Michael Goldman, MD

In This Edition

• Generic vs. brand-name drugs.
• Rapid-response teams and mortality.
• A new prediction rule for mortality in acute pancreatitis.
• Viral causes of community-acquired pneumonia.
• Intensive insulin therapy in the ICU.
• New preoperative and intraoperative risk factors.
• Timing of ICU feedings and mortality.
• Aspirin as primary prevention in diabetics.

Generic, Brand-Name Drugs Used for Cardiovascular Disease Are Clinically Equivalent

Clinical question: Is there a clinical risk when substituting generic drugs for brand-name drugs in the treatment of cardiovascular disease?

Background: Spending on healthcare in the U.S. has reached critical levels. Increasing prescription drug costs make up a large portion of healthcare expenditures. The high cost of medicines directly affect adherence to treatment regimens and contribute to poor health outcomes. Cardiovascular drugs make up the largest portion of outpatient prescription drug spending.

Study design: Systematic review of relevant articles with a meta-analysis performed to determine an aggregate effect size.

Setting: Multiple locations and varied patient populations.

Synopsis: A total of 47 articles were included in the review, of which 38 were randomized controlled trials (RCTs). The studies measured both clinical efficacy and safety end points. More than half the articles were published prior to 2000. Clinical equivalence was noted in all seven beta-blocker RCTs; 10 of 11 diuretic RCTs; five of seven calcium-channel-blocker RCTs; all three antiplatelet-agent RCTs (clopidogrel, enteric-coated aspirin); two statin RCTs; one ACE-inhibitor RCT; and one alpha-blocker RCT. For drugs with a narrow therapeutic index, clinical equivalence was noted in all five warfarin RCTs and a single Class 1 anti-arrhythmic-agent RCT.

The aggregate effect size was -0.03 (95% CI, -0.15 to 0.08), which indicates nearly complete overlap of the generic and brand-name distributions. The data show no evidence of superiority of brand-name to generic drugs in clinical outcomes measured in the various studies.

In a separate review of editorials addressing generic substitution for cardiovascular drugs, 53% expressed a negative view of generic-drug substitution.

Bottom line: There is clinical equivalency between generic and brand-name drugs used in the treatment of cardiovascular disease. Despite this conclusion, a substantial number of editorials advise against generic substitution, which affects both patient and physician drug preferences.

Citation: Kesselheim A, Misono A, Lee J, et al. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA. 2008; 300(21):2514-2526.

PEDIATRIC LITERATURE

Oral Prednisolone Does Not Shorten Hospitalization in Preschool-Age Children with Acute Virus-Induced Wheezing

Clinical question: Does oral prednisolone shorten duration of hospitalization in preschool-age children with acute virus-induced wheezing?

Background: Wheezing illnesses in young children are commonly associated with viral infections and may resolve with age without further stigmata of atopic asthma. Although systemic corticosteroids are commonly recommended for this population, evidence of their effectiveness is limited.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Three hospitals in the United Kingdom.

Synopsis: Children between 10 and 60 months that presented to a hospital with a physician-diagnosed attack of wheezing preceded by a viral infection were randomized to receive oral prednisolone or a placebo. There was no significant difference between the groups in the time to hospital discharge. There also was no difference in the prespecified subgroup analysis of children at high risk for atopic asthma.

The median time between presentation and “fit for discharge” was relatively low in this sample—12 hours in the placebo group and 10.1 hours in the prednisolone group. Nearly half the patients were discharged within the first several hours after presentation, and not all patients were admitted to a pediatric ward. A short-stay observation ward within the ED was an option. Thus, the results may be most applicable to patients with mild to moderate disease, some of which may not be admitted to a traditional inpatient unit.

Bottom line: Systemic corticosteroids do not dramatically shorten hospital and ED stays in preschool-aged children with mild to moderate virus-induced wheezing.

Citation: Panickar J, Lakhanpaul M, Lambert P, et al. Oral prednisolone for preschool children with acute virus-induced wheezing. N Engl J Med. 2009;360(4):329-338.

Reviewed by pediatric editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

RRT Implement-ation Doesn’t Affect Hospitalwide Code Rates or Mortality

Clinical question: Does the use of a rapid-response team (RRT) affect hospitalwide code rates and mortality?

Background: In the 100,000 Lives campaign, the Institute for Healthcare Improvement recommended that hospitals implement RRTs to help reduce preventable, in-hospital deaths. Studies have demonstrated that rates of non-ICU codes decrease after RRT implementation. It is unclear if this translates to changes in mortality rates.

Study design: Prospective cohort study of adult inpatients.

Setting: Saint Luke’s Hospital, a 404-bed tertiary-care academic hospital in Kansas City, Mo.

Synopsis: The hospital documented a total of 376 RRT activations. After RRT implementation, mean hospitalwide code rates decreased to 7.5 per 1,000 admissions from 11.2 per 1,000 admissions. This was not associated with a statistically significant reduction in hospitalwide code rates (adjusted odds ratio 0.76; 95% CI; 0.57-1.01; P=0.06). Secondary analyses noted lower rates of non-ICU codes (0.59; 95% CI, 0.40-0.89) compared with ICU codes (0.95; 95% CI; 0.64-1.43; P=0.03 for interaction). Finally, the RRT implementation was not associated with lower hospital-wide mortality (0.95; 95% CI; 0.81-1.11; P=0.52).

Secondary analyses also revealed few instances of RRT undertreatment or underutilization that may have affected the mortality numbers.

A limitation of this study is that it was slightly underpowered (78%) to detect a significant mortality difference. The findings also represent a single institution experience, and may not be generalized to other adult hospital settings or RRT programs.

Bottom line: Implementation of an RRT does not confer lower rates of hospital-wide code arrests or mortality.

Citation: Chan P, Khalid A, Longmore L, et al. Hospital-wide code rates and mortality before and after implementation of a rapid response team. JAMA. 2008;300(21):2506-2513.

Simple Scoring System Provides Timely Prediction of Mortality in Acute Pancreatitis

Clinical question: How can physicians predict mortality in acute pancreatitis?

Background: Historical predictors of mortality in acute pancreatitis require up to 48 hours of data, such as with the Ranson Criteria, or extensive amounts of data, such as with the APACHE II score. An easier tool is needed to predict which patients are at higher risk of mortality.

Study design: Retrospective cohort.

Setting: Patients in the Cardinal Health clinical outcomes research database, which supports public reporting of hospital performance.

Synopsis: The authors identified patients with the principal diagnosis of pancreatitis from 2000-2001 and explored numerous diagnostic findings available within the first 24 hours. Ultimately, BUN >25, impaired mental status, presence of SIRS (systemic inflammatory response syndrome), age >60, and presence of a pleural effusion were found to be predictive of mortality. These diagnostic findings correspond to the mnemonic BISAP. The BISAP score was then validated in a second cohort that included patients from 2004-2005.

Each finding in the BISAP score was given one point. A score of less than 2 was present in approximately 60% of patients admitted with acute pancreatitis, and corresponded to a mortality of less than 1%. A score of 2 corresponded to a mortality of 2%. Higher scores were associated with steeply increasing mortality, with a score of 5 corresponding with greater than 20% mortality.

The BISAP score performed similarly to the APACHE II score, but the former is easier to calculate on the day of admission and has fewer parameters. A more challenging research step will be to demonstrate that using the BISAP score to determine treatment strategies can affect patient outcomes.

Bottom line: The easy-to-calculate BISAP score is a new method for predicting mortality in patients with acute pancreatitis. This tool should help hospitalists determine, on the day of admission, to what extent patients with acute pancreatitis need aggressive management, such as ICU admission and early involvement of specialists.

Citation: Wu B, Johannes R, Sun X, Tabak Y, Conwell D, Banks P. The early prediction of mortality in acute pancreatitis: a large population-based study. Gut. 2008;57(12): 1698-1703.

Nasal Swabs Identify Viral Causes in CAP Patients

Clinical question: How often is viral infection associated with community-acquired pneumonia (CAP) in adults?

Background: CAP is a clinically important disease that is associated with significant hospitalization and mortality. CAP treatment guidelines acknowledge respiratory viruses as an etiology for pneumonia, but few recommendations are made regarding management of these viral infections.

Study design: Prospective study.

Setting: Five hospitals in Edmonton, Alberta, from 2004-2006.

Synopsis: The authors enrolled 193 hospitalized adults, median age 71. Nucleic amplification tests (NATs) from nasopharyngeal swab specimens were tested for human metapneumovirus, respiratory syncytial virus, rhinovirus, parainfluenza virus 1-4, coronaviruses, and adenovirus.

Fifteen percent of these patients had a nasal swab positive for a viral infection. Interestingly, 4% of patients had both a positive viral nasal swab and positive bacterial cultures. Compared with bacterial infection, patients with viral infection tended to be older (76 vs. 64 years, P=0.01), have limited ambulation (66% vs. 32%, P=0.006), and have a history of cardiac disease (66% vs. 32%, P=0.02). Patients with bacterial pneumonia showed a statistically significant trend toward having chest pain, an abnormal white blood count, and a lobar infiltrate on chest X-ray.

Further investigations might look at how nasal swab data could be used to improve infection control within the hospital for patients found to have easily transmissible viruses. Further research could explore the feasibility of avoiding antibiotic use in patients found to have viral pneumonia, assuming bacterial co-infection is reliably excluded.

Bottom line: Nasal swabs using NAT technology could play a significant role in identifying pathogens in CAP patients. How this technology should affect clinical decision-making and how it might improve outcomes remains unknown.

Citation: Johnstone J, Majumdar S, Fox J, Marrie T. Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation. Chest. 2008;134(6):1141-1148.

Intensive Insulin Therapy Doesn’t Reduce ICU Mortality

Clinical question: Does the use of intensive insulin therapy decrease mortality in the intensive-care unit (ICU)?

Background: In 2001, Van den Berghe et al (N Engl J Med. 2001;345(19):1359-67) reported a reduction in morbidity and mortality with intensive insulin therapy (IIT) in surgical ICU patients. This study led to the adoption of IIT protocols in many hospitals. Since 2001, further studies have failed to reproduce the same dramatic benefit of IIT.

Study design: Randomized, controlled trial.

Setting: National Guard King Abdulaziz Medical City, a tertiary-care teaching hospital in Saudi Arabia.

Synopsis: Patients were included in this study if they were 18 years or older with serum glucose levels greater than 110 mg/dL during the first 24 hours of ICU admission. There were multiple exclusion criteria, including patients with Type I diabetes, documented hypoglycemia on ICU admission (glucose <40), or diabetic ketoacidosis.

Enrolled patients were randomized to IIT or conventional insulin therapy (CIT). A multidisciplinary team designed the protocols to maintain glucose levels of 80 to 110 mg/dL and 180 to 200 mg/dL in the IIT and the CIT groups, respectively. The primary endpoint measured was ICU mortality.

The study did not produce a statistically significant difference in ICU mortality (13.5% for IIT vs. 17.1% for CIT; P=0.30). The adjusted hypoglycemia rate was 6.8 per 100 treatment days with IIT and 0.4 per 100 treatment days with CIT (P<0.0001). Patients with hypoglycemia had higher ICU mortality (23.8% vs. 13.7%, P=0.02).

In the measurement of secondary endpoints, there was a trend toward lower episodes of severe sepsis and septic shock in the IIT group (20.7% in IIT vs. 27.2% in CIT, P=0.08). However, this result was not statistically significant.

Bottom line: This well-designed study failed to show a survival benefit with IIT use in the critical-care setting. Given the findings of this and several other recent studies, one should question whether IIT should be prescribed as the standard of care in all critically-ill patients.

Citation: Arabi Y, Dabbagh O, Tamim H, et al. Intensive versus conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients. Crit Care Med. 2008;36(12):3190-3197.

Preoperative and Intraoperative Predictors of Cardiac Adverse Events

Clinical question: What are the incidence and risk factors for perioperative cardiac adverse events after noncardiac surgery?

Background: In the past few decades, the incidence of cardiac adverse events (CAEs) for a general surgery population has remained largely unchanged (approximately 1%). This is in spite of multiple studies evaluating predictive models and attempts at preventive treatment, including preoperative coronary revascularization and perioperative beta blockers.

Study design: Prospective observational study.

Setting: Single, large, tertiary-care university hospital.

Synopsis: A total of 7,740 cases were reviewed in this study, which consisted of general surgery (4,937), vascular surgery (1,846), and urological surgery (957). A trained nurse followed up for perioperative CAEs as many as 30 days after the operation via medical chart review, phone calls, and letters. CAEs were defined as: Q-wave myocardial infarction (MI), non-ST elevation MI, cardiac arrest, or new cardiac dysrhythmia. A total of 83 CAEs (1.1% of patients) had cardiac arrest, with cardiac dysrhythmia being most common.

A total of seven preoperative risk factors were identified as independent predictors for CAEs: age 68, BMI 30, emergent surgery, prior coronary intervention or cardiac surgery, active congestive heart failure, cerebrovascular disease, and hypertension. In addition, two intraoperative risk factors were identified: intraoperative transfusion of packed red blood cells and operative duration of 3.8 hours. (The P value was 0.05 for all independent predictors.)

A further evaluation of intraoperative parameters of high-risk patients experiencing a CAE showed that these patients were more likely to have an episode of mean arterial pressure (MAP) <50 mmHg, an episode of 40% decrease in MAP, and an episode of tachycardia (heart rate >100).

Bottom line: A combination of preoperative predictors and intraoperative elements can help improve risk assessment for perioperative CAEs after noncardiac surgery.

Citation: Kheterpal S, O’Reilly M, Englesbe M, et al. Preoperative and intraoperative predictors of cardiac adverse events after general, vascular, and urological surgery. Anesthesiology. 2009;110(1):58-66.

Early Feeding in the ICU Does Not Affect Hospital Mortality

Clinical question: Will implementing evidence-based feeding guidelines improve feeding practices and reduce mortality in ICU patients?

Background: There is evidence suggesting that providing nutritional support to ICU patients within 24 hours of admission may decrease mortality. It is widely understood that patient care varies between ICUs, and there exist no uniform, evidence-based guidelines for nutritional support. Many patients remain unfed after 48 hours.

Study design: Cluster, randomized-controlled trial.

Setting: ICUs in 27 community and tertiary-care hospitals in Australia and New Zealand.

Synopsis: Hospitals were randomized to intervention or control groups. Dietitian and intensivist co-investigators from intervention ICUs developed guidelines using the Clinical Practice Guideline Development Cycle. Control ICUs were requested to make no new ICU nutritional management changes. The study enrolled 1,118 eligible patients and included adults expected to stay longer than two days. Excluded were patients taking oral diets, patients receiving palliative care or with suspected brain death, and patients sent from other facilities.

Guidelines were implemented using several methods—educational outreach visits, one-on-one conversations, active reminders, passive reminders, and educational in-services. The guidelines were successful in evoking significant practice changes in all of the intervention ICUs. Significantly more patients received nutritional support during their ICU stays in guideline ICUs, and patients in these ICUs were fed significantly earlier. There were, however, no significant differences between guideline and control ICUs with regard to hospital discharge mortality (28.9% vs. 27.4%; 95% CI; -6.3% to 12.0%; P=0.75). The groups also showed no statistical difference in hospital or ICU length of stay.

Bottom line: Significantly more patients in the guideline ICUs were fed within 24 hours, but this did not translate into improvements in mortality or other clinical outcomes.

Citation: Doig G, Simpson F, Finfer S, et al. Effect of evidence-based feeding guidelines on mortality of critically ill adults: a cluster randomized controlled trial. JAMA. 2008;300(23):2731-2741.

Low-Dose Aspirin Doesn’t Reduce Cardiovascular Events in Type 2 Diabetes Patients

Clinical question: Is low-dose aspirin effective for the primary prevention of atherosclerotic events in patients with Type 2 diabetes?

Background: Diabetes is a significant risk factor for cardiovascular events. Several prior studies have shown that aspirin therapy is effective as a secondary prevention strategy for cardiovascular events. The American Diabetes Association also recommends use of aspirin as a primary prevention strategy. Clinical trial data is currently insufficient in this area.

Study design: Prospective, randomized, open-label, controlled trial with blinded endpoint assessment.

Setting: 163 institutions in Japan.

Synopsis: The study enrolled 2,539 diabetic patients between 30 and 85 years old—mean age was 65—and included patients without EKG changes or a significant history or ongoing treatment of atherosclerotic disease. Patients were randomly assigned into an aspirin group (81 mg or 100 mg once daily) or a nonaspirin group. Patients had a median follow up of 4.37 years.

The primary endpoint was any atherosclerotic event, ranging from sudden death to ischemic heart disease or stroke. The incidence of atherosclerotic events was not statistically different in the aspirin group (68 events, 5.4%) than in the nonaspirin group (86 events, 6.7%) (HR, 0.80; 95% CI; 0.58-1.10; log-rank test, P=0.16). However, there was a suggested benefit of primary prevention in the subgroup aged 65 years or older. In addition, the combined endpoint of fatal coronary and cerebrovascular events occurred in one patient in the aspirin group and 10 patients in the nonaspirin group (HR, 0.10; 95 % CI, 0.01-0.79; P=.0037). This study is limited by the low incidence of atherosclerotic disease in Japan.

Bottom line: Low-dose aspirin used in patients with Type 2 diabetes does not significantly demonstrate primary prevention of cardiovascular events.

Citation: Ogawa H, Nakayama M, Morimoto T, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300(18):2134-2141. TH

In This Edition

• Generic vs. brand-name drugs.
• Rapid-response teams and mortality.
• A new prediction rule for mortality in acute pancreatitis.
• Viral causes of community-acquired pneumonia.
• Intensive insulin therapy in the ICU.
• New preoperative and intraoperative risk factors.
• Timing of ICU feedings and mortality.
• Aspirin as primary prevention in diabetics.

Generic, Brand-Name Drugs Used for Cardiovascular Disease Are Clinically Equivalent

Clinical question: Is there a clinical risk when substituting generic drugs for brand-name drugs in the treatment of cardiovascular disease?

Background: Spending on healthcare in the U.S. has reached critical levels. Increasing prescription drug costs make up a large portion of healthcare expenditures. The high cost of medicines directly affect adherence to treatment regimens and contribute to poor health outcomes. Cardiovascular drugs make up the largest portion of outpatient prescription drug spending.

Study design: Systematic review of relevant articles with a meta-analysis performed to determine an aggregate effect size.

Setting: Multiple locations and varied patient populations.

Synopsis: A total of 47 articles were included in the review, of which 38 were randomized controlled trials (RCTs). The studies measured both clinical efficacy and safety end points. More than half the articles were published prior to 2000. Clinical equivalence was noted in all seven beta-blocker RCTs; 10 of 11 diuretic RCTs; five of seven calcium-channel-blocker RCTs; all three antiplatelet-agent RCTs (clopidogrel, enteric-coated aspirin); two statin RCTs; one ACE-inhibitor RCT; and one alpha-blocker RCT. For drugs with a narrow therapeutic index, clinical equivalence was noted in all five warfarin RCTs and a single Class 1 anti-arrhythmic-agent RCT.

The aggregate effect size was -0.03 (95% CI, -0.15 to 0.08), which indicates nearly complete overlap of the generic and brand-name distributions. The data show no evidence of superiority of brand-name to generic drugs in clinical outcomes measured in the various studies.

In a separate review of editorials addressing generic substitution for cardiovascular drugs, 53% expressed a negative view of generic-drug substitution.

Bottom line: There is clinical equivalency between generic and brand-name drugs used in the treatment of cardiovascular disease. Despite this conclusion, a substantial number of editorials advise against generic substitution, which affects both patient and physician drug preferences.

Citation: Kesselheim A, Misono A, Lee J, et al. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA. 2008; 300(21):2514-2526.

PEDIATRIC LITERATURE

Oral Prednisolone Does Not Shorten Hospitalization in Preschool-Age Children with Acute Virus-Induced Wheezing

Clinical question: Does oral prednisolone shorten duration of hospitalization in preschool-age children with acute virus-induced wheezing?

Background: Wheezing illnesses in young children are commonly associated with viral infections and may resolve with age without further stigmata of atopic asthma. Although systemic corticosteroids are commonly recommended for this population, evidence of their effectiveness is limited.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Three hospitals in the United Kingdom.

Synopsis: Children between 10 and 60 months that presented to a hospital with a physician-diagnosed attack of wheezing preceded by a viral infection were randomized to receive oral prednisolone or a placebo. There was no significant difference between the groups in the time to hospital discharge. There also was no difference in the prespecified subgroup analysis of children at high risk for atopic asthma.

The median time between presentation and “fit for discharge” was relatively low in this sample—12 hours in the placebo group and 10.1 hours in the prednisolone group. Nearly half the patients were discharged within the first several hours after presentation, and not all patients were admitted to a pediatric ward. A short-stay observation ward within the ED was an option. Thus, the results may be most applicable to patients with mild to moderate disease, some of which may not be admitted to a traditional inpatient unit.

Bottom line: Systemic corticosteroids do not dramatically shorten hospital and ED stays in preschool-aged children with mild to moderate virus-induced wheezing.

Citation: Panickar J, Lakhanpaul M, Lambert P, et al. Oral prednisolone for preschool children with acute virus-induced wheezing. N Engl J Med. 2009;360(4):329-338.

Reviewed by pediatric editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

RRT Implement-ation Doesn’t Affect Hospitalwide Code Rates or Mortality

Clinical question: Does the use of a rapid-response team (RRT) affect hospitalwide code rates and mortality?

Background: In the 100,000 Lives campaign, the Institute for Healthcare Improvement recommended that hospitals implement RRTs to help reduce preventable, in-hospital deaths. Studies have demonstrated that rates of non-ICU codes decrease after RRT implementation. It is unclear if this translates to changes in mortality rates.

Study design: Prospective cohort study of adult inpatients.

Setting: Saint Luke’s Hospital, a 404-bed tertiary-care academic hospital in Kansas City, Mo.

Synopsis: The hospital documented a total of 376 RRT activations. After RRT implementation, mean hospitalwide code rates decreased to 7.5 per 1,000 admissions from 11.2 per 1,000 admissions. This was not associated with a statistically significant reduction in hospitalwide code rates (adjusted odds ratio 0.76; 95% CI; 0.57-1.01; P=0.06). Secondary analyses noted lower rates of non-ICU codes (0.59; 95% CI, 0.40-0.89) compared with ICU codes (0.95; 95% CI; 0.64-1.43; P=0.03 for interaction). Finally, the RRT implementation was not associated with lower hospital-wide mortality (0.95; 95% CI; 0.81-1.11; P=0.52).

Secondary analyses also revealed few instances of RRT undertreatment or underutilization that may have affected the mortality numbers.

A limitation of this study is that it was slightly underpowered (78%) to detect a significant mortality difference. The findings also represent a single institution experience, and may not be generalized to other adult hospital settings or RRT programs.

Bottom line: Implementation of an RRT does not confer lower rates of hospital-wide code arrests or mortality.

Citation: Chan P, Khalid A, Longmore L, et al. Hospital-wide code rates and mortality before and after implementation of a rapid response team. JAMA. 2008;300(21):2506-2513.

Simple Scoring System Provides Timely Prediction of Mortality in Acute Pancreatitis

Clinical question: How can physicians predict mortality in acute pancreatitis?

Background: Historical predictors of mortality in acute pancreatitis require up to 48 hours of data, such as with the Ranson Criteria, or extensive amounts of data, such as with the APACHE II score. An easier tool is needed to predict which patients are at higher risk of mortality.

Study design: Retrospective cohort.

Setting: Patients in the Cardinal Health clinical outcomes research database, which supports public reporting of hospital performance.

Synopsis: The authors identified patients with the principal diagnosis of pancreatitis from 2000-2001 and explored numerous diagnostic findings available within the first 24 hours. Ultimately, BUN >25, impaired mental status, presence of SIRS (systemic inflammatory response syndrome), age >60, and presence of a pleural effusion were found to be predictive of mortality. These diagnostic findings correspond to the mnemonic BISAP. The BISAP score was then validated in a second cohort that included patients from 2004-2005.

Each finding in the BISAP score was given one point. A score of less than 2 was present in approximately 60% of patients admitted with acute pancreatitis, and corresponded to a mortality of less than 1%. A score of 2 corresponded to a mortality of 2%. Higher scores were associated with steeply increasing mortality, with a score of 5 corresponding with greater than 20% mortality.

The BISAP score performed similarly to the APACHE II score, but the former is easier to calculate on the day of admission and has fewer parameters. A more challenging research step will be to demonstrate that using the BISAP score to determine treatment strategies can affect patient outcomes.

Bottom line: The easy-to-calculate BISAP score is a new method for predicting mortality in patients with acute pancreatitis. This tool should help hospitalists determine, on the day of admission, to what extent patients with acute pancreatitis need aggressive management, such as ICU admission and early involvement of specialists.

Citation: Wu B, Johannes R, Sun X, Tabak Y, Conwell D, Banks P. The early prediction of mortality in acute pancreatitis: a large population-based study. Gut. 2008;57(12): 1698-1703.

Nasal Swabs Identify Viral Causes in CAP Patients

Clinical question: How often is viral infection associated with community-acquired pneumonia (CAP) in adults?

Background: CAP is a clinically important disease that is associated with significant hospitalization and mortality. CAP treatment guidelines acknowledge respiratory viruses as an etiology for pneumonia, but few recommendations are made regarding management of these viral infections.

Study design: Prospective study.

Setting: Five hospitals in Edmonton, Alberta, from 2004-2006.

Synopsis: The authors enrolled 193 hospitalized adults, median age 71. Nucleic amplification tests (NATs) from nasopharyngeal swab specimens were tested for human metapneumovirus, respiratory syncytial virus, rhinovirus, parainfluenza virus 1-4, coronaviruses, and adenovirus.

Fifteen percent of these patients had a nasal swab positive for a viral infection. Interestingly, 4% of patients had both a positive viral nasal swab and positive bacterial cultures. Compared with bacterial infection, patients with viral infection tended to be older (76 vs. 64 years, P=0.01), have limited ambulation (66% vs. 32%, P=0.006), and have a history of cardiac disease (66% vs. 32%, P=0.02). Patients with bacterial pneumonia showed a statistically significant trend toward having chest pain, an abnormal white blood count, and a lobar infiltrate on chest X-ray.

Further investigations might look at how nasal swab data could be used to improve infection control within the hospital for patients found to have easily transmissible viruses. Further research could explore the feasibility of avoiding antibiotic use in patients found to have viral pneumonia, assuming bacterial co-infection is reliably excluded.

Bottom line: Nasal swabs using NAT technology could play a significant role in identifying pathogens in CAP patients. How this technology should affect clinical decision-making and how it might improve outcomes remains unknown.

Citation: Johnstone J, Majumdar S, Fox J, Marrie T. Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation. Chest. 2008;134(6):1141-1148.

Intensive Insulin Therapy Doesn’t Reduce ICU Mortality

Clinical question: Does the use of intensive insulin therapy decrease mortality in the intensive-care unit (ICU)?

Background: In 2001, Van den Berghe et al (N Engl J Med. 2001;345(19):1359-67) reported a reduction in morbidity and mortality with intensive insulin therapy (IIT) in surgical ICU patients. This study led to the adoption of IIT protocols in many hospitals. Since 2001, further studies have failed to reproduce the same dramatic benefit of IIT.

Study design: Randomized, controlled trial.

Setting: National Guard King Abdulaziz Medical City, a tertiary-care teaching hospital in Saudi Arabia.

Synopsis: Patients were included in this study if they were 18 years or older with serum glucose levels greater than 110 mg/dL during the first 24 hours of ICU admission. There were multiple exclusion criteria, including patients with Type I diabetes, documented hypoglycemia on ICU admission (glucose <40), or diabetic ketoacidosis.

Enrolled patients were randomized to IIT or conventional insulin therapy (CIT). A multidisciplinary team designed the protocols to maintain glucose levels of 80 to 110 mg/dL and 180 to 200 mg/dL in the IIT and the CIT groups, respectively. The primary endpoint measured was ICU mortality.

The study did not produce a statistically significant difference in ICU mortality (13.5% for IIT vs. 17.1% for CIT; P=0.30). The adjusted hypoglycemia rate was 6.8 per 100 treatment days with IIT and 0.4 per 100 treatment days with CIT (P<0.0001). Patients with hypoglycemia had higher ICU mortality (23.8% vs. 13.7%, P=0.02).

In the measurement of secondary endpoints, there was a trend toward lower episodes of severe sepsis and septic shock in the IIT group (20.7% in IIT vs. 27.2% in CIT, P=0.08). However, this result was not statistically significant.

Bottom line: This well-designed study failed to show a survival benefit with IIT use in the critical-care setting. Given the findings of this and several other recent studies, one should question whether IIT should be prescribed as the standard of care in all critically-ill patients.

Citation: Arabi Y, Dabbagh O, Tamim H, et al. Intensive versus conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients. Crit Care Med. 2008;36(12):3190-3197.

Preoperative and Intraoperative Predictors of Cardiac Adverse Events

Clinical question: What are the incidence and risk factors for perioperative cardiac adverse events after noncardiac surgery?

Background: In the past few decades, the incidence of cardiac adverse events (CAEs) for a general surgery population has remained largely unchanged (approximately 1%). This is in spite of multiple studies evaluating predictive models and attempts at preventive treatment, including preoperative coronary revascularization and perioperative beta blockers.

Study design: Prospective observational study.

Setting: Single, large, tertiary-care university hospital.

Synopsis: A total of 7,740 cases were reviewed in this study, which consisted of general surgery (4,937), vascular surgery (1,846), and urological surgery (957). A trained nurse followed up for perioperative CAEs as many as 30 days after the operation via medical chart review, phone calls, and letters. CAEs were defined as: Q-wave myocardial infarction (MI), non-ST elevation MI, cardiac arrest, or new cardiac dysrhythmia. A total of 83 CAEs (1.1% of patients) had cardiac arrest, with cardiac dysrhythmia being most common.

A total of seven preoperative risk factors were identified as independent predictors for CAEs: age 68, BMI 30, emergent surgery, prior coronary intervention or cardiac surgery, active congestive heart failure, cerebrovascular disease, and hypertension. In addition, two intraoperative risk factors were identified: intraoperative transfusion of packed red blood cells and operative duration of 3.8 hours. (The P value was 0.05 for all independent predictors.)

A further evaluation of intraoperative parameters of high-risk patients experiencing a CAE showed that these patients were more likely to have an episode of mean arterial pressure (MAP) <50 mmHg, an episode of 40% decrease in MAP, and an episode of tachycardia (heart rate >100).

Bottom line: A combination of preoperative predictors and intraoperative elements can help improve risk assessment for perioperative CAEs after noncardiac surgery.

Citation: Kheterpal S, O’Reilly M, Englesbe M, et al. Preoperative and intraoperative predictors of cardiac adverse events after general, vascular, and urological surgery. Anesthesiology. 2009;110(1):58-66.

Early Feeding in the ICU Does Not Affect Hospital Mortality

Clinical question: Will implementing evidence-based feeding guidelines improve feeding practices and reduce mortality in ICU patients?

Background: There is evidence suggesting that providing nutritional support to ICU patients within 24 hours of admission may decrease mortality. It is widely understood that patient care varies between ICUs, and there exist no uniform, evidence-based guidelines for nutritional support. Many patients remain unfed after 48 hours.

Study design: Cluster, randomized-controlled trial.

Setting: ICUs in 27 community and tertiary-care hospitals in Australia and New Zealand.

Synopsis: Hospitals were randomized to intervention or control groups. Dietitian and intensivist co-investigators from intervention ICUs developed guidelines using the Clinical Practice Guideline Development Cycle. Control ICUs were requested to make no new ICU nutritional management changes. The study enrolled 1,118 eligible patients and included adults expected to stay longer than two days. Excluded were patients taking oral diets, patients receiving palliative care or with suspected brain death, and patients sent from other facilities.

Guidelines were implemented using several methods—educational outreach visits, one-on-one conversations, active reminders, passive reminders, and educational in-services. The guidelines were successful in evoking significant practice changes in all of the intervention ICUs. Significantly more patients received nutritional support during their ICU stays in guideline ICUs, and patients in these ICUs were fed significantly earlier. There were, however, no significant differences between guideline and control ICUs with regard to hospital discharge mortality (28.9% vs. 27.4%; 95% CI; -6.3% to 12.0%; P=0.75). The groups also showed no statistical difference in hospital or ICU length of stay.

Bottom line: Significantly more patients in the guideline ICUs were fed within 24 hours, but this did not translate into improvements in mortality or other clinical outcomes.

Citation: Doig G, Simpson F, Finfer S, et al. Effect of evidence-based feeding guidelines on mortality of critically ill adults: a cluster randomized controlled trial. JAMA. 2008;300(23):2731-2741.

Low-Dose Aspirin Doesn’t Reduce Cardiovascular Events in Type 2 Diabetes Patients

Clinical question: Is low-dose aspirin effective for the primary prevention of atherosclerotic events in patients with Type 2 diabetes?

Background: Diabetes is a significant risk factor for cardiovascular events. Several prior studies have shown that aspirin therapy is effective as a secondary prevention strategy for cardiovascular events. The American Diabetes Association also recommends use of aspirin as a primary prevention strategy. Clinical trial data is currently insufficient in this area.

Study design: Prospective, randomized, open-label, controlled trial with blinded endpoint assessment.

Setting: 163 institutions in Japan.

Synopsis: The study enrolled 2,539 diabetic patients between 30 and 85 years old—mean age was 65—and included patients without EKG changes or a significant history or ongoing treatment of atherosclerotic disease. Patients were randomly assigned into an aspirin group (81 mg or 100 mg once daily) or a nonaspirin group. Patients had a median follow up of 4.37 years.

The primary endpoint was any atherosclerotic event, ranging from sudden death to ischemic heart disease or stroke. The incidence of atherosclerotic events was not statistically different in the aspirin group (68 events, 5.4%) than in the nonaspirin group (86 events, 6.7%) (HR, 0.80; 95% CI; 0.58-1.10; log-rank test, P=0.16). However, there was a suggested benefit of primary prevention in the subgroup aged 65 years or older. In addition, the combined endpoint of fatal coronary and cerebrovascular events occurred in one patient in the aspirin group and 10 patients in the nonaspirin group (HR, 0.10; 95 % CI, 0.01-0.79; P=.0037). This study is limited by the low incidence of atherosclerotic disease in Japan.

Bottom line: Low-dose aspirin used in patients with Type 2 diabetes does not significantly demonstrate primary prevention of cardiovascular events.

Citation: Ogawa H, Nakayama M, Morimoto T, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300(18):2134-2141. TH

In This Edition

• Generic vs. brand-name drugs.
• Rapid-response teams and mortality.
• A new prediction rule for mortality in acute pancreatitis.
• Viral causes of community-acquired pneumonia.
• Intensive insulin therapy in the ICU.
• New preoperative and intraoperative risk factors.
• Timing of ICU feedings and mortality.
• Aspirin as primary prevention in diabetics.

Generic, Brand-Name Drugs Used for Cardiovascular Disease Are Clinically Equivalent

Clinical question: Is there a clinical risk when substituting generic drugs for brand-name drugs in the treatment of cardiovascular disease?

Background: Spending on healthcare in the U.S. has reached critical levels. Increasing prescription drug costs make up a large portion of healthcare expenditures. The high cost of medicines directly affect adherence to treatment regimens and contribute to poor health outcomes. Cardiovascular drugs make up the largest portion of outpatient prescription drug spending.

Study design: Systematic review of relevant articles with a meta-analysis performed to determine an aggregate effect size.

Setting: Multiple locations and varied patient populations.

Synopsis: A total of 47 articles were included in the review, of which 38 were randomized controlled trials (RCTs). The studies measured both clinical efficacy and safety end points. More than half the articles were published prior to 2000. Clinical equivalence was noted in all seven beta-blocker RCTs; 10 of 11 diuretic RCTs; five of seven calcium-channel-blocker RCTs; all three antiplatelet-agent RCTs (clopidogrel, enteric-coated aspirin); two statin RCTs; one ACE-inhibitor RCT; and one alpha-blocker RCT. For drugs with a narrow therapeutic index, clinical equivalence was noted in all five warfarin RCTs and a single Class 1 anti-arrhythmic-agent RCT.

The aggregate effect size was -0.03 (95% CI, -0.15 to 0.08), which indicates nearly complete overlap of the generic and brand-name distributions. The data show no evidence of superiority of brand-name to generic drugs in clinical outcomes measured in the various studies.

In a separate review of editorials addressing generic substitution for cardiovascular drugs, 53% expressed a negative view of generic-drug substitution.

Bottom line: There is clinical equivalency between generic and brand-name drugs used in the treatment of cardiovascular disease. Despite this conclusion, a substantial number of editorials advise against generic substitution, which affects both patient and physician drug preferences.

Citation: Kesselheim A, Misono A, Lee J, et al. Clinical equivalence of generic and brand-name drugs used in cardiovascular disease: a systematic review and meta-analysis. JAMA. 2008; 300(21):2514-2526.

PEDIATRIC LITERATURE

Oral Prednisolone Does Not Shorten Hospitalization in Preschool-Age Children with Acute Virus-Induced Wheezing

Clinical question: Does oral prednisolone shorten duration of hospitalization in preschool-age children with acute virus-induced wheezing?

Background: Wheezing illnesses in young children are commonly associated with viral infections and may resolve with age without further stigmata of atopic asthma. Although systemic corticosteroids are commonly recommended for this population, evidence of their effectiveness is limited.

Study design: Randomized, double-blind, placebo-controlled trial.

Setting: Three hospitals in the United Kingdom.

Synopsis: Children between 10 and 60 months that presented to a hospital with a physician-diagnosed attack of wheezing preceded by a viral infection were randomized to receive oral prednisolone or a placebo. There was no significant difference between the groups in the time to hospital discharge. There also was no difference in the prespecified subgroup analysis of children at high risk for atopic asthma.

The median time between presentation and “fit for discharge” was relatively low in this sample—12 hours in the placebo group and 10.1 hours in the prednisolone group. Nearly half the patients were discharged within the first several hours after presentation, and not all patients were admitted to a pediatric ward. A short-stay observation ward within the ED was an option. Thus, the results may be most applicable to patients with mild to moderate disease, some of which may not be admitted to a traditional inpatient unit.

Bottom line: Systemic corticosteroids do not dramatically shorten hospital and ED stays in preschool-aged children with mild to moderate virus-induced wheezing.

Citation: Panickar J, Lakhanpaul M, Lambert P, et al. Oral prednisolone for preschool children with acute virus-induced wheezing. N Engl J Med. 2009;360(4):329-338.

Reviewed by pediatric editor Mark Shen, MD, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

RRT Implement-ation Doesn’t Affect Hospitalwide Code Rates or Mortality

Clinical question: Does the use of a rapid-response team (RRT) affect hospitalwide code rates and mortality?

Background: In the 100,000 Lives campaign, the Institute for Healthcare Improvement recommended that hospitals implement RRTs to help reduce preventable, in-hospital deaths. Studies have demonstrated that rates of non-ICU codes decrease after RRT implementation. It is unclear if this translates to changes in mortality rates.

Study design: Prospective cohort study of adult inpatients.

Setting: Saint Luke’s Hospital, a 404-bed tertiary-care academic hospital in Kansas City, Mo.

Synopsis: The hospital documented a total of 376 RRT activations. After RRT implementation, mean hospitalwide code rates decreased to 7.5 per 1,000 admissions from 11.2 per 1,000 admissions. This was not associated with a statistically significant reduction in hospitalwide code rates (adjusted odds ratio 0.76; 95% CI; 0.57-1.01; P=0.06). Secondary analyses noted lower rates of non-ICU codes (0.59; 95% CI, 0.40-0.89) compared with ICU codes (0.95; 95% CI; 0.64-1.43; P=0.03 for interaction). Finally, the RRT implementation was not associated with lower hospital-wide mortality (0.95; 95% CI; 0.81-1.11; P=0.52).

Secondary analyses also revealed few instances of RRT undertreatment or underutilization that may have affected the mortality numbers.

A limitation of this study is that it was slightly underpowered (78%) to detect a significant mortality difference. The findings also represent a single institution experience, and may not be generalized to other adult hospital settings or RRT programs.

Bottom line: Implementation of an RRT does not confer lower rates of hospital-wide code arrests or mortality.

Citation: Chan P, Khalid A, Longmore L, et al. Hospital-wide code rates and mortality before and after implementation of a rapid response team. JAMA. 2008;300(21):2506-2513.

Simple Scoring System Provides Timely Prediction of Mortality in Acute Pancreatitis

Clinical question: How can physicians predict mortality in acute pancreatitis?

Background: Historical predictors of mortality in acute pancreatitis require up to 48 hours of data, such as with the Ranson Criteria, or extensive amounts of data, such as with the APACHE II score. An easier tool is needed to predict which patients are at higher risk of mortality.

Study design: Retrospective cohort.

Setting: Patients in the Cardinal Health clinical outcomes research database, which supports public reporting of hospital performance.

Synopsis: The authors identified patients with the principal diagnosis of pancreatitis from 2000-2001 and explored numerous diagnostic findings available within the first 24 hours. Ultimately, BUN >25, impaired mental status, presence of SIRS (systemic inflammatory response syndrome), age >60, and presence of a pleural effusion were found to be predictive of mortality. These diagnostic findings correspond to the mnemonic BISAP. The BISAP score was then validated in a second cohort that included patients from 2004-2005.

Each finding in the BISAP score was given one point. A score of less than 2 was present in approximately 60% of patients admitted with acute pancreatitis, and corresponded to a mortality of less than 1%. A score of 2 corresponded to a mortality of 2%. Higher scores were associated with steeply increasing mortality, with a score of 5 corresponding with greater than 20% mortality.

The BISAP score performed similarly to the APACHE II score, but the former is easier to calculate on the day of admission and has fewer parameters. A more challenging research step will be to demonstrate that using the BISAP score to determine treatment strategies can affect patient outcomes.

Bottom line: The easy-to-calculate BISAP score is a new method for predicting mortality in patients with acute pancreatitis. This tool should help hospitalists determine, on the day of admission, to what extent patients with acute pancreatitis need aggressive management, such as ICU admission and early involvement of specialists.

Citation: Wu B, Johannes R, Sun X, Tabak Y, Conwell D, Banks P. The early prediction of mortality in acute pancreatitis: a large population-based study. Gut. 2008;57(12): 1698-1703.

Nasal Swabs Identify Viral Causes in CAP Patients

Clinical question: How often is viral infection associated with community-acquired pneumonia (CAP) in adults?

Background: CAP is a clinically important disease that is associated with significant hospitalization and mortality. CAP treatment guidelines acknowledge respiratory viruses as an etiology for pneumonia, but few recommendations are made regarding management of these viral infections.

Study design: Prospective study.

Setting: Five hospitals in Edmonton, Alberta, from 2004-2006.

Synopsis: The authors enrolled 193 hospitalized adults, median age 71. Nucleic amplification tests (NATs) from nasopharyngeal swab specimens were tested for human metapneumovirus, respiratory syncytial virus, rhinovirus, parainfluenza virus 1-4, coronaviruses, and adenovirus.

Fifteen percent of these patients had a nasal swab positive for a viral infection. Interestingly, 4% of patients had both a positive viral nasal swab and positive bacterial cultures. Compared with bacterial infection, patients with viral infection tended to be older (76 vs. 64 years, P=0.01), have limited ambulation (66% vs. 32%, P=0.006), and have a history of cardiac disease (66% vs. 32%, P=0.02). Patients with bacterial pneumonia showed a statistically significant trend toward having chest pain, an abnormal white blood count, and a lobar infiltrate on chest X-ray.

Further investigations might look at how nasal swab data could be used to improve infection control within the hospital for patients found to have easily transmissible viruses. Further research could explore the feasibility of avoiding antibiotic use in patients found to have viral pneumonia, assuming bacterial co-infection is reliably excluded.

Bottom line: Nasal swabs using NAT technology could play a significant role in identifying pathogens in CAP patients. How this technology should affect clinical decision-making and how it might improve outcomes remains unknown.

Citation: Johnstone J, Majumdar S, Fox J, Marrie T. Viral infection in adults hospitalized with community-acquired pneumonia: prevalence, pathogens, and presentation. Chest. 2008;134(6):1141-1148.

Intensive Insulin Therapy Doesn’t Reduce ICU Mortality

Clinical question: Does the use of intensive insulin therapy decrease mortality in the intensive-care unit (ICU)?

Background: In 2001, Van den Berghe et al (N Engl J Med. 2001;345(19):1359-67) reported a reduction in morbidity and mortality with intensive insulin therapy (IIT) in surgical ICU patients. This study led to the adoption of IIT protocols in many hospitals. Since 2001, further studies have failed to reproduce the same dramatic benefit of IIT.

Study design: Randomized, controlled trial.

Setting: National Guard King Abdulaziz Medical City, a tertiary-care teaching hospital in Saudi Arabia.

Synopsis: Patients were included in this study if they were 18 years or older with serum glucose levels greater than 110 mg/dL during the first 24 hours of ICU admission. There were multiple exclusion criteria, including patients with Type I diabetes, documented hypoglycemia on ICU admission (glucose <40), or diabetic ketoacidosis.

Enrolled patients were randomized to IIT or conventional insulin therapy (CIT). A multidisciplinary team designed the protocols to maintain glucose levels of 80 to 110 mg/dL and 180 to 200 mg/dL in the IIT and the CIT groups, respectively. The primary endpoint measured was ICU mortality.

The study did not produce a statistically significant difference in ICU mortality (13.5% for IIT vs. 17.1% for CIT; P=0.30). The adjusted hypoglycemia rate was 6.8 per 100 treatment days with IIT and 0.4 per 100 treatment days with CIT (P<0.0001). Patients with hypoglycemia had higher ICU mortality (23.8% vs. 13.7%, P=0.02).

In the measurement of secondary endpoints, there was a trend toward lower episodes of severe sepsis and septic shock in the IIT group (20.7% in IIT vs. 27.2% in CIT, P=0.08). However, this result was not statistically significant.

Bottom line: This well-designed study failed to show a survival benefit with IIT use in the critical-care setting. Given the findings of this and several other recent studies, one should question whether IIT should be prescribed as the standard of care in all critically-ill patients.

Citation: Arabi Y, Dabbagh O, Tamim H, et al. Intensive versus conventional insulin therapy: a randomized controlled trial in medical and surgical critically ill patients. Crit Care Med. 2008;36(12):3190-3197.

Preoperative and Intraoperative Predictors of Cardiac Adverse Events

Clinical question: What are the incidence and risk factors for perioperative cardiac adverse events after noncardiac surgery?

Background: In the past few decades, the incidence of cardiac adverse events (CAEs) for a general surgery population has remained largely unchanged (approximately 1%). This is in spite of multiple studies evaluating predictive models and attempts at preventive treatment, including preoperative coronary revascularization and perioperative beta blockers.

Study design: Prospective observational study.

Setting: Single, large, tertiary-care university hospital.

Synopsis: A total of 7,740 cases were reviewed in this study, which consisted of general surgery (4,937), vascular surgery (1,846), and urological surgery (957). A trained nurse followed up for perioperative CAEs as many as 30 days after the operation via medical chart review, phone calls, and letters. CAEs were defined as: Q-wave myocardial infarction (MI), non-ST elevation MI, cardiac arrest, or new cardiac dysrhythmia. A total of 83 CAEs (1.1% of patients) had cardiac arrest, with cardiac dysrhythmia being most common.

A total of seven preoperative risk factors were identified as independent predictors for CAEs: age 68, BMI 30, emergent surgery, prior coronary intervention or cardiac surgery, active congestive heart failure, cerebrovascular disease, and hypertension. In addition, two intraoperative risk factors were identified: intraoperative transfusion of packed red blood cells and operative duration of 3.8 hours. (The P value was 0.05 for all independent predictors.)

A further evaluation of intraoperative parameters of high-risk patients experiencing a CAE showed that these patients were more likely to have an episode of mean arterial pressure (MAP) <50 mmHg, an episode of 40% decrease in MAP, and an episode of tachycardia (heart rate >100).

Bottom line: A combination of preoperative predictors and intraoperative elements can help improve risk assessment for perioperative CAEs after noncardiac surgery.

Citation: Kheterpal S, O’Reilly M, Englesbe M, et al. Preoperative and intraoperative predictors of cardiac adverse events after general, vascular, and urological surgery. Anesthesiology. 2009;110(1):58-66.

Early Feeding in the ICU Does Not Affect Hospital Mortality

Clinical question: Will implementing evidence-based feeding guidelines improve feeding practices and reduce mortality in ICU patients?

Background: There is evidence suggesting that providing nutritional support to ICU patients within 24 hours of admission may decrease mortality. It is widely understood that patient care varies between ICUs, and there exist no uniform, evidence-based guidelines for nutritional support. Many patients remain unfed after 48 hours.

Study design: Cluster, randomized-controlled trial.

Setting: ICUs in 27 community and tertiary-care hospitals in Australia and New Zealand.

Synopsis: Hospitals were randomized to intervention or control groups. Dietitian and intensivist co-investigators from intervention ICUs developed guidelines using the Clinical Practice Guideline Development Cycle. Control ICUs were requested to make no new ICU nutritional management changes. The study enrolled 1,118 eligible patients and included adults expected to stay longer than two days. Excluded were patients taking oral diets, patients receiving palliative care or with suspected brain death, and patients sent from other facilities.

Guidelines were implemented using several methods—educational outreach visits, one-on-one conversations, active reminders, passive reminders, and educational in-services. The guidelines were successful in evoking significant practice changes in all of the intervention ICUs. Significantly more patients received nutritional support during their ICU stays in guideline ICUs, and patients in these ICUs were fed significantly earlier. There were, however, no significant differences between guideline and control ICUs with regard to hospital discharge mortality (28.9% vs. 27.4%; 95% CI; -6.3% to 12.0%; P=0.75). The groups also showed no statistical difference in hospital or ICU length of stay.

Bottom line: Significantly more patients in the guideline ICUs were fed within 24 hours, but this did not translate into improvements in mortality or other clinical outcomes.

Citation: Doig G, Simpson F, Finfer S, et al. Effect of evidence-based feeding guidelines on mortality of critically ill adults: a cluster randomized controlled trial. JAMA. 2008;300(23):2731-2741.

Low-Dose Aspirin Doesn’t Reduce Cardiovascular Events in Type 2 Diabetes Patients

Clinical question: Is low-dose aspirin effective for the primary prevention of atherosclerotic events in patients with Type 2 diabetes?

Background: Diabetes is a significant risk factor for cardiovascular events. Several prior studies have shown that aspirin therapy is effective as a secondary prevention strategy for cardiovascular events. The American Diabetes Association also recommends use of aspirin as a primary prevention strategy. Clinical trial data is currently insufficient in this area.

Study design: Prospective, randomized, open-label, controlled trial with blinded endpoint assessment.

Setting: 163 institutions in Japan.

Synopsis: The study enrolled 2,539 diabetic patients between 30 and 85 years old—mean age was 65—and included patients without EKG changes or a significant history or ongoing treatment of atherosclerotic disease. Patients were randomly assigned into an aspirin group (81 mg or 100 mg once daily) or a nonaspirin group. Patients had a median follow up of 4.37 years.

The primary endpoint was any atherosclerotic event, ranging from sudden death to ischemic heart disease or stroke. The incidence of atherosclerotic events was not statistically different in the aspirin group (68 events, 5.4%) than in the nonaspirin group (86 events, 6.7%) (HR, 0.80; 95% CI; 0.58-1.10; log-rank test, P=0.16). However, there was a suggested benefit of primary prevention in the subgroup aged 65 years or older. In addition, the combined endpoint of fatal coronary and cerebrovascular events occurred in one patient in the aspirin group and 10 patients in the nonaspirin group (HR, 0.10; 95 % CI, 0.01-0.79; P=.0037). This study is limited by the low incidence of atherosclerotic disease in Japan.

Bottom line: Low-dose aspirin used in patients with Type 2 diabetes does not significantly demonstrate primary prevention of cardiovascular events.

Citation: Ogawa H, Nakayama M, Morimoto T, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300(18):2134-2141. TH

Literature at a Glance

A guide to this month’s studies.

• Survival of in-hospital cardiac arrest decreases during nights and weekends.
• C-reactive protein levels predict severity and complications in community-acquired pneumonia.
• Adherence to current guidelines improves outcome in treatment of prosthetic joint infection.
• Sodium phosphate bowel prep use is associated with a decline in GFR.
• Minimally interrupted cardiac resuscitation improves survival.
• Lower aPTT increases risk for future VTE.
• Warfarin combined with antiplatelet therapy increases hemorrhage rate.
• Creatinine rise during MI hospitalization is associated with long-term risk of death and ESRD.
• Communication improves patient adherence to beta-blockers after MI.

Does Time of Day Affect Survival of Cardiac Arrest Patients?

Background: In-hospital cardiac arrest is a major public health problem. Small studies have demonstrated survival after cardiac arrest is worse at night as compared with all other times. Multiple hypothesis are proffered for this decreased survival, including less effective detection and treatment of the warning signs of impending arrest during the night hours.

Study design: Prospective registry.

Setting: 507 hospitals participating through the National Registry of Cardiopulmonary Resuscitation.

Synopsis: 86,748 consecutive, inpatient cardiac arrests were reported from Jan. 1, 2000, through Feb. 1, 2007, including 58,593 cases during day/evening hours and 28,155 cases during night hours.

Rates of survival to discharge (14.7 % vs. 19.8%), survival at 24 hours (28.9% vs. 35.4%), and favorable neurological outcomes (11.0% vs. 15.2%) were substantially lower during the night compared with day/evening (all p values < 0.001). The first documented rhythm at night was more frequently asystole as opposed to ventricular fibrillation during the day/evening. There also was a higher survival rate with cardiac arrests during day/evening hours occurring on weekdays compared with weekends (odds ratio [OR] 1.15). There was no difference in survival rates between weekdays or weekends among cardiac arrests occurring during the night hours.

Bottom line: Survival rates for in-hospital cardiac arrest are lower during nights and weekends, which may relate to differential physician and hospital staffing patterns during these hours.

Citation: Peberdy MA, Ornato JP, Larkin GL et al. Survival from in-hospital cardiac arrest during nights and weekends. JAMA 2008;299:785-792.

Can CRP Identify Risk in CAP Patients?

Background: Small initial studies suggest an elevated C-reactive protein (CRP) is relatively nonspecific but may have a role in predicting disease severity in community-acquired pneumonia (CAP).

Study design: Prospective study.

Setting: Large academic center in the United Kingdom.

Synopsis: In this study of 570 patients over a two-year time period, all patients presenting to the hospital with a diagnosis of CAP and the absence of exclusion criteria were evaluated. CRP was measured on admission and repeated on day four of hospitalization.

Low CRP levels (less than 100 mg/L) were independently associated with a reduced risk of 30-day mortality (OR 0.18; p=0.03), need for invasive ventilation and/or inotropic support (OR 0.21; p=0.002), and complicated pneumonia (OR 0.05; p=0.003). In addition, the failure of CRP to fall by 50% or more at day four of hospitalization was associated with an increased risk of 30-day mortality (OR 24.5; p<0.0001), need for mechanical ventilation and/or inotropic support (OR 7.1; p<0.0001), and complicated pneumonia (OR 15.4; p<0.0001).

Patients with chronic lung disease, immunosuppression, active malignancy or hospital-acquired pneumonia were excluded from the study and the conclusions cannot be extrapolated to these higher risk populations.

Bottom line: C-reactive protein is an independent marker of severity in CAP, and low levels can be used as an adjunct to clinical judgment to help identify patients who may be safely discharged from the hospital.

Citation: Chalmers JD, Singanayagam A, Hill AT. C-reactive protein is an independent predictor of severity in community-acquired pneumonia. Am J of Med. 2008;121:219-225.

Do Aggressive Surgical Intervention and Antimicrobial Treatment Improve Outcomes in Patients Suffering PJI?

Background: Prosthetic joint infection (PJI) is a severe complication, causing significant morbidity and healthcare costs. A recent article put forth up to date guidelines for the management of PJI. The purpose of this current study was to evaluate the external clinical validity of these treatment recommendations.

Study design: Retrospective cohort analysis.

Setting: 1,000-bed tertiary care center in Switzerland.

Synopsis: 68 consecutive episodes of PJI from January 1995 through December 2004 were reviewed. Patients with polymicrobial infections and with treatment failures prior to referral to this center were included.

The success rate for treatment of PJI was highest (67%) when the surgical strategy met current recommendations and antimicrobial treatment was adequate or partially adequate. The preferred surgical strategy was a two-stage exchange. The risk of treatment failure was higher for PJI treated with a surgical strategy other than that recommended (hazard ratio [HR] 2.34, p=0.01) and for PJIs treated with antibiotics not corresponding to recommendations (HR 3.45, p=0.002).

This study was limited by its small sample size and retrospective nature. Patients were not randomized, and cure rates for PJI were significantly lower than in prior published studies.

Bottom line: Treatment of PJI in higher risk populations in accordance with currently recommended surgical and antimicrobial treatment recommendations is associated with better outcomes and cure rates.

Citation: Betsch BY, Eggli S, Siebenrock KA, Tauber MG, Muhlemann K. Treatment of joint prosthesis infection in accordance with current recommendations improves outcome. Clin Infect Dis. 2008;46:1221-1226.

Do Oral Sodium Phosphate Drugs in Large Bowel Prep for Endoscopy Worsen Renal Function?

Background: Proper bowel preparation is essential for adequate colonoscopy and flexible sigmoidoscopy. Oral agents that are most commonly used for bowel preparation are sodium phosphate drugs, polyethylglycol and magnesium citrate. Sodium phosphate drugs are often preferred because of the decreased amount of fluid necessary for bowel preparation.

Study design: Retrospective study.

Setting: Scott and White Clinic, Temple, Texas.

Synopsis: Researchers compared 286 patients receiving an oral sodium phosphate solution for colonoscopy bowel preparation with 125 patients with similar comorbidities who received a non-sodium phosphate solution for bowel preparation. All patients had normal baseline creatinine levels.

The baseline, six-month, and one-year glomerular filtration rates (GFR) were compared between the two groups. GFR declined from 79 to 73 to 71 ml/min/1.73 m2 in the study group vs. 76 to 74 to 74 ml/min/1.73 m2 in the control group for the baseline, six-month, and one-year time periods, respectively.

This is an observational study and thus limited by its non-randomized nature. Sodium phosphate has a black-box warning in stage four and five chronic kidney disease because of its deleterious effect on renal function and the potential for inducing electrolyte abnormalities. Given the findings of this study and the availability of other effective preps alternative regimens should be considered for colonic preparation.

Bottom line: Oral sodium phosphate drugs may cause an acute and chronic decline in renal function as measured by the GFR.

Citation: Khurana A, McLean L, Atkinson S, Foulks C. The effect of oral sodium phosphate drug products on renal function in adults is undergoing bowel endoscopy. Arch Intern Med. 2008; 168(6):593-597.

Does MICR Improve Survival-to-hospital Discharge vs. Traditional CPR and ACLS in Cardiac Arrest Outside the Hospital?

Background: Minimally interrupted cardiac resuscitation (MICR), also known as cardiocerebral resuscitation, is hypothesized to increase survival compared with traditional CPR and advanced cardiac life support (ACLS) in out-of-hospital cardiac arrest. In MICR, 200 “pre-shock” chest compressions (100 compressions/minute) are initially given. The rhythm is then analyzed, with a single shock given if indicated.

Study design: Prospective study.

Setting: Two cities in Arizona.

Synopsis: Using data in the Save Heart in Arizona Registry and Education (SHARE) program, outcomes of 218 individuals with cardiac arrest receiving traditional CPR/ACLS were compared to 668 individuals after MICR training was instituted in the same two metropolitan cities. Survival-to-hospital discharge increased from 1.8% (4/218) before MICR training to 5.4% (36/668) after MICR training. The authors then compared the outcomes of 1,799 individuals with cardiac arrest resuscitated by emergency medical services (EMS) who did not receive training in MICR to 661 individuals who received MICR training over the same period. Survival-to-hospital discharge was 9.1% (60/601) in the patients cared from by EMS that received MICR training versus 3.8% (69/1730) in their non-MICR trained colleagues.

This study is limited by its observational nature and lack of randomization. Surprisingly, more individuals were intubated in the MICR groups. For hospitalists, the results could have a dramatic affect on cardiac arrest survival and lead to future changes to CPR/ACLS protocols.

Bottom line: MICR has a significant impact on survival in out-of-hospital cardiac arrest as compared with traditional CPR and ACLS.

Citation: Bobrow B, Clark L, Ewy G, et al. Minimally interrupted cardiac resuscitation by emergency medical services for out-of-hospital cardiac arrest. JAMA. 2008;299(10):1158-1165.

Does Lower aPTT Increase Future VTE Independent of Other Pro-coagulant Factors?

Background: Certain factors, such as obesity, D-dimer levels, and factor V Leiden gene mutations, increase the risk of future venous thromboembolism (VTE) events. This study sought to determine whether lower baseline levels of activated partial thromboplastin time aPTT also increase this risk.

Study design: Prospective multicenter cohort study.

Setting: Longitudinal Investigation of Thromboembolism Etiology research study (Atherosclerosis Risk in Communities portion) in four U.S. communities.

Synopsis: 13,880 individuals with baseline aPTT measurements were followed for 13 years for future VTE events. Of those, 260 developed a VTE of which 111 were described as idiopathic. Individuals in the lowest two quartiles of aPTT compared with the highest fourth quartile had a 2.4-fold and 1.9-fold increase in the risk of VTE, respectively. A lower aPTT further increased the risk of VTE when associated with obesity, elevated D-dimer level, and particularly factor V Leiden.

This study was limited by the relatively small number of VTE events. It also did not clarify whether aPTT measurements in high-risk groups such as those with positive family history of VTE were useful for predicting risk of future VTE. For hospitalists, patients with a lower initial aPTT may warrant more aggressive inpatient DVT prophylaxis.

Bottom line: aPTT below the median level increases the risk of future VTE events, especially if associated with obesity, elevated D-dimer levels, and/or factor V Leiden.

Citation: Zakai NA, Ohira T, White R, Folsom A, Cushman M. Activated partial thromboplastin time and risk of future venous thromboembolism. Am J of Med. 2008;121:231-238.

What Bleeding Outcomes are Associated with Using Warfarin with Antiplatelet Agents?

Background: Despite a high prevalence of combining antiplatelet and warfarin therapy, the timing, safety, and efficacy of this strategy remain controversial.

Study design: Retrospective cohort study.

Setting: Kaiser Permanente Colorado.

Synopsis: Using a pharmacy database, the authors identified 2,560 patients receiving warfarin alone (monotherapy cohort) and 1,623 patients receiving warfarin combined with antiplatelet agents (combination therapy cohort).

In the combination therapy cohort, aspirin was the most common antiplatelet agent (37%) followed by clopidogrel (13%) and dipyridamole (2%). During a six-month period, the combination therapy cohort had a 4.2% risk of hemorrhage and a 2.0% risk of major hemorrhage. Warfarin monotherapy was associated with a 2% risk of hemorrhage and 0.9% risk of major hemorrhage.

At baseline, the combination therapy patients were twice as likely to have diabetes or congestive heart failure and four times as likely to have coronary artery disease. In both cohorts, the most common reason for warfarin therapy was atrial fibrillation.

Since this was a retrospective investigation, hospitalists should be careful about drawing conclusions from this study alone, but are reminded to discuss risks carefully and engage in shared decision-making with patients when using combined warfarin and antiplatelet therapy.

Bottom line: Warfarin use in combination with antiplatelet therapy is associated with more than double the risk of bleeding compared with warfarin monotherapy.

Citation: Johnson SG, Rogers K, Delate T, Witt DM. Outcomes associated with combined antiplatelet and anticoagulant therapy. Chest. 2008;133:948-954.

Does a Rise in Serum Creatinine Affect Post-hospitalization Mortality and ESRD in Elderly MI Patients?

Background: Previous studies found an association between small changes in serum creatinine during hospitalization and short-term mortality. Data has shown patients experiencing a rise in creatinine at the time of CABG have increased in-hospital and long-term follow-up mortality.

Study design: Retrospective cohort study

Setting: Nationwide Medicare database of acute MI hospitalizations.

Synopsis: The authors reviewed outcomes data for 87,094 patients hospitalized for acute myocardial infarction (MI) from 1994-1995 with follow-up data through 2004. Patients were classified into groups with no rise in creatinine during hospitalization and those with rises of 0.1 mg/dL, 0.2 mg/dL, 0.3-0.5 mg/dL, and 0.6-3 mg/dL.

Compared with patients with no rise in creatinine, a rise of 0.1 mg/dL was associated with an adjusted hazard ratio of 1.45 for end-stage renal disease (ESRD) and 1.14 for post-hospitalization death during long-term follow-up. An incremental increase in poor outcomes was seen with more dramatic increases in creatinine, with patients in the group with a 0.6-3 mg/dL rise in creatinine having an adjusted hazard ratio of 3.26 for ESRD and 1.39 for post-hospitalization death. Among patients with a creatinine rise, the absolute risk of mortality (15% annually) was greater than that of ESRD (0.3% annually).

Hospitalists should note limitations of this retrospective study, including its restriction to hospitalized elderly patients.

Bottom line: Even small rises in serum creatinine during acute hospitalization for MI are associated with long-term risk for death and ESRD in elderly patients.

Citation: Newsome BB, Warnock DG, McClellan WM, et al. Long-term risk of mortality and end-stage renal disease among the elderly after small increases in serum creatinine level during hospitalization for acute myocardial infarction. Arch Intern Med. 2008;168(6):609-616.

Does Direct-to-patient Communication Improve Adherence to Beta-blocker Therapy Following an MI?

Background: The joint American Heart Association and American College of Cardiology guidelines have specific treatment recommendations regarding care of a patient post-myocardial infarction (MI). A key component of this regimen is beta-blocker therapy. Beta-blockers routinely are prescribed at hospital discharge following MI; however, patient adherence has been shown to decline substantially over time.

Study design: Cluster randomized control trial.

Setting: Four health maintenance organizations in Boston, Minneapolis, Atlanta, and Portland, Ore.

Synopsis: 836 post-MI patients were given a beta-blocker prescription upon discharge from the hospital. The intervention group received two mailed communications. The first was a personalized, simply worded letter from a health plan physician-administrator, followed two months later by a similar letter with a brochure. Mailers were low cost and easily replicable; they addressed the importance of these medications, the risks of non-adherence, and adverse effects.

The primary outcome measure was beta-blocker adherence. Medication adherence was analyzed as a continuous measure and as a monthly proportion of days covered (PDC) of 80% or greater. Across all months of follow-up, a mean of 64.8% of intervention patients had a PDC of more than 80% compared with 58.5% of control group patients (number needed to treat=16). The intervention group was 17% more likely to have a PDC of 80% or greater over the entire post-intervention period.

These interventions were studied in a prepaid integrated care delivery system—limiting generalization to other insurance types. Nevertheless, finding ways to improve patient compliance and decrease recurrent cardiac events is liking to result in cost saving to any healthcare plan.

Bottom line: A low-cost direct-to-patient communication effort can have a positive effect on beta-blocker adherence following MI.

Citation: Smith DH, Kramer JM, Perrin N, et al. A randomized trial of direct-to-patient communication to enhance adherence to beta-blocker therapy following myocardial infarction. Arch Intern Med. 2008;168(5):477-483. TH

Literature at a Glance

A guide to this month’s studies.

• Survival of in-hospital cardiac arrest decreases during nights and weekends.
• C-reactive protein levels predict severity and complications in community-acquired pneumonia.
• Adherence to current guidelines improves outcome in treatment of prosthetic joint infection.
• Sodium phosphate bowel prep use is associated with a decline in GFR.
• Minimally interrupted cardiac resuscitation improves survival.
• Lower aPTT increases risk for future VTE.
• Warfarin combined with antiplatelet therapy increases hemorrhage rate.
• Creatinine rise during MI hospitalization is associated with long-term risk of death and ESRD.
• Communication improves patient adherence to beta-blockers after MI.

Does Time of Day Affect Survival of Cardiac Arrest Patients?

Background: In-hospital cardiac arrest is a major public health problem. Small studies have demonstrated survival after cardiac arrest is worse at night as compared with all other times. Multiple hypothesis are proffered for this decreased survival, including less effective detection and treatment of the warning signs of impending arrest during the night hours.

Study design: Prospective registry.

Setting: 507 hospitals participating through the National Registry of Cardiopulmonary Resuscitation.

Synopsis: 86,748 consecutive, inpatient cardiac arrests were reported from Jan. 1, 2000, through Feb. 1, 2007, including 58,593 cases during day/evening hours and 28,155 cases during night hours.

Rates of survival to discharge (14.7 % vs. 19.8%), survival at 24 hours (28.9% vs. 35.4%), and favorable neurological outcomes (11.0% vs. 15.2%) were substantially lower during the night compared with day/evening (all p values < 0.001). The first documented rhythm at night was more frequently asystole as opposed to ventricular fibrillation during the day/evening. There also was a higher survival rate with cardiac arrests during day/evening hours occurring on weekdays compared with weekends (odds ratio [OR] 1.15). There was no difference in survival rates between weekdays or weekends among cardiac arrests occurring during the night hours.

Bottom line: Survival rates for in-hospital cardiac arrest are lower during nights and weekends, which may relate to differential physician and hospital staffing patterns during these hours.

Citation: Peberdy MA, Ornato JP, Larkin GL et al. Survival from in-hospital cardiac arrest during nights and weekends. JAMA 2008;299:785-792.

Can CRP Identify Risk in CAP Patients?

Background: Small initial studies suggest an elevated C-reactive protein (CRP) is relatively nonspecific but may have a role in predicting disease severity in community-acquired pneumonia (CAP).

Study design: Prospective study.

Setting: Large academic center in the United Kingdom.

Synopsis: In this study of 570 patients over a two-year time period, all patients presenting to the hospital with a diagnosis of CAP and the absence of exclusion criteria were evaluated. CRP was measured on admission and repeated on day four of hospitalization.

Low CRP levels (less than 100 mg/L) were independently associated with a reduced risk of 30-day mortality (OR 0.18; p=0.03), need for invasive ventilation and/or inotropic support (OR 0.21; p=0.002), and complicated pneumonia (OR 0.05; p=0.003). In addition, the failure of CRP to fall by 50% or more at day four of hospitalization was associated with an increased risk of 30-day mortality (OR 24.5; p<0.0001), need for mechanical ventilation and/or inotropic support (OR 7.1; p<0.0001), and complicated pneumonia (OR 15.4; p<0.0001).

Patients with chronic lung disease, immunosuppression, active malignancy or hospital-acquired pneumonia were excluded from the study and the conclusions cannot be extrapolated to these higher risk populations.

Bottom line: C-reactive protein is an independent marker of severity in CAP, and low levels can be used as an adjunct to clinical judgment to help identify patients who may be safely discharged from the hospital.

Citation: Chalmers JD, Singanayagam A, Hill AT. C-reactive protein is an independent predictor of severity in community-acquired pneumonia. Am J of Med. 2008;121:219-225.

Do Aggressive Surgical Intervention and Antimicrobial Treatment Improve Outcomes in Patients Suffering PJI?

Background: Prosthetic joint infection (PJI) is a severe complication, causing significant morbidity and healthcare costs. A recent article put forth up to date guidelines for the management of PJI. The purpose of this current study was to evaluate the external clinical validity of these treatment recommendations.

Study design: Retrospective cohort analysis.

Setting: 1,000-bed tertiary care center in Switzerland.

Synopsis: 68 consecutive episodes of PJI from January 1995 through December 2004 were reviewed. Patients with polymicrobial infections and with treatment failures prior to referral to this center were included.

The success rate for treatment of PJI was highest (67%) when the surgical strategy met current recommendations and antimicrobial treatment was adequate or partially adequate. The preferred surgical strategy was a two-stage exchange. The risk of treatment failure was higher for PJI treated with a surgical strategy other than that recommended (hazard ratio [HR] 2.34, p=0.01) and for PJIs treated with antibiotics not corresponding to recommendations (HR 3.45, p=0.002).

This study was limited by its small sample size and retrospective nature. Patients were not randomized, and cure rates for PJI were significantly lower than in prior published studies.

Bottom line: Treatment of PJI in higher risk populations in accordance with currently recommended surgical and antimicrobial treatment recommendations is associated with better outcomes and cure rates.

Citation: Betsch BY, Eggli S, Siebenrock KA, Tauber MG, Muhlemann K. Treatment of joint prosthesis infection in accordance with current recommendations improves outcome. Clin Infect Dis. 2008;46:1221-1226.

Do Oral Sodium Phosphate Drugs in Large Bowel Prep for Endoscopy Worsen Renal Function?

Background: Proper bowel preparation is essential for adequate colonoscopy and flexible sigmoidoscopy. Oral agents that are most commonly used for bowel preparation are sodium phosphate drugs, polyethylglycol and magnesium citrate. Sodium phosphate drugs are often preferred because of the decreased amount of fluid necessary for bowel preparation.

Study design: Retrospective study.

Setting: Scott and White Clinic, Temple, Texas.

Synopsis: Researchers compared 286 patients receiving an oral sodium phosphate solution for colonoscopy bowel preparation with 125 patients with similar comorbidities who received a non-sodium phosphate solution for bowel preparation. All patients had normal baseline creatinine levels.

The baseline, six-month, and one-year glomerular filtration rates (GFR) were compared between the two groups. GFR declined from 79 to 73 to 71 ml/min/1.73 m2 in the study group vs. 76 to 74 to 74 ml/min/1.73 m2 in the control group for the baseline, six-month, and one-year time periods, respectively.

This is an observational study and thus limited by its non-randomized nature. Sodium phosphate has a black-box warning in stage four and five chronic kidney disease because of its deleterious effect on renal function and the potential for inducing electrolyte abnormalities. Given the findings of this study and the availability of other effective preps alternative regimens should be considered for colonic preparation.

Bottom line: Oral sodium phosphate drugs may cause an acute and chronic decline in renal function as measured by the GFR.

Citation: Khurana A, McLean L, Atkinson S, Foulks C. The effect of oral sodium phosphate drug products on renal function in adults is undergoing bowel endoscopy. Arch Intern Med. 2008; 168(6):593-597.

Does MICR Improve Survival-to-hospital Discharge vs. Traditional CPR and ACLS in Cardiac Arrest Outside the Hospital?

Background: Minimally interrupted cardiac resuscitation (MICR), also known as cardiocerebral resuscitation, is hypothesized to increase survival compared with traditional CPR and advanced cardiac life support (ACLS) in out-of-hospital cardiac arrest. In MICR, 200 “pre-shock” chest compressions (100 compressions/minute) are initially given. The rhythm is then analyzed, with a single shock given if indicated.

Study design: Prospective study.

Setting: Two cities in Arizona.

Synopsis: Using data in the Save Heart in Arizona Registry and Education (SHARE) program, outcomes of 218 individuals with cardiac arrest receiving traditional CPR/ACLS were compared to 668 individuals after MICR training was instituted in the same two metropolitan cities. Survival-to-hospital discharge increased from 1.8% (4/218) before MICR training to 5.4% (36/668) after MICR training. The authors then compared the outcomes of 1,799 individuals with cardiac arrest resuscitated by emergency medical services (EMS) who did not receive training in MICR to 661 individuals who received MICR training over the same period. Survival-to-hospital discharge was 9.1% (60/601) in the patients cared from by EMS that received MICR training versus 3.8% (69/1730) in their non-MICR trained colleagues.

This study is limited by its observational nature and lack of randomization. Surprisingly, more individuals were intubated in the MICR groups. For hospitalists, the results could have a dramatic affect on cardiac arrest survival and lead to future changes to CPR/ACLS protocols.

Bottom line: MICR has a significant impact on survival in out-of-hospital cardiac arrest as compared with traditional CPR and ACLS.

Citation: Bobrow B, Clark L, Ewy G, et al. Minimally interrupted cardiac resuscitation by emergency medical services for out-of-hospital cardiac arrest. JAMA. 2008;299(10):1158-1165.

Does Lower aPTT Increase Future VTE Independent of Other Pro-coagulant Factors?

Background: Certain factors, such as obesity, D-dimer levels, and factor V Leiden gene mutations, increase the risk of future venous thromboembolism (VTE) events. This study sought to determine whether lower baseline levels of activated partial thromboplastin time aPTT also increase this risk.

Study design: Prospective multicenter cohort study.

Setting: Longitudinal Investigation of Thromboembolism Etiology research study (Atherosclerosis Risk in Communities portion) in four U.S. communities.

Synopsis: 13,880 individuals with baseline aPTT measurements were followed for 13 years for future VTE events. Of those, 260 developed a VTE of which 111 were described as idiopathic. Individuals in the lowest two quartiles of aPTT compared with the highest fourth quartile had a 2.4-fold and 1.9-fold increase in the risk of VTE, respectively. A lower aPTT further increased the risk of VTE when associated with obesity, elevated D-dimer level, and particularly factor V Leiden.

This study was limited by the relatively small number of VTE events. It also did not clarify whether aPTT measurements in high-risk groups such as those with positive family history of VTE were useful for predicting risk of future VTE. For hospitalists, patients with a lower initial aPTT may warrant more aggressive inpatient DVT prophylaxis.

Bottom line: aPTT below the median level increases the risk of future VTE events, especially if associated with obesity, elevated D-dimer levels, and/or factor V Leiden.

Citation: Zakai NA, Ohira T, White R, Folsom A, Cushman M. Activated partial thromboplastin time and risk of future venous thromboembolism. Am J of Med. 2008;121:231-238.

What Bleeding Outcomes are Associated with Using Warfarin with Antiplatelet Agents?

Background: Despite a high prevalence of combining antiplatelet and warfarin therapy, the timing, safety, and efficacy of this strategy remain controversial.

Study design: Retrospective cohort study.

Setting: Kaiser Permanente Colorado.

Synopsis: Using a pharmacy database, the authors identified 2,560 patients receiving warfarin alone (monotherapy cohort) and 1,623 patients receiving warfarin combined with antiplatelet agents (combination therapy cohort).

In the combination therapy cohort, aspirin was the most common antiplatelet agent (37%) followed by clopidogrel (13%) and dipyridamole (2%). During a six-month period, the combination therapy cohort had a 4.2% risk of hemorrhage and a 2.0% risk of major hemorrhage. Warfarin monotherapy was associated with a 2% risk of hemorrhage and 0.9% risk of major hemorrhage.

At baseline, the combination therapy patients were twice as likely to have diabetes or congestive heart failure and four times as likely to have coronary artery disease. In both cohorts, the most common reason for warfarin therapy was atrial fibrillation.

Since this was a retrospective investigation, hospitalists should be careful about drawing conclusions from this study alone, but are reminded to discuss risks carefully and engage in shared decision-making with patients when using combined warfarin and antiplatelet therapy.

Bottom line: Warfarin use in combination with antiplatelet therapy is associated with more than double the risk of bleeding compared with warfarin monotherapy.

Citation: Johnson SG, Rogers K, Delate T, Witt DM. Outcomes associated with combined antiplatelet and anticoagulant therapy. Chest. 2008;133:948-954.

Does a Rise in Serum Creatinine Affect Post-hospitalization Mortality and ESRD in Elderly MI Patients?

Background: Previous studies found an association between small changes in serum creatinine during hospitalization and short-term mortality. Data has shown patients experiencing a rise in creatinine at the time of CABG have increased in-hospital and long-term follow-up mortality.

Study design: Retrospective cohort study

Setting: Nationwide Medicare database of acute MI hospitalizations.

Synopsis: The authors reviewed outcomes data for 87,094 patients hospitalized for acute myocardial infarction (MI) from 1994-1995 with follow-up data through 2004. Patients were classified into groups with no rise in creatinine during hospitalization and those with rises of 0.1 mg/dL, 0.2 mg/dL, 0.3-0.5 mg/dL, and 0.6-3 mg/dL.

Compared with patients with no rise in creatinine, a rise of 0.1 mg/dL was associated with an adjusted hazard ratio of 1.45 for end-stage renal disease (ESRD) and 1.14 for post-hospitalization death during long-term follow-up. An incremental increase in poor outcomes was seen with more dramatic increases in creatinine, with patients in the group with a 0.6-3 mg/dL rise in creatinine having an adjusted hazard ratio of 3.26 for ESRD and 1.39 for post-hospitalization death. Among patients with a creatinine rise, the absolute risk of mortality (15% annually) was greater than that of ESRD (0.3% annually).

Hospitalists should note limitations of this retrospective study, including its restriction to hospitalized elderly patients.

Bottom line: Even small rises in serum creatinine during acute hospitalization for MI are associated with long-term risk for death and ESRD in elderly patients.

Citation: Newsome BB, Warnock DG, McClellan WM, et al. Long-term risk of mortality and end-stage renal disease among the elderly after small increases in serum creatinine level during hospitalization for acute myocardial infarction. Arch Intern Med. 2008;168(6):609-616.

Does Direct-to-patient Communication Improve Adherence to Beta-blocker Therapy Following an MI?

Background: The joint American Heart Association and American College of Cardiology guidelines have specific treatment recommendations regarding care of a patient post-myocardial infarction (MI). A key component of this regimen is beta-blocker therapy. Beta-blockers routinely are prescribed at hospital discharge following MI; however, patient adherence has been shown to decline substantially over time.

Study design: Cluster randomized control trial.

Setting: Four health maintenance organizations in Boston, Minneapolis, Atlanta, and Portland, Ore.

Synopsis: 836 post-MI patients were given a beta-blocker prescription upon discharge from the hospital. The intervention group received two mailed communications. The first was a personalized, simply worded letter from a health plan physician-administrator, followed two months later by a similar letter with a brochure. Mailers were low cost and easily replicable; they addressed the importance of these medications, the risks of non-adherence, and adverse effects.

The primary outcome measure was beta-blocker adherence. Medication adherence was analyzed as a continuous measure and as a monthly proportion of days covered (PDC) of 80% or greater. Across all months of follow-up, a mean of 64.8% of intervention patients had a PDC of more than 80% compared with 58.5% of control group patients (number needed to treat=16). The intervention group was 17% more likely to have a PDC of 80% or greater over the entire post-intervention period.

These interventions were studied in a prepaid integrated care delivery system—limiting generalization to other insurance types. Nevertheless, finding ways to improve patient compliance and decrease recurrent cardiac events is liking to result in cost saving to any healthcare plan.

Bottom line: A low-cost direct-to-patient communication effort can have a positive effect on beta-blocker adherence following MI.

Citation: Smith DH, Kramer JM, Perrin N, et al. A randomized trial of direct-to-patient communication to enhance adherence to beta-blocker therapy following myocardial infarction. Arch Intern Med. 2008;168(5):477-483. TH

Literature at a Glance

A guide to this month’s studies.

• Survival of in-hospital cardiac arrest decreases during nights and weekends.
• C-reactive protein levels predict severity and complications in community-acquired pneumonia.
• Adherence to current guidelines improves outcome in treatment of prosthetic joint infection.
• Sodium phosphate bowel prep use is associated with a decline in GFR.
• Minimally interrupted cardiac resuscitation improves survival.
• Lower aPTT increases risk for future VTE.
• Warfarin combined with antiplatelet therapy increases hemorrhage rate.
• Creatinine rise during MI hospitalization is associated with long-term risk of death and ESRD.
• Communication improves patient adherence to beta-blockers after MI.

Does Time of Day Affect Survival of Cardiac Arrest Patients?

Background: In-hospital cardiac arrest is a major public health problem. Small studies have demonstrated survival after cardiac arrest is worse at night as compared with all other times. Multiple hypothesis are proffered for this decreased survival, including less effective detection and treatment of the warning signs of impending arrest during the night hours.

Study design: Prospective registry.

Setting: 507 hospitals participating through the National Registry of Cardiopulmonary Resuscitation.

Synopsis: 86,748 consecutive, inpatient cardiac arrests were reported from Jan. 1, 2000, through Feb. 1, 2007, including 58,593 cases during day/evening hours and 28,155 cases during night hours.

Rates of survival to discharge (14.7 % vs. 19.8%), survival at 24 hours (28.9% vs. 35.4%), and favorable neurological outcomes (11.0% vs. 15.2%) were substantially lower during the night compared with day/evening (all p values < 0.001). The first documented rhythm at night was more frequently asystole as opposed to ventricular fibrillation during the day/evening. There also was a higher survival rate with cardiac arrests during day/evening hours occurring on weekdays compared with weekends (odds ratio [OR] 1.15). There was no difference in survival rates between weekdays or weekends among cardiac arrests occurring during the night hours.

Bottom line: Survival rates for in-hospital cardiac arrest are lower during nights and weekends, which may relate to differential physician and hospital staffing patterns during these hours.

Citation: Peberdy MA, Ornato JP, Larkin GL et al. Survival from in-hospital cardiac arrest during nights and weekends. JAMA 2008;299:785-792.

Can CRP Identify Risk in CAP Patients?

Background: Small initial studies suggest an elevated C-reactive protein (CRP) is relatively nonspecific but may have a role in predicting disease severity in community-acquired pneumonia (CAP).

Study design: Prospective study.

Setting: Large academic center in the United Kingdom.

Synopsis: In this study of 570 patients over a two-year time period, all patients presenting to the hospital with a diagnosis of CAP and the absence of exclusion criteria were evaluated. CRP was measured on admission and repeated on day four of hospitalization.

Low CRP levels (less than 100 mg/L) were independently associated with a reduced risk of 30-day mortality (OR 0.18; p=0.03), need for invasive ventilation and/or inotropic support (OR 0.21; p=0.002), and complicated pneumonia (OR 0.05; p=0.003). In addition, the failure of CRP to fall by 50% or more at day four of hospitalization was associated with an increased risk of 30-day mortality (OR 24.5; p<0.0001), need for mechanical ventilation and/or inotropic support (OR 7.1; p<0.0001), and complicated pneumonia (OR 15.4; p<0.0001).

Patients with chronic lung disease, immunosuppression, active malignancy or hospital-acquired pneumonia were excluded from the study and the conclusions cannot be extrapolated to these higher risk populations.

Bottom line: C-reactive protein is an independent marker of severity in CAP, and low levels can be used as an adjunct to clinical judgment to help identify patients who may be safely discharged from the hospital.

Citation: Chalmers JD, Singanayagam A, Hill AT. C-reactive protein is an independent predictor of severity in community-acquired pneumonia. Am J of Med. 2008;121:219-225.

Do Aggressive Surgical Intervention and Antimicrobial Treatment Improve Outcomes in Patients Suffering PJI?

Background: Prosthetic joint infection (PJI) is a severe complication, causing significant morbidity and healthcare costs. A recent article put forth up to date guidelines for the management of PJI. The purpose of this current study was to evaluate the external clinical validity of these treatment recommendations.

Study design: Retrospective cohort analysis.

Setting: 1,000-bed tertiary care center in Switzerland.

Synopsis: 68 consecutive episodes of PJI from January 1995 through December 2004 were reviewed. Patients with polymicrobial infections and with treatment failures prior to referral to this center were included.

The success rate for treatment of PJI was highest (67%) when the surgical strategy met current recommendations and antimicrobial treatment was adequate or partially adequate. The preferred surgical strategy was a two-stage exchange. The risk of treatment failure was higher for PJI treated with a surgical strategy other than that recommended (hazard ratio [HR] 2.34, p=0.01) and for PJIs treated with antibiotics not corresponding to recommendations (HR 3.45, p=0.002).

This study was limited by its small sample size and retrospective nature. Patients were not randomized, and cure rates for PJI were significantly lower than in prior published studies.

Bottom line: Treatment of PJI in higher risk populations in accordance with currently recommended surgical and antimicrobial treatment recommendations is associated with better outcomes and cure rates.

Citation: Betsch BY, Eggli S, Siebenrock KA, Tauber MG, Muhlemann K. Treatment of joint prosthesis infection in accordance with current recommendations improves outcome. Clin Infect Dis. 2008;46:1221-1226.

Do Oral Sodium Phosphate Drugs in Large Bowel Prep for Endoscopy Worsen Renal Function?

Background: Proper bowel preparation is essential for adequate colonoscopy and flexible sigmoidoscopy. Oral agents that are most commonly used for bowel preparation are sodium phosphate drugs, polyethylglycol and magnesium citrate. Sodium phosphate drugs are often preferred because of the decreased amount of fluid necessary for bowel preparation.

Study design: Retrospective study.

Setting: Scott and White Clinic, Temple, Texas.

Synopsis: Researchers compared 286 patients receiving an oral sodium phosphate solution for colonoscopy bowel preparation with 125 patients with similar comorbidities who received a non-sodium phosphate solution for bowel preparation. All patients had normal baseline creatinine levels.

The baseline, six-month, and one-year glomerular filtration rates (GFR) were compared between the two groups. GFR declined from 79 to 73 to 71 ml/min/1.73 m2 in the study group vs. 76 to 74 to 74 ml/min/1.73 m2 in the control group for the baseline, six-month, and one-year time periods, respectively.

This is an observational study and thus limited by its non-randomized nature. Sodium phosphate has a black-box warning in stage four and five chronic kidney disease because of its deleterious effect on renal function and the potential for inducing electrolyte abnormalities. Given the findings of this study and the availability of other effective preps alternative regimens should be considered for colonic preparation.

Bottom line: Oral sodium phosphate drugs may cause an acute and chronic decline in renal function as measured by the GFR.

Citation: Khurana A, McLean L, Atkinson S, Foulks C. The effect of oral sodium phosphate drug products on renal function in adults is undergoing bowel endoscopy. Arch Intern Med. 2008; 168(6):593-597.

Does MICR Improve Survival-to-hospital Discharge vs. Traditional CPR and ACLS in Cardiac Arrest Outside the Hospital?

Background: Minimally interrupted cardiac resuscitation (MICR), also known as cardiocerebral resuscitation, is hypothesized to increase survival compared with traditional CPR and advanced cardiac life support (ACLS) in out-of-hospital cardiac arrest. In MICR, 200 “pre-shock” chest compressions (100 compressions/minute) are initially given. The rhythm is then analyzed, with a single shock given if indicated.

Study design: Prospective study.

Setting: Two cities in Arizona.

Synopsis: Using data in the Save Heart in Arizona Registry and Education (SHARE) program, outcomes of 218 individuals with cardiac arrest receiving traditional CPR/ACLS were compared to 668 individuals after MICR training was instituted in the same two metropolitan cities. Survival-to-hospital discharge increased from 1.8% (4/218) before MICR training to 5.4% (36/668) after MICR training. The authors then compared the outcomes of 1,799 individuals with cardiac arrest resuscitated by emergency medical services (EMS) who did not receive training in MICR to 661 individuals who received MICR training over the same period. Survival-to-hospital discharge was 9.1% (60/601) in the patients cared from by EMS that received MICR training versus 3.8% (69/1730) in their non-MICR trained colleagues.

This study is limited by its observational nature and lack of randomization. Surprisingly, more individuals were intubated in the MICR groups. For hospitalists, the results could have a dramatic affect on cardiac arrest survival and lead to future changes to CPR/ACLS protocols.

Bottom line: MICR has a significant impact on survival in out-of-hospital cardiac arrest as compared with traditional CPR and ACLS.

Citation: Bobrow B, Clark L, Ewy G, et al. Minimally interrupted cardiac resuscitation by emergency medical services for out-of-hospital cardiac arrest. JAMA. 2008;299(10):1158-1165.

Does Lower aPTT Increase Future VTE Independent of Other Pro-coagulant Factors?

Background: Certain factors, such as obesity, D-dimer levels, and factor V Leiden gene mutations, increase the risk of future venous thromboembolism (VTE) events. This study sought to determine whether lower baseline levels of activated partial thromboplastin time aPTT also increase this risk.

Study design: Prospective multicenter cohort study.

Setting: Longitudinal Investigation of Thromboembolism Etiology research study (Atherosclerosis Risk in Communities portion) in four U.S. communities.

Synopsis: 13,880 individuals with baseline aPTT measurements were followed for 13 years for future VTE events. Of those, 260 developed a VTE of which 111 were described as idiopathic. Individuals in the lowest two quartiles of aPTT compared with the highest fourth quartile had a 2.4-fold and 1.9-fold increase in the risk of VTE, respectively. A lower aPTT further increased the risk of VTE when associated with obesity, elevated D-dimer level, and particularly factor V Leiden.

This study was limited by the relatively small number of VTE events. It also did not clarify whether aPTT measurements in high-risk groups such as those with positive family history of VTE were useful for predicting risk of future VTE. For hospitalists, patients with a lower initial aPTT may warrant more aggressive inpatient DVT prophylaxis.

Bottom line: aPTT below the median level increases the risk of future VTE events, especially if associated with obesity, elevated D-dimer levels, and/or factor V Leiden.

Citation: Zakai NA, Ohira T, White R, Folsom A, Cushman M. Activated partial thromboplastin time and risk of future venous thromboembolism. Am J of Med. 2008;121:231-238.

What Bleeding Outcomes are Associated with Using Warfarin with Antiplatelet Agents?

Background: Despite a high prevalence of combining antiplatelet and warfarin therapy, the timing, safety, and efficacy of this strategy remain controversial.

Study design: Retrospective cohort study.

Setting: Kaiser Permanente Colorado.

Synopsis: Using a pharmacy database, the authors identified 2,560 patients receiving warfarin alone (monotherapy cohort) and 1,623 patients receiving warfarin combined with antiplatelet agents (combination therapy cohort).

In the combination therapy cohort, aspirin was the most common antiplatelet agent (37%) followed by clopidogrel (13%) and dipyridamole (2%). During a six-month period, the combination therapy cohort had a 4.2% risk of hemorrhage and a 2.0% risk of major hemorrhage. Warfarin monotherapy was associated with a 2% risk of hemorrhage and 0.9% risk of major hemorrhage.

At baseline, the combination therapy patients were twice as likely to have diabetes or congestive heart failure and four times as likely to have coronary artery disease. In both cohorts, the most common reason for warfarin therapy was atrial fibrillation.

Since this was a retrospective investigation, hospitalists should be careful about drawing conclusions from this study alone, but are reminded to discuss risks carefully and engage in shared decision-making with patients when using combined warfarin and antiplatelet therapy.

Bottom line: Warfarin use in combination with antiplatelet therapy is associated with more than double the risk of bleeding compared with warfarin monotherapy.

Citation: Johnson SG, Rogers K, Delate T, Witt DM. Outcomes associated with combined antiplatelet and anticoagulant therapy. Chest. 2008;133:948-954.

Does a Rise in Serum Creatinine Affect Post-hospitalization Mortality and ESRD in Elderly MI Patients?

Background: Previous studies found an association between small changes in serum creatinine during hospitalization and short-term mortality. Data has shown patients experiencing a rise in creatinine at the time of CABG have increased in-hospital and long-term follow-up mortality.

Study design: Retrospective cohort study

Setting: Nationwide Medicare database of acute MI hospitalizations.

Synopsis: The authors reviewed outcomes data for 87,094 patients hospitalized for acute myocardial infarction (MI) from 1994-1995 with follow-up data through 2004. Patients were classified into groups with no rise in creatinine during hospitalization and those with rises of 0.1 mg/dL, 0.2 mg/dL, 0.3-0.5 mg/dL, and 0.6-3 mg/dL.

Compared with patients with no rise in creatinine, a rise of 0.1 mg/dL was associated with an adjusted hazard ratio of 1.45 for end-stage renal disease (ESRD) and 1.14 for post-hospitalization death during long-term follow-up. An incremental increase in poor outcomes was seen with more dramatic increases in creatinine, with patients in the group with a 0.6-3 mg/dL rise in creatinine having an adjusted hazard ratio of 3.26 for ESRD and 1.39 for post-hospitalization death. Among patients with a creatinine rise, the absolute risk of mortality (15% annually) was greater than that of ESRD (0.3% annually).

Hospitalists should note limitations of this retrospective study, including its restriction to hospitalized elderly patients.

Bottom line: Even small rises in serum creatinine during acute hospitalization for MI are associated with long-term risk for death and ESRD in elderly patients.

Citation: Newsome BB, Warnock DG, McClellan WM, et al. Long-term risk of mortality and end-stage renal disease among the elderly after small increases in serum creatinine level during hospitalization for acute myocardial infarction. Arch Intern Med. 2008;168(6):609-616.

Does Direct-to-patient Communication Improve Adherence to Beta-blocker Therapy Following an MI?

Background: The joint American Heart Association and American College of Cardiology guidelines have specific treatment recommendations regarding care of a patient post-myocardial infarction (MI). A key component of this regimen is beta-blocker therapy. Beta-blockers routinely are prescribed at hospital discharge following MI; however, patient adherence has been shown to decline substantially over time.

Study design: Cluster randomized control trial.

Setting: Four health maintenance organizations in Boston, Minneapolis, Atlanta, and Portland, Ore.

Synopsis: 836 post-MI patients were given a beta-blocker prescription upon discharge from the hospital. The intervention group received two mailed communications. The first was a personalized, simply worded letter from a health plan physician-administrator, followed two months later by a similar letter with a brochure. Mailers were low cost and easily replicable; they addressed the importance of these medications, the risks of non-adherence, and adverse effects.

The primary outcome measure was beta-blocker adherence. Medication adherence was analyzed as a continuous measure and as a monthly proportion of days covered (PDC) of 80% or greater. Across all months of follow-up, a mean of 64.8% of intervention patients had a PDC of more than 80% compared with 58.5% of control group patients (number needed to treat=16). The intervention group was 17% more likely to have a PDC of 80% or greater over the entire post-intervention period.

These interventions were studied in a prepaid integrated care delivery system—limiting generalization to other insurance types. Nevertheless, finding ways to improve patient compliance and decrease recurrent cardiac events is liking to result in cost saving to any healthcare plan.

Bottom line: A low-cost direct-to-patient communication effort can have a positive effect on beta-blocker adherence following MI.

Citation: Smith DH, Kramer JM, Perrin N, et al. A randomized trial of direct-to-patient communication to enhance adherence to beta-blocker therapy following myocardial infarction. Arch Intern Med. 2008;168(5):477-483. TH