Rebecca Helfrich, MD

 

Clinical Question: Can HERDOO2 guide anticoagulation cessation in women with unprovoked venous thromboembolism (VTE)?

Background: Patients with unprovoked VTE have increased recurrence rates after stopping anticoagulation, but no tools have been validated to identify low risk patients.

Study Design: A prospective cohort study.

Setting: Forty-four referral centers in seven countries.

Synopsis: Of patients with unprovoked, symptomatic VTE, 2,747 were evaluated after receiving anticoagulation for 5-12 months. HERDOO2 was used to classify women as low (0-1 points) or high (equal to or greater than 2 points) risk categories. Men were considered high risk. Anticoagulation was stopped for low risk patients. Treatment of high risk patients was left to physician choice.

Overall, high risk patients who continued anticoagulation had a 1.6% recurrence rate. Low risk women who stopped anticoagulation had a 3% recurrence rate per patient year, but postmenopausal women aged 50 years or older had a rate of 5.7%. High risk patients who stopped anticoagulation had a 7.4% recurrence rate. This study included multiple sites, but only 44% of participants were women. HERDOO2 should be used cautiously in postmenopausal women aged 50 years or older and in nonwhite women.

Bottom Line: HERDOO2 may help guide the decision to stop anticoagulation in select low-risk women with unprovoked VTE.

Citation: Rodger MA, Gregoire LG, Anderson DR, et al. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: Multinational prospective cohort management study. BMJ. 2017 March;356:j1065.

Dr. Helfrich is an assistant professor in the University of Kentucky division of hospital medicine.

 

Clinical Question: Can HERDOO2 guide anticoagulation cessation in women with unprovoked venous thromboembolism (VTE)?

Background: Patients with unprovoked VTE have increased recurrence rates after stopping anticoagulation, but no tools have been validated to identify low risk patients.

Study Design: A prospective cohort study.

Setting: Forty-four referral centers in seven countries.

Synopsis: Of patients with unprovoked, symptomatic VTE, 2,747 were evaluated after receiving anticoagulation for 5-12 months. HERDOO2 was used to classify women as low (0-1 points) or high (equal to or greater than 2 points) risk categories. Men were considered high risk. Anticoagulation was stopped for low risk patients. Treatment of high risk patients was left to physician choice.

Overall, high risk patients who continued anticoagulation had a 1.6% recurrence rate. Low risk women who stopped anticoagulation had a 3% recurrence rate per patient year, but postmenopausal women aged 50 years or older had a rate of 5.7%. High risk patients who stopped anticoagulation had a 7.4% recurrence rate. This study included multiple sites, but only 44% of participants were women. HERDOO2 should be used cautiously in postmenopausal women aged 50 years or older and in nonwhite women.

Bottom Line: HERDOO2 may help guide the decision to stop anticoagulation in select low-risk women with unprovoked VTE.

Citation: Rodger MA, Gregoire LG, Anderson DR, et al. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: Multinational prospective cohort management study. BMJ. 2017 March;356:j1065.

Dr. Helfrich is an assistant professor in the University of Kentucky division of hospital medicine.

 

Clinical Question: Can HERDOO2 guide anticoagulation cessation in women with unprovoked venous thromboembolism (VTE)?

Background: Patients with unprovoked VTE have increased recurrence rates after stopping anticoagulation, but no tools have been validated to identify low risk patients.

Study Design: A prospective cohort study.

Setting: Forty-four referral centers in seven countries.

Synopsis: Of patients with unprovoked, symptomatic VTE, 2,747 were evaluated after receiving anticoagulation for 5-12 months. HERDOO2 was used to classify women as low (0-1 points) or high (equal to or greater than 2 points) risk categories. Men were considered high risk. Anticoagulation was stopped for low risk patients. Treatment of high risk patients was left to physician choice.

Overall, high risk patients who continued anticoagulation had a 1.6% recurrence rate. Low risk women who stopped anticoagulation had a 3% recurrence rate per patient year, but postmenopausal women aged 50 years or older had a rate of 5.7%. High risk patients who stopped anticoagulation had a 7.4% recurrence rate. This study included multiple sites, but only 44% of participants were women. HERDOO2 should be used cautiously in postmenopausal women aged 50 years or older and in nonwhite women.

Bottom Line: HERDOO2 may help guide the decision to stop anticoagulation in select low-risk women with unprovoked VTE.

Citation: Rodger MA, Gregoire LG, Anderson DR, et al. Validating the HERDOO2 rule to guide treatment duration for women with unprovoked venous thrombosis: Multinational prospective cohort management study. BMJ. 2017 March;356:j1065.

Dr. Helfrich is an assistant professor in the University of Kentucky division of hospital medicine.

 

Clinical Question: Will a simplified HOSPITAL score accurately predict 30-day readmissions?

Background: Hospital readmissions stress patients and health care systems. Interventions to prevent avoidable readmissions are complex and expensive. The HOSPITAL score predicts 30-day readmissions which may help direct resources toward high risk patients.

Study Design: A retrospective study.

Setting: Nine hospitals in four countries.

Synopsis: The HOSPITAL score was simplified by removing the procedure variable, expanding the oncology criteria to include a diagnosis of cancer, and dividing patients into high and low risk groups. The simplified HOSPITAL score was used to predict avoidable readmissions of 117,065 patients from nine hospitals. Readmission rates predicted by the simplified HOSPITAL score matched observed outcomes with a sensitivity of 94% and specificity of 73%. Its discriminatory power was comparable with the original HOSPITAL score.

This was a robust study of medical patients but may not be generalizable to surgical patients. The score does not include patients’ socioeconomic status or support systems. It also cannot indicate what type of intervention may prevent readmissions.

Bottom Line: The simplified HOSPITAL score accurately predicts avoidable 30-day readmission rates.

Citation: Aubert CE, Schnipper JL, Williams MV, et al. Simplification of the HOSPITAL score for predicting 30-day readmissions. BMJ Qual Saf. Published online first. 17 Apr 2017. doi: 10.1136/bmjqs-2016-006239.

Dr. Helfrich is an assistant professor in the University of Kentucky division of hospital medicine.

 

Clinical Question: Will a simplified HOSPITAL score accurately predict 30-day readmissions?

Background: Hospital readmissions stress patients and health care systems. Interventions to prevent avoidable readmissions are complex and expensive. The HOSPITAL score predicts 30-day readmissions which may help direct resources toward high risk patients.

Study Design: A retrospective study.

Setting: Nine hospitals in four countries.

Synopsis: The HOSPITAL score was simplified by removing the procedure variable, expanding the oncology criteria to include a diagnosis of cancer, and dividing patients into high and low risk groups. The simplified HOSPITAL score was used to predict avoidable readmissions of 117,065 patients from nine hospitals. Readmission rates predicted by the simplified HOSPITAL score matched observed outcomes with a sensitivity of 94% and specificity of 73%. Its discriminatory power was comparable with the original HOSPITAL score.

This was a robust study of medical patients but may not be generalizable to surgical patients. The score does not include patients’ socioeconomic status or support systems. It also cannot indicate what type of intervention may prevent readmissions.

Bottom Line: The simplified HOSPITAL score accurately predicts avoidable 30-day readmission rates.

Citation: Aubert CE, Schnipper JL, Williams MV, et al. Simplification of the HOSPITAL score for predicting 30-day readmissions. BMJ Qual Saf. Published online first. 17 Apr 2017. doi: 10.1136/bmjqs-2016-006239.

Dr. Helfrich is an assistant professor in the University of Kentucky division of hospital medicine.

 

Clinical Question: Will a simplified HOSPITAL score accurately predict 30-day readmissions?

Background: Hospital readmissions stress patients and health care systems. Interventions to prevent avoidable readmissions are complex and expensive. The HOSPITAL score predicts 30-day readmissions which may help direct resources toward high risk patients.

Study Design: A retrospective study.

Setting: Nine hospitals in four countries.

Synopsis: The HOSPITAL score was simplified by removing the procedure variable, expanding the oncology criteria to include a diagnosis of cancer, and dividing patients into high and low risk groups. The simplified HOSPITAL score was used to predict avoidable readmissions of 117,065 patients from nine hospitals. Readmission rates predicted by the simplified HOSPITAL score matched observed outcomes with a sensitivity of 94% and specificity of 73%. Its discriminatory power was comparable with the original HOSPITAL score.

This was a robust study of medical patients but may not be generalizable to surgical patients. The score does not include patients’ socioeconomic status or support systems. It also cannot indicate what type of intervention may prevent readmissions.

Bottom Line: The simplified HOSPITAL score accurately predicts avoidable 30-day readmission rates.

Citation: Aubert CE, Schnipper JL, Williams MV, et al. Simplification of the HOSPITAL score for predicting 30-day readmissions. BMJ Qual Saf. Published online first. 17 Apr 2017. doi: 10.1136/bmjqs-2016-006239.

Dr. Helfrich is an assistant professor in the University of Kentucky division of hospital medicine.

Clinical question: Are beta-2 agonists as effective when administered through a holding chamber (spacer) as they are when administered by a nebulizer?

Background: During an acute asthma attack, beta-2 agonists must be delivered to the peripheral airways. There has been considerable controversy regarding the use of a spacer compared with a nebulizer. Aside from admission rates and length of stay, factors taken into account include cost, maintenance of nebulizer machines, and infection control (potential of cross-infection via nebulizers).

Study design: Meta-analysis review of randomized controlled trials (RCTs).

Setting: Multi-centered, worldwide studies from community setting and EDs.

Synopsis: In 39 studies of patients with an acute asthma attack (selected from Cochrane Airways Group Specialized Register), the hospital admission rates did not differ on the basis of delivery method in 729 adults (risk ratio=0.94, confidence interval 0.61-1.43) or in 1,897 children (risk ratio=0.71, confidence interval 0.47-1.08). Secondary outcomes included the duration of time in the ED and the duration of hospital admission. Time spent in the ED varied for adults but was shorter for children with spacers (based on three studies). Duration of hospital admission also did not differ when modes of delivery were compared.

Bottom line: Providing beta-2 agonists using nebulizers during an acute asthma attack is not more effective than administration using a spacer.

Citation: Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013;9:CD000052.

Clinical question: Are beta-2 agonists as effective when administered through a holding chamber (spacer) as they are when administered by a nebulizer?

Background: During an acute asthma attack, beta-2 agonists must be delivered to the peripheral airways. There has been considerable controversy regarding the use of a spacer compared with a nebulizer. Aside from admission rates and length of stay, factors taken into account include cost, maintenance of nebulizer machines, and infection control (potential of cross-infection via nebulizers).

Study design: Meta-analysis review of randomized controlled trials (RCTs).

Setting: Multi-centered, worldwide studies from community setting and EDs.

Synopsis: In 39 studies of patients with an acute asthma attack (selected from Cochrane Airways Group Specialized Register), the hospital admission rates did not differ on the basis of delivery method in 729 adults (risk ratio=0.94, confidence interval 0.61-1.43) or in 1,897 children (risk ratio=0.71, confidence interval 0.47-1.08). Secondary outcomes included the duration of time in the ED and the duration of hospital admission. Time spent in the ED varied for adults but was shorter for children with spacers (based on three studies). Duration of hospital admission also did not differ when modes of delivery were compared.

Bottom line: Providing beta-2 agonists using nebulizers during an acute asthma attack is not more effective than administration using a spacer.

Citation: Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013;9:CD000052.

Clinical question: Are beta-2 agonists as effective when administered through a holding chamber (spacer) as they are when administered by a nebulizer?

Background: During an acute asthma attack, beta-2 agonists must be delivered to the peripheral airways. There has been considerable controversy regarding the use of a spacer compared with a nebulizer. Aside from admission rates and length of stay, factors taken into account include cost, maintenance of nebulizer machines, and infection control (potential of cross-infection via nebulizers).

Study design: Meta-analysis review of randomized controlled trials (RCTs).

Setting: Multi-centered, worldwide studies from community setting and EDs.

Synopsis: In 39 studies of patients with an acute asthma attack (selected from Cochrane Airways Group Specialized Register), the hospital admission rates did not differ on the basis of delivery method in 729 adults (risk ratio=0.94, confidence interval 0.61-1.43) or in 1,897 children (risk ratio=0.71, confidence interval 0.47-1.08). Secondary outcomes included the duration of time in the ED and the duration of hospital admission. Time spent in the ED varied for adults but was shorter for children with spacers (based on three studies). Duration of hospital admission also did not differ when modes of delivery were compared.

Bottom line: Providing beta-2 agonists using nebulizers during an acute asthma attack is not more effective than administration using a spacer.

Citation: Cates CJ, Welsh EJ, Rowe BH. Holding chambers (spacers) versus nebulisers for beta-agonist treatment of acute asthma. Cochrane Database Syst Rev. 2013;9:CD000052.

Clinical question: Are a longer duration of delirium and higher doses of sedatives associated with cognitive impairment in the hospital?

Background: Survivors of critical illness are at risk for prolonged cognitive dysfunction. Delirium (and factors associated with delirium, namely sedative and analgesic medications) has been implicated in cognitive dysfunction.

Study design: Prospective cohort study.

Setting: Multi-center, academic, and acute care hospitals.

Synopsis: The study examined 821 adults admitted to the ICU with respiratory failure, cardiogenic shock, or septic shock. Patients excluded were those with pre-existing cognitive impairment, those with psychotic disorders, and those for whom follow-up would not be possible. Two risk factors measured were duration of delirium and use of sedative/analgesics. Delirium was assessed at three and 12 months using the CAM-ICU algorithm in the ICU by trained psychology professionals who were unaware of the patients’ in-hospital course.

At three months, 40% of patients had global cognition scores that were 1.5 standard deviations (SD) below population mean (similar to traumatic brain injury), and 26% had scores two SD below population mean (similar to mild Alzheimer’s). At 12 months, 34% had scores similar to traumatic brain injury patients, and 24% had scores similar to mild Alzheimer’s. A longer duration of delirium was associated with worse global cognition at three and 12 months. Use of sedatives/analgesics was not associated with cognitive impairment.

Bottom line: Critically ill patients in the ICU who experience a longer duration of delirium are at risk of long-term cognitive impairments lasting 12 months.

Citation: Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-1316.

Clinical question: Are a longer duration of delirium and higher doses of sedatives associated with cognitive impairment in the hospital?

Background: Survivors of critical illness are at risk for prolonged cognitive dysfunction. Delirium (and factors associated with delirium, namely sedative and analgesic medications) has been implicated in cognitive dysfunction.

Study design: Prospective cohort study.

Setting: Multi-center, academic, and acute care hospitals.

Synopsis: The study examined 821 adults admitted to the ICU with respiratory failure, cardiogenic shock, or septic shock. Patients excluded were those with pre-existing cognitive impairment, those with psychotic disorders, and those for whom follow-up would not be possible. Two risk factors measured were duration of delirium and use of sedative/analgesics. Delirium was assessed at three and 12 months using the CAM-ICU algorithm in the ICU by trained psychology professionals who were unaware of the patients’ in-hospital course.

At three months, 40% of patients had global cognition scores that were 1.5 standard deviations (SD) below population mean (similar to traumatic brain injury), and 26% had scores two SD below population mean (similar to mild Alzheimer’s). At 12 months, 34% had scores similar to traumatic brain injury patients, and 24% had scores similar to mild Alzheimer’s. A longer duration of delirium was associated with worse global cognition at three and 12 months. Use of sedatives/analgesics was not associated with cognitive impairment.

Bottom line: Critically ill patients in the ICU who experience a longer duration of delirium are at risk of long-term cognitive impairments lasting 12 months.

Citation: Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-1316.

Clinical question: Are a longer duration of delirium and higher doses of sedatives associated with cognitive impairment in the hospital?

Background: Survivors of critical illness are at risk for prolonged cognitive dysfunction. Delirium (and factors associated with delirium, namely sedative and analgesic medications) has been implicated in cognitive dysfunction.

Study design: Prospective cohort study.

Setting: Multi-center, academic, and acute care hospitals.

Synopsis: The study examined 821 adults admitted to the ICU with respiratory failure, cardiogenic shock, or septic shock. Patients excluded were those with pre-existing cognitive impairment, those with psychotic disorders, and those for whom follow-up would not be possible. Two risk factors measured were duration of delirium and use of sedative/analgesics. Delirium was assessed at three and 12 months using the CAM-ICU algorithm in the ICU by trained psychology professionals who were unaware of the patients’ in-hospital course.

At three months, 40% of patients had global cognition scores that were 1.5 standard deviations (SD) below population mean (similar to traumatic brain injury), and 26% had scores two SD below population mean (similar to mild Alzheimer’s). At 12 months, 34% had scores similar to traumatic brain injury patients, and 24% had scores similar to mild Alzheimer’s. A longer duration of delirium was associated with worse global cognition at three and 12 months. Use of sedatives/analgesics was not associated with cognitive impairment.

Bottom line: Critically ill patients in the ICU who experience a longer duration of delirium are at risk of long-term cognitive impairments lasting 12 months.

Citation: Pandharipande PP, Girard TD, Jackson JC, et al. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-1316.

Clinical question: How does endoscopic cystogastrostomy for pancreatic pseudocyst drainage compare to the standard surgical approach?

Background: Pancreatic pseudocysts are a common complication of pancreatitis and necessitate decompression when they are accompanied by pain, infection, or obstruction. Decompression of the pseudocyst can be accomplished using either endoscopic or surgical cystogastrostomy.

Study design: Open-label, single-center, randomized trial.

Setting: Single-center U.S. hospital.

Synopsis: A total of 40 patients were randomly equalized to both treatment arms; 20 patients underwent endoscopic and 20 patients underwent surgical cystogastrostomy. Zero patients in the endoscopic therapy had a pseudocyst recurrence, compared with one patient treated surgically. Length of stay (LOS) and cost were lower for the endoscopic group compared to the surgical group (two days vs. six days, P<0.001, $7,011 vs. $15,052, P=0.003).

This study is limited due to several factors. First, patients with pancreatic necrosis were excluded; had these patients been included, the complication rates and LOS would have been higher. Second, cost difference cannot be generalized across the U.S., because Medicare payments are based on provider types and regions.

Bottom line: Endoscopic cystogastrostomy for pancreatic pseudocyst is equal to the standard surgical therapy and results in decreased LOS and reduced costs.

Citation: Varadarajulu S, Bang JY, Sutton BS, Trevino JM, Christein JD, Wilcox CM. Equal efficacy of endoscopic and surgical cystogastrostomy for pancreatic pseudocyst drainage in a randomized trial. Gastroenterology. 2013;145(3):583-590.

Clinical question: How does endoscopic cystogastrostomy for pancreatic pseudocyst drainage compare to the standard surgical approach?

Background: Pancreatic pseudocysts are a common complication of pancreatitis and necessitate decompression when they are accompanied by pain, infection, or obstruction. Decompression of the pseudocyst can be accomplished using either endoscopic or surgical cystogastrostomy.

Study design: Open-label, single-center, randomized trial.

Setting: Single-center U.S. hospital.

Synopsis: A total of 40 patients were randomly equalized to both treatment arms; 20 patients underwent endoscopic and 20 patients underwent surgical cystogastrostomy. Zero patients in the endoscopic therapy had a pseudocyst recurrence, compared with one patient treated surgically. Length of stay (LOS) and cost were lower for the endoscopic group compared to the surgical group (two days vs. six days, P<0.001, $7,011 vs. $15,052, P=0.003).

This study is limited due to several factors. First, patients with pancreatic necrosis were excluded; had these patients been included, the complication rates and LOS would have been higher. Second, cost difference cannot be generalized across the U.S., because Medicare payments are based on provider types and regions.

Bottom line: Endoscopic cystogastrostomy for pancreatic pseudocyst is equal to the standard surgical therapy and results in decreased LOS and reduced costs.

Citation: Varadarajulu S, Bang JY, Sutton BS, Trevino JM, Christein JD, Wilcox CM. Equal efficacy of endoscopic and surgical cystogastrostomy for pancreatic pseudocyst drainage in a randomized trial. Gastroenterology. 2013;145(3):583-590.

Clinical question: How does endoscopic cystogastrostomy for pancreatic pseudocyst drainage compare to the standard surgical approach?

Background: Pancreatic pseudocysts are a common complication of pancreatitis and necessitate decompression when they are accompanied by pain, infection, or obstruction. Decompression of the pseudocyst can be accomplished using either endoscopic or surgical cystogastrostomy.

Study design: Open-label, single-center, randomized trial.

Setting: Single-center U.S. hospital.

Synopsis: A total of 40 patients were randomly equalized to both treatment arms; 20 patients underwent endoscopic and 20 patients underwent surgical cystogastrostomy. Zero patients in the endoscopic therapy had a pseudocyst recurrence, compared with one patient treated surgically. Length of stay (LOS) and cost were lower for the endoscopic group compared to the surgical group (two days vs. six days, P<0.001, $7,011 vs. $15,052, P=0.003).

This study is limited due to several factors. First, patients with pancreatic necrosis were excluded; had these patients been included, the complication rates and LOS would have been higher. Second, cost difference cannot be generalized across the U.S., because Medicare payments are based on provider types and regions.

Bottom line: Endoscopic cystogastrostomy for pancreatic pseudocyst is equal to the standard surgical therapy and results in decreased LOS and reduced costs.

Citation: Varadarajulu S, Bang JY, Sutton BS, Trevino JM, Christein JD, Wilcox CM. Equal efficacy of endoscopic and surgical cystogastrostomy for pancreatic pseudocyst drainage in a randomized trial. Gastroenterology. 2013;145(3):583-590.

Clinical question: Is dual antiplatelet therapy more beneficial or harmful than monotherapy after ischemic stroke?

Background: It is recommended that patients with ischemic stroke or transient ischemic attack (TIA) receive lifelong antiplatelet therapy; however, there have been insufficient studies evaluating the long-term safety of dual antiplatelet therapy.

Study design: Meta-analysis of randomized controlled trials (RCTs)

Setting: Data from PubMed, Embase, and the Cochrane Central Register of Controlled Trials.

Synopsis: Data from seven RCTs, including 39,574 patients with recent TIA or ischemic stroke, were reviewed. Comparisons were made regarding occurrence of intracranial hemorrhage (ICH) and recurrent stroke between patients receiving dual antiplatelet therapy and those receiving aspirin or clopidogrel monotherapy. All patients were treated for at least one year.

There was no difference in recurrent stroke or ICH between patients on dual antiplatelet therapy versus aspirin monotherapy. Patients treated with dual antiplatelet therapy did have a 46% increased risk of ICH without any additional protective benefit for recurrent stroke or TIA when compared with patients on clopidogrel monotherapy.

This information should not be applied in the acute setting, given the high risk of stroke after TIA or ischemic stroke. One major limitation of this study was that the individual trials used different combinations of dual antiplatelet therapy.

Bottom line: The risk of recurrent stroke or TIA after dual antiplatelet therapy and after monotherapy with aspirin or clopidogrel is equal, but the risk of ICH compared to clopidogrel monotherapy is increased.

Citation: Lee M, Saver JL, Hong KS, Rao NM, Wu YL, Ovbiagele B. Risk-benefit profile of long-term dual- versus single-antiplatelet therapy among patients with ischemic stroke: a systematic review and meta-analysis. Ann Intern Med. 2013;159(7):463-470.

Clinical question: Is dual antiplatelet therapy more beneficial or harmful than monotherapy after ischemic stroke?

Background: It is recommended that patients with ischemic stroke or transient ischemic attack (TIA) receive lifelong antiplatelet therapy; however, there have been insufficient studies evaluating the long-term safety of dual antiplatelet therapy.

Study design: Meta-analysis of randomized controlled trials (RCTs)

Setting: Data from PubMed, Embase, and the Cochrane Central Register of Controlled Trials.

Synopsis: Data from seven RCTs, including 39,574 patients with recent TIA or ischemic stroke, were reviewed. Comparisons were made regarding occurrence of intracranial hemorrhage (ICH) and recurrent stroke between patients receiving dual antiplatelet therapy and those receiving aspirin or clopidogrel monotherapy. All patients were treated for at least one year.

There was no difference in recurrent stroke or ICH between patients on dual antiplatelet therapy versus aspirin monotherapy. Patients treated with dual antiplatelet therapy did have a 46% increased risk of ICH without any additional protective benefit for recurrent stroke or TIA when compared with patients on clopidogrel monotherapy.

This information should not be applied in the acute setting, given the high risk of stroke after TIA or ischemic stroke. One major limitation of this study was that the individual trials used different combinations of dual antiplatelet therapy.

Bottom line: The risk of recurrent stroke or TIA after dual antiplatelet therapy and after monotherapy with aspirin or clopidogrel is equal, but the risk of ICH compared to clopidogrel monotherapy is increased.

Citation: Lee M, Saver JL, Hong KS, Rao NM, Wu YL, Ovbiagele B. Risk-benefit profile of long-term dual- versus single-antiplatelet therapy among patients with ischemic stroke: a systematic review and meta-analysis. Ann Intern Med. 2013;159(7):463-470.

Clinical question: Is dual antiplatelet therapy more beneficial or harmful than monotherapy after ischemic stroke?

Background: It is recommended that patients with ischemic stroke or transient ischemic attack (TIA) receive lifelong antiplatelet therapy; however, there have been insufficient studies evaluating the long-term safety of dual antiplatelet therapy.

Study design: Meta-analysis of randomized controlled trials (RCTs)

Setting: Data from PubMed, Embase, and the Cochrane Central Register of Controlled Trials.

Synopsis: Data from seven RCTs, including 39,574 patients with recent TIA or ischemic stroke, were reviewed. Comparisons were made regarding occurrence of intracranial hemorrhage (ICH) and recurrent stroke between patients receiving dual antiplatelet therapy and those receiving aspirin or clopidogrel monotherapy. All patients were treated for at least one year.

There was no difference in recurrent stroke or ICH between patients on dual antiplatelet therapy versus aspirin monotherapy. Patients treated with dual antiplatelet therapy did have a 46% increased risk of ICH without any additional protective benefit for recurrent stroke or TIA when compared with patients on clopidogrel monotherapy.

This information should not be applied in the acute setting, given the high risk of stroke after TIA or ischemic stroke. One major limitation of this study was that the individual trials used different combinations of dual antiplatelet therapy.

Bottom line: The risk of recurrent stroke or TIA after dual antiplatelet therapy and after monotherapy with aspirin or clopidogrel is equal, but the risk of ICH compared to clopidogrel monotherapy is increased.

Citation: Lee M, Saver JL, Hong KS, Rao NM, Wu YL, Ovbiagele B. Risk-benefit profile of long-term dual- versus single-antiplatelet therapy among patients with ischemic stroke: a systematic review and meta-analysis. Ann Intern Med. 2013;159(7):463-470.

Clinical question: Do thrombin and factor Xa inhibitors increase the risk of gastrointestinal (GI) bleeding when compared to vitamin K antagonists and heparins?

Background: New oral anticoagulants (thrombin and factor Xa inhibitors) are available and being used with increased frequency due to equal efficacy and ease of administration. Some studies indicate a higher risk of GI bleeding with these agents. Further evaluation is needed, because no reversal therapy is available.

Study design: Systematic review and meta-analysis.

Setting: Data from MEDLINE, Embase, and the Cochrane Library.

Synopsis: More than 150,000 patients from 43 randomized controlled trials were evaluated for risk of GI bleed when treated with new anticoagulants versus traditional therapy. Patients were treated for one of the following: embolism prevention from atrial fibrillation, venous thromboembolism (VTE) prophylaxis post orthopedic surgery, VTE prophylaxis of medical patients, acute VTE, and acute coronary syndrome (ACS). Use of aspirin or NSAIDs was discouraged but not documented. The odds ratio for GI bleeding with use of the new anticoagulants was 1.45, with a number needed to harm of 500. Evaluation of subgroups revealed increased GI bleed risk in patients treated for ACS and acute thrombosis versus prophylaxis. Post-surgical patients had the lowest risk.

This study was limited by the heterogeneity and differing primary outcomes (mostly efficacy rather than safety) of the included trials. Studies excluded high-risk patients, which the authors estimate to be 25%-40% of actual patients. More studies need to be done that include high-risk patients and focus on GI bleed as a primary outcome.

Bottom line: The new anticoagulants tend to have a higher incidence of GI bleed than traditional therapy, but this varies based on indication of therapy and needs further evaluation to clarify risk.

Citation: Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ET. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology. 2013;145(1):105-112.

Clinical question: Do thrombin and factor Xa inhibitors increase the risk of gastrointestinal (GI) bleeding when compared to vitamin K antagonists and heparins?

Background: New oral anticoagulants (thrombin and factor Xa inhibitors) are available and being used with increased frequency due to equal efficacy and ease of administration. Some studies indicate a higher risk of GI bleeding with these agents. Further evaluation is needed, because no reversal therapy is available.

Study design: Systematic review and meta-analysis.

Setting: Data from MEDLINE, Embase, and the Cochrane Library.

Synopsis: More than 150,000 patients from 43 randomized controlled trials were evaluated for risk of GI bleed when treated with new anticoagulants versus traditional therapy. Patients were treated for one of the following: embolism prevention from atrial fibrillation, venous thromboembolism (VTE) prophylaxis post orthopedic surgery, VTE prophylaxis of medical patients, acute VTE, and acute coronary syndrome (ACS). Use of aspirin or NSAIDs was discouraged but not documented. The odds ratio for GI bleeding with use of the new anticoagulants was 1.45, with a number needed to harm of 500. Evaluation of subgroups revealed increased GI bleed risk in patients treated for ACS and acute thrombosis versus prophylaxis. Post-surgical patients had the lowest risk.

This study was limited by the heterogeneity and differing primary outcomes (mostly efficacy rather than safety) of the included trials. Studies excluded high-risk patients, which the authors estimate to be 25%-40% of actual patients. More studies need to be done that include high-risk patients and focus on GI bleed as a primary outcome.

Bottom line: The new anticoagulants tend to have a higher incidence of GI bleed than traditional therapy, but this varies based on indication of therapy and needs further evaluation to clarify risk.

Citation: Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ET. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology. 2013;145(1):105-112.

Clinical question: Do thrombin and factor Xa inhibitors increase the risk of gastrointestinal (GI) bleeding when compared to vitamin K antagonists and heparins?

Background: New oral anticoagulants (thrombin and factor Xa inhibitors) are available and being used with increased frequency due to equal efficacy and ease of administration. Some studies indicate a higher risk of GI bleeding with these agents. Further evaluation is needed, because no reversal therapy is available.

Study design: Systematic review and meta-analysis.

Setting: Data from MEDLINE, Embase, and the Cochrane Library.

Synopsis: More than 150,000 patients from 43 randomized controlled trials were evaluated for risk of GI bleed when treated with new anticoagulants versus traditional therapy. Patients were treated for one of the following: embolism prevention from atrial fibrillation, venous thromboembolism (VTE) prophylaxis post orthopedic surgery, VTE prophylaxis of medical patients, acute VTE, and acute coronary syndrome (ACS). Use of aspirin or NSAIDs was discouraged but not documented. The odds ratio for GI bleeding with use of the new anticoagulants was 1.45, with a number needed to harm of 500. Evaluation of subgroups revealed increased GI bleed risk in patients treated for ACS and acute thrombosis versus prophylaxis. Post-surgical patients had the lowest risk.

This study was limited by the heterogeneity and differing primary outcomes (mostly efficacy rather than safety) of the included trials. Studies excluded high-risk patients, which the authors estimate to be 25%-40% of actual patients. More studies need to be done that include high-risk patients and focus on GI bleed as a primary outcome.

Bottom line: The new anticoagulants tend to have a higher incidence of GI bleed than traditional therapy, but this varies based on indication of therapy and needs further evaluation to clarify risk.

Citation: Holster IL, Valkhoff VE, Kuipers EJ, Tjwa ET. New oral anticoagulants increase risk for gastrointestinal bleeding: a systematic review and meta-analysis. Gastroenterology. 2013;145(1):105-112.

Clinical question: Does tailoring antibiotics based on known pathogens impact mortality for patients with severe sepsis or shock?

Background: In patients with sepsis, the use of early empiric antibiotics reduces morbidity and mortality. De-escalation therapy refers to narrowing the broad-spectrum antibiotics once the pathogen and sensitivities are known; however, no randomized controlled studies have assessed the impact of this therapy on critically ill patients.

Study design: Prospective observational study.

Setting: Academic hospital ICU in Spain.

Synopsis: From January 2008 to May 2012, 628 adult patients were treated empirically with broad-spectrum antibiotics. De-escalation was applied to 219 patients (34.9%). Outcomes measured were ICU mortality, hospital mortality, and 90-day mortality in patients who received de-escalation therapy, patients whose antibiotics were not changed, and patients for whom antibiotics were escalated.

The in-hospital mortality rate was 27.4% in patients who were de-escalated, 32.6% in the unchanged group, and 42.9% in the escalation group. ICU and 90-day mortality were lower in the de-escalation group. De-escalation was more commonly used in medical than in surgical patients.

This study is limited because it is not a randomized controlled study and was single-centered, so it might only be applicable on the larger scale. Also, multi-drug resistant organisms were not evaluated.

Overall, it is safe to narrow empiric antibiotics in severe sepsis and shock when the pathogen and sensitivities are known.

Bottom line: De-escalation of antibiotics in severe sepsis and septic shock is associated with a lower mortality.

Citation: Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32-40.

Clinical question: Does tailoring antibiotics based on known pathogens impact mortality for patients with severe sepsis or shock?

Background: In patients with sepsis, the use of early empiric antibiotics reduces morbidity and mortality. De-escalation therapy refers to narrowing the broad-spectrum antibiotics once the pathogen and sensitivities are known; however, no randomized controlled studies have assessed the impact of this therapy on critically ill patients.

Study design: Prospective observational study.

Setting: Academic hospital ICU in Spain.

Synopsis: From January 2008 to May 2012, 628 adult patients were treated empirically with broad-spectrum antibiotics. De-escalation was applied to 219 patients (34.9%). Outcomes measured were ICU mortality, hospital mortality, and 90-day mortality in patients who received de-escalation therapy, patients whose antibiotics were not changed, and patients for whom antibiotics were escalated.

The in-hospital mortality rate was 27.4% in patients who were de-escalated, 32.6% in the unchanged group, and 42.9% in the escalation group. ICU and 90-day mortality were lower in the de-escalation group. De-escalation was more commonly used in medical than in surgical patients.

This study is limited because it is not a randomized controlled study and was single-centered, so it might only be applicable on the larger scale. Also, multi-drug resistant organisms were not evaluated.

Overall, it is safe to narrow empiric antibiotics in severe sepsis and shock when the pathogen and sensitivities are known.

Bottom line: De-escalation of antibiotics in severe sepsis and septic shock is associated with a lower mortality.

Citation: Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32-40.

Clinical question: Does tailoring antibiotics based on known pathogens impact mortality for patients with severe sepsis or shock?

Background: In patients with sepsis, the use of early empiric antibiotics reduces morbidity and mortality. De-escalation therapy refers to narrowing the broad-spectrum antibiotics once the pathogen and sensitivities are known; however, no randomized controlled studies have assessed the impact of this therapy on critically ill patients.

Study design: Prospective observational study.

Setting: Academic hospital ICU in Spain.

Synopsis: From January 2008 to May 2012, 628 adult patients were treated empirically with broad-spectrum antibiotics. De-escalation was applied to 219 patients (34.9%). Outcomes measured were ICU mortality, hospital mortality, and 90-day mortality in patients who received de-escalation therapy, patients whose antibiotics were not changed, and patients for whom antibiotics were escalated.

The in-hospital mortality rate was 27.4% in patients who were de-escalated, 32.6% in the unchanged group, and 42.9% in the escalation group. ICU and 90-day mortality were lower in the de-escalation group. De-escalation was more commonly used in medical than in surgical patients.

This study is limited because it is not a randomized controlled study and was single-centered, so it might only be applicable on the larger scale. Also, multi-drug resistant organisms were not evaluated.

Overall, it is safe to narrow empiric antibiotics in severe sepsis and shock when the pathogen and sensitivities are known.

Bottom line: De-escalation of antibiotics in severe sepsis and septic shock is associated with a lower mortality.

Citation: Garnacho-Montero J, Gutierrez-Pizarraya A, Escoresca-Ortega A, et al. De-escalation of empirical therapy is associated with lower mortality in patients with severe sepsis and septic shock. Intensive Care Med. 2014;40(1):32-40.

Clinical question: Is short-term, dual antiplatelet therapy noninferior to long-term therapy in zotarolimus-eluting stents?

Background: Current guidelines recommend long-term (>12 months) dual antiplatelet therapy after the placement of drug-eluting stents. The optimal therapy duration in second-generation drug-eluting stents has not been studied; moreover, some studies with multiple drug-eluting stents have suggested no added benefit from long-term therapy.

Study design: Randomized controlled trial.

Setting: Brazil, multi-center.

Synopsis: Researchers randomized 3,211 patients with stable coronary artery disease (CAD) or low-risk acute coronary syndrome (ACS) undergoing intervention with zotarolimus-eluting stents to short-term (three months) or long-term (12 months) dual antiplatelet therapy. Exclusion criteria included ST-elevation myocardial infarction (STEMI), previous drug-eluting stent, scheduled elective surgery within 12 months, or contraindication to aspirin or clopidogrel. Primary endpoints were a composite of death from any cause, MI, stroke, or major bleeding. Secondary endpoints were stent thrombosis, target lesion revascularization, adverse cardiac event, and any bleed.

At one-year follow-up, the short-term group had similar primary (6.0% vs. 5.8%) and secondary (8.3% vs. 7.4%) outcomes compared to the long-term. The short-term group’s noninferiority also was seen in several key subgroups.

This study included patients with stable CAD or low-risk ACS and cannot be generalized to higher-risk patients. Results for zotarolimus-eluting stents cannot be generalized to other second-generation drug-eluting stents.

Bottom line: Zotarolimus-eluting stents, followed by three months of dual antiplatelet therapy, were noninferior to 12 months of therapy in patients with stable CAD or low-risk ACS.

Citation: Feres F, Costa RA, Abizaid A, et al. Three vs. twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310(23):2510-2522.

Clinical question: Is short-term, dual antiplatelet therapy noninferior to long-term therapy in zotarolimus-eluting stents?

Background: Current guidelines recommend long-term (>12 months) dual antiplatelet therapy after the placement of drug-eluting stents. The optimal therapy duration in second-generation drug-eluting stents has not been studied; moreover, some studies with multiple drug-eluting stents have suggested no added benefit from long-term therapy.

Study design: Randomized controlled trial.

Setting: Brazil, multi-center.

Synopsis: Researchers randomized 3,211 patients with stable coronary artery disease (CAD) or low-risk acute coronary syndrome (ACS) undergoing intervention with zotarolimus-eluting stents to short-term (three months) or long-term (12 months) dual antiplatelet therapy. Exclusion criteria included ST-elevation myocardial infarction (STEMI), previous drug-eluting stent, scheduled elective surgery within 12 months, or contraindication to aspirin or clopidogrel. Primary endpoints were a composite of death from any cause, MI, stroke, or major bleeding. Secondary endpoints were stent thrombosis, target lesion revascularization, adverse cardiac event, and any bleed.

At one-year follow-up, the short-term group had similar primary (6.0% vs. 5.8%) and secondary (8.3% vs. 7.4%) outcomes compared to the long-term. The short-term group’s noninferiority also was seen in several key subgroups.

This study included patients with stable CAD or low-risk ACS and cannot be generalized to higher-risk patients. Results for zotarolimus-eluting stents cannot be generalized to other second-generation drug-eluting stents.

Bottom line: Zotarolimus-eluting stents, followed by three months of dual antiplatelet therapy, were noninferior to 12 months of therapy in patients with stable CAD or low-risk ACS.

Citation: Feres F, Costa RA, Abizaid A, et al. Three vs. twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310(23):2510-2522.

Clinical question: Is short-term, dual antiplatelet therapy noninferior to long-term therapy in zotarolimus-eluting stents?

Background: Current guidelines recommend long-term (>12 months) dual antiplatelet therapy after the placement of drug-eluting stents. The optimal therapy duration in second-generation drug-eluting stents has not been studied; moreover, some studies with multiple drug-eluting stents have suggested no added benefit from long-term therapy.

Study design: Randomized controlled trial.

Setting: Brazil, multi-center.

Synopsis: Researchers randomized 3,211 patients with stable coronary artery disease (CAD) or low-risk acute coronary syndrome (ACS) undergoing intervention with zotarolimus-eluting stents to short-term (three months) or long-term (12 months) dual antiplatelet therapy. Exclusion criteria included ST-elevation myocardial infarction (STEMI), previous drug-eluting stent, scheduled elective surgery within 12 months, or contraindication to aspirin or clopidogrel. Primary endpoints were a composite of death from any cause, MI, stroke, or major bleeding. Secondary endpoints were stent thrombosis, target lesion revascularization, adverse cardiac event, and any bleed.

At one-year follow-up, the short-term group had similar primary (6.0% vs. 5.8%) and secondary (8.3% vs. 7.4%) outcomes compared to the long-term. The short-term group’s noninferiority also was seen in several key subgroups.

This study included patients with stable CAD or low-risk ACS and cannot be generalized to higher-risk patients. Results for zotarolimus-eluting stents cannot be generalized to other second-generation drug-eluting stents.

Bottom line: Zotarolimus-eluting stents, followed by three months of dual antiplatelet therapy, were noninferior to 12 months of therapy in patients with stable CAD or low-risk ACS.

Citation: Feres F, Costa RA, Abizaid A, et al. Three vs. twelve months of dual antiplatelet therapy after zotarolimus-eluting stents: the OPTIMIZE randomized trial. JAMA. 2013;310(23):2510-2522.

Clinical question: Can an algorithm based on risk for multidrug-resistant (MDR) organisms and illness severity guide antibiotic selection in healthcare-associated pneumonia (HCAP)?

Background: The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines identify patients with HCAP as those with recent contact with a healthcare environment, including nursing homes and hemodialysis; however, previous studies have shown that not all patients with healthcare contact have equal risk for MDR organisms.

Study design: Prospective cohort study.

Setting: Japan, multi-center.

Synopsis: Of the 445 enrolled patients, 124 were diagnosed with community-acquired pneumonia (CAP) and 321 with HCAP. Patients with HCAP were classified based on severity of illness or MDR pathogen risk factors (immune suppression, hospitalization within the last 90 days, poor functional status, and antibiotics within the past six months). Patients with low risk (0-1 factors) for MDR organisms were treated for CAP, and patients with high risk (≥2 factors) or moderate risk (≥1 factor) for severe illness were treated for HCAP.

HCAP patients had a higher 30-day mortality rate (13.7% vs. 5.6%, P=0.017), but mortality rate was less in the patients at low risk for MDR pathogens (8.6% vs. 18.2%, P=0.012). Of the HCAP patients, only 7.1% received inappropriate therapy (pathogen resistant to initial antibiotic regimen), and treatment failure was 19.3%.

Appropriateness of initial empiric therapy was determined not to be a mortality risk; however, this trial might be limited by its location, because Japan appears to have fewer MDR pathogens than the U.S.

Bottom line: A treatment algorithm based on risk for MDR organisms and severity of illness can be used to guide empiric antibiotic therapy in patients with HCAP, and, ideally, to reduce excessive use of broad-spectrum antibiotics.

Citation: Maruyama T, Fujisawa T, Okuno M, et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis. 2013;57(10):1373-1383.

Clinical question: Can an algorithm based on risk for multidrug-resistant (MDR) organisms and illness severity guide antibiotic selection in healthcare-associated pneumonia (HCAP)?

Background: The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines identify patients with HCAP as those with recent contact with a healthcare environment, including nursing homes and hemodialysis; however, previous studies have shown that not all patients with healthcare contact have equal risk for MDR organisms.

Study design: Prospective cohort study.

Setting: Japan, multi-center.

Synopsis: Of the 445 enrolled patients, 124 were diagnosed with community-acquired pneumonia (CAP) and 321 with HCAP. Patients with HCAP were classified based on severity of illness or MDR pathogen risk factors (immune suppression, hospitalization within the last 90 days, poor functional status, and antibiotics within the past six months). Patients with low risk (0-1 factors) for MDR organisms were treated for CAP, and patients with high risk (≥2 factors) or moderate risk (≥1 factor) for severe illness were treated for HCAP.

HCAP patients had a higher 30-day mortality rate (13.7% vs. 5.6%, P=0.017), but mortality rate was less in the patients at low risk for MDR pathogens (8.6% vs. 18.2%, P=0.012). Of the HCAP patients, only 7.1% received inappropriate therapy (pathogen resistant to initial antibiotic regimen), and treatment failure was 19.3%.

Appropriateness of initial empiric therapy was determined not to be a mortality risk; however, this trial might be limited by its location, because Japan appears to have fewer MDR pathogens than the U.S.

Bottom line: A treatment algorithm based on risk for MDR organisms and severity of illness can be used to guide empiric antibiotic therapy in patients with HCAP, and, ideally, to reduce excessive use of broad-spectrum antibiotics.

Citation: Maruyama T, Fujisawa T, Okuno M, et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis. 2013;57(10):1373-1383.

Clinical question: Can an algorithm based on risk for multidrug-resistant (MDR) organisms and illness severity guide antibiotic selection in healthcare-associated pneumonia (HCAP)?

Background: The 2005 American Thoracic Society/Infectious Diseases Society of America (ATS/IDSA) guidelines identify patients with HCAP as those with recent contact with a healthcare environment, including nursing homes and hemodialysis; however, previous studies have shown that not all patients with healthcare contact have equal risk for MDR organisms.

Study design: Prospective cohort study.

Setting: Japan, multi-center.

Synopsis: Of the 445 enrolled patients, 124 were diagnosed with community-acquired pneumonia (CAP) and 321 with HCAP. Patients with HCAP were classified based on severity of illness or MDR pathogen risk factors (immune suppression, hospitalization within the last 90 days, poor functional status, and antibiotics within the past six months). Patients with low risk (0-1 factors) for MDR organisms were treated for CAP, and patients with high risk (≥2 factors) or moderate risk (≥1 factor) for severe illness were treated for HCAP.

HCAP patients had a higher 30-day mortality rate (13.7% vs. 5.6%, P=0.017), but mortality rate was less in the patients at low risk for MDR pathogens (8.6% vs. 18.2%, P=0.012). Of the HCAP patients, only 7.1% received inappropriate therapy (pathogen resistant to initial antibiotic regimen), and treatment failure was 19.3%.

Appropriateness of initial empiric therapy was determined not to be a mortality risk; however, this trial might be limited by its location, because Japan appears to have fewer MDR pathogens than the U.S.

Bottom line: A treatment algorithm based on risk for MDR organisms and severity of illness can be used to guide empiric antibiotic therapy in patients with HCAP, and, ideally, to reduce excessive use of broad-spectrum antibiotics.

Citation: Maruyama T, Fujisawa T, Okuno M, et al. A new strategy for healthcare-associated pneumonia: a 2-year prospective multicenter cohort study using risk factors for multidrug-resistant pathogens to select initial empiric therapy. Clin Infect Dis. 2013;57(10):1373-1383.