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Do C-reactive Protein Levels Predict Death from Heart Failure?

Background: Ultra-sensitive quantitative assessment of C-reactive protein (CRP), a surrogate marker of systemic inflammation, has previously been shown to predict plaque instability in acute coronary syndromes. Data are lacking as to whether this blood test can also predict subsequent risk of heart failure or death on presentation in patients admitted for acute myocardial infarction (MI).

Study design: Prospec-tive observational study.

Setting: Olmstead County, Minn.


Resident Work-Hour Regulations Improve Outcomes

Compared with a nonteaching service, a resident teaching service had improvements in ICU utilization, favorable discharge disposition, and decreased pharmacist correction of drug errors after implementation of work-hour rules.

Citation: Horwitz LI, Kosiborod M, Lin Z. Changes in outcomes for internal medicine inpatients after work-hour regulations. Ann Intern Med. 2007;147


Lower Mortality in Medical Patients after Resident Work-Hour Limits

Medicine patients had 0.25% absolute reductions in mortality and 3.75% reduction in relative risk of death after work-hour rules were implemented, but neither reduction was seen in surgical patients.

Citation: Shetty KD, Bharracharya J. Changes in hospital mortality associated with residency work-hour regulations. Ann Intern Med. 2007;147(2):73-80.

Dark Chocolate Cuts Blood Pressure in Patients with Mild Hypertension

In a study that pleased clinicians and patients alike, low-stage and pre-hypertensive patients on a regular dark chocolate-containing diet had improvements in blood pressure and circulating vasodilator levels.

Citation: Taubert D, Roesen R, Lehmann C, et al. Effects of low habitual cocoa intake on blood pressure and bioactive nitric oxide: a randomized controlled trial. JAMA. 2007;298(1):49-60.

Hyperglycemia Associated with Mortality Increase in STEMI

Patients undergoing angioplasty for ST-elevation myocardial infarction had a higher in-hospital mortality if they were diabetics and mortality was commensurate to the degree to which admission glucose levels were elevated.

Citation: Worthley MI, Shrive FM, Anderson TJ, et al. Prognostic implications of hyperglycemia in myocardial infarction and primary angioplasty. Am J Med. 2007;120(7):643.e1-643.e7.

Vitamin Therapy in Elevated Homocysteine Levels Does Not Reduce VTE

Daily supplementation of folate, B6, and B12 did reduce levels of homocysteine in patients with multiple cardiac risk factors but did not reduce the risk of venous thromboembolism.

Citation: Ray JG, Kearon C, Qilong Y, et al. Homocysteine-lowering therapy and risk for venous thromboembolism. Ann Intern Med. 2007;146(11):761-767

Synopsis: Ultra-sensitive quantitative serum CRP levels were obtained a median of 6.1 hours following onset of symptoms in 329 patients admitted with acute MI. The patients were stratified into tertiles based levels of CRP less than 3 mg/L, 3-15 mg/L, and more than 15 mg/L.

Tertiles were similar in respect to age, male-predominance, most cardiac risk factors, body mass index, and electrocardiographic (EKG) changes. However, there were statistically significant differences between groups, particularly the frequency of diabetes (10.7%, 31.2%, and 38.0%), previous MI history (2.7%, 4.6%, and 9.3%), Killip class greater than one (15.2%, 31.2%, and 39.8%), peak cardiac enzyme levels (both were higher in the bottom tertile, and lowest in the top tertile), and likelihood of significant comorbidities (lower likelihood in the bottom tertile, higher likelihood in the top tertile).

One-year survival was highly correlated with CRP tertile (93%, 84%, and 62% respectively). Once corrected for age, gender, peak cardiac enzymes, Killip class, coronary history, and recurring ischemic events, there remained a robust hazard ratio for heart failure and death at one year based on CRP tertile (1.00, 1.73, and 3.96, respectively).

Bottom line: Ultra-sensitive quantitative CRP levels obtained on admission for acute MI predict one-year risk for heart failure or death. The ability to generalize these results into clinical practice may be limited due to heterogeneity of the studied groups with a higher frequency of diabetes, prior coronary disease, and higher comorbidities in the group that had the highest CRP levels and thus more mortality and heart failure.

Citation: Bursi F, Weston SA, Killian JM, et al. C-reactive protein and heart failure after myocardial infarction in the community. Am J Med. 2007;120(7):616-622.

Do Selective Serotonin Reuptake Inhibitors Confer Cardiac Benefit?

Background: Selective serotonin reuptake inhibitors (SSRIs) theoretically lead to qualitative platelet dysfunction due to inhibition of serotonin-induced platelet activation (and thus resultant inhibition of platelet aggregation and vasoconstriction).

Study design: Retrospective observational study.

Setting: Large teaching hospital in Baltimore.

Synopsis: Of 1,254 patients admitted during the three-year study, 158 patients were on an SSRI at the time of admission. Of the remaining 1,096 patients, a cohort of 158 propensity-matched patients was identified who were statistically similar to the study group in all comorbidities (except for depression, which was higher in the SSRI group).

There were no statistically significant differences between the SSRI group and the propensity-matched group in regards to treatment for acute coronary syndrome (ACS). Almost all received aspirin (98.7% versus 99.4%), clopidogrel (95.6% versus 93.7%), unfractionated heparin (96.8% versus 99.4%), and a glycoprotein IIb/IIIa inhibitor (100% in both).

Patients in the SSRI group had a statistically lower incidence of minor adverse cardiac events (7.0% versus 13.9%), but had increased bleeding events (37.3% versus 26.6%). Minor cardiac events were defined as recurrent EKG findings of ischemia without resultant cardiac enzyme increase, new heart failure, or asymptomatic cardiac enzyme elevation without EKG changes.

Bottom line: Patients taking SSRIs when admitted with an ACS (for an unknown duration) appear to be at lower risk for minor cardiac complications compared with patients not taking an SSRI on admission. These patients also appear to be at elevated risk for bleeding in the setting of maximum antiplatelet and heparin therapy typical in management of ACS.

Citation: Ziegelstein RC, Meuchel J, Kim TJ, et al. Selective serotonin reuptake inhibitor use by patients with acute coronary syndromes. Am J Med. 2007;120(6):525-530.

When Is Vancomycin Superior in Treating C. difficile-Associated Diarrhea?

Background: Epidemic strains of C. difficile raise issues about which antibiotic treatment for C. difficile-associated diarrhea (CDAD) may be superior, particularly due to the availability of more potent antibiotics that can wipe out the protective flora of the intestinal tract.

Study design: Prospec-tive, randomized, double-blind, placebo-controlled trial over 7.5 years.

Setting: A teaching hospital in Chicago.

Synopsis: One hundred seventy-two patients with diarrhea were stratified into mild (fewer than two risks) or severe (two or more risks) disease groups within 48 hours of randomization. These patients were older than 60, with temperature greater than 38.3°C, albumin level lower than 2.5 mg/dL, or peripheral white blood count greater than 15,000 cells/mm. Patients requiring intensive care unit treatment or those with colonscopic evidence of pseudomembranous colitis received an additional risk score of two. 

One hundred fifty patients completed the study, 71 in the vancomycin group (125 mg orally, four times a day) and 79 in the metronidazole group (250 mg orally, four times a day). Both groups were similar in composition and numbers of patients with mild and severe CDAD. Patients received placebo plus either vancomycin or metronidazole. 

Cure was defined as resolution of diarrhea by day six of therapy and negative C. difficile toxin A assays on days six and 10 of therapy. Results were statistically similar in both treatment groups with mild disease (98% vancomycin versus 90% metronidazole), but favored vancomycin in severe disease (97% versus 76%). 

Relapse were not statistically different in either group (7% versus 14%). An albumin level less than 2.5 mg/dL or the presence of colonoscopy-confirmed pseudomembranous colitis showed statistically significant correlation with metronidazole treatment failure (relative risks of 12.70 and 6.67, respectively).

Bottom line: Oral vancomycin, with its commensurate potential for inducing vancomycin-resistant Enterococcus, proved to be equally effective as metronidazole in treating mild CDAD. It was statistically superior to metronidazole in severe disease with hypoalbuminemia and pseudomembranous colitis predicting failure of metronidazole therapy.

Citation: Zar FA, Bakkanagari SR, Moorthi KM, et al. A comparison of vancomycin and metronidazole for the treatment of C. difficile-associated diarrhea, stratified by disease severity. Clin Infect Dis. 2007;45(3):302-307.

What Risk Factors Affect VTE Development in Outpatients?

Background: Decreasing lengths of stay have raised concern that treatments that previously would have continued during the longer hospital stays in the past, such as deep vein thrombosis prophylaxis, may result in unintended adverse consequences after discharge.

Study design: Retrospective observational study

Setting: Worcester, Mass., in 1999, 2001, and 2003, comprising residents who had diagnosis of venous thromboembolism (VTE) at any one of the 12 hospitals in the region

Synopsis: VTE was diagnosed in 1,897 residents (71.1%, 15.0% had pulmonary embolism [PE], and 13.9% had both). Further, 73.7% of the patients presented as an outpatient or were diagnosed within one day of hospital admission.

Compared with inpatients with VTE, outpatients were younger (63.3 years versus 67.4), were less likely to have had a recent infection (18.6% versus 46.8%), central venous catheter (10.4% versus 41.0%), recent fracture (7.3% versus 18.7%), heart failure (4.2% versus 16.5%), cardiac procedures (2.9% versus 7.8%), or recent intensive care unit care stay (8.7% versus 38.2%), but were more likely to have had a prior episode of VTE (19.9% versus 10.2%) or to be taking hormonal therapy (8.0% versus 3.0%).

The prevalence of malignancy was similar in both groups (29.0% versus 32.3%). Most outpatients diagnosed with VTE (59.9%) had been hospitalized in the preceding three months with a majority of VTEs diagnosed within 30 days of discharge. Only 59.7% of those previously hospitalized had any DVT prophylaxis (42.8% received anticoagulants, 16.9% had mechanical prophylaxis).

Bottom line: In an era of decreasing lengths of stay, the possible high level of outpatient VTE attributable to recent hospitalization may be at least partially due to inadequate inpatient pharmacologic VTE prophylaxis in more than 50% of the patients.

Citation: Spencer FA, Lessard D, Emery C, et al. Venous thromboembolism in the outpatient setting. Arch Intern Med. 2007;167(14):1471-1475.

How Has C. difficile Colitis Changed in Severity and Prevalence?

Background: Recent epidemic strains of Clostridium difficile have been reported with several studies suggesting that C. difficile infection has become more serious with risks for sepsis, colectomy, and death.

Study design: Cohort analysis of nationwide inpatient sample (NIS) discharge data for 11 years.

Synopsis: Of the more than 78 million discharge abstracts available for analysis, 299,453 patients were discharged with either a principle or secondary diagnosis of Clostridium difficile colitis (CDC). Demographics trends comparing the early period (1993-1996) versus the middle period (1997-2000) versus the late period (2001-2003) showed CDC incidence:

  • Increased in older groups (65.6 years, 66.9 years, 67.6 years);
  • Decreased in females (59.8%, 59.1%, 58.9%); and
  • Decreased in Caucasians (70.90%, 67.20%, 59.10%).

From 1993 to 2003, the prevalence of CDC discharge diagnoses increased from 261 to 546 cases per 100,000; the colectomy rate due to CDC increased from 1.2 up to 3.4 per 1000, and the case fatality rate statistically significantly increased from 7.84% to 9.26%.

Bottom line: Despite the limitations of using discharge coding abstracts, this study confirms the significantly increasing prevalence (particularly in older, non-Caucasian men) and severity of CDC over the previous decade. This has resulted in a higher incidence of colectomy and death.

Citation: Ricciardi R, Rothenberger DA, Madoff RD. Increasing prevalence and severity of Clostridium difficile colitis in hospitalized patients in the United States. Arch Surg. 2007;142(7):624-631.

How Often Do Clinicians Deviate from Recommended Enoxaparin Doses?

Background: Low molecular heparins have been increasingly utilized in the setting of non-ST-segment elevation myocardial infarctions (NSTEMI) in place of unfractionated heparin. They require careful dose adjustment to ensure appropriate therapeutic effect and prevent bleeding and thrombotic complications.

Study design: Retrospective observational cohort study.

Setting: Medical centers throughout the U.S. that participated in the Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the ACC/AHA Guidelines (CRUSADE) initiative.

Synopsis: A total of 10,687 patients from 332 hospitals received enoxaparin for NSTEMI as part of CRUSADE. Patients were stratified by whether they received:

  • The recommended dose of enoxaparin (1 mg/kg twice daily for glomerular filtration rate (GFR) more than 30 mL/min versus 0.5 mg/kg twice daily for estimated GFR of 30 mL/min or less; 52.1%);
  • An excess dose (more than 10 mg/day over recommended dose; 18.7%); or
  • A lower-than-recommended dose (more than 10 mg/day less than the recommended dose; 29.2%).

Those receiving an excess dose were more likely to be older, have lower body-mass indexes (BMI), weigh less, be female, have estimated GFRs less than 60 mL/min, and smoke. Those receiving less-than-recommended dosing were more likely to have a higher BMI, weigh more, and be male. Major bleeding episodes (14.2%) and deaths (5.6%) were more common statistically in the excess dose group compared with the recommended dose group (7.3% and 2.4%, respectively). Deaths, but not bleeding, also were higher in the lower-than-recommended dose group (3.3% versus 2.4%).

Bottom line: A little more than half of patients received the correct dose of enoxaparin in NSTEMIs. Those who received too high a dose had marked increases in risk of bleeding and death, and those receiving subtherapeutic doses suffered increased mortality.

Citation: LaPointe NMA, Chen AY, Alexander KP, et al. Enoxaparin dosing and associated risk of in-hospital bleeding and death in patients with non-ST-segment elevation acute coronary syndromes. Arch Intern Med. 2007;167(14):1539-1344.

Does Poor Health Literacy Predict Mortality?

Background: Prior studies have shown increased hospitalization rates in patients with poor health literacy (e.g., inability to comprehend prescriptions or educational materials). At least one study has shown an increase in mortality in 70-to-79-year-olds with impaired health literacy.

Study design: Prospective cohort study.

Setting: Four U.S. metropolitan areas.

Synopsis: Poor health literacy predicts patients’ inability to understand basic health information, such as prescription information, drug dosing intervals, or follow-up schedules. In 1997, 3,260 patients age 65 or older were included in the study, which used a face-to-face standardized test to quantify health literacy.

Patients were tracked via the National Death Index through 2003. Patients were stratified as having adequate, marginal, or inadequate health literacy (64.2%, 11.2%, and 24.5% of patients, respectively). Marginal and inadequate health literacy were strongly associated with increasing age, African American race, lower incomes, lower levels of education, worse physical and mental health, limitations in activities of daily living (ADLs), and lower BMIs. These patients were also less likely to perform vigorous exercise, and less likely to have smoked or used alcohol.

Health literacy (adequate, marginal, or inadequate) predicted unadjusted mortality rates (18.9%, 28.7%, and 39.4%, respectively). Adjusting for socioeconomic status, demographics, and baseline health, all-cause mortality hazard ratios of marginal and inadequate literacy (compared with adequate health literacy) were 1.13 (0.90-1.41 not statistically significant) and 1.52 (1.26-1.83, statistically significant).

Bottom line: Limited data exists regarding how to improve health literacy, and there is no easy bedside test to identify patients with varying levels of literacy. But there appears to be a strong, independent correlation to health literacy and mortality. Physicians need to remain vigilant in their patients’ understanding of their disease, treatment, and follow-up.

Citation: Baker DW, Wolf MS, Feinglass J, et al. Health literacy and mortality among elderly persons. Arch Intern Med. 2007;167(14):1503-1509.

Which Factors Predict Delirium at Discharge?

Background: Delirium at hospital discharge, which can persist for months following hospitalization, may be a contributing factor to dementia, results in increased medical errors during the traditionally high-risk period between discharge and follow-up. Further, it results in serious complications, and, if unrecognized, a high mortality rate.

Study design: Prospective validation model.

Synopsis: A model to predict delirium at hospital discharge was studied in a development cohort of 491 patients age 70 or older who had no evidence of delirium on admission. Of twenty-two different candidate factors, five factors correlated with high odds ratios of delirium at discharge in the 106 (21.6%) of those in the study group who developed delirium: dementia, vision impairment, inability to perform more than one ADL, multiple comorbidities (based on a Charlson score of four or more), and restraint use during delirium.

Patients were stratified into low-risk (zero-one factors), intermediate risk (two-three factors), or high risk (four or more factors) for delirium at hospital discharge. Relative risks (RR) for each group were 1, 4.4, and 15.3, respectively; RR for nursing home placement or death (NHPOD) at one year was 1, 2.4, and 3.4, respectively. A validation cohort of 461 statistically similar patients showed RR for development in the low-, intermediate-, and high-risk groups of 1, 5.4, 10.2, respectively; and RR at one year for NHPOD was 1, 2.7, and 4.4, respectively.

Bottom line: Dementia, vision impairment, inability to perform at least one ADL, multiple comorbidities, and use of restraints are risk factors that can stratify patients into low, intermediate, and high risk for delirium at hospital discharge. Commensurate risks exist for nursing home placement or death at one year.

Citation: Inouye SK, Zhang Y, Jones RN. Risk factors for delirium at discharge. Arch Intern Med. 2007;167(13):1406-1413.

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