CONCLUSIONS
After 36 months, the educational intervention maintained a beneficial trend toward a healthy lifestyle in children and their parents.
doi:10.1016/j.amjmed.2013.06.021
PMCID: PMC4106297  PMID: 24262725
Cardiovascular disease (CVD); Global health; Health education; Noncommunicable disease (NCD); Preschool children
17.  Mobile Health Messages Help Sustain Recent Weight Loss 
The American journal of medicine  2013;126(11):10.1016/j.amjmed.2013.07.001.
BACKGROUND
Using regulatory focus theory, an intervention of daily weight loss-sustaining messages was developed and tested for acceptability, feasibility, and efficacy on helping people sustain weight loss.
METHODS
Participants (n = 120) were randomized to a promotion, prevention, or an attention-control text message group after completion of a weight loss program. Participants completed baseline assessments, and reported their weight at 1 and 3 months postbaseline.
RESULTS
Participants found the message content and intervention acceptable and valuable. A minimum of one message per day delivered at approximately 8:00 am was deemed the optimal delivery time and frequency. The sustained weight loss rate at month 3 for the control, promotion, and prevention groups was 90%, 95%, and 100%, respectively. Medium-to-large effects were observed for the promotion and prevention groups at month 1 and for prevention at month 3 relative to controls. The mean weight loss for promotion and prevention was 15 pounds, compared with 10 in the controls at month 3.
CONCLUSION
A clinically significant decrease in mean weight, higher rate of sustained weight loss, and medium-to-large effects on sustained weight loss occurred in the promotion and prevention interventions. Tools such as this text message-based intervention that are constructed and guided by evidence-based content and theoretical constructs show promise in helping people sustain healthy behaviors that can lead to improved health outcomes.
doi:10.1016/j.amjmed.2013.07.001
PMCID: PMC3820279  PMID: 24050486
Behavior change; Informatics; mHealth; Mobile health; Obesity; SMS; Text messaging; Weight loss
18.  Commonly Utilized Data Collection Approaches in Clinical Research 
The American journal of medicine  2013;126(11):10.1016/j.amjmed.2013.04.016.
In this article we provide an overview of the different data collection approaches that are commonly utilized in carrying out clinical, public health, and translational research. We discuss several of the factors researchers need to consider in using data collected in questionnaire surveys, from proxy informants, through the review of medical records, and in the collection of biologic samples. We hope that the points raised in this overview will lead to the collection of rich and high quality data in observational studies and randomized controlled trials.
doi:10.1016/j.amjmed.2013.04.016
PMCID: PMC3827694  PMID: 24050485
data collection approaches; clinical research; observational studies
19.  Rate-Control versus Rhythm-Control Strategies and Outcomes in Septuagenarian Patients with Atrial Fibrillation 
The American journal of medicine  2013;126(10):10.1016/j.amjmed.2013.04.021.
Background
The prevalence of atrial fibrillation substantially increases after 70 years of age. However, the effect of rate-control versus rhythm-control strategies on outcomes in these patients remains unclear.
Methods
In the randomized Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial, 4060 patients (mean age, 70, range, 49–80 years) with paroxysmal and persistent atrial fibrillation were randomized to rate-control versus rhythm-control strategies. Of these, 2248 were 70–80 years, of whom 1118 were in the rate-control group. Propensity scores for rate-control strategy were estimated for each of the 2248 patients and were used to assemble a cohort of 937 pairs of patients receiving rate-control versus rhythm-control strategies, balanced on 45 baseline characteristics.
Results
Matched patients had a mean age of 75 years, 45% were women, 7% were non-white, and 47% had prior hospitalizations due to arrhythmias. During 3.4 years of mean follow-up, all-cause mortality occurred in 18% and 23% of matched patients in the rate-control and rhythm-control groups, respectively (hazard ratio {HR} associated with rate-control, 0.77; 95% confidence interval {CI}, 0.63–0.94; p=0.010). HRs (95% CIs) for cardiovascular and non-cardiovascular mortality associated with rate-control were 0.88 (0.65–1.18) and 0.62 (0.46–0.84), respectively. All-cause hospitalization occurred in 61% and 68% of rate-control and rhythm-control patients, respectively (HR, 0.76; 95% CI, 0.68–0.86). HRs (95% CIs) for cardiovascular and non-cardiovascular hospitalization were 0.66 (0.56–0.77) and 1.07 (0.91–1.27).
Conclusion
In septuagenarian patients with atrial fibrillation, compared with rhythm-control, a rate-control strategy was associated with significantly lower mortality and hospitalization.
doi:10.1016/j.amjmed.2013.04.021
PMCID: PMC3818786  PMID: 24054956
atrial fibrillation; rate control; rhythm control; hospitalization; mortality; propensity score; older adults
20.  Barriers to Non-HDL Cholesterol Goal Attainment by Providers 
The American journal of medicine  2011;124(9):876-80.e2.
Purpose
Despite improvements in low-density lipoprotein cholesterol goal attainment, non–high-density lipoprotein cholesterol (non-HDL-C) goal attainment remains poor. This study assessed providers’ knowledge of, attitude toward, and practice regarding non-HDL-C.
Methods
Based on a conceptual model, we designed a questionnaire which was administered to internal medicine, family practice, cardiology, and endocrinology providers attending continuous medical education conferences. Responses were compared to those of providers attending a clinical lipidology conference.
Results
Response rate was 33.3% (354/1,063). Among providers attending nonlipidology conferences, only 26% knew that non-HDL-C was a secondary treatment target, 34% knew non-HDL-C treatment goals, 56% could calculate non-HDL-C levels, and 66% knew that non-HDL-C levels could be calculated from a standard lipid panel. Compared with providers attending the lipidology conference, the other providers were less likely (p≤0.01) to have read the Adult Treatment Panel III (ATP III) guidelines (46% vs. 98%) or to use non-HDL-C (36% vs. 91%). No differences were found between primary care and specialty providers. Lack of familiarity with ATP III guidelines (34%) and of knowledge regarding non-HDL-C importance (21%) and calculation (22.7%) were the most common barriers identified.
Conclusions
Major gaps remain in providers’ awareness regarding non-HDL-C definition, calculation, and goals. System-level interventions are needed across specialties to address these gaps.
doi:10.1016/j.amjmed.2011.02.012
PMCID: PMC4180871  PMID: 21854896
guideline adherence; non-HDL cholesterol; Adult Treatment Panel III guidelines; provider knowledge; treatment practice
21.  Extended-Release Niacin Acutely Suppresses Postprandial Triglyceridemia 
The American journal of medicine  2012;125(10):1026-1035.
Background
Postprandial triglyceridemia predicts cardiovascular events. Niacin might lower postprandial triglycerides (TG) by restricting free fatty acid (FFA). Immediate-release niacin reduced postprandial TGs, but extended-release niacin failed to do so when dosed the night before a fat challenge.
Aims
1) Determine whether extended-release niacin dosed before a fat challenge suppresses postprandial TG. 2) Determine whether postprandial TG is related to FFA restriction.
Methods
Double-blinded, placebo-controlled, random-order crossover experiment, where healthy volunteers took 2 g extended-release niacin or placebo 1 hour before heavy cream. We sampled blood over 12 hours, and report TG and FFA as means±SD for incremental area under the curve (iAUC) and nadir.
Results
Combining 43 fat challenges from 22 subjects, postprandial TG iAUC was +312±200 on placebo vs +199±200 mg/dL*h on extended-release niacin (33% drop, p= 0.02). The incremental nadir for FFA was −0.07±0.15 on placebo vs −0.27±0.13 mmol/L on extended-release niacin (p<0.0001), and FFA iAUC fell from +2.9±1.5 to +1.5±1.5 mmol/L*h on extended-release niacin (20% drop, p=0.0015). The TG iAUC was strongly related to the post-dose drop in FFA (r=+0.58, p=0.0007).
Conclusions
Given right before a fat meal, even a single dose of extended-release niacin suppresses postprandial triglyceridemia. This establishes that postprandial TG suppression is an acute pharmacodynamic effect of extended-release niacin, probably the result of marked FFA restriction. Further study is warranted to determine whether mealtime dosing would augment the clinical efficacy of extended-release niacin therapy.
doi:10.1016/j.amjmed.2012.03.017
PMCID: PMC4170918  PMID: 22840917
adult; African Americans; clinical trial; dietary fats; drug; evaluation; free fatty acids; humans; hydroxybutyrate; ketones; lipoprotein; lipids; niacin; niacin/pharmacology; niacin/therapeutic use; postprandial; randomized controlled trial; triglycerides
22.  Smoking Behavior among US Adults with Diabetes or Impaired Fasting Glucose 
The American journal of medicine  2013;126(6):541.e15-541.e18.
BACKGROUND
Cigarette smoking is a well-known cardiovascular risk factor and its impact on cardiovascular disease is even greater among people with diabetes. The aim of this study is to compare the prevalence and determinants of smoking among US adults with diabetes or impaired fasting glucose, and those without diabetes or impaired fasting glucose.
METHODS
We analyzed data from the National Health and Nutrition Examination Surveys (1999–2008). Age-adjusted prevalence of smoking was calculated, and we used logistic regression models to identify the correlates of smoking among people with diabetes, impaired fasting glucose, and normal glucose metabolism.
RESULTS
Among 24,649 participants ≥20 years old, age-adjusted smoking prevalence was 25.7% in 3111 individuals with diabetes, 24.2% in 3557 individuals with impaired fasting glucose, and 24.1% in 17,981 individuals without diabetes. Smoking prevalence did not differ across groups or change over time (1999–2008) in any group. Younger age, less education, more alcohol consumption, less physical activity, and major depression symptoms were associated with smoking in people with diabetes, impaired fasting glucose, and normal glucose metabolism.
CONCLUSIONS
In the US, smoking prevalence among people with diabetes and impaired fasting glucose has not changed and is comparable with the nondiabetic population. Tobacco control efforts should be intensified among this population at high risk for complications and mortality.
doi:10.1016/j.amjmed.2012.11.029
PMCID: PMC4151048  PMID: 23597801
Diabetes; Impaired fasting glucose; Smoking
23.  Encouraging Trends in Acute Myocardial Infarction Survival in the Oldest Old 
The American journal of medicine  2013;126(9):10.1016/j.amjmed.2013.02.026.
Background
There are limited data informing the optimal treatment strategy for acute myocardial infarction in the oldest old (aged ≥85 years). The study aim was to examine whether decade-long increases in guideline-based cardiac medication use mediate declines in post-discharge mortality among oldest old patients hospitalized with acute myocardial infarction.
Methods
The study sample included 1137 patients aged ≥85 years hospitalized in 6 biennial periods between 1997 and 2007 for acute myocardial infarction at all 11 greater Worcester, Massachusetts, medical centers. We examined trends in 90-day survival after hospital discharge and guideline-based medication use (aspirin, angiotensin-converting enzyme inhibitors/angiotensin receptor blockers, beta-blockers, lipid-lowering agents) for acute myocardial infarction during hospitalization and at discharge. Sequential multivariable Cox regression models examined the relationship among guideline-based medication use, study year, and 90-day post-discharge survival rates.
Results
Patients hospitalized between 2003 and 2007 experienced higher 90-day survival rates than those hospitalized between 1997 and 2001 (69.1% vs 59.8%, P < .05). Between 1997 and 2007, the average number of guideline-based medications prescribed at discharge increased significantly (1.8 to 2.9, P < .001). The unadjusted hazard ratio for 90-day post-discharge mortality in 2003-2007 compared with 1997-2001 was 0.73 (95% confidence interval, 0.60-0.89); after adjustment for patient characteristics and guideline-based cardiac medication use, this relationship was no longer significant (hazard ratio, 1.26; 95% confidence interval, 1.00-1.58).
Conclusions
Between 1997 and 2007, 90-day survival improved among a population-based sample of patients aged ≥85 years hospitalized for acute myocardial infarction. This encouraging trend was explained by increased use of guideline-based medications.
doi:10.1016/j.amjmed.2013.02.026
PMCID: PMC3840395  PMID: 23835196
Acute myocardial infarction; Geriatrics; Medication effects; Post-discharge survival

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