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In the Literature
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