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1.  Using quality improvement techniques to increase colon cancer screening 
The American journal of medicine  2009;122(5):419-420.
doi:10.1016/j.amjmed.2008.10.029
PMCID: PMC3983943  PMID: 19375547
colorectal cancer; screening; quality improvement; decision aids
2.  Improving Herpes Zoster Vaccination Rates Through Use of a Clinical Pharmacist and a Personal Health Record 
The American journal of medicine  2013;126(9):832.e1-832.e6.
BACKGROUND
Preventative health services, including herpes zoster vaccination rates, remain low despite known benefits. A new care model to improve preventative health services is warranted. The objective of this study is to investigate whether the functions of an electronic medical record, in combination with a pharmacist as part of the care team, can improve the herpes zoster vaccination rate.
METHODS
This study was a 6-month, randomized controlled trial at a General Internal Medicine clinic at The Ohio State University. The 2589 patients aged 60 years and older without documented herpes zoster vaccination in the electronic medical record were stratified on the basis of activated personal health record status, an online tool used to share health information between patient and provider. Of the 674 personal health record users, 250 were randomized to receive information regarding the herpes zoster vaccination via an electronic message and 424 were randomized to standard of care. Likewise, of the 1915 nonpersonal health record users, 250 were randomized to receive the same information via the US Postal Service and 1665 were randomized to standard of care. After pharmacist chart review, eligible patients were mailed a herpes zoster vaccine prescription. Herpes zoster vaccination rates were compared by chi-square tests.
RESULTS
Intervention recipients had significantly higher vaccination rates than controls in both personal health record (relative risk, 2.7; P = .0007) and nonpersonal health record (relative risk, 2.9; P = .0001) patient populations.
CONCLUSIONS
Communication outside of face-to-face office visits, by both personal health record electronic message and information by mail, can improve preventative health intervention rates compared with standard care.
doi:10.1016/j.amjmed.2013.02.018
PMCID: PMC3980553  PMID: 23830534
Electronic medical record; Electronic patient portal; Herpes zoster vaccine; Immunizations; Personal health record; Pharmacist; Primary care
4.  Jumpstarting academic careers with a novel intern research rotation: the Academic Internal Medicine Scholarship (AIMS) rotation 
The American journal of medicine  2009;122(11):1061-1066.
doi:10.1016/j.amjmed.2009.06.017
PMCID: PMC3974546  PMID: 19854338
graduate medical education; research curricula; residency
5.  Risk Factors and Outcomes in Transfusion-associated Circulatory Overload 
The American journal of medicine  2013;126(4):357.e29-357.e38.
BACKGROUND
Transfusion-associated circulatory overload is characterized by new respiratory distress and hydrostatic pulmonary edema within 6 hours after blood transfusion, but its risk factors and outcomes are poorly characterized.
METHODS
Using a case control design, we enrolled 83 patients with severe transfusion-associated circulatory overload identified by active surveillance for hypoxemia and 163 transfused controls at the University of California, San Francisco (UCSF) and Mayo Clinic (Rochester, Minn) hospitals. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using multivariable logistic regression, and survival and length of stay were analyzed using proportional hazard models.
RESULTS
Transfusion-associated circulatory overload was associated with chronic renal failure (OR 27.0; 95% CI, 5.2–143), a past history of heart failure (OR 6.6; 95% CI, 2.1–21), hemorrhagic shock (OR 113; 95% CI, 14.1–903), number of blood products transfused (OR 1.11 per unit; 95% CI, 1.01–1.22), and fluid balance per hour (OR 9.4 per liter; 95% CI, 3.1–28). Patients with transfusion-associated circulatory overload had significantly increased in-hospital mortality (hazard ratio 3.20; 95% CI, 1.23–8.10) after controlling for Acute Physiology and Chronic Health Evaluation-II (APACHE-II) score, and longer hospital and intensive care unit lengths of stay.
CONCLUSIONS
The risk of transfusion-associated circulatory overload increases with the number of blood products administered and a positive fluid balance, and in patients with pre-existing heart failure and chronic renal failure. These data, if replicated, could be used to construct predictive algorithms for transfusion-associated circulatory overload, and subsequent modifications of transfusion practice might prevent morbidity and mortality associated with this complication.
doi:10.1016/j.amjmed.2012.08.019
PMCID: PMC3652681  PMID: 23357450
Blood transfusion; Morbidity; Mortality; Pulmonary edema; Risk factors
6.  Effects of Clinical Pathways for Common Outpatient Infections on Antibiotic Prescribing 
The American journal of medicine  2013;126(4):327-335.e12.
Background
Antibiotic overuse in the primary care setting is common. Our objective was to evaluate the effect of a clinical pathway-based intervention on antibiotic use.
Methods
Eight primary care clinics were randomized to receive clinical pathways for upper respiratory infection, acute bronchitis, acute rhinosinusitis, pharyngitis, acute otitis media, urinary tract infection, skin infections, and pneumonia and patient education materials (study group) versus no intervention (control group). Generalized linear mixed effects models were used to assess trends in antibiotic prescriptions for non-pneumonia acute respiratory infections and broad-spectrum antibiotic use for all eight conditions during a 2-year baseline and 1-year intervention period.
Results
In the study group, antibiotic prescriptions for non-pneumonia acute respiratory infections decreased from 42.7% of cases at baseline to 37.9% during the intervention period (11.2% relative reduction) (p <.0001) and from 39.8% to 38.7%, respectively, in the control group (2.8% relative reduction) (p=0.25). Overall use of broad-spectrum antibiotics in the study group decreased from 26.4% to 22.6% of cases, respectively, (14.4% relative reduction) (p <.0001) and from 20.0% to 19.4%, respectively, in the control group (3.0% relative reduction) (p=0.35). There were significant differences in the trends of prescriptions for acute respiratory infections (p<.0001) and broad-spectrum antibiotic use (p=0.001) between the study and control groups during the intervention period, with greater declines in the study group.
Conclusions
This intervention was associated with declining antibiotic prescriptions for non-pneumonia acute respiratory infections and use of broad-spectrum antibiotics over the first year. Evaluation of the impact over a longer study period is warranted.
doi:10.1016/j.amjmed.2012.10.027
PMCID: PMC3666348  PMID: 23507206
Clinical pathways; guidelines; antimicrobial stewardship; antibiotic prescribing; primary care; acute respiratory infection
7.  Direct-to-Consumer Advertising of Pharmaceuticals 
The American journal of medicine  2007;120(6):475-480.
Since the FDA released new guidelines on broadcast direct-to-consumer advertising in 1997, the prevalence of direct-to-consumer advertising of prescription drugs has increased exponentially. The impact on providers, patients and the health care system is varied and dynamic, and the rapid changes in the last several years have markedly altered the health care landscape. To continue providing optimal medical care, physicians and other health-care providers must be able to manage this influence on their practice, and a more thorough understanding of this phenomenon is an integral step toward this goal. This review will summarize the history of direct-to-consumer drug advertisements and the current regulations governing them. It will summarize the evidence concerning the impact of direct-to-consumer advertising on the public, providers and the health care system and conclude with observations regarding the future of direct-to-consumer advertising.
doi:10.1016/j.amjmed.2006.09.030
PMCID: PMC3967783  PMID: 17524744
Pharmaceutical preparations; Advertising; Marketing; Direct-to-Consumer; United States Food and Drug Administration
8.  Hypertension and Chronic Kidney Disease Progression: Why the Suboptimal Outcomes? 
The American journal of medicine  2012;125(11):1057-1062.
Current therapeutic interventions to retard the progression of chronic kidney disease have yielded disappointing outcomes despite adequate renin-angiotensin system blockade. The parameters to gauge the adequacy of blood pressure control need to be reassessed because clinic blood pressure constitutes a poor gauge of such control. The biologically relevant parameter for hypertensive target organ damage is total blood pressure burden, and reliance on isolated clinic blood pressure measurements per se does not accurately reflect the total blood pressure burden. This is particularly relevant to the population with chronic kidney disease in whom masked daytime or nocturnal hypertension and blood pressure lability are both widely prevalent and more difficult to control. Consequently, it is possible that the limited success currently being achieved in preventing or attenuating chronic kidney disease progression may be attributable in part to suboptimal 24-hour blood pressure control. Recent data and analyses also indicate that blood pressure variability, instability, episodic and nocturnal blood pressure elevations, and maximum systolic blood pressure may constitute additional strong predictors of the risk of target organ damage independently of mean systolic blood pressure. Accordingly, we suggest that future research should include the development of safe and effective strategies to achieve around-the-clock blood pressure control in addition to targeting mechanisms that reduce intrarenal blood pressure transmission or interrupt subsequent downstream pathways. Meanwhile, more aggressive use of patient education and home blood pressure monitoring with selection of longer-acting antihypertensive agents or nocturnal dosing should be considered to improve the current suboptimal results.
doi:10.1016/j.amjmed.2012.04.008
PMCID: PMC3943135  PMID: 22906957
Ambulatory blood pressure monitoring; Antihypertensive agents; Blood pressure lability; Masked hypertension; Renal autoregulation
9.  Vascular risk factors, cardiovascular disease and restless legs syndrome in men 
The American journal of medicine  2013;126(3):228-235.e2.
Background
Prevalences of vascular risk factors, cardiovascular disease and restless legs syndrome increase with age. Prior studies analyzing the associations between vascular risk factors, cardiovascular disease, and restless legs syndrome found controversial results. We therefore aim to evaluate the association between prevalent vascular risk factors, prevalent cardiovascular disease and restless legs syndrome.
Methods
We conducted a cross-sectional study among 22,786 participants of the US Physicians’ Health Studies I and II. Restless legs syndrome was classified according to the four minimal diagnostic criteria. Vascular risk factors and restless legs syndrome symptoms were self-reported. Prevalent cardiovascular disease events including major cardiovascular disease, stroke and myocardial infarction were confirmed by medical record review. Age- and multivariable-adjusted logistic regression models were used to evaluate the association between vascular risk factors, prevalent cardiovascular disease events and restless legs syndrome.
Results
The mean age of the cohort 67.8 years. Restless legs syndrome prevalence was 7.5% and increased significantly with age. Diabetes significantly increased the odds (OR: 1.41, 95%CI: 1.21–1.65), while frequent exercise (OR: 0.78, 95%CI: 0.67–0.91) and alcohol consumption of one or more drinks per day (OR: 0.80, 95%CI: 0.69–0.92) significantly reduced the odds of restless legs syndrome in multivariable-adjusted models. Prevalent stroke showed an increased multivariable-adjusted OR of 1.40 (1.05–1.86) while men with prevalent myocardial infarction had a decreased OR of 0.73 (0.55–0.97) for restless legs syndrome.
Conclusions
The restless legs syndrome prevalence among US male physicians is similar to men of the same age group in other western countries. A history of diabetes is the most consistent risk factor associated with restless legs syndrome. Prevalent stroke and myocardial infarction are related to restless legs syndrome prevalence.
doi:10.1016/j.amjmed.2012.06.039
PMCID: PMC3574273  PMID: 23410563
Vascular risk factors; cardiovascular disease; Restless legs syndrome; cohort study
10.  The long-term effectiveness of a lifestyle intervention in severely obese individuals 
The American journal of medicine  2013;126(3):236-242.e2.
Objective
Severe obesity (BMI≥40kg/m2) is a serious public health concern. Although bariatric surgery is an efficacious treatment approach, it is limited in reach; thus non-surgical treatment alternatives are needed. We examined the 4-year effects of an intensive lifestyle intervention on body weight and cardiovascular disease risk factors among severely obese, compared to overweight (25≤BMI<30), class I (30≤BMI<35), and class II obese (35≤BMI<40) participants.
Methods
5,145 individuals with type 2 diabetes (45–76 years, BMI≥25kg/m2) were randomized to an intensive lifestyle intervention or diabetes support and education. The lifestyle intervention received a behavioral weight loss program which included group and individuals meetings, a ≥10% weight loss goal, calorie restriction, and increased physical activity. Diabetes support and education received a less intense educational intervention. 4-year changes in body weight and cardiovascular disease risk factors were assessed.
Results
Across BMI categories, 4-year changes in body weight were significantly greater in lifestyle participants compared to diabetes support and education (p’s<0.05). At year 4, severely obese lifestyle participants lost 4.9±8.5% which was similar to class I (4.8±7.2%) and class II obese (4.4±7.6%) and significantly greater than overweight (3.4±7.0%; p<0.05). 4-year changes in LDL-cholesterol, triglycerides, diastolic blood pressure, HbA1c, and blood glucose were similar across BMI categories in lifestyle participants; however the severely obese had less favorable improvements in HDL-cholesterol (3.1±0.4mg/dL) and systolic blood pressure (−1.4±0.7mmHg) compared to the less obese (p’s<0.05).
Conclusion
Lifestyle interventions can result in important long-term weight losses and improvements in cardiovascular disease risk factors among a significant proportion of severely obese individuals.
doi:10.1016/j.amjmed.2012.10.010
PMCID: PMC3574274  PMID: 23410564
Severe obesity; weight loss; lifestyle intervention; diabetes; cardiovascular disease
11.  Vascular risk factors, cardiovascular disease and restless legs syndrome in women 
The American journal of medicine  2013;126(3):220-227.e2.
Background
Previous studies evaluating the association between cardiovascular disease and vascular risk factors with restless legs syndrome showed inconsistent results, especially for the potential relation between various vascular risk factors and restless legs syndrome. We therefore aimed to analyze the relationship between vascular risk factors, prevalent cardiovascular disease and restless legs syndrome.
Methods
This is a cross-sectional study of 30,262 female health professionals participating in the Women's Health Study (WHS). Restless legs syndrome was defined according to diagnostic criteria of the International Restless Legs Study Group. Information on vascular risk factors (diabetes, hypertension, hypercholesterolemia, body mass index, alcohol, smoking, exercise, family history of myocardial infarction) was self-reported. Cardiovascular disease events (coronary revascularization, myocardial infarction, stroke) were confirmed by medical record review. Prevalent major cardiovascular disease was defined as non-fatal stroke or non-fatal myocardial infarction. Logistic regression models were used to evaluate the association between vascular risk factors, prevalent cardiovascular disease and restless legs syndrome.
Results
Of the 30,262 participants (mean age: 63.6 years), 3,624 (12.0%) reported restless legs syndrome. In multivariable-adjusted models, body mass index (OR for BMI ≥35kg/m2: 1.35, 95% CI: 1.17–1.56), diabetes (OR: 1.19, 95%CI: 1.04–1.35), hypercholesterolemia (OR: 1.17, 95% CI: 1.09–1.26), smoking status (OR for ≥15 cigarettes/day: 1.41, 95%CI: 1.19–1.66) and exercise (OR for exercise ≥ 4 times/week: 0.84, 95%CI: 0.74–0.95) were associated with restless legs syndrome prevalence. We found no association between prevalent cardiovascular disease (major cardiovascular disease, myocardial infarction, stroke) and restless legs syndrome prevalence. Women who underwent coronary revascularization had a multivariable-adjusted OR of 1.39 (1.10–1.77) for restless legs syndrome.
Conclusion
In this large cohort of female health professionals, various vascular risk factors are associated with restless legs syndrome prevalence. We could not confirm results of previous reports indicating an association between prevalent cardiovascular disease and restless legs syndrome.
doi:10.1016/j.amjmed.2012.06.040
PMCID: PMC3574635  PMID: 23410562
Vascular risk factors; cardiovascular disease; Restless legs syndrome; cohort study
12.  Prevalence and Morbidity Associated with Muscle Cramps in Patients with Cirrhosis 
The American journal of medicine  2012;125(10):1019-1025.
PURPOSE
Patients with cirrhosis often experience muscle cramps with varying severity. We investigated the factors associated with the prevalence and morbidity associated with muscle cramps.
METHODS
A total of 150 adult patients with cirrhosis were enrolled consecutively. Cramp questionnaire with visual analogue scale for pain, Chronic Liver Disease Questionnaire (CLDQ), and blood for measurement of 25-(OH) vitamin D levels were obtained after informed consent.
RESULTS
A total of 101 patients (67%) reported muscle cramps in the preceding 3 months. Patients with cramps had significantly lower serum albumin (3.1 ± 0.6 g/dL vs 3.3 ± 0.7 g/dL, P = .04) and CLDQ scores (107 ± 37 vs 137 ± 34, P < .0001) compared with those without cramps. The median composite symptom score, defined as product of frequency and severity of cramps, in the study cohort was 12 with a range of 0.3 to 200. There were no clinical or biochemical predictors for occurrence of any cramps or severe cramps (composite symptom score > 12). Muscle cramps (P < .001) and hepatic encephalopathy (P = .009) were associated independently with decreased CLDQ scores. Vitamin D deficiency was seen in 66% of the study cohort, but the serum 25-(OH) vitamin D levels were not significantly different between patients with and without cramps (18.0 ± 8.9 ng/mL vs 19.6 ± 9.5 ng/mL, P = .49).
CONCLUSIONS
Muscle cramps are associated with significantly diminished quality of life in patients with cirrhosis. More research is needed to better understand their mechanism to develop effective treatment.
doi:10.1016/j.amjmed.2012.03.012
PMCID: PMC3932181  PMID: 22835465
Chronic liver disease questionnaire; Cirrhosis; Muscle cramps
13.  Surgical and Obstetric Outcomes in Adults with Sickle Cell Disease 
The American journal of medicine  2008;121(10):916-921.
BACKGROUND
Sickle cell disease patients are more likely than the general population to undergo surgery and usually do so at a younger age. Female sickle cell disease patients also have special gynecological and obstetric issues related to their disease.
METHODS
We collected data through standardized clinical report forms, patient interviews, and medical records from 509 adult sickle cell disease patients. Logistic regression was used to estimate the association between multiple variables and each of the surgery types. We also determined the prevalence and outcomes of pregnancy in 284 women with sickle cell disease in this population.
RESULTS
Almost 50% of patients aged 18–27 years had had a cholecystectomy. Mean corpuscular hemoglobin, total bilirubin, and lactate dehydrogenase were significantly higher in the postcholecystectomy group; 9.5% of 504 individuals had undergone splenectomy. Hematocrit, body mass index, and red blood cell count were significantly higher in the postsplenectomy group. Hip replacement had been performed in 9.2% of individuals, with the prevalence increasing as early as the fourth decade and continuing to increase through the sixth decade of life. A history of pregnancy was present in 190 women (67%). Of 410 pregnancies, only 53.9% resulted in live births, 16.6% were voluntarily terminated, and 29.5% were complicated by miscarriage, still birth, or ectopic implantation.
CONCLUSIONS
Sickle cell disease continues to have a strong effect on the mean age for common surgeries and impacts pregnancy outcomes. We conclude that this population has a unique surgical and obstetric history that should be further studied to provide insight into potentially more effective preventive approaches to end-organ damage.
doi:10.1016/j.amjmed.2008.04.040
PMCID: PMC3928637  PMID: 18823864
Cholecystectomy; Pregnancy; Pregnancy complications; Sickle cell disease; Surgery
14.  B-cell-depleting Therapy in Systemic Lupus Erythematosus 
The American journal of medicine  2012;125(4):327-336.
The emergence of a new class of agents (B-cell-depleting therapies) has opened a new era in the therapeutic approach to systemic lupus erythematosus, with belimumab being the first drug licensed for use in systemic lupus erythematosus in more than 50 years. Four agents deserve specific mention: rituximab, ocrelizumab, epratuzumab, and belimumab. Controlled trials have shown negative results for rituximab, promising results for epratuzumab, and positive results for belimumab. Despite these negative results, rituximab is the most-used agent in patients who do not respond or are intolerant to standard therapy and those with life-threatening presentations. B-cell-depleting agents should not be used in patients with mild disease and should be tailored according to individual patient characteristics, including ethnicity, organ involvement, and the immunological profile. Forthcoming studies of B-cell-directed strategies, particularly data from investigations of off-label rituximab use and postmarketing studies of belimumab, will provide new insights into the utility of these treatments in the routine management of patients with systemic lupus erythematosus.
doi:10.1016/j.amjmed.2011.09.010
PMCID: PMC3925418  PMID: 22444096
Belimumab; Epratuzumab; Ocrelizumab; Rituximab; Systemic lupus erythematosus
15.  Cardiovascular and Non-Cardiovascular Disease Associations with Hip Fractures 
The American journal of medicine  2013;126(2):169.e19-169.e26.
BACKGROUND
There is growing awareness of an association between cardiovascular disease and fractures, and a temporal increase in fracture risk after myocardial infarction has been identified. To further explore the nature of this relationship, we systematically examined the association of hip fracture with all disease categories and assessed related secular trends.
METHODS
Using resources of the Rochester Epidemiology Project, a population-based incident case-control study was conducted. Disease history was compared between all Olmsted County, Minnesota, residents aged 50 years or older with a first radiographically confirmed hip fracture in 1985–2006 and community control subjects individually matched (1:1) to cases on age, sex, and index year (n=3,808; mean age [SD], 82 [9] years; 76% women).
RESULTS
All cardiovascular and numerous non-cardiovascular disease categories (e.g., infectious diseases, nutritional and metabolic diseases, mental disorders, diseases of the nervous system and sense organs, and diseases of the respiratory system) were associated with fracture risk. However, increasing temporal trends were almost exclusively detected in cardiovascular disease categories. The largest increases in association were observed for ischemic heart disease, other forms of heart disease (including heart failure), hypertension, and diabetes and were more pronounced among elderly women than among other demographic subgroups.
CONCLUSIONS
While the association with hip fracture was not specific to cardiovascular disease, temporal increases were mainly detected in cardio-metabolic diseases, all of which have also been linked previously to frailty. This mechanism and others warrant further investigation.
doi:10.1016/j.amjmed.2012.06.032
PMCID: PMC3552333  PMID: 23331448
Cardiovascular Disease; Hip Fracture; Epidemiology; Population Studies; Frailty; Surveillance
16.  Greater Knowledge and Appreciation of Commonly Used Research Study Designs 
The American journal of medicine  2013;126(2):169.e1-169.e8.
In this article, we provide an overview of the different study designs commonly utilized in carrying out clinical and public health research and of the points to consider in reviewing these study designs. The design and conduct of cross-sectional health surveys, case-control, prospective, and case-crossover observational studies, and randomized controlled trials, are discussed in this review article. Careful attention to the concerns we have raised will hopefully lead to the design and conduct of high quality research projects and their write-up.
doi:10.1016/j.amjmed.2012.09.011
PMCID: PMC3553494  PMID: 23331447
clinical research; study design
17.  Cognitive Impairment in Older Adults with Heart Failure: Prevalence, Documentation, and Impact on Outcomes 
The American journal of medicine  2013;126(2):120-126.
Background
Despite the fact that 80% of patients with heart failure are over age 65, recognition of cognitive impairment by physicians in this population has received relatively little attention. The purpose of our study was to evaluate physician documentation (as a measure of recognition) of cognitive impairment at time of discharge in a cohort of older adults hospitalized for heart failure.
Methods
We performed a prospective cohort study of older adults hospitalized with a primary diagnosis of heart failure. Cognitive status was evaluated with the Folstein Mini-Mental State Examination (MMSE) at the time of hospitalization. A score of 21–24 was used to indicate mild cognitive impairment, and a score of ≤20 to indicate moderate to severe impairment. To evaluate physician documentation of cognitive impairment, we used a standardized form with a targeted keyword strategy to review hospital discharge summaries. We calculated the proportion of patients with cognitive impairment documented as such by physicians, and compared characteristics between groups with and without documented cognitive impairment. We then analyzed the association of cognitive impairment, and documentation of cognitive impairment, with 6-month mortality or readmission using Cox proportional hazards regression.
Results
A total of 282 patients completed the cognitive assessment. Their mean age was 80 years of age, 18.8% were nonwhite, and 53.2% were female. Cognitive impairment was present in 132/282 patients (46.8% overall; 25.2% mild, 21.6% moderate-severe). Among those with cognitive impairment, 30/132 (22.7%) were documented as such by physicians. Compared with patients whose cognitive impairment was documented by physicians, those whose impairment was not documented were younger (81.3 years vs. 85.2 years, P<0.05) and had less severe impairment (median MMSE score 22.0 vs. 18.0, P<0.01). After multivariable adjustment, patients whose cognitive impairment was not documented were significantly more likely to experience 6-month mortality or hospital readmission than patients without cognitive impairment.
Conclusions
Cognitive impairment is common in older adults hospitalized for heart failure, yet frequently not documented by physicians. Implementation of strategies to improve recognition and documentation of cognitive impairment may improve the care of these patients, particularly at the time of hospital discharge.
doi:10.1016/j.amjmed.2012.05.029
PMCID: PMC3553506  PMID: 23331439
heart failure; aging; cognition
18.  Renin-Angiotensin Inhibition in Diastolic Heart Failure and Chronic Kidney Disease 
The American journal of medicine  2013;126(2):150-161.
BACKGROUND
The role of renin-angiotensin inhibition in older patients with diastolic heart failure and chronic kidney disease remains unclear.
METHODS
Of the 1340 patients (age ≥65 years), with diastolic heart failure (ejection fraction ≥45%) and chronic kidney disease (estimated glomerular filtration rate <60 ml/min/1.73 m2), 717 received angiotensin-converting enzyme inhibitors or angiotensin receptor blockers. Propensity scores for the use of these drugs, estimated for each of the 1340 patients, were used to assemble a cohort of 421 pairs of patients, receiving and not receiving these drugs, who were balanced on 56 baseline characteristics.
RESULTS
During more than 8 years of follow-up, all-cause mortality occurred in 63% and 69% of matched patients with chronic kidney disease receiving and not receiving angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, respectively (hazard ratio {HR}, 0.82; 95% confidence interval {CI}, 0.70–0.97; p=0.021). There was no association with heart failure hospitalization (HR, 0.98; 95% CI, 0.82–1.18; p=0.816). Similar mortality reduction (HR, 0.81; 95% CI, 0.66–0.995; p=0.045) occurred in a subgroup of matched patients with an estimated glomerular filtration rate <45 ml/min/1.73 m2. Among 207 pairs of propensity-matched patients without chronic kidney disease, the use of these drugs was not associated with mortality (HR, 1.03; 95% CI, 0.80–1.33; p=0.826) or heart failure hospitalization (HR, 0.99; 95% CI, 0.76–1.30; p=0.946).
CONCLUSIONS
A discharge prescription for angiotensin-converting enzyme inhibitors or angiotensin receptor blockers was associated with a significant reduction in all-cause mortality in older patients with diastolic heart failure and chronic kidney disease including those with more advanced chronic kidney disease.
doi:10.1016/j.amjmed.2012.06.031
PMCID: PMC3575519  PMID: 23331442
Angiotensin-converting enzyme inhibitors; Angiotensin receptor blockers; Chronic kidney disease; Diastolic heart failure
19.  Identifying Factors that Influence Hospital Length of Stay in Patients with Non-ST-segment Elevation Myocardial Infarction: Insights from the Acute Coronary Treatment Intervention Outcomes Network Registry®-Get With The Guidelines™ 
The American journal of medicine  2012;125(11):10.1016/j.amjmed.2012.04.038.
PURPOSE
Substantial heterogeneity in hospital length of stay (LOS) exists among patients admitted with non-ST-segment elevation myocardial infarction (NSTEMI). Furthermore, little is known about the factors that impact LOS and our ability to modify them.
METHODS
We examined 39,107 NSTEMI patients admitted to 351 ACTION Registry®-GWTG™ hospitals from 1/1/07–3/31/09 who underwent cardiac catheterization and survived to discharge. Length of stay was categorized into four groups (≤2, 3–4, 5–7, and ≥8 days), where prolonged LOS was defined as >4 days.
RESULTS
The overall median (25th, 75th) LOS was 3 (2, 5) days. Patients with a LOS of >2 days were older with more comorbidities, but were less likely to receive evidence-based therapies or percutaneous coronary intervention (PCI). Among the factors associated with prolonged LOS >4 days were delay to cardiac catheterization >48 hours, heart failure or shock on admission, female gender, insurance type, and admission to the hospital on a Friday afternoon or evening. Hospital characteristics such as number of beds, academic versus non-academic, or urban versus rural setting, were not associated with prolonged LOS.
CONCLUSION
Patients with longer LOS have more comorbidities and in-hospital complications, yet paradoxically, are less often treated with evidence-based medications and are less likely to receive PCI. Hospital admission on a Friday afternoon or evening and delays to catheterization appear to significantly impact LOS. A better understanding of factors associated with LOS in patients with NSTEMI is needed to promote safe and early discharge in an era of increasingly restrictive healthcare resources.
doi:10.1016/j.amjmed.2012.04.038
PMCID: PMC3884687  PMID: 22921886
non-ST-segment elevation myocardial infarction; length of stay; hospital discharge
20.  RESPIRATORY IMPAIRMENT IN OLDER PERSONS: WHEN LESS MEANS MORE 
The American journal of medicine  2012;126(1):49-57.
Background
Among older persons, within the clinical context of respiratory symptoms and mobility, evidence suggests that improvements are warranted regarding the current approach for identifying respiratory impairment (i.e., a reduction in pulmonary function).
Methods
Among 3,583 white participants aged 65–80 (Cardiovascular Health Study), we calculated the prevalence of respiratory impairment using the current spirometric standard from the Global Initiative for Obstructive Lung Disease (GOLD) and an alternative spirometric approach termed Lambda-Mu-Sigma (LMS). Results for GOLD- and LMS-defined respiratory impairment were evaluated for their (cross-sectional) association with respiratory symptoms and gait speed, and also for the 5-year cumulative incidence probability of mobility disability.
Results
The prevalence of respiratory impairment was 49.7% (1,780/3,583) when using GOLD and 23.2% (831/3,583) when using LMS. Differences in prevalence were most evident among participants who had no respiratory symptoms, with respiratory impairment classified more often by GOLD (38.1% [326/855]) than LMS (12.3% [105/855]); as well as among participants who had normal gait speed, with respiratory impairment classified more often by GOLD (46.4% [1,003/2,164]) than LMS (19.3% [417/2,164]). Conversely, the 5-year cumulative incidence probability of mobility disability for respiratory impairment was higher for LMS than GOLD (0.313 and 0.249 for never-smokers, and 0.352 and 0.289 for ever-smokers, respectively), but was similar for normal spirometry by LMS or GOLD (0.193 and 0.185 for never-smokers, and 0.219 and 0.216 for ever-smokers, respectively).
Conclusion
Among older persons, the LMS approach (versus the GOLD approach) classifies respiratory impairment less frequently in those who are asymptomatic, and is also more strongly associated with mobility disability.
doi:10.1016/j.amjmed.2012.07.016
PMCID: PMC3529831  PMID: 23177541
respiratory impairment; respiratory symptoms; gait speed; mobility disability
21.  Pneumonia: An Arrhythmogenic Disease? 
The American journal of medicine  2012;126(1):43-48.
Introduction
Recent studies suggest that there is an increase in cardiovascular disease after pneumonia, however there is little information on cardiac arrhythmias after pneumonia. The aims of this study were to assess the incidence of, and examine risk factors for, cardiac arrhythmias after hospitalization for pneumonia.
Methods
We conducted a national cohort study using Department of Veterans Affairs (VA) administrative data including patients ≥65 years hospitalized with pneumonia in fiscal years 2002–2007, receiving antibiotics within 48 hours of admission, who did not have a prior diagnosis of a cardiac arrhythmia, and having at least one year of VA care. We included only the first pneumonia-related hospitalization, and follow-up was for the 90 days after admission. Cardiac arrhythmias included atrial fibrillation, ventricular tachycardia/fibrillation, cardiac arrest, and symptomatic bradycardia. We used a multilevel regression model, adjusting for hospital of admission, to examine risk factors for cardiac arrhythmias.
Results
We identified 32,689 patients who met the inclusion criteria. Of these, 3,919 (12%) had a new diagnosis of cardiac arrhythmia within 90-days of admission. Variables significantly associated with increased risk of cardiac arrhythmia included increasing age, history of congestive heart failure, and a need for mechanical ventilation or vasopressors. Beta-blocker use was associated with a decreased incidence of events.
Conclusion
An important number of patients have new cardiac arrhythmia during and post-hospitalization for pneumonia. Additional research is needed to determine if use of cardioprotective medications will improve outcomes for patients hospitalized with pneumonia. At risk patients hospitalized with pneumonia should be monitored for cardiac arrhythmias during the hospitalization.
doi:10.1016/j.amjmed.2012.08.005
PMCID: PMC3615552  PMID: 23177550
22.  A Randomized Trial of Cognitive Behavioral Therapy in Primary Care-based Buprenorphine 
The American journal of medicine  2013;126(1):74.e11-74.e17.
OBJECTIVE
To determine the impact of cognitive behavioral therapy on outcomes in primary care, office-based buprenorphine/naloxone treatment of opioid dependence.
METHODS
We conducted a 24-week randomized clinical trial in 141 opioid-dependent patients in a primary care clinic. Patients were randomized to physician management or physician management plus cognitive behavioral therapy. Physician management was brief, manual guided, and medically focused; cognitive behavioral therapy was manual guided and provided for the first 12 weeks of treatment. The primary outcome measures were self-reported frequency of illicit opioid use and the maximum number of consecutive weeks of abstinence from illicit opioids, as documented by urine toxicology and self-report.
RESULTS
The 2 treatments had similar effectiveness with respect to reduction in the mean self-reported frequency of opioid use, from 5.3 days per week (95% confidence interval, 5.1–5.5) at baseline to 0.4 (95% confidence interval, 0.1–0.6) for the second half of maintenance (P<.001 for the comparisons of induction and maintenance with baseline), with no differences between the 2 groups (P=.96) or between the treatments over time (P=.44). For the maximum consecutive weeks of opioid abstinence there was a significant main effect of time (P<.001), but the interaction (P=.11) and main effect of group (P=.84) were not significant. No differences were observed on the basis of treatment assignment with respect to cocaine use or study completion.
CONCLUSIONS
Among patients receiving buprenorphine/naloxone in primary care for opioid dependence, the effectiveness of physician management did not differ significantly from that of physician management plus cognitive behavioral therapy.
doi:10.1016/j.amjmed.2012.07.005
PMCID: PMC3621718  PMID: 23260506
Analgesics; Buprenorphine; Cognitive therapy; Opioid; Opioid-related Disorders; Primary health care
23.  United States counties with low black male mortality rates 
The American journal of medicine  2013;126(1):10.1016/j.amjmed.2012.06.019.
OBJECTIVE
In the United States, young and middle-aged black men have significantly higher total mortality than any other racial or ethnic group. We describe the characteristics of US counties with low non–Hispanic Black or African American male mortality (ages 25-64 years, 1999-2007).
METHODS
Information was accessed through public data, the US Census, the US Compressed Mortality File, and the Native American Graves Repatriation Act military database.
RESULTS
Of 1307 counties with black mortality rates classified as reliable by the National Center for Health Statistics (at least 20 deaths), 66 recorded lower mortality among black men than corresponding US whites. Most notable, 97% of the 66 counties were home to or adjacent a military installation versus 37% of comparable US counties (P .001). Blacks in these counties had less poverty, higher percentages of elderly civilian veterans, and higher per capita income. Within these counties, national black:white disparities in mortality were eliminated for ischemic heart disease, accidents, diseases of the liver, chronic lower respiratory diseases, and mental disorder from psychoactive substance use. Application of age-, race-, ethnicity-, gender-, and urbanization-specific mortality rates from counties with relatively low mortality would reduce the black:white mortality rate ratio for black men aged 25 to 64 years from 1.67 to 1.20 nationally and to 1.00 in areas outside large central metropolitan areas.
CONCLUSIONS
These descriptive data demonstrate a small number of communities with low mortality rates among young and middle-aged black/African American men. Their characteristics may provide clinical and public health insights to reduce these higher mortality rates in the US population. Analytic epidemiologic studies are necessary to test these hypotheses.
doi:10.1016/j.amjmed.2012.06.019
PMCID: PMC3856918  PMID: 23260504
low mortality; black men; clinical characteristics
24.  TAILORING COLORECTAL CANCER SCREENING BY CONSIDERING RISK OF ADVANCED PROXIMAL NEOPLASIA 
The American journal of medicine  2012;125(12):1181-1187.
BACKGROUND
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.
METHODS
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.
RESULTS
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).
CONCLUSION
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.
doi:10.1016/j.amjmed.2012.05.026
PMCID: PMC3529406  PMID: 23062404
Cancer screening; colonoscopy; colorectal cancer; colorectal neoplasm
25.  Impact of Age, Sex, Obesity, and Steroid Use on Quinolone-Associated Tendon Disorders 
The American journal of medicine  2012;125(12):1228.e23-1228.e28.
BACKGROUND
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.
METHODS
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).
RESULTS
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.
CONCLUSION
Quinolone-associated tendinopathy is more pronounced among elderly, non-obese persons, and individuals with concurrent use of glucocorticoids.
doi:10.1016/j.amjmed.2012.05.027
PMCID: PMC3502655  PMID: 23026288
quinolone; fluoroquinolone; tendon rupture; tendonitis

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