User login
ITL: Physician Reviews of HM-Relevant Research
Clinical question: Is the risk of recurrence of Clostridium difficile infection (CDI) increased by the use of “non-CDI” antimicrobial agents (inactive against C. diff) during or after CDI therapy?
Background: Recurrence of CDI is expected to increase with use of non-CDI antimicrobials. Previous studies have not distinguished between the timing of non-CDI agents during and after CDI treatment, nor examined the effect of frequency, duration, or type of non-CDI antibiotic therapy.
Study design: Retrospective cohort.
Setting: Academic Veterans Affairs medical center.
Synopsis: All patients with CDI over a three-year period were evaluated to determine the association between non-CDI antimicrobial during or within 30 days following CDI therapy and 90-day CDI recurrence. Of 246 patients, 57% received concurrent or subsequent non-CDI antimicrobials. CDI recurred in 40% of patients who received non-CDI antimicrobials and in 16% of those who did not (OR: 3.5, 95% CI: 1.9 to 6.5).
After multivariable adjustment (including age, duration of CDI treatment, comorbidity, hospital and ICU admission, and gastric acid suppression), those who received non-CDI antimicrobials during CDI therapy had no increased risk of recurrence. However, those who received any non-CDI antimicrobials after initial CDI treatment had an absolute recurrence rate of 48% with an adjusted OR of 3.02 (95% CI: 1.65 to 5.52). This increased risk of recurrence was unaffected by the number or duration of non-CDI antimicrobial prescriptions. Subgroup analysis by antimicrobial class revealed statistically significant associations only with beta-lactams and fluoroquinolones.
Bottom line: The risk of recurrence of CDI is tripled by exposure to non-CDI antimicrobials within 30 days after CDI treatment, irrespective of the number or duration of such exposures.
Citation: Drekonja DM, Amundson WH, DeCarolis DD, Kuskowski MA, Lederle FA, Johnson JR. Antimicrobial use and risk for recurrent Clostridium difficile infection. Am J Med. 2011;124:1081.e1-1081.e7.
Clinical question: Is the risk of recurrence of Clostridium difficile infection (CDI) increased by the use of “non-CDI” antimicrobial agents (inactive against C. diff) during or after CDI therapy?
Background: Recurrence of CDI is expected to increase with use of non-CDI antimicrobials. Previous studies have not distinguished between the timing of non-CDI agents during and after CDI treatment, nor examined the effect of frequency, duration, or type of non-CDI antibiotic therapy.
Study design: Retrospective cohort.
Setting: Academic Veterans Affairs medical center.
Synopsis: All patients with CDI over a three-year period were evaluated to determine the association between non-CDI antimicrobial during or within 30 days following CDI therapy and 90-day CDI recurrence. Of 246 patients, 57% received concurrent or subsequent non-CDI antimicrobials. CDI recurred in 40% of patients who received non-CDI antimicrobials and in 16% of those who did not (OR: 3.5, 95% CI: 1.9 to 6.5).
After multivariable adjustment (including age, duration of CDI treatment, comorbidity, hospital and ICU admission, and gastric acid suppression), those who received non-CDI antimicrobials during CDI therapy had no increased risk of recurrence. However, those who received any non-CDI antimicrobials after initial CDI treatment had an absolute recurrence rate of 48% with an adjusted OR of 3.02 (95% CI: 1.65 to 5.52). This increased risk of recurrence was unaffected by the number or duration of non-CDI antimicrobial prescriptions. Subgroup analysis by antimicrobial class revealed statistically significant associations only with beta-lactams and fluoroquinolones.
Bottom line: The risk of recurrence of CDI is tripled by exposure to non-CDI antimicrobials within 30 days after CDI treatment, irrespective of the number or duration of such exposures.
Citation: Drekonja DM, Amundson WH, DeCarolis DD, Kuskowski MA, Lederle FA, Johnson JR. Antimicrobial use and risk for recurrent Clostridium difficile infection. Am J Med. 2011;124:1081.e1-1081.e7.
Clinical question: Is the risk of recurrence of Clostridium difficile infection (CDI) increased by the use of “non-CDI” antimicrobial agents (inactive against C. diff) during or after CDI therapy?
Background: Recurrence of CDI is expected to increase with use of non-CDI antimicrobials. Previous studies have not distinguished between the timing of non-CDI agents during and after CDI treatment, nor examined the effect of frequency, duration, or type of non-CDI antibiotic therapy.
Study design: Retrospective cohort.
Setting: Academic Veterans Affairs medical center.
Synopsis: All patients with CDI over a three-year period were evaluated to determine the association between non-CDI antimicrobial during or within 30 days following CDI therapy and 90-day CDI recurrence. Of 246 patients, 57% received concurrent or subsequent non-CDI antimicrobials. CDI recurred in 40% of patients who received non-CDI antimicrobials and in 16% of those who did not (OR: 3.5, 95% CI: 1.9 to 6.5).
After multivariable adjustment (including age, duration of CDI treatment, comorbidity, hospital and ICU admission, and gastric acid suppression), those who received non-CDI antimicrobials during CDI therapy had no increased risk of recurrence. However, those who received any non-CDI antimicrobials after initial CDI treatment had an absolute recurrence rate of 48% with an adjusted OR of 3.02 (95% CI: 1.65 to 5.52). This increased risk of recurrence was unaffected by the number or duration of non-CDI antimicrobial prescriptions. Subgroup analysis by antimicrobial class revealed statistically significant associations only with beta-lactams and fluoroquinolones.
Bottom line: The risk of recurrence of CDI is tripled by exposure to non-CDI antimicrobials within 30 days after CDI treatment, irrespective of the number or duration of such exposures.
Citation: Drekonja DM, Amundson WH, DeCarolis DD, Kuskowski MA, Lederle FA, Johnson JR. Antimicrobial use and risk for recurrent Clostridium difficile infection. Am J Med. 2011;124:1081.e1-1081.e7.
ITL: Physician Reviews of HM-Relevant Research
Clinical question: Is it safe to perform esophagogastroduodenoscopy (EGD) in patients with upper gastrointestinal (GI) hemorrhage and low hematocrit?
Background: Patients admitted with GI hemorrhage are generally volume-resuscitated aggressively upon admission. After hemodynamic stability has been achieved, some would advocate delaying EGD until the hemoglobin and hematocrit are above 10 g/dL and 30%, respectively. This study attempted to determine whether EGD is safe in the setting of low hematocrit levels.
Study design: Prospective cohort.
Setting: Parkland Memorial Hospital, Dallas.
Synopsis: The 920 patients with upper GI bleeding were divided into two groups: a low (<30%) hematocrit group and a high (>30%) hematocrit group. They were analyzed for differences in rates of cardiovascular events, requirement for surgery, angiography, mortality, or ICU transfer. Overall event rates were extremely low, with no differences between the two groups.
Bottom line: Transfusing to a target hematocrit of >30% should not be a prerequisite for EGD in patients who present with upper GI bleeding.
Citation: Balderas V, Bhore R, Lara LF, Spesivtseva J, Rockey DC. The hematocrit level in upper gastrointestinal hemorrhage: safety of endoscopy and outcomes. Am J Med. 2011;124:970-976.
Clinical question: Is it safe to perform esophagogastroduodenoscopy (EGD) in patients with upper gastrointestinal (GI) hemorrhage and low hematocrit?
Background: Patients admitted with GI hemorrhage are generally volume-resuscitated aggressively upon admission. After hemodynamic stability has been achieved, some would advocate delaying EGD until the hemoglobin and hematocrit are above 10 g/dL and 30%, respectively. This study attempted to determine whether EGD is safe in the setting of low hematocrit levels.
Study design: Prospective cohort.
Setting: Parkland Memorial Hospital, Dallas.
Synopsis: The 920 patients with upper GI bleeding were divided into two groups: a low (<30%) hematocrit group and a high (>30%) hematocrit group. They were analyzed for differences in rates of cardiovascular events, requirement for surgery, angiography, mortality, or ICU transfer. Overall event rates were extremely low, with no differences between the two groups.
Bottom line: Transfusing to a target hematocrit of >30% should not be a prerequisite for EGD in patients who present with upper GI bleeding.
Citation: Balderas V, Bhore R, Lara LF, Spesivtseva J, Rockey DC. The hematocrit level in upper gastrointestinal hemorrhage: safety of endoscopy and outcomes. Am J Med. 2011;124:970-976.
Clinical question: Is it safe to perform esophagogastroduodenoscopy (EGD) in patients with upper gastrointestinal (GI) hemorrhage and low hematocrit?
Background: Patients admitted with GI hemorrhage are generally volume-resuscitated aggressively upon admission. After hemodynamic stability has been achieved, some would advocate delaying EGD until the hemoglobin and hematocrit are above 10 g/dL and 30%, respectively. This study attempted to determine whether EGD is safe in the setting of low hematocrit levels.
Study design: Prospective cohort.
Setting: Parkland Memorial Hospital, Dallas.
Synopsis: The 920 patients with upper GI bleeding were divided into two groups: a low (<30%) hematocrit group and a high (>30%) hematocrit group. They were analyzed for differences in rates of cardiovascular events, requirement for surgery, angiography, mortality, or ICU transfer. Overall event rates were extremely low, with no differences between the two groups.
Bottom line: Transfusing to a target hematocrit of >30% should not be a prerequisite for EGD in patients who present with upper GI bleeding.
Citation: Balderas V, Bhore R, Lara LF, Spesivtseva J, Rockey DC. The hematocrit level in upper gastrointestinal hemorrhage: safety of endoscopy and outcomes. Am J Med. 2011;124:970-976.
In the Literature: Physician Reviews of HM-Related Research
In This Edition
Literature At A Glance
A guide to this month’s studies
- IDSA/ATS guidelines for community-acquired pneumonia
- Improved asthma with IL-13 antibody
- Rivaroxaban vs. warfarin for stroke prevention in atrial fibrillation
- Apixaban vs. warfarin for stroke prevention in atrial fibrillation
- Ultrasonography more sensitive than chest radiograph for pneumothorax
- Current readmission risk models inadequate
- Optimal fluid volume for acute pancreatitis
- Low mortality in saddle pulmonary embolism
Triage Decisions for Patients with Severe Community-Acquired Pneumonia Should Be Based on IDSA/ATS Guidelines, Not Inflammatory Biomarkers
Clinical question: Can C-reactive protein levels (CRP), procalcitonin, TNF-alpha, and cytokine levels predict the need for intensive-care admission more accurately than IDSA/ATS guidelines in patients with severe community-acquired pneumonia (CAP)?
Background: Inflammatory biomarkers, such as CRP and procalcitonin, have diagnostic and prognostic utility in patients with CAP. Whether these inflammatory biomarkers can help triage patients to the appropriate level of care is unknown.
Study design: Prospective case control study.
Setting: Two university hospitals in Spain.
Synopsis: The study included 685 patients with severe CAP who did not require mechanical ventilation or vasopressor support. Serum levels of CRP, procalcitonin, TNF-alpha, IL-1, IL-6, IL-8, and IL-10, as well as Infectious Diseases Society of American/American Thoracic Society (IDSA/ATS) minor severity criteria data, were collected on admission. After controlling for age, comorbidities, and PSI risk class, serum levels of CRP and procalcitonin were found to be significantly higher in ICU patients compared with non-ICU patients. Despite this, these inflammatory biomarkers did not augment the IDSA/ATS guidelines, suggesting that patients who have three or more minor criteria be considered for ICU admission.
The study did suggest that patients with severe CAP and low levels of IL-6 and procalcitonin could potentially be managed safely outside of the ICU. However, hospitalists should be wary of applying the study results due to the small number of ICU patients in this study and the lack of real-time availability of these biomarkers at most institutions.
Bottom line: More studies of inflammatory biomarkers are needed before using them to determine the level of care required for patients with CAP. Until these data are available, physicians should use the IDSA/ATS guidelines to triage patients to the appropriate level of care.
Citation: Ramirez P, Ferrer M, Torres A, et al. Inflammatory biomarkers and prediction for intensive care unit admission pneumonia. Crit Care Med. 2011;39:2211-2217.
IL-13 Antibody Lebrikizumab Shows Promise as a New Therapy for Adults with Uncontrolled Asthma
Clinical question: Can lebrikizumab, an IL-13 antibody, improve asthma control in patients with uncontrolled asthma?
Background: Asthma is a complex disease, with varied patient response to treatment. Some patients have uncontrolled asthma despite inhaled glucocorticoids. It is postulated that IL-13 may account for this variability and that some patients with uncontrolled asthma are poorly controlled due to glucocorticoid resistance mediated by IL-13. Lebrikizumab is an IgG4 monoclonal antibody that binds to and inhibits the function of IL-13. This study was performed to see if this antibody would be effective in patients with uncontrolled asthma despite inhaled glucocorticoid therapy.
Study design: Randomized double-blinded placebo-controlled trial.
Setting: Multiple centers.
Synopsis: The study randomized 219 adult asthma patients who were inadequately controlled despite inhaled corticosteroids to a placebo or lebrikizumab. The primary outcome was improvement in prebronchodilator FEV1 from baseline. Secondary outcomes were exacerbations, use of rescue medications, and symptom scores. Patients were also stratified and analyzed based on surrogate markers for IL-13, which included serum IGE levels, eosinophil counts, and periostin levels.
In patients who were randomized to the lebrikizumab treatment, there was a statistically significant improvement in FEV1 of 5.5%, which occurred almost immediately and was sustained for the entire 32 weeks of the study. The improvement was more significant in patients who had high surrogate markers for IL-13. Despite this improvement in FEV1, there were no differences in secondary outcomes except in patients who had surrogate markers for high IL-13 levels.
Bottom line: In adults with asthma who remained uncontrolled despite inhaled corticosteroid therapy, IL-13 antagonism with lebrikizumab improved FEV1. However, the clinical relevance of these modest improvements remains unclear.
Citation: Corren J, Lemanske R, Matthews J, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365:1088-1098.
Rivaroxaban Is Noninferior to Warfarin for Stroke Prevention in Atrial Fibrillation
Clinical question: How does rivaroxaban compare with warfarin in the prevention of stroke or systemic embolism in patients with nonvalvular atrial fibrillation?
Background: Warfarin is effective for the prevention of stroke in atrial fibrillation, but it requires close monitoring and adjustment. Rivaroxaban, an oral Xa inhibitor, may be safer, easier, and more effective than warfarin.
Study design: Multicenter, randomized, double-blind, double-dummy trial.
Setting: 1,178 sites in 45 countries.
Synopsis: The study included 14,264 patients with nonvalvular atrial fibrillation who were randomized to either fixed-dose rivaroxaban (20 mg daily or 15 mg daily for CrCl 30-49 mL/min) plus placebo or adjusted-dose warfarin (target INR 2.0 to 3.0) plus placebo. The mean CHADS2 score was 3.5. The primary endpoint (stroke or systemic embolism) occurred in 1.7% of patients per year in the rivaroxaban group and 2.2% per year in the warfarin group (hazard ratio for rivaroxaban 0.79; 95% CI: 0.66 to 0.96, P<0.001 for noninferiority). There was no difference in major or nonmajor clinically significant bleeding between the two groups (14.9% rivaroxaban vs. 14.5% warfarin, hazard ratio=1.03, 95% CI: 0.96 to 1.11, P=0.44). There were fewer intracranial hemorrhages (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group.
Bottom line: In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolization, with a similar risk of major bleeding and a lower risk of intracranial hemorrhage or fatal bleeding.
Citation: Patel MR, Mahaffey K, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883-891.
Apixaban More Effective and Safer than Warfarin for Stroke Prevention in Atrial Fibrillation
Clinical question: How does the effectiveness and safety of apixaban compare with warfarin for stroke prevention in atrial fibrillation?
Background: Until recently, warfarin has been the only available oral anticoagulant for stroke prevention in patients with atrial fibrillation (AF). The oral factor Xa inhibitors have shown similar efficacy and safety, without the monitoring requirement and drug interactions associated with warfarin.
Study design: Prospective randomized double-blind controlled trial.
Setting: More than 1,000 clinical sites in 39 countries.
Synopsis: This study randomized 18,201 patients with atrial fibrillation or flutter and at least one CHADS2 risk factor for stroke to receive oral apixaban or warfarin therapy. Exclusion criteria were prosthetic valves and severe kidney disease. The median duration of follow-up was 1.8 years, and the major endpoints were incidence of stroke, systemic embolism, bleeding complications, and mortality.
Compared with warfarin, apixaban reduced the annual incidence of stroke and systemic embolism from 1.6% to 1.3% (HR 0.79, 95%: CI 0.66 to 0.95, P=0.01 for superiority), and reduced mortality (HR: 0.89, 95% CI: 0.80 to 0.998). For the combined endpoint of stroke, systemic embolism, MI, or death, the annual rate was reduced from 5.5% to 4.9% (HR: 0.88, 95% CI: 0.80 to 0.97). All measures of bleeding were less frequent with apixaban: major 2.1% vs. 3.1% (HR: 0.69, 95% CI: 0.60 to 0.80), and combined major and minor bleeding 4.1% vs. 6.0% (HR: 0.68, 95% CI: 0.61 to 0.75). The annual rate for the net outcome of stroke, embolism, or major bleeding was 3.2% with apixaban and 4.1% with warfarin (HR: 0.77, 95% CI: 0.69 to 0.86).
Bottom line: Compared with warfarin therapy, apixaban is more effective and safer for stroke prevention in patients with atrial fibrillation.
Citation: Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-992.
Ultrasonography Is Useful in Diagnosis of Pneumothorax
Clinical question: Is transthoracic ultrasonography a useful tool to diagnose pneumothorax?
Background: CT is the diagnostic gold standard for pneumothorax, but it is associated with radiation exposure and requires patient transport. Chest radiograph is easy to perform but may be too insensitive for adequate diagnosis. Ultrasonography’s diagnostic performance for detecting pneumothorax needs further evaluation.
Study design: Systematic review and meta-analysis.
Setting: Critically ill, trauma, or post-biopsy patients were identified in each of the studies.
Synopsis: The meta-analysis of 20 eligible studies found a pooled sensitivity of ultrasound for the detection of pneumothorax of 0.88 (95% CI: 0.85 to 0.91) and specificity of 0.99 (0.98 to 0.99) compared with sensitivity of 0.52 (0.49 to 0.55) and specificity of 1.00 (1.00 to 1.00) for chest radiograph. Although the overall ROC curve was not significantly different between these modalities, the accuracy of ultrasonography was highly dependent on the skill of the operator.
Bottom line: When performed by a skilled operator, transthoracic ultrasonography is as specific, and more sensitive, than chest radiograph in diagnosing pneumothorax.
Citation: Ding W, Shen Y, Yang J, He X, Zhang M. Diagnosis of pneumothorax by radiography and ultrasonography: a meta-analysis. Chest. 2011;140:859-866.
Risk Prediction for Hospital Readmission Remains Challenging
Clinical question: Can readmission risk assessment be used to identify which patients would benefit most from care-transition interventions, or to risk-adjust readmission rates for hospital comparison?
Background: Multiple models to predict hospital readmission have been described and validated. Identifying patients at high risk for readmission could allow for customized care-transition interventions, or could be used to risk-adjust readmission rates to compare publicly reported rates by hospital.
Study design: Systematic review with qualitative synthesis of results.
Setting: Thirty studies (23 from the U.S.) tested 26 unique readmission models.
Synopsis: Each model had been tested in both a derivation and validation cohort. Fourteen models (nine from the U.S.), using retrospective administrative data to compare risk-adjusted rates between hospitals, had poor discriminative capacity (c statistic range: 0.55 to 0.65). Seven models could be used to identify high-risk patients early in the hospitalization (c statistic range: 0.56 to 0.72) and five could be used to identify high-risk patients at discharge (c statistic range: 0.68 to 0.83), but these also had poor to moderate discriminative capacity. Multiple variables were considered in each of the models; most incorporated medical comorbidities and prior use of healthcare services.
Bottom line: Current readmission risk prediction models do not perform adequately for comparative or clinical purposes.
Citation: Kansagara D, Englander H, Salanitro A, et. al. Risk prediction models for hospital readmission: a systematic review. JAMA. 2011;306:1688-1698.
Intravenous Fluids for Acute Pancreatitis: More May Be Less
Clinical question: What is the optimal volume of fluid administration for treatment of acute pancreatitis?
Background: Current guidelines for management of acute pancreatitis emphasize vigorous administration of intravenous fluids to reduce the risk of pancreatic necrosis and organ failure. This recommendation is based upon animal studies, and has not been subjected to clinical evaluation in humans.
Study design: Prospective observational cohort.
Setting: University-affiliated tertiary-care public hospital in Spain.
Synopsis: This study enrolled 247 patients admitted with acute pancreatitis to determine the association between the volume of fluid administered during the first 24 hours and the development of persistent organ failure, pancreatic fluid collection or necrosis, and mortality. The volume and rate of fluid administered were determined by the treating physician. Patients were classified into three groups: those receiving a volume <3.1 L, 3.1 to 4.1 L, or >4.1 L.
After multivariate adjustment, those receiving <3.1 L had no increased risk of necrosis or any other adverse outcome, compared with those who received the middle range of fluid volume.
Patients receiving >4.1 L had a higher risk of persistent organ failure (OR: 7.7, 95% CI: 1.5 to 38.7), particularly renal and respiratory insufficiency, and fluid collection development (OR: 1.9, 95% CI: 1 to 3.7) independent of disease severity. Pancreatic necrosis and mortality were similar in the three groups.
Bottom line: Administration of large-volume intravenous fluids (>4.1 L) in
the first 24 hours was associated with worse outcomes, although residual confounding cannot be excluded in this nonrandomized study.
Citation: de-Madaria E, Soler-Sala G, Sanchez-Paya J, et al. Influence of fluid therapy on the prognosis of acute pancreatitis: a prospective cohort study. Am J Gastroenterol. 2011;106:1843-1850.
Clinical Outcomes in Saddle Pulmonary Embolism
Clinical question: What are the treatments used and outcomes associated with saddle pulmonary embolism?
Background: Saddle pulmonary embolism is a risk for right ventricular dysfunction and sudden hemodynamic collapse. There are limited data on the clinical presentation and outcomes in these patients.
Study design: Retrospective case review.
Setting: Single academic medical center.
Synopsis: In this retrospective review of 680 patients diagnosed with pulmonary embolism on CT at a single academic medical center from 2004 to 2009, 5.4% (37 patients) had a saddle pulmonary embolism.
Most patients with saddle pulmonary embolism were hemodynamically stable and responded to standard therapy with unfractionated heparin. The mean length of stay was nine days, 46% received an inferior vena cava filter, 41% were treated in an ICU, and 5.4% (two patients) died in the hospital. Thrombolytics were used in only 11% of patients, most of which had sustained hypotension and/or were mechanically ventilated.
Bottom line: Most patients with saddle pulmonary embolus in this single institution study did not receive thrombolytics and had overall low mortality.
Citation: Sardi A, Gluskin J, Guttentag A, Kotler MN, Braitman LE, Lippmann M. Saddle pulmonary embolism: is it as bad as it looks? A community hospital experience. Crit Care Med. 2011;39:2413-2418.
In This Edition
Literature At A Glance
A guide to this month’s studies
- IDSA/ATS guidelines for community-acquired pneumonia
- Improved asthma with IL-13 antibody
- Rivaroxaban vs. warfarin for stroke prevention in atrial fibrillation
- Apixaban vs. warfarin for stroke prevention in atrial fibrillation
- Ultrasonography more sensitive than chest radiograph for pneumothorax
- Current readmission risk models inadequate
- Optimal fluid volume for acute pancreatitis
- Low mortality in saddle pulmonary embolism
Triage Decisions for Patients with Severe Community-Acquired Pneumonia Should Be Based on IDSA/ATS Guidelines, Not Inflammatory Biomarkers
Clinical question: Can C-reactive protein levels (CRP), procalcitonin, TNF-alpha, and cytokine levels predict the need for intensive-care admission more accurately than IDSA/ATS guidelines in patients with severe community-acquired pneumonia (CAP)?
Background: Inflammatory biomarkers, such as CRP and procalcitonin, have diagnostic and prognostic utility in patients with CAP. Whether these inflammatory biomarkers can help triage patients to the appropriate level of care is unknown.
Study design: Prospective case control study.
Setting: Two university hospitals in Spain.
Synopsis: The study included 685 patients with severe CAP who did not require mechanical ventilation or vasopressor support. Serum levels of CRP, procalcitonin, TNF-alpha, IL-1, IL-6, IL-8, and IL-10, as well as Infectious Diseases Society of American/American Thoracic Society (IDSA/ATS) minor severity criteria data, were collected on admission. After controlling for age, comorbidities, and PSI risk class, serum levels of CRP and procalcitonin were found to be significantly higher in ICU patients compared with non-ICU patients. Despite this, these inflammatory biomarkers did not augment the IDSA/ATS guidelines, suggesting that patients who have three or more minor criteria be considered for ICU admission.
The study did suggest that patients with severe CAP and low levels of IL-6 and procalcitonin could potentially be managed safely outside of the ICU. However, hospitalists should be wary of applying the study results due to the small number of ICU patients in this study and the lack of real-time availability of these biomarkers at most institutions.
Bottom line: More studies of inflammatory biomarkers are needed before using them to determine the level of care required for patients with CAP. Until these data are available, physicians should use the IDSA/ATS guidelines to triage patients to the appropriate level of care.
Citation: Ramirez P, Ferrer M, Torres A, et al. Inflammatory biomarkers and prediction for intensive care unit admission pneumonia. Crit Care Med. 2011;39:2211-2217.
IL-13 Antibody Lebrikizumab Shows Promise as a New Therapy for Adults with Uncontrolled Asthma
Clinical question: Can lebrikizumab, an IL-13 antibody, improve asthma control in patients with uncontrolled asthma?
Background: Asthma is a complex disease, with varied patient response to treatment. Some patients have uncontrolled asthma despite inhaled glucocorticoids. It is postulated that IL-13 may account for this variability and that some patients with uncontrolled asthma are poorly controlled due to glucocorticoid resistance mediated by IL-13. Lebrikizumab is an IgG4 monoclonal antibody that binds to and inhibits the function of IL-13. This study was performed to see if this antibody would be effective in patients with uncontrolled asthma despite inhaled glucocorticoid therapy.
Study design: Randomized double-blinded placebo-controlled trial.
Setting: Multiple centers.
Synopsis: The study randomized 219 adult asthma patients who were inadequately controlled despite inhaled corticosteroids to a placebo or lebrikizumab. The primary outcome was improvement in prebronchodilator FEV1 from baseline. Secondary outcomes were exacerbations, use of rescue medications, and symptom scores. Patients were also stratified and analyzed based on surrogate markers for IL-13, which included serum IGE levels, eosinophil counts, and periostin levels.
In patients who were randomized to the lebrikizumab treatment, there was a statistically significant improvement in FEV1 of 5.5%, which occurred almost immediately and was sustained for the entire 32 weeks of the study. The improvement was more significant in patients who had high surrogate markers for IL-13. Despite this improvement in FEV1, there were no differences in secondary outcomes except in patients who had surrogate markers for high IL-13 levels.
Bottom line: In adults with asthma who remained uncontrolled despite inhaled corticosteroid therapy, IL-13 antagonism with lebrikizumab improved FEV1. However, the clinical relevance of these modest improvements remains unclear.
Citation: Corren J, Lemanske R, Matthews J, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365:1088-1098.
Rivaroxaban Is Noninferior to Warfarin for Stroke Prevention in Atrial Fibrillation
Clinical question: How does rivaroxaban compare with warfarin in the prevention of stroke or systemic embolism in patients with nonvalvular atrial fibrillation?
Background: Warfarin is effective for the prevention of stroke in atrial fibrillation, but it requires close monitoring and adjustment. Rivaroxaban, an oral Xa inhibitor, may be safer, easier, and more effective than warfarin.
Study design: Multicenter, randomized, double-blind, double-dummy trial.
Setting: 1,178 sites in 45 countries.
Synopsis: The study included 14,264 patients with nonvalvular atrial fibrillation who were randomized to either fixed-dose rivaroxaban (20 mg daily or 15 mg daily for CrCl 30-49 mL/min) plus placebo or adjusted-dose warfarin (target INR 2.0 to 3.0) plus placebo. The mean CHADS2 score was 3.5. The primary endpoint (stroke or systemic embolism) occurred in 1.7% of patients per year in the rivaroxaban group and 2.2% per year in the warfarin group (hazard ratio for rivaroxaban 0.79; 95% CI: 0.66 to 0.96, P<0.001 for noninferiority). There was no difference in major or nonmajor clinically significant bleeding between the two groups (14.9% rivaroxaban vs. 14.5% warfarin, hazard ratio=1.03, 95% CI: 0.96 to 1.11, P=0.44). There were fewer intracranial hemorrhages (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group.
Bottom line: In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolization, with a similar risk of major bleeding and a lower risk of intracranial hemorrhage or fatal bleeding.
Citation: Patel MR, Mahaffey K, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883-891.
Apixaban More Effective and Safer than Warfarin for Stroke Prevention in Atrial Fibrillation
Clinical question: How does the effectiveness and safety of apixaban compare with warfarin for stroke prevention in atrial fibrillation?
Background: Until recently, warfarin has been the only available oral anticoagulant for stroke prevention in patients with atrial fibrillation (AF). The oral factor Xa inhibitors have shown similar efficacy and safety, without the monitoring requirement and drug interactions associated with warfarin.
Study design: Prospective randomized double-blind controlled trial.
Setting: More than 1,000 clinical sites in 39 countries.
Synopsis: This study randomized 18,201 patients with atrial fibrillation or flutter and at least one CHADS2 risk factor for stroke to receive oral apixaban or warfarin therapy. Exclusion criteria were prosthetic valves and severe kidney disease. The median duration of follow-up was 1.8 years, and the major endpoints were incidence of stroke, systemic embolism, bleeding complications, and mortality.
Compared with warfarin, apixaban reduced the annual incidence of stroke and systemic embolism from 1.6% to 1.3% (HR 0.79, 95%: CI 0.66 to 0.95, P=0.01 for superiority), and reduced mortality (HR: 0.89, 95% CI: 0.80 to 0.998). For the combined endpoint of stroke, systemic embolism, MI, or death, the annual rate was reduced from 5.5% to 4.9% (HR: 0.88, 95% CI: 0.80 to 0.97). All measures of bleeding were less frequent with apixaban: major 2.1% vs. 3.1% (HR: 0.69, 95% CI: 0.60 to 0.80), and combined major and minor bleeding 4.1% vs. 6.0% (HR: 0.68, 95% CI: 0.61 to 0.75). The annual rate for the net outcome of stroke, embolism, or major bleeding was 3.2% with apixaban and 4.1% with warfarin (HR: 0.77, 95% CI: 0.69 to 0.86).
Bottom line: Compared with warfarin therapy, apixaban is more effective and safer for stroke prevention in patients with atrial fibrillation.
Citation: Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-992.
Ultrasonography Is Useful in Diagnosis of Pneumothorax
Clinical question: Is transthoracic ultrasonography a useful tool to diagnose pneumothorax?
Background: CT is the diagnostic gold standard for pneumothorax, but it is associated with radiation exposure and requires patient transport. Chest radiograph is easy to perform but may be too insensitive for adequate diagnosis. Ultrasonography’s diagnostic performance for detecting pneumothorax needs further evaluation.
Study design: Systematic review and meta-analysis.
Setting: Critically ill, trauma, or post-biopsy patients were identified in each of the studies.
Synopsis: The meta-analysis of 20 eligible studies found a pooled sensitivity of ultrasound for the detection of pneumothorax of 0.88 (95% CI: 0.85 to 0.91) and specificity of 0.99 (0.98 to 0.99) compared with sensitivity of 0.52 (0.49 to 0.55) and specificity of 1.00 (1.00 to 1.00) for chest radiograph. Although the overall ROC curve was not significantly different between these modalities, the accuracy of ultrasonography was highly dependent on the skill of the operator.
Bottom line: When performed by a skilled operator, transthoracic ultrasonography is as specific, and more sensitive, than chest radiograph in diagnosing pneumothorax.
Citation: Ding W, Shen Y, Yang J, He X, Zhang M. Diagnosis of pneumothorax by radiography and ultrasonography: a meta-analysis. Chest. 2011;140:859-866.
Risk Prediction for Hospital Readmission Remains Challenging
Clinical question: Can readmission risk assessment be used to identify which patients would benefit most from care-transition interventions, or to risk-adjust readmission rates for hospital comparison?
Background: Multiple models to predict hospital readmission have been described and validated. Identifying patients at high risk for readmission could allow for customized care-transition interventions, or could be used to risk-adjust readmission rates to compare publicly reported rates by hospital.
Study design: Systematic review with qualitative synthesis of results.
Setting: Thirty studies (23 from the U.S.) tested 26 unique readmission models.
Synopsis: Each model had been tested in both a derivation and validation cohort. Fourteen models (nine from the U.S.), using retrospective administrative data to compare risk-adjusted rates between hospitals, had poor discriminative capacity (c statistic range: 0.55 to 0.65). Seven models could be used to identify high-risk patients early in the hospitalization (c statistic range: 0.56 to 0.72) and five could be used to identify high-risk patients at discharge (c statistic range: 0.68 to 0.83), but these also had poor to moderate discriminative capacity. Multiple variables were considered in each of the models; most incorporated medical comorbidities and prior use of healthcare services.
Bottom line: Current readmission risk prediction models do not perform adequately for comparative or clinical purposes.
Citation: Kansagara D, Englander H, Salanitro A, et. al. Risk prediction models for hospital readmission: a systematic review. JAMA. 2011;306:1688-1698.
Intravenous Fluids for Acute Pancreatitis: More May Be Less
Clinical question: What is the optimal volume of fluid administration for treatment of acute pancreatitis?
Background: Current guidelines for management of acute pancreatitis emphasize vigorous administration of intravenous fluids to reduce the risk of pancreatic necrosis and organ failure. This recommendation is based upon animal studies, and has not been subjected to clinical evaluation in humans.
Study design: Prospective observational cohort.
Setting: University-affiliated tertiary-care public hospital in Spain.
Synopsis: This study enrolled 247 patients admitted with acute pancreatitis to determine the association between the volume of fluid administered during the first 24 hours and the development of persistent organ failure, pancreatic fluid collection or necrosis, and mortality. The volume and rate of fluid administered were determined by the treating physician. Patients were classified into three groups: those receiving a volume <3.1 L, 3.1 to 4.1 L, or >4.1 L.
After multivariate adjustment, those receiving <3.1 L had no increased risk of necrosis or any other adverse outcome, compared with those who received the middle range of fluid volume.
Patients receiving >4.1 L had a higher risk of persistent organ failure (OR: 7.7, 95% CI: 1.5 to 38.7), particularly renal and respiratory insufficiency, and fluid collection development (OR: 1.9, 95% CI: 1 to 3.7) independent of disease severity. Pancreatic necrosis and mortality were similar in the three groups.
Bottom line: Administration of large-volume intravenous fluids (>4.1 L) in
the first 24 hours was associated with worse outcomes, although residual confounding cannot be excluded in this nonrandomized study.
Citation: de-Madaria E, Soler-Sala G, Sanchez-Paya J, et al. Influence of fluid therapy on the prognosis of acute pancreatitis: a prospective cohort study. Am J Gastroenterol. 2011;106:1843-1850.
Clinical Outcomes in Saddle Pulmonary Embolism
Clinical question: What are the treatments used and outcomes associated with saddle pulmonary embolism?
Background: Saddle pulmonary embolism is a risk for right ventricular dysfunction and sudden hemodynamic collapse. There are limited data on the clinical presentation and outcomes in these patients.
Study design: Retrospective case review.
Setting: Single academic medical center.
Synopsis: In this retrospective review of 680 patients diagnosed with pulmonary embolism on CT at a single academic medical center from 2004 to 2009, 5.4% (37 patients) had a saddle pulmonary embolism.
Most patients with saddle pulmonary embolism were hemodynamically stable and responded to standard therapy with unfractionated heparin. The mean length of stay was nine days, 46% received an inferior vena cava filter, 41% were treated in an ICU, and 5.4% (two patients) died in the hospital. Thrombolytics were used in only 11% of patients, most of which had sustained hypotension and/or were mechanically ventilated.
Bottom line: Most patients with saddle pulmonary embolus in this single institution study did not receive thrombolytics and had overall low mortality.
Citation: Sardi A, Gluskin J, Guttentag A, Kotler MN, Braitman LE, Lippmann M. Saddle pulmonary embolism: is it as bad as it looks? A community hospital experience. Crit Care Med. 2011;39:2413-2418.
In This Edition
Literature At A Glance
A guide to this month’s studies
- IDSA/ATS guidelines for community-acquired pneumonia
- Improved asthma with IL-13 antibody
- Rivaroxaban vs. warfarin for stroke prevention in atrial fibrillation
- Apixaban vs. warfarin for stroke prevention in atrial fibrillation
- Ultrasonography more sensitive than chest radiograph for pneumothorax
- Current readmission risk models inadequate
- Optimal fluid volume for acute pancreatitis
- Low mortality in saddle pulmonary embolism
Triage Decisions for Patients with Severe Community-Acquired Pneumonia Should Be Based on IDSA/ATS Guidelines, Not Inflammatory Biomarkers
Clinical question: Can C-reactive protein levels (CRP), procalcitonin, TNF-alpha, and cytokine levels predict the need for intensive-care admission more accurately than IDSA/ATS guidelines in patients with severe community-acquired pneumonia (CAP)?
Background: Inflammatory biomarkers, such as CRP and procalcitonin, have diagnostic and prognostic utility in patients with CAP. Whether these inflammatory biomarkers can help triage patients to the appropriate level of care is unknown.
Study design: Prospective case control study.
Setting: Two university hospitals in Spain.
Synopsis: The study included 685 patients with severe CAP who did not require mechanical ventilation or vasopressor support. Serum levels of CRP, procalcitonin, TNF-alpha, IL-1, IL-6, IL-8, and IL-10, as well as Infectious Diseases Society of American/American Thoracic Society (IDSA/ATS) minor severity criteria data, were collected on admission. After controlling for age, comorbidities, and PSI risk class, serum levels of CRP and procalcitonin were found to be significantly higher in ICU patients compared with non-ICU patients. Despite this, these inflammatory biomarkers did not augment the IDSA/ATS guidelines, suggesting that patients who have three or more minor criteria be considered for ICU admission.
The study did suggest that patients with severe CAP and low levels of IL-6 and procalcitonin could potentially be managed safely outside of the ICU. However, hospitalists should be wary of applying the study results due to the small number of ICU patients in this study and the lack of real-time availability of these biomarkers at most institutions.
Bottom line: More studies of inflammatory biomarkers are needed before using them to determine the level of care required for patients with CAP. Until these data are available, physicians should use the IDSA/ATS guidelines to triage patients to the appropriate level of care.
Citation: Ramirez P, Ferrer M, Torres A, et al. Inflammatory biomarkers and prediction for intensive care unit admission pneumonia. Crit Care Med. 2011;39:2211-2217.
IL-13 Antibody Lebrikizumab Shows Promise as a New Therapy for Adults with Uncontrolled Asthma
Clinical question: Can lebrikizumab, an IL-13 antibody, improve asthma control in patients with uncontrolled asthma?
Background: Asthma is a complex disease, with varied patient response to treatment. Some patients have uncontrolled asthma despite inhaled glucocorticoids. It is postulated that IL-13 may account for this variability and that some patients with uncontrolled asthma are poorly controlled due to glucocorticoid resistance mediated by IL-13. Lebrikizumab is an IgG4 monoclonal antibody that binds to and inhibits the function of IL-13. This study was performed to see if this antibody would be effective in patients with uncontrolled asthma despite inhaled glucocorticoid therapy.
Study design: Randomized double-blinded placebo-controlled trial.
Setting: Multiple centers.
Synopsis: The study randomized 219 adult asthma patients who were inadequately controlled despite inhaled corticosteroids to a placebo or lebrikizumab. The primary outcome was improvement in prebronchodilator FEV1 from baseline. Secondary outcomes were exacerbations, use of rescue medications, and symptom scores. Patients were also stratified and analyzed based on surrogate markers for IL-13, which included serum IGE levels, eosinophil counts, and periostin levels.
In patients who were randomized to the lebrikizumab treatment, there was a statistically significant improvement in FEV1 of 5.5%, which occurred almost immediately and was sustained for the entire 32 weeks of the study. The improvement was more significant in patients who had high surrogate markers for IL-13. Despite this improvement in FEV1, there were no differences in secondary outcomes except in patients who had surrogate markers for high IL-13 levels.
Bottom line: In adults with asthma who remained uncontrolled despite inhaled corticosteroid therapy, IL-13 antagonism with lebrikizumab improved FEV1. However, the clinical relevance of these modest improvements remains unclear.
Citation: Corren J, Lemanske R, Matthews J, et al. Lebrikizumab treatment in adults with asthma. N Engl J Med. 2011;365:1088-1098.
Rivaroxaban Is Noninferior to Warfarin for Stroke Prevention in Atrial Fibrillation
Clinical question: How does rivaroxaban compare with warfarin in the prevention of stroke or systemic embolism in patients with nonvalvular atrial fibrillation?
Background: Warfarin is effective for the prevention of stroke in atrial fibrillation, but it requires close monitoring and adjustment. Rivaroxaban, an oral Xa inhibitor, may be safer, easier, and more effective than warfarin.
Study design: Multicenter, randomized, double-blind, double-dummy trial.
Setting: 1,178 sites in 45 countries.
Synopsis: The study included 14,264 patients with nonvalvular atrial fibrillation who were randomized to either fixed-dose rivaroxaban (20 mg daily or 15 mg daily for CrCl 30-49 mL/min) plus placebo or adjusted-dose warfarin (target INR 2.0 to 3.0) plus placebo. The mean CHADS2 score was 3.5. The primary endpoint (stroke or systemic embolism) occurred in 1.7% of patients per year in the rivaroxaban group and 2.2% per year in the warfarin group (hazard ratio for rivaroxaban 0.79; 95% CI: 0.66 to 0.96, P<0.001 for noninferiority). There was no difference in major or nonmajor clinically significant bleeding between the two groups (14.9% rivaroxaban vs. 14.5% warfarin, hazard ratio=1.03, 95% CI: 0.96 to 1.11, P=0.44). There were fewer intracranial hemorrhages (0.5% vs. 0.7%, P=0.02) and fatal bleeding (0.2% vs. 0.5%, P=0.003) in the rivaroxaban group.
Bottom line: In patients with atrial fibrillation, rivaroxaban was noninferior to warfarin for the prevention of stroke or systemic embolization, with a similar risk of major bleeding and a lower risk of intracranial hemorrhage or fatal bleeding.
Citation: Patel MR, Mahaffey K, Garg J, et al. Rivaroxaban versus warfarin in nonvalvular atrial fibrillation. N Engl J Med. 2011;365:883-891.
Apixaban More Effective and Safer than Warfarin for Stroke Prevention in Atrial Fibrillation
Clinical question: How does the effectiveness and safety of apixaban compare with warfarin for stroke prevention in atrial fibrillation?
Background: Until recently, warfarin has been the only available oral anticoagulant for stroke prevention in patients with atrial fibrillation (AF). The oral factor Xa inhibitors have shown similar efficacy and safety, without the monitoring requirement and drug interactions associated with warfarin.
Study design: Prospective randomized double-blind controlled trial.
Setting: More than 1,000 clinical sites in 39 countries.
Synopsis: This study randomized 18,201 patients with atrial fibrillation or flutter and at least one CHADS2 risk factor for stroke to receive oral apixaban or warfarin therapy. Exclusion criteria were prosthetic valves and severe kidney disease. The median duration of follow-up was 1.8 years, and the major endpoints were incidence of stroke, systemic embolism, bleeding complications, and mortality.
Compared with warfarin, apixaban reduced the annual incidence of stroke and systemic embolism from 1.6% to 1.3% (HR 0.79, 95%: CI 0.66 to 0.95, P=0.01 for superiority), and reduced mortality (HR: 0.89, 95% CI: 0.80 to 0.998). For the combined endpoint of stroke, systemic embolism, MI, or death, the annual rate was reduced from 5.5% to 4.9% (HR: 0.88, 95% CI: 0.80 to 0.97). All measures of bleeding were less frequent with apixaban: major 2.1% vs. 3.1% (HR: 0.69, 95% CI: 0.60 to 0.80), and combined major and minor bleeding 4.1% vs. 6.0% (HR: 0.68, 95% CI: 0.61 to 0.75). The annual rate for the net outcome of stroke, embolism, or major bleeding was 3.2% with apixaban and 4.1% with warfarin (HR: 0.77, 95% CI: 0.69 to 0.86).
Bottom line: Compared with warfarin therapy, apixaban is more effective and safer for stroke prevention in patients with atrial fibrillation.
Citation: Granger CB, Alexander JH, McMurray JJ, et al. Apixaban versus warfarin in patients with atrial fibrillation. N Engl J Med. 2011;365:981-992.
Ultrasonography Is Useful in Diagnosis of Pneumothorax
Clinical question: Is transthoracic ultrasonography a useful tool to diagnose pneumothorax?
Background: CT is the diagnostic gold standard for pneumothorax, but it is associated with radiation exposure and requires patient transport. Chest radiograph is easy to perform but may be too insensitive for adequate diagnosis. Ultrasonography’s diagnostic performance for detecting pneumothorax needs further evaluation.
Study design: Systematic review and meta-analysis.
Setting: Critically ill, trauma, or post-biopsy patients were identified in each of the studies.
Synopsis: The meta-analysis of 20 eligible studies found a pooled sensitivity of ultrasound for the detection of pneumothorax of 0.88 (95% CI: 0.85 to 0.91) and specificity of 0.99 (0.98 to 0.99) compared with sensitivity of 0.52 (0.49 to 0.55) and specificity of 1.00 (1.00 to 1.00) for chest radiograph. Although the overall ROC curve was not significantly different between these modalities, the accuracy of ultrasonography was highly dependent on the skill of the operator.
Bottom line: When performed by a skilled operator, transthoracic ultrasonography is as specific, and more sensitive, than chest radiograph in diagnosing pneumothorax.
Citation: Ding W, Shen Y, Yang J, He X, Zhang M. Diagnosis of pneumothorax by radiography and ultrasonography: a meta-analysis. Chest. 2011;140:859-866.
Risk Prediction for Hospital Readmission Remains Challenging
Clinical question: Can readmission risk assessment be used to identify which patients would benefit most from care-transition interventions, or to risk-adjust readmission rates for hospital comparison?
Background: Multiple models to predict hospital readmission have been described and validated. Identifying patients at high risk for readmission could allow for customized care-transition interventions, or could be used to risk-adjust readmission rates to compare publicly reported rates by hospital.
Study design: Systematic review with qualitative synthesis of results.
Setting: Thirty studies (23 from the U.S.) tested 26 unique readmission models.
Synopsis: Each model had been tested in both a derivation and validation cohort. Fourteen models (nine from the U.S.), using retrospective administrative data to compare risk-adjusted rates between hospitals, had poor discriminative capacity (c statistic range: 0.55 to 0.65). Seven models could be used to identify high-risk patients early in the hospitalization (c statistic range: 0.56 to 0.72) and five could be used to identify high-risk patients at discharge (c statistic range: 0.68 to 0.83), but these also had poor to moderate discriminative capacity. Multiple variables were considered in each of the models; most incorporated medical comorbidities and prior use of healthcare services.
Bottom line: Current readmission risk prediction models do not perform adequately for comparative or clinical purposes.
Citation: Kansagara D, Englander H, Salanitro A, et. al. Risk prediction models for hospital readmission: a systematic review. JAMA. 2011;306:1688-1698.
Intravenous Fluids for Acute Pancreatitis: More May Be Less
Clinical question: What is the optimal volume of fluid administration for treatment of acute pancreatitis?
Background: Current guidelines for management of acute pancreatitis emphasize vigorous administration of intravenous fluids to reduce the risk of pancreatic necrosis and organ failure. This recommendation is based upon animal studies, and has not been subjected to clinical evaluation in humans.
Study design: Prospective observational cohort.
Setting: University-affiliated tertiary-care public hospital in Spain.
Synopsis: This study enrolled 247 patients admitted with acute pancreatitis to determine the association between the volume of fluid administered during the first 24 hours and the development of persistent organ failure, pancreatic fluid collection or necrosis, and mortality. The volume and rate of fluid administered were determined by the treating physician. Patients were classified into three groups: those receiving a volume <3.1 L, 3.1 to 4.1 L, or >4.1 L.
After multivariate adjustment, those receiving <3.1 L had no increased risk of necrosis or any other adverse outcome, compared with those who received the middle range of fluid volume.
Patients receiving >4.1 L had a higher risk of persistent organ failure (OR: 7.7, 95% CI: 1.5 to 38.7), particularly renal and respiratory insufficiency, and fluid collection development (OR: 1.9, 95% CI: 1 to 3.7) independent of disease severity. Pancreatic necrosis and mortality were similar in the three groups.
Bottom line: Administration of large-volume intravenous fluids (>4.1 L) in
the first 24 hours was associated with worse outcomes, although residual confounding cannot be excluded in this nonrandomized study.
Citation: de-Madaria E, Soler-Sala G, Sanchez-Paya J, et al. Influence of fluid therapy on the prognosis of acute pancreatitis: a prospective cohort study. Am J Gastroenterol. 2011;106:1843-1850.
Clinical Outcomes in Saddle Pulmonary Embolism
Clinical question: What are the treatments used and outcomes associated with saddle pulmonary embolism?
Background: Saddle pulmonary embolism is a risk for right ventricular dysfunction and sudden hemodynamic collapse. There are limited data on the clinical presentation and outcomes in these patients.
Study design: Retrospective case review.
Setting: Single academic medical center.
Synopsis: In this retrospective review of 680 patients diagnosed with pulmonary embolism on CT at a single academic medical center from 2004 to 2009, 5.4% (37 patients) had a saddle pulmonary embolism.
Most patients with saddle pulmonary embolism were hemodynamically stable and responded to standard therapy with unfractionated heparin. The mean length of stay was nine days, 46% received an inferior vena cava filter, 41% were treated in an ICU, and 5.4% (two patients) died in the hospital. Thrombolytics were used in only 11% of patients, most of which had sustained hypotension and/or were mechanically ventilated.
Bottom line: Most patients with saddle pulmonary embolus in this single institution study did not receive thrombolytics and had overall low mortality.
Citation: Sardi A, Gluskin J, Guttentag A, Kotler MN, Braitman LE, Lippmann M. Saddle pulmonary embolism: is it as bad as it looks? A community hospital experience. Crit Care Med. 2011;39:2413-2418.
ITL: Physician Reviews of HM-Relevant Research
Clinical question: Is the risk of recurrence of Clostridium difficile infection (CDI) increased by the use of "non-CDI" antimicrobial agents (inactive against C. diff) during or after CDI therapy?
Background: Recurrence of CDI is expected to increase with use of non-CDI antimicrobials. Previous studies have not distinguished between the timing of non-CDI agents during and after CDI treatment, nor examined the effect of frequency, duration, or type of non-CDI antibiotic therapy.
Study design: Retrospective cohort.
Setting: Academic Veterans Affairs medical center.
Synopsis: All patients with CDI over a three-year period were evaluated to determine the association between non-CDI antimicrobial during or within 30 days following CDI therapy and 90-day CDI recurrence. Of 246 patients, 57% received concurrent or subsequent non-CDI antimicrobials. CDI recurred in 40% of patients who received non-CDI antimicrobials and in 16% of those who did not (OR: 3.5, 95% CI: 1.9 to 6.5).
After multivariable adjustment (including age, duration of CDI treatment, comorbidity, hospital and ICU admission, and gastric acid suppression), those who received non-CDI antimicrobials during CDI therapy had no increased risk of recurrence. However, those who received any non-CDI antimicrobials after initial CDI treatment had an absolute recurrence rate of 48% with an adjusted OR of 3.02 (95% CI: 1.65 to 5.52). This increased risk of recurrence was unaffected by the number or duration of non-CDI antimicrobial prescriptions. Subgroup analysis by antimicrobial class revealed statistically significant associations only with beta-lactams and fluoroquinolones.
Bottom line: The risk of recurrence of CDI is tripled by exposure to non-CDI antimicrobials within 30 days after CDI treatment, irrespective of the number or duration of such exposures.
Citation: Drekonja DM, Amundson WH, DeCarolis DD, Kuskowski MA, Lederle FA, Johnson JR. Antimicrobial use and risk for recurrent Clostridium difficile infection. Am J Med. 2011;124:1081.e1-1081.e7.
Clinical question: Is the risk of recurrence of Clostridium difficile infection (CDI) increased by the use of "non-CDI" antimicrobial agents (inactive against C. diff) during or after CDI therapy?
Background: Recurrence of CDI is expected to increase with use of non-CDI antimicrobials. Previous studies have not distinguished between the timing of non-CDI agents during and after CDI treatment, nor examined the effect of frequency, duration, or type of non-CDI antibiotic therapy.
Study design: Retrospective cohort.
Setting: Academic Veterans Affairs medical center.
Synopsis: All patients with CDI over a three-year period were evaluated to determine the association between non-CDI antimicrobial during or within 30 days following CDI therapy and 90-day CDI recurrence. Of 246 patients, 57% received concurrent or subsequent non-CDI antimicrobials. CDI recurred in 40% of patients who received non-CDI antimicrobials and in 16% of those who did not (OR: 3.5, 95% CI: 1.9 to 6.5).
After multivariable adjustment (including age, duration of CDI treatment, comorbidity, hospital and ICU admission, and gastric acid suppression), those who received non-CDI antimicrobials during CDI therapy had no increased risk of recurrence. However, those who received any non-CDI antimicrobials after initial CDI treatment had an absolute recurrence rate of 48% with an adjusted OR of 3.02 (95% CI: 1.65 to 5.52). This increased risk of recurrence was unaffected by the number or duration of non-CDI antimicrobial prescriptions. Subgroup analysis by antimicrobial class revealed statistically significant associations only with beta-lactams and fluoroquinolones.
Bottom line: The risk of recurrence of CDI is tripled by exposure to non-CDI antimicrobials within 30 days after CDI treatment, irrespective of the number or duration of such exposures.
Citation: Drekonja DM, Amundson WH, DeCarolis DD, Kuskowski MA, Lederle FA, Johnson JR. Antimicrobial use and risk for recurrent Clostridium difficile infection. Am J Med. 2011;124:1081.e1-1081.e7.
Clinical question: Is the risk of recurrence of Clostridium difficile infection (CDI) increased by the use of "non-CDI" antimicrobial agents (inactive against C. diff) during or after CDI therapy?
Background: Recurrence of CDI is expected to increase with use of non-CDI antimicrobials. Previous studies have not distinguished between the timing of non-CDI agents during and after CDI treatment, nor examined the effect of frequency, duration, or type of non-CDI antibiotic therapy.
Study design: Retrospective cohort.
Setting: Academic Veterans Affairs medical center.
Synopsis: All patients with CDI over a three-year period were evaluated to determine the association between non-CDI antimicrobial during or within 30 days following CDI therapy and 90-day CDI recurrence. Of 246 patients, 57% received concurrent or subsequent non-CDI antimicrobials. CDI recurred in 40% of patients who received non-CDI antimicrobials and in 16% of those who did not (OR: 3.5, 95% CI: 1.9 to 6.5).
After multivariable adjustment (including age, duration of CDI treatment, comorbidity, hospital and ICU admission, and gastric acid suppression), those who received non-CDI antimicrobials during CDI therapy had no increased risk of recurrence. However, those who received any non-CDI antimicrobials after initial CDI treatment had an absolute recurrence rate of 48% with an adjusted OR of 3.02 (95% CI: 1.65 to 5.52). This increased risk of recurrence was unaffected by the number or duration of non-CDI antimicrobial prescriptions. Subgroup analysis by antimicrobial class revealed statistically significant associations only with beta-lactams and fluoroquinolones.
Bottom line: The risk of recurrence of CDI is tripled by exposure to non-CDI antimicrobials within 30 days after CDI treatment, irrespective of the number or duration of such exposures.
Citation: Drekonja DM, Amundson WH, DeCarolis DD, Kuskowski MA, Lederle FA, Johnson JR. Antimicrobial use and risk for recurrent Clostridium difficile infection. Am J Med. 2011;124:1081.e1-1081.e7.
Clear writing, clear thinking and the disappearing art of the problem list
My hospital's electronic medical record helpfully informs me after 1 week on service that there are 524 data available for my attention, a statistic that would be paralyzing without a cognitive framework for organizing and interpreting them in a manner that can be shared among my colleagues. Accurate information flow among clinicians was identified early on as an imperative of hospital medicine. Much attention has been focused on communication during transitions of care, such as that between inpatient and outpatient services and between inpatient teams, taking the form of the discharge summary and the sign‐out, respectively. But communication among physicians, consultants, and allied therapists must and inevitably does occur continuously day by day during even the most uneventful hospital stay. On academic services the need to keep multiple and ever‐rotating team members on the same page, so to speak, is particularly pressing.
The succinct and accurate problem list, formulated at the end of the history and physical examination and propagated through daily progress notes, is a powerful tool for promoting clear diagnostic and therapeutic planning and is ideally suited to meeting the need for continuous information flow among clinicians. Sadly, this inexpensive and potentially elegant device has fallen into disuse and disrepair and is in need of restoration.
In the 1960s, Dr. Lawrence Weed, the inventor of the SOAP note and a pioneer of medical informatics, wrote of the power of the problem list to impose order on the chaos of clinical information and to aid clear diagnostic thinking, in contrast with the simply chronological record popular in earlier years:
It is this multiplicity of problems with which the physician must deal in his daily work.[T]he multiplicity is inevitable but a random approach to the difficulties it creates is not. The instruction of physicians should be based on a system that helps them to define and follow clinical problems one by one and then systematically to relate and resolve them.[T]the basic criterion of the physician is how well he can identify the patient's problems and organize them for solution.1
Weed proposed that the product of our diagnostic thinking and investigations should be a concise list of diagnoses, as precisely as we are able to identify them, or, in their absence, a clear understanding of the specific problems awaiting resolution and a clear appreciation of the interrelationships among these entities:
The list shouldstate the problems at a level of refinement consistent with the physician's understanding, running the gamut from the precise diagnosis to the isolated, unexplained finding. Each item should be classified as one of the following: (1) a diagnosis, e.g., ASHD, followed by the principal manifestation that requires management; (2) a physiological finding, e.g., heart failure, followed by either the phrase etiology unknown or secondary to a diagnosis; (3) a symptom or physical finding, e.g., shortness of breath; or (4) an abnormal laboratory finding, e.g., an abnormal EKG. If a given diagnosis has several major manifestations, each of which requires individual management and separate, carefully delineated progress notes, then the second manifestation is presented as a second problem and designated as secondary to the major diagnosis.1
These principles were widely praised and adopted. An editorial in the New England Journal of Medicine proclaimed that his system is the essence of education itself,3 and it reigned throughout my own formal medical education.
In the decade that has seen our specialty flourish, with the attendant imperatives of clear thinking and communication, in teaching hospitals the problem list seems to have become an endangered species. The general pattern of its decline is that it is often supplanted by a list of organs, or worse, medical subspecialties, each followed by some assessment of its condition, whether diseased or not. The format resembles that used in critical care units for patients with multiple vital functions in jeopardy, on which survival depends from minute to minute, sometimes regardless of the original etiology of their failure. It is not clear how these notes began to spread from the ICU to the medical floor, where puzzles are solved and progress has goals more varied than mere survival. None of the residents I have queried over the years seem to know. The prevalence of this habit is also unknown, but it is widespread at both institutions at which I have been recently affiliated, and from the generation of notes in this format by trainees freshly graduated from medical schools across the land, I infer that it is no mere regional phenomenon. There may be an unspoken assumption that if this format is used for the sickest patients, it must be the superior format to use for all patients. Perhaps it reflects subspecialists teaching inpatient medicine, equipping trainees with vast technical knowledge of specific diseases and placing less emphasis on formulating coherent assessments. I believe its effects are pernicious and far‐reaching, affecting not only the quality of information flow among clinicians, but also the quality and rigor of diagnostic thinking of those in our training programs.
The history and physical examination properly culminate in the formulation of a problem list that establishes the framework for subsequent investigations and therapy. For each problem a narrative thread is initiated that can be followed in progress notes to resolution and succinctly reviewed in the discharge summary. It is now common to see diagnostic formulations arranged not by problem but by organ or subspecialty, for example, Endocrine: DKA. As everyone understands DKA to be an endocrine problem, the organ system preface adds nothing useful and only serves to bury the diagnosis in text. More tortured prose follows attempts to cram into the header all organs or specialties touched by the problem; hence pneumonia is often preceded by pulmonary/ID. A more egregious recent example was an esophageal variceal hemorrhage designated GI/Heme. And efforts to force an undifferentiated problem into an organ group can reach absurdity: Heme: Asymmetric leg swelling raised concern for DVT, but ultrasound was negative.
The organ preface at best merely adds clutter; the difficulty is compounded when the actual diagnosis or problem is omitted entirely in favor of mention of the organs, for example, for pneumonia: Pulm/ID: begin antibiotics. The reader may be left to guess exactly what is being treated, as with CV: begin heparin and beta‐blocker. The assessment and subsequent notes become even more unwieldy when the unifying diagnosis is approached circuitously on paper by way of its component elements, as with a recent patient with typical lobar pneumonia who was assessed by the house officer as having (1) ID: fever probably due to pneumonia; (2) Pulm: Hypoxia, sputum production and infiltrate on CXR consistent with pneumonia; and (3) Heme: leukocytosis likely due to pneumonia as well. Synthesis, the holy grail of the H&P, is thus replaced by analysis. Each tree is closely inspected, but we are lost in the forest. Weed wrote of such notes:
Failure to integrate findings into a valid single entity can almost always be traced to incomplete understanding.If a beginner puts cardiomegaly, edema, hepatomegaly and shortness of breath as four separate problems, it is his way of clearly admitting that he does not recognize cardiac failure when he sees it.2
Often, however, as in the example above, the physician fully understands the unifying diagnosis but nonetheless insists on addressing involved systems separately. Each feature is then apt to be separately followed in isolation through the progress notes, sometimes without any further mention of pneumonia as such. Many progress notes thus omit stating what is actually thought to be wrong with the patient.
The failure to commit to a diagnosis on paper, even when having done so in practice, ultimately can make its way to the discharge summary, propagating confusion to the outpatient department and ricocheting it into future admissions. It also robs us of the satisfaction of declaring a puzzle solved. I was compelled to write this piece in part by the recent case of a young woman who presented with fever and dyspnea. Through an elegant series of imaging studies and serologic tests, a diagnosis of lupus pericarditis was established, and steroid therapy produced dramatic remission of her symptomsa diagnostic triumph by any measure. How disheartening then to read the resident's final diagnosis for posterity in the discharge summary: fever and dyspnea.
The disembodied organ list thus sows confusion and redundant, convoluted prose throughout the medical record. Perhaps even more destructive is its effect on diagnostic thinking when applied to undifferentiated symptoms or problems, the general internist's pice de rsistance. Language shapes thought, and premature assignment of symptoms to a single organ or subspecialty constrains the imagination needed to puzzle things out. Examples are everywhere. Fever of unknown origin may be peremptorily designated ID, by implication excluding inflammatory, neoplastic, and iatrogenic causes from consideration. The asymmetrically swollen legs cited earlier are not hematologic, but they are still swollen. Undiagnosed problems should be labeled as such, with comment as to the differential diagnosis as it stands at the time and the status of the investigation. When a diagnosis is established, it should replace the undifferentiated symptom or abnormal finding in the list, with cardinal manifestations addressed as such when necessary. Thus, for example, fever in an intravenous drug user becomes endocarditis, and anasarca becomes nephrotic syndrome becomes glomerulonephritis as the diagnosis is established and refined. Weed saw the promise of the well‐groomed, problem‐based record in teaching diagnostic thinking:
The education of a physicianshould be based on his clinical experience and should be reflected in the records he maintains on his patients.The educationbecomes defective not when he is given too much or too little training in basic sciencebut rather when he is allowed to ignore or slight the elementary definition and the progressive adjustment of the problems that comprise his clinical experience. The teacher who ultimately benefits students the most is the one who is willing to establish parameters of discipline in the not unsophisticated but often unappreciated task of preventing this imprecision and disorganization.1
Hospitalists as generalist clinician‐educators have an opportunity to teach fundamental principles of medicine that span subspecialties. These principles must include clear organization and prioritization of complex medical information to enable coherent diagnostic and therapeutic planning and smooth continuity of care. The sign‐out and the all‐important discharge summary can be only as clear and as logical as the diagnoses that inform them. To these ends, let us maintain and reinvigorate the art of the problem list. As an exercise at morning report and attending rounds, we should emphasize the development of an accurate, comprehensive list of active problems before moving on to detailed discussion of any single issue, as Weed suggested nearly 40 years ago:
A serious mistake in teaching medicine is to expose the student, the house officer, or the physician to an analytical discussion of the diagnosis and management of one problem before establishing whether or not he is capable of identifying and defining all of the patient's problems at the outset1
We should expect this list to be formulated at the end of the admission history and physical examination. We must ensure that trainees can correctly identify the level of resolution achieved for each item. They must learn to distinguish among undifferentiated symptoms, for example, passed out; undifferentiated problems, expressed by medical terms with precise meaning, such as syncope; and precise etiologic diagnoses, such as ventricular tachycardia. Daily progress notes and sign‐out documents must reflect the progressive refinement in classification of each item and give the current status of the diagnostic evaluation. When therapy has been established, daily notes must reflect its precise status relative to its end points; examples include place in the timeline for antibiotics or, for a bleeding patient, a tally of blood products and their impact. In the end, we must ensure that the discharge summary reflects the highest level of diagnostic resolution achieved for each problem we have identified. In so doing, we will help to ensure coherent and efficient care for our patients, save time and spare confusion for our colleagues, and teach our trainees to think and communicate clearly about our collective efforts.
- .Medical Records, Medical Education and Patient Care.Cleveland, OH:Press of Case Western Reserve University;1971.
- .Medical records that guide and teach (concluded).N Engl J Med.1968;278:593–600.
- .Ten reasons why Lawrence Weed is right.N Engl J Med.1971;284:51–52.
My hospital's electronic medical record helpfully informs me after 1 week on service that there are 524 data available for my attention, a statistic that would be paralyzing without a cognitive framework for organizing and interpreting them in a manner that can be shared among my colleagues. Accurate information flow among clinicians was identified early on as an imperative of hospital medicine. Much attention has been focused on communication during transitions of care, such as that between inpatient and outpatient services and between inpatient teams, taking the form of the discharge summary and the sign‐out, respectively. But communication among physicians, consultants, and allied therapists must and inevitably does occur continuously day by day during even the most uneventful hospital stay. On academic services the need to keep multiple and ever‐rotating team members on the same page, so to speak, is particularly pressing.
The succinct and accurate problem list, formulated at the end of the history and physical examination and propagated through daily progress notes, is a powerful tool for promoting clear diagnostic and therapeutic planning and is ideally suited to meeting the need for continuous information flow among clinicians. Sadly, this inexpensive and potentially elegant device has fallen into disuse and disrepair and is in need of restoration.
In the 1960s, Dr. Lawrence Weed, the inventor of the SOAP note and a pioneer of medical informatics, wrote of the power of the problem list to impose order on the chaos of clinical information and to aid clear diagnostic thinking, in contrast with the simply chronological record popular in earlier years:
It is this multiplicity of problems with which the physician must deal in his daily work.[T]he multiplicity is inevitable but a random approach to the difficulties it creates is not. The instruction of physicians should be based on a system that helps them to define and follow clinical problems one by one and then systematically to relate and resolve them.[T]the basic criterion of the physician is how well he can identify the patient's problems and organize them for solution.1
Weed proposed that the product of our diagnostic thinking and investigations should be a concise list of diagnoses, as precisely as we are able to identify them, or, in their absence, a clear understanding of the specific problems awaiting resolution and a clear appreciation of the interrelationships among these entities:
The list shouldstate the problems at a level of refinement consistent with the physician's understanding, running the gamut from the precise diagnosis to the isolated, unexplained finding. Each item should be classified as one of the following: (1) a diagnosis, e.g., ASHD, followed by the principal manifestation that requires management; (2) a physiological finding, e.g., heart failure, followed by either the phrase etiology unknown or secondary to a diagnosis; (3) a symptom or physical finding, e.g., shortness of breath; or (4) an abnormal laboratory finding, e.g., an abnormal EKG. If a given diagnosis has several major manifestations, each of which requires individual management and separate, carefully delineated progress notes, then the second manifestation is presented as a second problem and designated as secondary to the major diagnosis.1
These principles were widely praised and adopted. An editorial in the New England Journal of Medicine proclaimed that his system is the essence of education itself,3 and it reigned throughout my own formal medical education.
In the decade that has seen our specialty flourish, with the attendant imperatives of clear thinking and communication, in teaching hospitals the problem list seems to have become an endangered species. The general pattern of its decline is that it is often supplanted by a list of organs, or worse, medical subspecialties, each followed by some assessment of its condition, whether diseased or not. The format resembles that used in critical care units for patients with multiple vital functions in jeopardy, on which survival depends from minute to minute, sometimes regardless of the original etiology of their failure. It is not clear how these notes began to spread from the ICU to the medical floor, where puzzles are solved and progress has goals more varied than mere survival. None of the residents I have queried over the years seem to know. The prevalence of this habit is also unknown, but it is widespread at both institutions at which I have been recently affiliated, and from the generation of notes in this format by trainees freshly graduated from medical schools across the land, I infer that it is no mere regional phenomenon. There may be an unspoken assumption that if this format is used for the sickest patients, it must be the superior format to use for all patients. Perhaps it reflects subspecialists teaching inpatient medicine, equipping trainees with vast technical knowledge of specific diseases and placing less emphasis on formulating coherent assessments. I believe its effects are pernicious and far‐reaching, affecting not only the quality of information flow among clinicians, but also the quality and rigor of diagnostic thinking of those in our training programs.
The history and physical examination properly culminate in the formulation of a problem list that establishes the framework for subsequent investigations and therapy. For each problem a narrative thread is initiated that can be followed in progress notes to resolution and succinctly reviewed in the discharge summary. It is now common to see diagnostic formulations arranged not by problem but by organ or subspecialty, for example, Endocrine: DKA. As everyone understands DKA to be an endocrine problem, the organ system preface adds nothing useful and only serves to bury the diagnosis in text. More tortured prose follows attempts to cram into the header all organs or specialties touched by the problem; hence pneumonia is often preceded by pulmonary/ID. A more egregious recent example was an esophageal variceal hemorrhage designated GI/Heme. And efforts to force an undifferentiated problem into an organ group can reach absurdity: Heme: Asymmetric leg swelling raised concern for DVT, but ultrasound was negative.
The organ preface at best merely adds clutter; the difficulty is compounded when the actual diagnosis or problem is omitted entirely in favor of mention of the organs, for example, for pneumonia: Pulm/ID: begin antibiotics. The reader may be left to guess exactly what is being treated, as with CV: begin heparin and beta‐blocker. The assessment and subsequent notes become even more unwieldy when the unifying diagnosis is approached circuitously on paper by way of its component elements, as with a recent patient with typical lobar pneumonia who was assessed by the house officer as having (1) ID: fever probably due to pneumonia; (2) Pulm: Hypoxia, sputum production and infiltrate on CXR consistent with pneumonia; and (3) Heme: leukocytosis likely due to pneumonia as well. Synthesis, the holy grail of the H&P, is thus replaced by analysis. Each tree is closely inspected, but we are lost in the forest. Weed wrote of such notes:
Failure to integrate findings into a valid single entity can almost always be traced to incomplete understanding.If a beginner puts cardiomegaly, edema, hepatomegaly and shortness of breath as four separate problems, it is his way of clearly admitting that he does not recognize cardiac failure when he sees it.2
Often, however, as in the example above, the physician fully understands the unifying diagnosis but nonetheless insists on addressing involved systems separately. Each feature is then apt to be separately followed in isolation through the progress notes, sometimes without any further mention of pneumonia as such. Many progress notes thus omit stating what is actually thought to be wrong with the patient.
The failure to commit to a diagnosis on paper, even when having done so in practice, ultimately can make its way to the discharge summary, propagating confusion to the outpatient department and ricocheting it into future admissions. It also robs us of the satisfaction of declaring a puzzle solved. I was compelled to write this piece in part by the recent case of a young woman who presented with fever and dyspnea. Through an elegant series of imaging studies and serologic tests, a diagnosis of lupus pericarditis was established, and steroid therapy produced dramatic remission of her symptomsa diagnostic triumph by any measure. How disheartening then to read the resident's final diagnosis for posterity in the discharge summary: fever and dyspnea.
The disembodied organ list thus sows confusion and redundant, convoluted prose throughout the medical record. Perhaps even more destructive is its effect on diagnostic thinking when applied to undifferentiated symptoms or problems, the general internist's pice de rsistance. Language shapes thought, and premature assignment of symptoms to a single organ or subspecialty constrains the imagination needed to puzzle things out. Examples are everywhere. Fever of unknown origin may be peremptorily designated ID, by implication excluding inflammatory, neoplastic, and iatrogenic causes from consideration. The asymmetrically swollen legs cited earlier are not hematologic, but they are still swollen. Undiagnosed problems should be labeled as such, with comment as to the differential diagnosis as it stands at the time and the status of the investigation. When a diagnosis is established, it should replace the undifferentiated symptom or abnormal finding in the list, with cardinal manifestations addressed as such when necessary. Thus, for example, fever in an intravenous drug user becomes endocarditis, and anasarca becomes nephrotic syndrome becomes glomerulonephritis as the diagnosis is established and refined. Weed saw the promise of the well‐groomed, problem‐based record in teaching diagnostic thinking:
The education of a physicianshould be based on his clinical experience and should be reflected in the records he maintains on his patients.The educationbecomes defective not when he is given too much or too little training in basic sciencebut rather when he is allowed to ignore or slight the elementary definition and the progressive adjustment of the problems that comprise his clinical experience. The teacher who ultimately benefits students the most is the one who is willing to establish parameters of discipline in the not unsophisticated but often unappreciated task of preventing this imprecision and disorganization.1
Hospitalists as generalist clinician‐educators have an opportunity to teach fundamental principles of medicine that span subspecialties. These principles must include clear organization and prioritization of complex medical information to enable coherent diagnostic and therapeutic planning and smooth continuity of care. The sign‐out and the all‐important discharge summary can be only as clear and as logical as the diagnoses that inform them. To these ends, let us maintain and reinvigorate the art of the problem list. As an exercise at morning report and attending rounds, we should emphasize the development of an accurate, comprehensive list of active problems before moving on to detailed discussion of any single issue, as Weed suggested nearly 40 years ago:
A serious mistake in teaching medicine is to expose the student, the house officer, or the physician to an analytical discussion of the diagnosis and management of one problem before establishing whether or not he is capable of identifying and defining all of the patient's problems at the outset1
We should expect this list to be formulated at the end of the admission history and physical examination. We must ensure that trainees can correctly identify the level of resolution achieved for each item. They must learn to distinguish among undifferentiated symptoms, for example, passed out; undifferentiated problems, expressed by medical terms with precise meaning, such as syncope; and precise etiologic diagnoses, such as ventricular tachycardia. Daily progress notes and sign‐out documents must reflect the progressive refinement in classification of each item and give the current status of the diagnostic evaluation. When therapy has been established, daily notes must reflect its precise status relative to its end points; examples include place in the timeline for antibiotics or, for a bleeding patient, a tally of blood products and their impact. In the end, we must ensure that the discharge summary reflects the highest level of diagnostic resolution achieved for each problem we have identified. In so doing, we will help to ensure coherent and efficient care for our patients, save time and spare confusion for our colleagues, and teach our trainees to think and communicate clearly about our collective efforts.
My hospital's electronic medical record helpfully informs me after 1 week on service that there are 524 data available for my attention, a statistic that would be paralyzing without a cognitive framework for organizing and interpreting them in a manner that can be shared among my colleagues. Accurate information flow among clinicians was identified early on as an imperative of hospital medicine. Much attention has been focused on communication during transitions of care, such as that between inpatient and outpatient services and between inpatient teams, taking the form of the discharge summary and the sign‐out, respectively. But communication among physicians, consultants, and allied therapists must and inevitably does occur continuously day by day during even the most uneventful hospital stay. On academic services the need to keep multiple and ever‐rotating team members on the same page, so to speak, is particularly pressing.
The succinct and accurate problem list, formulated at the end of the history and physical examination and propagated through daily progress notes, is a powerful tool for promoting clear diagnostic and therapeutic planning and is ideally suited to meeting the need for continuous information flow among clinicians. Sadly, this inexpensive and potentially elegant device has fallen into disuse and disrepair and is in need of restoration.
In the 1960s, Dr. Lawrence Weed, the inventor of the SOAP note and a pioneer of medical informatics, wrote of the power of the problem list to impose order on the chaos of clinical information and to aid clear diagnostic thinking, in contrast with the simply chronological record popular in earlier years:
It is this multiplicity of problems with which the physician must deal in his daily work.[T]he multiplicity is inevitable but a random approach to the difficulties it creates is not. The instruction of physicians should be based on a system that helps them to define and follow clinical problems one by one and then systematically to relate and resolve them.[T]the basic criterion of the physician is how well he can identify the patient's problems and organize them for solution.1
Weed proposed that the product of our diagnostic thinking and investigations should be a concise list of diagnoses, as precisely as we are able to identify them, or, in their absence, a clear understanding of the specific problems awaiting resolution and a clear appreciation of the interrelationships among these entities:
The list shouldstate the problems at a level of refinement consistent with the physician's understanding, running the gamut from the precise diagnosis to the isolated, unexplained finding. Each item should be classified as one of the following: (1) a diagnosis, e.g., ASHD, followed by the principal manifestation that requires management; (2) a physiological finding, e.g., heart failure, followed by either the phrase etiology unknown or secondary to a diagnosis; (3) a symptom or physical finding, e.g., shortness of breath; or (4) an abnormal laboratory finding, e.g., an abnormal EKG. If a given diagnosis has several major manifestations, each of which requires individual management and separate, carefully delineated progress notes, then the second manifestation is presented as a second problem and designated as secondary to the major diagnosis.1
These principles were widely praised and adopted. An editorial in the New England Journal of Medicine proclaimed that his system is the essence of education itself,3 and it reigned throughout my own formal medical education.
In the decade that has seen our specialty flourish, with the attendant imperatives of clear thinking and communication, in teaching hospitals the problem list seems to have become an endangered species. The general pattern of its decline is that it is often supplanted by a list of organs, or worse, medical subspecialties, each followed by some assessment of its condition, whether diseased or not. The format resembles that used in critical care units for patients with multiple vital functions in jeopardy, on which survival depends from minute to minute, sometimes regardless of the original etiology of their failure. It is not clear how these notes began to spread from the ICU to the medical floor, where puzzles are solved and progress has goals more varied than mere survival. None of the residents I have queried over the years seem to know. The prevalence of this habit is also unknown, but it is widespread at both institutions at which I have been recently affiliated, and from the generation of notes in this format by trainees freshly graduated from medical schools across the land, I infer that it is no mere regional phenomenon. There may be an unspoken assumption that if this format is used for the sickest patients, it must be the superior format to use for all patients. Perhaps it reflects subspecialists teaching inpatient medicine, equipping trainees with vast technical knowledge of specific diseases and placing less emphasis on formulating coherent assessments. I believe its effects are pernicious and far‐reaching, affecting not only the quality of information flow among clinicians, but also the quality and rigor of diagnostic thinking of those in our training programs.
The history and physical examination properly culminate in the formulation of a problem list that establishes the framework for subsequent investigations and therapy. For each problem a narrative thread is initiated that can be followed in progress notes to resolution and succinctly reviewed in the discharge summary. It is now common to see diagnostic formulations arranged not by problem but by organ or subspecialty, for example, Endocrine: DKA. As everyone understands DKA to be an endocrine problem, the organ system preface adds nothing useful and only serves to bury the diagnosis in text. More tortured prose follows attempts to cram into the header all organs or specialties touched by the problem; hence pneumonia is often preceded by pulmonary/ID. A more egregious recent example was an esophageal variceal hemorrhage designated GI/Heme. And efforts to force an undifferentiated problem into an organ group can reach absurdity: Heme: Asymmetric leg swelling raised concern for DVT, but ultrasound was negative.
The organ preface at best merely adds clutter; the difficulty is compounded when the actual diagnosis or problem is omitted entirely in favor of mention of the organs, for example, for pneumonia: Pulm/ID: begin antibiotics. The reader may be left to guess exactly what is being treated, as with CV: begin heparin and beta‐blocker. The assessment and subsequent notes become even more unwieldy when the unifying diagnosis is approached circuitously on paper by way of its component elements, as with a recent patient with typical lobar pneumonia who was assessed by the house officer as having (1) ID: fever probably due to pneumonia; (2) Pulm: Hypoxia, sputum production and infiltrate on CXR consistent with pneumonia; and (3) Heme: leukocytosis likely due to pneumonia as well. Synthesis, the holy grail of the H&P, is thus replaced by analysis. Each tree is closely inspected, but we are lost in the forest. Weed wrote of such notes:
Failure to integrate findings into a valid single entity can almost always be traced to incomplete understanding.If a beginner puts cardiomegaly, edema, hepatomegaly and shortness of breath as four separate problems, it is his way of clearly admitting that he does not recognize cardiac failure when he sees it.2
Often, however, as in the example above, the physician fully understands the unifying diagnosis but nonetheless insists on addressing involved systems separately. Each feature is then apt to be separately followed in isolation through the progress notes, sometimes without any further mention of pneumonia as such. Many progress notes thus omit stating what is actually thought to be wrong with the patient.
The failure to commit to a diagnosis on paper, even when having done so in practice, ultimately can make its way to the discharge summary, propagating confusion to the outpatient department and ricocheting it into future admissions. It also robs us of the satisfaction of declaring a puzzle solved. I was compelled to write this piece in part by the recent case of a young woman who presented with fever and dyspnea. Through an elegant series of imaging studies and serologic tests, a diagnosis of lupus pericarditis was established, and steroid therapy produced dramatic remission of her symptomsa diagnostic triumph by any measure. How disheartening then to read the resident's final diagnosis for posterity in the discharge summary: fever and dyspnea.
The disembodied organ list thus sows confusion and redundant, convoluted prose throughout the medical record. Perhaps even more destructive is its effect on diagnostic thinking when applied to undifferentiated symptoms or problems, the general internist's pice de rsistance. Language shapes thought, and premature assignment of symptoms to a single organ or subspecialty constrains the imagination needed to puzzle things out. Examples are everywhere. Fever of unknown origin may be peremptorily designated ID, by implication excluding inflammatory, neoplastic, and iatrogenic causes from consideration. The asymmetrically swollen legs cited earlier are not hematologic, but they are still swollen. Undiagnosed problems should be labeled as such, with comment as to the differential diagnosis as it stands at the time and the status of the investigation. When a diagnosis is established, it should replace the undifferentiated symptom or abnormal finding in the list, with cardinal manifestations addressed as such when necessary. Thus, for example, fever in an intravenous drug user becomes endocarditis, and anasarca becomes nephrotic syndrome becomes glomerulonephritis as the diagnosis is established and refined. Weed saw the promise of the well‐groomed, problem‐based record in teaching diagnostic thinking:
The education of a physicianshould be based on his clinical experience and should be reflected in the records he maintains on his patients.The educationbecomes defective not when he is given too much or too little training in basic sciencebut rather when he is allowed to ignore or slight the elementary definition and the progressive adjustment of the problems that comprise his clinical experience. The teacher who ultimately benefits students the most is the one who is willing to establish parameters of discipline in the not unsophisticated but often unappreciated task of preventing this imprecision and disorganization.1
Hospitalists as generalist clinician‐educators have an opportunity to teach fundamental principles of medicine that span subspecialties. These principles must include clear organization and prioritization of complex medical information to enable coherent diagnostic and therapeutic planning and smooth continuity of care. The sign‐out and the all‐important discharge summary can be only as clear and as logical as the diagnoses that inform them. To these ends, let us maintain and reinvigorate the art of the problem list. As an exercise at morning report and attending rounds, we should emphasize the development of an accurate, comprehensive list of active problems before moving on to detailed discussion of any single issue, as Weed suggested nearly 40 years ago:
A serious mistake in teaching medicine is to expose the student, the house officer, or the physician to an analytical discussion of the diagnosis and management of one problem before establishing whether or not he is capable of identifying and defining all of the patient's problems at the outset1
We should expect this list to be formulated at the end of the admission history and physical examination. We must ensure that trainees can correctly identify the level of resolution achieved for each item. They must learn to distinguish among undifferentiated symptoms, for example, passed out; undifferentiated problems, expressed by medical terms with precise meaning, such as syncope; and precise etiologic diagnoses, such as ventricular tachycardia. Daily progress notes and sign‐out documents must reflect the progressive refinement in classification of each item and give the current status of the diagnostic evaluation. When therapy has been established, daily notes must reflect its precise status relative to its end points; examples include place in the timeline for antibiotics or, for a bleeding patient, a tally of blood products and their impact. In the end, we must ensure that the discharge summary reflects the highest level of diagnostic resolution achieved for each problem we have identified. In so doing, we will help to ensure coherent and efficient care for our patients, save time and spare confusion for our colleagues, and teach our trainees to think and communicate clearly about our collective efforts.
- .Medical Records, Medical Education and Patient Care.Cleveland, OH:Press of Case Western Reserve University;1971.
- .Medical records that guide and teach (concluded).N Engl J Med.1968;278:593–600.
- .Ten reasons why Lawrence Weed is right.N Engl J Med.1971;284:51–52.
- .Medical Records, Medical Education and Patient Care.Cleveland, OH:Press of Case Western Reserve University;1971.
- .Medical records that guide and teach (concluded).N Engl J Med.1968;278:593–600.
- .Ten reasons why Lawrence Weed is right.N Engl J Med.1971;284:51–52.