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Constructing a collaborative neuroscience hospitalist program
In the Literature
Literature at a Glance
- Postoperative prophylactic LMWH should be considered for arthroscopic knee surgery patients.
- Individualized therapy is required for DVT prophylaxis in the neurosurgical patient.
- SMART-COP is a reasonable screening tool for ICU admission.
- Mediterranean and low-carb diets are safe and effective alternatives to low-fat diets.
- Admissions for ACS in both smokers and non-smokers decrease after implementation of smoking ban.
- Beta-blockers should be continued whenever possible in patients hospitalized for heart failure with LVSD.
- Non-invasive ventilation improved dyspnea, but did not improve short-term mortality rates in patients with acute cardiogenic pulmonary edema.
- COX-2 inhibitors should be used with caution in patients with increased cerebrovascular disease risk.
LMWH after Arthroscopic Knee Surgery May Prevent VTE Compared to Graduated Compression Stockings
Clinical question: Does low molecular weight heparin (LMWH) prevent venous thromboembolism (VTE) compared to compression stockings without increasing bleeding complications in arthroscopic knee surgery?
Background: Knee arthroscopy is a common orthopedic surgery and postoperative venous thromboprophylaxis is not routinely recommended.
Study design: Randomized, controlled trial with blinding of the investigators.
Setting: Single orthopedic clinic in Italy, with followup at a university hospital.
Synopsis: 1,761 consecutive patients undergoing knee arthroscopy were randomly assigned to full-length graduated compression stockings (CS) for seven days postoperatively, subcutaneous LMWH (nadoparin 3800 units daily) for seven or 14 days postoperatively. The primary outcome of asymptomatic proximal deep venous thrombosis (DVT), symptomatic VTE, and all-cause mortality within three months of surgery was higher with CS (3.2%) than with LMWH for seven or 14 days (0.9% in each group) (P=0.005). There was no significant difference in bleeding events between groups.
The study was underpowered to detect differences in bleeding risk. Furthermore, almost half the events making up the primary outcome were distal DVTs of uncertain clinical significance. Notably, the 14-day LMWH group was discontinued early because of unspecified safety concerns related to longer exposure to LMWH.
Bottom line: Postoperative prophylactic LMWH for seven days may prevent some thromboses after knee surgery and should be considered in higher-risk patients.
Citation: Camporese G, Bernardi E, Prandoni P, et al. Low-molecular-weight heparin versus compression stockings for thrombophylaxis after knee arthroscopy. Ann Intern Med. 2008;14(9):73-82.
Heparins and Compression Devices are Effective in Preventing VTE in a Mixed Neurosurgical Population
Clinical question: What is the efficacy and safety of LMWH, unfractionated heparin, and mechanical devices in preventing VTE in neurosurgical patients?
Background: Neurosurgical patients are at high risk for VTE, but concerns remain regarding the risk of bleeding complications with the use of LMWH or unfractionated heparin (UFH).
Study design: Meta-analysis of 18 randomized trials and 12 cohort studies.
Setting: Patients undergoing spinal surgery or craniotomy.
Synopsis: Among all patients, the pooled DVT rate was 15.5/100. Use of sequential compression devices (SCD) significantly reduced the risk of DVT compared with placebo (relative risk [RR] 0.41, 95% confidence interval [CI] 0.21-0.78). Subcutaneous LMWH was associated with a significantly reduced risk of DVT compared with CS (RR 0.60, 95% CI 0.44-0.81). No other head-to-head comparisons were associated with significant reductions in VTE risk. After adjusting for potential risk factors for DVT and study design, use of heparins or SCDs was associated with a lower risk of DVT. Intracranial hemorrhage (ICH), minor bleeding, major bleeding, or death was not statistically different between any of the groups, although, after adjustment, LMWH was associated with a slightly increased risk of ICH.
The quality of included studies varied considerably and inter-rater agreement on study quality was low, raising the possibility of study selection bias. Potential publication bias was not addressed. Bleeding complications were rare, so the estimates of risk may be imprecise.
Bottom line: Individualized therapy is required for DVT prophylaxis in the neurosurgical patient; SCDs reduce VTE risk and both pharmacologic and mechanical prophylaxis may be indicated in patients with increased VTE risk.
Citation: Collen JF, Jackson JL, Shorr AF, Moores LK. Prevention of venous thromboembolism in neurosurgery: A metaanalysis. Chest. 2008;13(4):237-249.
SMART-COP Predicts Need for ICU Care in CAP
Clinical question: Can a clinical tool predict the need for critical care in community acquired pneumonia (CAP)?
Background: Clinical tools predicting 30-day mortality in community acquired pneumonia (CAP) exist, but do not accurately identify who will require intensive care unit-level care, such as intensive respiratory or vasosuppressor support (IRVS).
Study design: Prospective multi-center observational study.
Setting: Six hospitals in Australia participating in the Australian Community Acquired Pneumonia Study (ACAPS).
Synopsis: Multivariate analysis of a dataset of 882 episodes of CAP identified eight factors that were associated with the need for IRVS, summarized by the mnemonic “SMART-COP” (Systolic blood pressure, Multilobar chest radiography involvement, low Albumin level, high Respiratory rate, Tachycardia, Confusion, poor Oxygenation, and low arterial pH). Assigning one point for five factors and two points for three factors (systolic blood pressure, poor oxygenation, and low arterial pH) a SMART-COP score >3 identified 92.3% (95% CI 84.8-96.9%) of patients who required IRVS, including 84% who did not initially require ICU care. Specificity was 62.3% (CI 58.8-65.7%). Test characteristics for predicting IRVS were superior to existing prediction rules (PSI and CURB-65).
Most patients were drawn from large, urban teaching hospitals in Australia, so the results may not be generalizable. The authors also presented a modification of SMART-COP, using pulse oximetry rather than blood gas results; this may be even more useful in the pre-hospital setting.
Bottom line: SMART-COP is a reasonable screening tool for predicting need for ICU-level care in patients admitted with CAP.
Citation: Charles PGP, Wolfe, R, Whitby, M, et. al. SMART-COP: a tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia. Clin Infect Dis. 2008;47(3):375-384.
Mediterranean and Low-Carbohydrate Diets are Effective for Weight Loss
Clinical question: Are dietary intervention with low-fat, Mediterranean or low-carbohydrate diets effective?
Background: Obesity is a growing, worldwide problem. Past trials comparing the effectiveness and safety of various dietary interventions have been limited by short follow up and high dropout rates.
Study design: Prospective randomized trial.
Setting: Employees of a research center in Israel.
Synopsis: 322 subjects (average BMI 31) were randomized to a low-fat/restricted-calorie, Mediterranean/ restricted-calorie, or a low-carbohydrate/non-restricted calorie diet. Diet adherence was 84.6% at two years and all groups lost significant amounts of weight. The Mediterranean and low-carbohydrate diets showed similar aver∆age weight loss of 4.4 kg and 4.7 kg, respectively. The low-fat diet group on average lost 2.9 kg. Diabetic patients had improved glycemic control and lower insulin levels with the Mediterranean diet. Subjects assigned to the low-carbohydrate diet had the greatest improvement in lipid profile (20% relative decrease of total cholesterol to HDL ratio).
The trial took place at a single site (a scientific research center in Israel) and included only 14% women, so its generalization is uncertain. The study was based on self-reported dietary intake and may be subject to reporting bias.
Bottom line: Mediterranean and low-carbohydrate diets are safe and effective alternatives to low-fat diets with favorable effects on glycemic control in diabetics and lipid metabolism, respectively.
Citation: Shai I, Schwarz-fuchs D, Henkin Y, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. NEJM. 2008;359(3):229-241.
Admissions for Acute Coronary Syndrome Decreased after Implementation of Smoke-free Legislation
Clinical question: Is there a reduction in admissions for acute coronary syndrome (ACS) after enactment of smoke-free legislation?
Background: Multiple, small, retrospective studies have shown a decrease in ACS after implementation of smoke-free legislation.
Study design: Prospective observational multi-center cohort study.
Setting: Nine hospitals in Scotland.
Synopsis: Data was collected on all patients admitted with ACS 10 months before and after implementation of smoke-free legislation, which prohibited smoking in all enclosed public and work places in Scotland. After the smoking ban, the number of ACS admissions fell by 17% (95% CI 16-18) in Scotland as a whole, compared with a 4% reduction in England during the same period (England does not have similar smoke-free legislation). Among smokers, former smokers and non-smokers, the number of ACS admissions decreased by 14% (95% CI 12-16), 19% (95% CI 17-21), and 21% (95% CI 18-24), respectively. Among non-smokers, self-reported exposure to second-hand smoke decreased significantly; these reductions were confirmed by measured reductions in serum cotinine levels, even among those who never smoked.
Results were limited by the observational nature of the study, although the authors did attempt to carefully match comparison cohorts by season and geography. Also, secular trends other than legislation may have reduced prevalent smoking in Scotland during the study period.
Bottom line: Admissions for ACS for both smokers and non-smokers decreased after implementation of smoke-free legislation.
Citation: Pell JP, Haw S, Cobbe S, et al. Smoke-free legislation and hospitalizations for acute coronary syndrome. NEJM. 2008;359(5):482-491.
Continuation of Beta-blockers in Patients Hospitalized for Heart Failure Improves Mortality
Clinical question: Does the withdrawal or continuation of beta-blockers in patients hospitalized with decompensated heart failure have any effect on clinical outcomes?
Background: Previous clinical trials have demonstrated mortality benefit with the use of beta-blockers in patients with symptomatic chronic heart failure and left ventricular systolic dysfunction (LVSD), however, controversy exists whether to continue these medications in acute decompensated heart failure.
Study design: Prospective cohort analysis from the OPTIMIZE-HF registry (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure).
Setting: 91 academic and community hospitals in the United States.
Synopsis: Data was analyzed on 2,373 registry patients with documented LVSD (EF <40) eligible for beta-blocker therapy. During hospitalization, 1,350 patients were continued on beta-blockers, 79 had therapy withdrawn, 303 were not started, and 632 had beta-blockade initiated. Compared with no beta-blocker treatment, adjusted hazard ratio (HR) for death at 60 and 90 days following discharge was lower in patients who were continued on beta-blockade (HR 0.60, 95% CI 0.37–0.99). Compared with continuation of beta-blockade, withdrawal of beta-blockade increased the risk of death (HR 2.3, 95% CI 1.2–4.6).
Results were limited by the observational nature of the study and short follow up. The reason for discontinuation or not starting beta-blockade was not captured in the database, so it is possible sicker patients had beta-blockers discontinued during hospitalization (although the authors attempted to control for this).
Bottom line: Beta-blockers should be continued whenever possible in patients hospitalized for heart failure with LVSD.
Citation: Fonarow GC, Abraham WT, Albert NM, et al. Influence of beta-blocker continuation or withdrawal on outcomes in patients hospitalized with heart failure. J Am Coll Cardiol. 2008;52(3):190-199.
Non-invasive Ventilation Does Not Improve Short-term Mortality in Acute Cardiogenic Pulmonary Edema
Clinical question: Does non-invasive ventilation reduce mortality in patients with acute cardiogenic pulmonary edema and are there differences in outcome between use of continuous positive airway pressure (CPAP) or non-invasive positive pressure ventilation (NIPPV)?
Background: In patients with acute cardiogenic pulmonary edema, noninvasive ventilation improves physiologic variables and symptoms, decreases rates of invasive ventilation, and may improve mortality.
Study design: Randomized multi center controlled trial.
Setting: 26 district and regional hospitals in the United Kingdom.
Synopsis: 1,156 patients admitted with acute cardiogenic pulmonary edema between July 2003 and April 2007 were randomized to standard oxygen therapy, versus CPAP or NIPPV. There were no significant differences in seven- or 30-day mortality rates between the standard oxygen therapy versus noninvasive ventilation. Mortality at seven days was 9.8% in the standard oxygen group versus 9.5% in the noninvasive ventilation group (P=0.87); 30-day mortality was 16% in the standard oxygen group and 15% in the non-invasive ventilation group (P=0.64). There were no major differences in treatment outcome with NIPPV compared to CPAP.
Although mortality was not decreased, non-invasive ventilation did improve dyspnea and tachycardia within one hour of therapy.
Bottom line: In patients admitted with acute cardiogenic pulmonary edema, noninvasive ventilation improved dyspnea and some physiological parameters, but did not improve short-term mortality rates.
Citation: Gray A, Goodacre S, Newby D, Masson M, Sampson F, Nicholl J. Noninvasive ventilation in acute cardiogenic pulmonary edema. NEJM. 2008;359(2):142-151.
Cyclooxygenase 2 Inhibitors May Increase the Risk of Ischemic Stroke
Clinical question: Do NSAIDs and COX-2 inhibitors increase the risk of ischemic or hemorrhagic stroke?
Background: Selected cyclooxygenase 2 (COX-2) inhibitors have been shown to increase cardiovascular morbidity in a dose-dependent manner and are now used with caution in patients at risk for cardiovascular disease. Little is known about the safety of these medications and non-aspirin, non-steroidal anti-inflammatory drugs (NSAIDS) in those at risk for cerebrovascular disease.
Study design: Retrospective observational cohort study.
Setting: Tennessee Medicaid Program enrollees.
Synopsis: Data was collected from the medical records of 336,906 subjects. Non-users had a baseline stroke rate of 4.51 strokes/1000 person-years. The rate increased to 5.15/1,000 person-years and 5.95/1,000 person-years for rofecoxib and valdecoxib, respectively. Celecoxib and other NSAIDs did not significantly increase the risk of stroke. Analysis of new users of rofexocib and valdecoxib yielded a similarly increased risk of stroke. Most strokes were ischemic.
Limitations include the ready availability of NSAIDs raising the possibility that some patients classified as non-users were actually users of NSAIDs. Other potential confounders may not have been measured and, therefore, not available for analysis.
Bottom line: COX-2 inhibitors should be used with caution in patients with increased cerebrovascular disease risk.
Citation: Roumie CL, Mitchel EF, Kaltenback L, Arbogast PG, Gideon P Griffen MR. Nonaspirin NSAIDs, cyclooxygenase 2 inhibitors, and the risk for stroke. Stroke. 2008;39:1037-2045.
Literature at a Glance
- Postoperative prophylactic LMWH should be considered for arthroscopic knee surgery patients.
- Individualized therapy is required for DVT prophylaxis in the neurosurgical patient.
- SMART-COP is a reasonable screening tool for ICU admission.
- Mediterranean and low-carb diets are safe and effective alternatives to low-fat diets.
- Admissions for ACS in both smokers and non-smokers decrease after implementation of smoking ban.
- Beta-blockers should be continued whenever possible in patients hospitalized for heart failure with LVSD.
- Non-invasive ventilation improved dyspnea, but did not improve short-term mortality rates in patients with acute cardiogenic pulmonary edema.
- COX-2 inhibitors should be used with caution in patients with increased cerebrovascular disease risk.
LMWH after Arthroscopic Knee Surgery May Prevent VTE Compared to Graduated Compression Stockings
Clinical question: Does low molecular weight heparin (LMWH) prevent venous thromboembolism (VTE) compared to compression stockings without increasing bleeding complications in arthroscopic knee surgery?
Background: Knee arthroscopy is a common orthopedic surgery and postoperative venous thromboprophylaxis is not routinely recommended.
Study design: Randomized, controlled trial with blinding of the investigators.
Setting: Single orthopedic clinic in Italy, with followup at a university hospital.
Synopsis: 1,761 consecutive patients undergoing knee arthroscopy were randomly assigned to full-length graduated compression stockings (CS) for seven days postoperatively, subcutaneous LMWH (nadoparin 3800 units daily) for seven or 14 days postoperatively. The primary outcome of asymptomatic proximal deep venous thrombosis (DVT), symptomatic VTE, and all-cause mortality within three months of surgery was higher with CS (3.2%) than with LMWH for seven or 14 days (0.9% in each group) (P=0.005). There was no significant difference in bleeding events between groups.
The study was underpowered to detect differences in bleeding risk. Furthermore, almost half the events making up the primary outcome were distal DVTs of uncertain clinical significance. Notably, the 14-day LMWH group was discontinued early because of unspecified safety concerns related to longer exposure to LMWH.
Bottom line: Postoperative prophylactic LMWH for seven days may prevent some thromboses after knee surgery and should be considered in higher-risk patients.
Citation: Camporese G, Bernardi E, Prandoni P, et al. Low-molecular-weight heparin versus compression stockings for thrombophylaxis after knee arthroscopy. Ann Intern Med. 2008;14(9):73-82.
Heparins and Compression Devices are Effective in Preventing VTE in a Mixed Neurosurgical Population
Clinical question: What is the efficacy and safety of LMWH, unfractionated heparin, and mechanical devices in preventing VTE in neurosurgical patients?
Background: Neurosurgical patients are at high risk for VTE, but concerns remain regarding the risk of bleeding complications with the use of LMWH or unfractionated heparin (UFH).
Study design: Meta-analysis of 18 randomized trials and 12 cohort studies.
Setting: Patients undergoing spinal surgery or craniotomy.
Synopsis: Among all patients, the pooled DVT rate was 15.5/100. Use of sequential compression devices (SCD) significantly reduced the risk of DVT compared with placebo (relative risk [RR] 0.41, 95% confidence interval [CI] 0.21-0.78). Subcutaneous LMWH was associated with a significantly reduced risk of DVT compared with CS (RR 0.60, 95% CI 0.44-0.81). No other head-to-head comparisons were associated with significant reductions in VTE risk. After adjusting for potential risk factors for DVT and study design, use of heparins or SCDs was associated with a lower risk of DVT. Intracranial hemorrhage (ICH), minor bleeding, major bleeding, or death was not statistically different between any of the groups, although, after adjustment, LMWH was associated with a slightly increased risk of ICH.
The quality of included studies varied considerably and inter-rater agreement on study quality was low, raising the possibility of study selection bias. Potential publication bias was not addressed. Bleeding complications were rare, so the estimates of risk may be imprecise.
Bottom line: Individualized therapy is required for DVT prophylaxis in the neurosurgical patient; SCDs reduce VTE risk and both pharmacologic and mechanical prophylaxis may be indicated in patients with increased VTE risk.
Citation: Collen JF, Jackson JL, Shorr AF, Moores LK. Prevention of venous thromboembolism in neurosurgery: A metaanalysis. Chest. 2008;13(4):237-249.
SMART-COP Predicts Need for ICU Care in CAP
Clinical question: Can a clinical tool predict the need for critical care in community acquired pneumonia (CAP)?
Background: Clinical tools predicting 30-day mortality in community acquired pneumonia (CAP) exist, but do not accurately identify who will require intensive care unit-level care, such as intensive respiratory or vasosuppressor support (IRVS).
Study design: Prospective multi-center observational study.
Setting: Six hospitals in Australia participating in the Australian Community Acquired Pneumonia Study (ACAPS).
Synopsis: Multivariate analysis of a dataset of 882 episodes of CAP identified eight factors that were associated with the need for IRVS, summarized by the mnemonic “SMART-COP” (Systolic blood pressure, Multilobar chest radiography involvement, low Albumin level, high Respiratory rate, Tachycardia, Confusion, poor Oxygenation, and low arterial pH). Assigning one point for five factors and two points for three factors (systolic blood pressure, poor oxygenation, and low arterial pH) a SMART-COP score >3 identified 92.3% (95% CI 84.8-96.9%) of patients who required IRVS, including 84% who did not initially require ICU care. Specificity was 62.3% (CI 58.8-65.7%). Test characteristics for predicting IRVS were superior to existing prediction rules (PSI and CURB-65).
Most patients were drawn from large, urban teaching hospitals in Australia, so the results may not be generalizable. The authors also presented a modification of SMART-COP, using pulse oximetry rather than blood gas results; this may be even more useful in the pre-hospital setting.
Bottom line: SMART-COP is a reasonable screening tool for predicting need for ICU-level care in patients admitted with CAP.
Citation: Charles PGP, Wolfe, R, Whitby, M, et. al. SMART-COP: a tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia. Clin Infect Dis. 2008;47(3):375-384.
Mediterranean and Low-Carbohydrate Diets are Effective for Weight Loss
Clinical question: Are dietary intervention with low-fat, Mediterranean or low-carbohydrate diets effective?
Background: Obesity is a growing, worldwide problem. Past trials comparing the effectiveness and safety of various dietary interventions have been limited by short follow up and high dropout rates.
Study design: Prospective randomized trial.
Setting: Employees of a research center in Israel.
Synopsis: 322 subjects (average BMI 31) were randomized to a low-fat/restricted-calorie, Mediterranean/ restricted-calorie, or a low-carbohydrate/non-restricted calorie diet. Diet adherence was 84.6% at two years and all groups lost significant amounts of weight. The Mediterranean and low-carbohydrate diets showed similar aver∆age weight loss of 4.4 kg and 4.7 kg, respectively. The low-fat diet group on average lost 2.9 kg. Diabetic patients had improved glycemic control and lower insulin levels with the Mediterranean diet. Subjects assigned to the low-carbohydrate diet had the greatest improvement in lipid profile (20% relative decrease of total cholesterol to HDL ratio).
The trial took place at a single site (a scientific research center in Israel) and included only 14% women, so its generalization is uncertain. The study was based on self-reported dietary intake and may be subject to reporting bias.
Bottom line: Mediterranean and low-carbohydrate diets are safe and effective alternatives to low-fat diets with favorable effects on glycemic control in diabetics and lipid metabolism, respectively.
Citation: Shai I, Schwarz-fuchs D, Henkin Y, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. NEJM. 2008;359(3):229-241.
Admissions for Acute Coronary Syndrome Decreased after Implementation of Smoke-free Legislation
Clinical question: Is there a reduction in admissions for acute coronary syndrome (ACS) after enactment of smoke-free legislation?
Background: Multiple, small, retrospective studies have shown a decrease in ACS after implementation of smoke-free legislation.
Study design: Prospective observational multi-center cohort study.
Setting: Nine hospitals in Scotland.
Synopsis: Data was collected on all patients admitted with ACS 10 months before and after implementation of smoke-free legislation, which prohibited smoking in all enclosed public and work places in Scotland. After the smoking ban, the number of ACS admissions fell by 17% (95% CI 16-18) in Scotland as a whole, compared with a 4% reduction in England during the same period (England does not have similar smoke-free legislation). Among smokers, former smokers and non-smokers, the number of ACS admissions decreased by 14% (95% CI 12-16), 19% (95% CI 17-21), and 21% (95% CI 18-24), respectively. Among non-smokers, self-reported exposure to second-hand smoke decreased significantly; these reductions were confirmed by measured reductions in serum cotinine levels, even among those who never smoked.
Results were limited by the observational nature of the study, although the authors did attempt to carefully match comparison cohorts by season and geography. Also, secular trends other than legislation may have reduced prevalent smoking in Scotland during the study period.
Bottom line: Admissions for ACS for both smokers and non-smokers decreased after implementation of smoke-free legislation.
Citation: Pell JP, Haw S, Cobbe S, et al. Smoke-free legislation and hospitalizations for acute coronary syndrome. NEJM. 2008;359(5):482-491.
Continuation of Beta-blockers in Patients Hospitalized for Heart Failure Improves Mortality
Clinical question: Does the withdrawal or continuation of beta-blockers in patients hospitalized with decompensated heart failure have any effect on clinical outcomes?
Background: Previous clinical trials have demonstrated mortality benefit with the use of beta-blockers in patients with symptomatic chronic heart failure and left ventricular systolic dysfunction (LVSD), however, controversy exists whether to continue these medications in acute decompensated heart failure.
Study design: Prospective cohort analysis from the OPTIMIZE-HF registry (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure).
Setting: 91 academic and community hospitals in the United States.
Synopsis: Data was analyzed on 2,373 registry patients with documented LVSD (EF <40) eligible for beta-blocker therapy. During hospitalization, 1,350 patients were continued on beta-blockers, 79 had therapy withdrawn, 303 were not started, and 632 had beta-blockade initiated. Compared with no beta-blocker treatment, adjusted hazard ratio (HR) for death at 60 and 90 days following discharge was lower in patients who were continued on beta-blockade (HR 0.60, 95% CI 0.37–0.99). Compared with continuation of beta-blockade, withdrawal of beta-blockade increased the risk of death (HR 2.3, 95% CI 1.2–4.6).
Results were limited by the observational nature of the study and short follow up. The reason for discontinuation or not starting beta-blockade was not captured in the database, so it is possible sicker patients had beta-blockers discontinued during hospitalization (although the authors attempted to control for this).
Bottom line: Beta-blockers should be continued whenever possible in patients hospitalized for heart failure with LVSD.
Citation: Fonarow GC, Abraham WT, Albert NM, et al. Influence of beta-blocker continuation or withdrawal on outcomes in patients hospitalized with heart failure. J Am Coll Cardiol. 2008;52(3):190-199.
Non-invasive Ventilation Does Not Improve Short-term Mortality in Acute Cardiogenic Pulmonary Edema
Clinical question: Does non-invasive ventilation reduce mortality in patients with acute cardiogenic pulmonary edema and are there differences in outcome between use of continuous positive airway pressure (CPAP) or non-invasive positive pressure ventilation (NIPPV)?
Background: In patients with acute cardiogenic pulmonary edema, noninvasive ventilation improves physiologic variables and symptoms, decreases rates of invasive ventilation, and may improve mortality.
Study design: Randomized multi center controlled trial.
Setting: 26 district and regional hospitals in the United Kingdom.
Synopsis: 1,156 patients admitted with acute cardiogenic pulmonary edema between July 2003 and April 2007 were randomized to standard oxygen therapy, versus CPAP or NIPPV. There were no significant differences in seven- or 30-day mortality rates between the standard oxygen therapy versus noninvasive ventilation. Mortality at seven days was 9.8% in the standard oxygen group versus 9.5% in the noninvasive ventilation group (P=0.87); 30-day mortality was 16% in the standard oxygen group and 15% in the non-invasive ventilation group (P=0.64). There were no major differences in treatment outcome with NIPPV compared to CPAP.
Although mortality was not decreased, non-invasive ventilation did improve dyspnea and tachycardia within one hour of therapy.
Bottom line: In patients admitted with acute cardiogenic pulmonary edema, noninvasive ventilation improved dyspnea and some physiological parameters, but did not improve short-term mortality rates.
Citation: Gray A, Goodacre S, Newby D, Masson M, Sampson F, Nicholl J. Noninvasive ventilation in acute cardiogenic pulmonary edema. NEJM. 2008;359(2):142-151.
Cyclooxygenase 2 Inhibitors May Increase the Risk of Ischemic Stroke
Clinical question: Do NSAIDs and COX-2 inhibitors increase the risk of ischemic or hemorrhagic stroke?
Background: Selected cyclooxygenase 2 (COX-2) inhibitors have been shown to increase cardiovascular morbidity in a dose-dependent manner and are now used with caution in patients at risk for cardiovascular disease. Little is known about the safety of these medications and non-aspirin, non-steroidal anti-inflammatory drugs (NSAIDS) in those at risk for cerebrovascular disease.
Study design: Retrospective observational cohort study.
Setting: Tennessee Medicaid Program enrollees.
Synopsis: Data was collected from the medical records of 336,906 subjects. Non-users had a baseline stroke rate of 4.51 strokes/1000 person-years. The rate increased to 5.15/1,000 person-years and 5.95/1,000 person-years for rofecoxib and valdecoxib, respectively. Celecoxib and other NSAIDs did not significantly increase the risk of stroke. Analysis of new users of rofexocib and valdecoxib yielded a similarly increased risk of stroke. Most strokes were ischemic.
Limitations include the ready availability of NSAIDs raising the possibility that some patients classified as non-users were actually users of NSAIDs. Other potential confounders may not have been measured and, therefore, not available for analysis.
Bottom line: COX-2 inhibitors should be used with caution in patients with increased cerebrovascular disease risk.
Citation: Roumie CL, Mitchel EF, Kaltenback L, Arbogast PG, Gideon P Griffen MR. Nonaspirin NSAIDs, cyclooxygenase 2 inhibitors, and the risk for stroke. Stroke. 2008;39:1037-2045.
Literature at a Glance
- Postoperative prophylactic LMWH should be considered for arthroscopic knee surgery patients.
- Individualized therapy is required for DVT prophylaxis in the neurosurgical patient.
- SMART-COP is a reasonable screening tool for ICU admission.
- Mediterranean and low-carb diets are safe and effective alternatives to low-fat diets.
- Admissions for ACS in both smokers and non-smokers decrease after implementation of smoking ban.
- Beta-blockers should be continued whenever possible in patients hospitalized for heart failure with LVSD.
- Non-invasive ventilation improved dyspnea, but did not improve short-term mortality rates in patients with acute cardiogenic pulmonary edema.
- COX-2 inhibitors should be used with caution in patients with increased cerebrovascular disease risk.
LMWH after Arthroscopic Knee Surgery May Prevent VTE Compared to Graduated Compression Stockings
Clinical question: Does low molecular weight heparin (LMWH) prevent venous thromboembolism (VTE) compared to compression stockings without increasing bleeding complications in arthroscopic knee surgery?
Background: Knee arthroscopy is a common orthopedic surgery and postoperative venous thromboprophylaxis is not routinely recommended.
Study design: Randomized, controlled trial with blinding of the investigators.
Setting: Single orthopedic clinic in Italy, with followup at a university hospital.
Synopsis: 1,761 consecutive patients undergoing knee arthroscopy were randomly assigned to full-length graduated compression stockings (CS) for seven days postoperatively, subcutaneous LMWH (nadoparin 3800 units daily) for seven or 14 days postoperatively. The primary outcome of asymptomatic proximal deep venous thrombosis (DVT), symptomatic VTE, and all-cause mortality within three months of surgery was higher with CS (3.2%) than with LMWH for seven or 14 days (0.9% in each group) (P=0.005). There was no significant difference in bleeding events between groups.
The study was underpowered to detect differences in bleeding risk. Furthermore, almost half the events making up the primary outcome were distal DVTs of uncertain clinical significance. Notably, the 14-day LMWH group was discontinued early because of unspecified safety concerns related to longer exposure to LMWH.
Bottom line: Postoperative prophylactic LMWH for seven days may prevent some thromboses after knee surgery and should be considered in higher-risk patients.
Citation: Camporese G, Bernardi E, Prandoni P, et al. Low-molecular-weight heparin versus compression stockings for thrombophylaxis after knee arthroscopy. Ann Intern Med. 2008;14(9):73-82.
Heparins and Compression Devices are Effective in Preventing VTE in a Mixed Neurosurgical Population
Clinical question: What is the efficacy and safety of LMWH, unfractionated heparin, and mechanical devices in preventing VTE in neurosurgical patients?
Background: Neurosurgical patients are at high risk for VTE, but concerns remain regarding the risk of bleeding complications with the use of LMWH or unfractionated heparin (UFH).
Study design: Meta-analysis of 18 randomized trials and 12 cohort studies.
Setting: Patients undergoing spinal surgery or craniotomy.
Synopsis: Among all patients, the pooled DVT rate was 15.5/100. Use of sequential compression devices (SCD) significantly reduced the risk of DVT compared with placebo (relative risk [RR] 0.41, 95% confidence interval [CI] 0.21-0.78). Subcutaneous LMWH was associated with a significantly reduced risk of DVT compared with CS (RR 0.60, 95% CI 0.44-0.81). No other head-to-head comparisons were associated with significant reductions in VTE risk. After adjusting for potential risk factors for DVT and study design, use of heparins or SCDs was associated with a lower risk of DVT. Intracranial hemorrhage (ICH), minor bleeding, major bleeding, or death was not statistically different between any of the groups, although, after adjustment, LMWH was associated with a slightly increased risk of ICH.
The quality of included studies varied considerably and inter-rater agreement on study quality was low, raising the possibility of study selection bias. Potential publication bias was not addressed. Bleeding complications were rare, so the estimates of risk may be imprecise.
Bottom line: Individualized therapy is required for DVT prophylaxis in the neurosurgical patient; SCDs reduce VTE risk and both pharmacologic and mechanical prophylaxis may be indicated in patients with increased VTE risk.
Citation: Collen JF, Jackson JL, Shorr AF, Moores LK. Prevention of venous thromboembolism in neurosurgery: A metaanalysis. Chest. 2008;13(4):237-249.
SMART-COP Predicts Need for ICU Care in CAP
Clinical question: Can a clinical tool predict the need for critical care in community acquired pneumonia (CAP)?
Background: Clinical tools predicting 30-day mortality in community acquired pneumonia (CAP) exist, but do not accurately identify who will require intensive care unit-level care, such as intensive respiratory or vasosuppressor support (IRVS).
Study design: Prospective multi-center observational study.
Setting: Six hospitals in Australia participating in the Australian Community Acquired Pneumonia Study (ACAPS).
Synopsis: Multivariate analysis of a dataset of 882 episodes of CAP identified eight factors that were associated with the need for IRVS, summarized by the mnemonic “SMART-COP” (Systolic blood pressure, Multilobar chest radiography involvement, low Albumin level, high Respiratory rate, Tachycardia, Confusion, poor Oxygenation, and low arterial pH). Assigning one point for five factors and two points for three factors (systolic blood pressure, poor oxygenation, and low arterial pH) a SMART-COP score >3 identified 92.3% (95% CI 84.8-96.9%) of patients who required IRVS, including 84% who did not initially require ICU care. Specificity was 62.3% (CI 58.8-65.7%). Test characteristics for predicting IRVS were superior to existing prediction rules (PSI and CURB-65).
Most patients were drawn from large, urban teaching hospitals in Australia, so the results may not be generalizable. The authors also presented a modification of SMART-COP, using pulse oximetry rather than blood gas results; this may be even more useful in the pre-hospital setting.
Bottom line: SMART-COP is a reasonable screening tool for predicting need for ICU-level care in patients admitted with CAP.
Citation: Charles PGP, Wolfe, R, Whitby, M, et. al. SMART-COP: a tool for predicting the need for intensive respiratory or vasopressor support in community-acquired pneumonia. Clin Infect Dis. 2008;47(3):375-384.
Mediterranean and Low-Carbohydrate Diets are Effective for Weight Loss
Clinical question: Are dietary intervention with low-fat, Mediterranean or low-carbohydrate diets effective?
Background: Obesity is a growing, worldwide problem. Past trials comparing the effectiveness and safety of various dietary interventions have been limited by short follow up and high dropout rates.
Study design: Prospective randomized trial.
Setting: Employees of a research center in Israel.
Synopsis: 322 subjects (average BMI 31) were randomized to a low-fat/restricted-calorie, Mediterranean/ restricted-calorie, or a low-carbohydrate/non-restricted calorie diet. Diet adherence was 84.6% at two years and all groups lost significant amounts of weight. The Mediterranean and low-carbohydrate diets showed similar aver∆age weight loss of 4.4 kg and 4.7 kg, respectively. The low-fat diet group on average lost 2.9 kg. Diabetic patients had improved glycemic control and lower insulin levels with the Mediterranean diet. Subjects assigned to the low-carbohydrate diet had the greatest improvement in lipid profile (20% relative decrease of total cholesterol to HDL ratio).
The trial took place at a single site (a scientific research center in Israel) and included only 14% women, so its generalization is uncertain. The study was based on self-reported dietary intake and may be subject to reporting bias.
Bottom line: Mediterranean and low-carbohydrate diets are safe and effective alternatives to low-fat diets with favorable effects on glycemic control in diabetics and lipid metabolism, respectively.
Citation: Shai I, Schwarz-fuchs D, Henkin Y, et al. Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet. NEJM. 2008;359(3):229-241.
Admissions for Acute Coronary Syndrome Decreased after Implementation of Smoke-free Legislation
Clinical question: Is there a reduction in admissions for acute coronary syndrome (ACS) after enactment of smoke-free legislation?
Background: Multiple, small, retrospective studies have shown a decrease in ACS after implementation of smoke-free legislation.
Study design: Prospective observational multi-center cohort study.
Setting: Nine hospitals in Scotland.
Synopsis: Data was collected on all patients admitted with ACS 10 months before and after implementation of smoke-free legislation, which prohibited smoking in all enclosed public and work places in Scotland. After the smoking ban, the number of ACS admissions fell by 17% (95% CI 16-18) in Scotland as a whole, compared with a 4% reduction in England during the same period (England does not have similar smoke-free legislation). Among smokers, former smokers and non-smokers, the number of ACS admissions decreased by 14% (95% CI 12-16), 19% (95% CI 17-21), and 21% (95% CI 18-24), respectively. Among non-smokers, self-reported exposure to second-hand smoke decreased significantly; these reductions were confirmed by measured reductions in serum cotinine levels, even among those who never smoked.
Results were limited by the observational nature of the study, although the authors did attempt to carefully match comparison cohorts by season and geography. Also, secular trends other than legislation may have reduced prevalent smoking in Scotland during the study period.
Bottom line: Admissions for ACS for both smokers and non-smokers decreased after implementation of smoke-free legislation.
Citation: Pell JP, Haw S, Cobbe S, et al. Smoke-free legislation and hospitalizations for acute coronary syndrome. NEJM. 2008;359(5):482-491.
Continuation of Beta-blockers in Patients Hospitalized for Heart Failure Improves Mortality
Clinical question: Does the withdrawal or continuation of beta-blockers in patients hospitalized with decompensated heart failure have any effect on clinical outcomes?
Background: Previous clinical trials have demonstrated mortality benefit with the use of beta-blockers in patients with symptomatic chronic heart failure and left ventricular systolic dysfunction (LVSD), however, controversy exists whether to continue these medications in acute decompensated heart failure.
Study design: Prospective cohort analysis from the OPTIMIZE-HF registry (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure).
Setting: 91 academic and community hospitals in the United States.
Synopsis: Data was analyzed on 2,373 registry patients with documented LVSD (EF <40) eligible for beta-blocker therapy. During hospitalization, 1,350 patients were continued on beta-blockers, 79 had therapy withdrawn, 303 were not started, and 632 had beta-blockade initiated. Compared with no beta-blocker treatment, adjusted hazard ratio (HR) for death at 60 and 90 days following discharge was lower in patients who were continued on beta-blockade (HR 0.60, 95% CI 0.37–0.99). Compared with continuation of beta-blockade, withdrawal of beta-blockade increased the risk of death (HR 2.3, 95% CI 1.2–4.6).
Results were limited by the observational nature of the study and short follow up. The reason for discontinuation or not starting beta-blockade was not captured in the database, so it is possible sicker patients had beta-blockers discontinued during hospitalization (although the authors attempted to control for this).
Bottom line: Beta-blockers should be continued whenever possible in patients hospitalized for heart failure with LVSD.
Citation: Fonarow GC, Abraham WT, Albert NM, et al. Influence of beta-blocker continuation or withdrawal on outcomes in patients hospitalized with heart failure. J Am Coll Cardiol. 2008;52(3):190-199.
Non-invasive Ventilation Does Not Improve Short-term Mortality in Acute Cardiogenic Pulmonary Edema
Clinical question: Does non-invasive ventilation reduce mortality in patients with acute cardiogenic pulmonary edema and are there differences in outcome between use of continuous positive airway pressure (CPAP) or non-invasive positive pressure ventilation (NIPPV)?
Background: In patients with acute cardiogenic pulmonary edema, noninvasive ventilation improves physiologic variables and symptoms, decreases rates of invasive ventilation, and may improve mortality.
Study design: Randomized multi center controlled trial.
Setting: 26 district and regional hospitals in the United Kingdom.
Synopsis: 1,156 patients admitted with acute cardiogenic pulmonary edema between July 2003 and April 2007 were randomized to standard oxygen therapy, versus CPAP or NIPPV. There were no significant differences in seven- or 30-day mortality rates between the standard oxygen therapy versus noninvasive ventilation. Mortality at seven days was 9.8% in the standard oxygen group versus 9.5% in the noninvasive ventilation group (P=0.87); 30-day mortality was 16% in the standard oxygen group and 15% in the non-invasive ventilation group (P=0.64). There were no major differences in treatment outcome with NIPPV compared to CPAP.
Although mortality was not decreased, non-invasive ventilation did improve dyspnea and tachycardia within one hour of therapy.
Bottom line: In patients admitted with acute cardiogenic pulmonary edema, noninvasive ventilation improved dyspnea and some physiological parameters, but did not improve short-term mortality rates.
Citation: Gray A, Goodacre S, Newby D, Masson M, Sampson F, Nicholl J. Noninvasive ventilation in acute cardiogenic pulmonary edema. NEJM. 2008;359(2):142-151.
Cyclooxygenase 2 Inhibitors May Increase the Risk of Ischemic Stroke
Clinical question: Do NSAIDs and COX-2 inhibitors increase the risk of ischemic or hemorrhagic stroke?
Background: Selected cyclooxygenase 2 (COX-2) inhibitors have been shown to increase cardiovascular morbidity in a dose-dependent manner and are now used with caution in patients at risk for cardiovascular disease. Little is known about the safety of these medications and non-aspirin, non-steroidal anti-inflammatory drugs (NSAIDS) in those at risk for cerebrovascular disease.
Study design: Retrospective observational cohort study.
Setting: Tennessee Medicaid Program enrollees.
Synopsis: Data was collected from the medical records of 336,906 subjects. Non-users had a baseline stroke rate of 4.51 strokes/1000 person-years. The rate increased to 5.15/1,000 person-years and 5.95/1,000 person-years for rofecoxib and valdecoxib, respectively. Celecoxib and other NSAIDs did not significantly increase the risk of stroke. Analysis of new users of rofexocib and valdecoxib yielded a similarly increased risk of stroke. Most strokes were ischemic.
Limitations include the ready availability of NSAIDs raising the possibility that some patients classified as non-users were actually users of NSAIDs. Other potential confounders may not have been measured and, therefore, not available for analysis.
Bottom line: COX-2 inhibitors should be used with caution in patients with increased cerebrovascular disease risk.
Citation: Roumie CL, Mitchel EF, Kaltenback L, Arbogast PG, Gideon P Griffen MR. Nonaspirin NSAIDs, cyclooxygenase 2 inhibitors, and the risk for stroke. Stroke. 2008;39:1037-2045.