Jessica Berwick, MD, MPH

Background: Previous research on the use of PFO closure to prevent recurrent stroke has yielded mixed results.

Study design: Gore REDUCE, CLOSE, and RESPECT were all multicenter, randomized, open-label superiority trials, with blinded adjudication of endpoint events. RESPECT data reflected an exploratory analysis of an extended follow up period.

Setting: Gore REDUCE was a multinational study conducted at 63 sites in Europe and North America, from 2008-2015. CLOSE was conducted at 34 sites in France and Germany, from 2007 to 2016. RESPECT was conducted at 69 sites in the United States and Canada, from 2003 to 2011.

Synopsis: Three trials reexamined the impact of PFO closure with standard antiplatelet treatment, with a total of 2,307 patients between the ages of 16 and 60 years. CLOSE included only patients with a PFO and an associated atrial septal aneurysm or a large interatrial shunt. Gore REDUCE and RESPECT were both industry funded. All three trials found a statistically significant reduction in risk of recurrent ischemic stroke associated with PFO closure and antiplatelet therapy compared to antiplatelet therapy alone (CLOSE HR 0.03 [95% CI 0-0.26; P less than .001], RESPECT HR 0.55 [95% CI 0.31-0.999; P = .046], Gore REDUCE HR 0.23 [95% CI 0.09-0.62; P = .002]). Gore REDUCE and CLOSE identified increased rates of postprocedural atrial fibrillation or flutter (6.6% vs. 0.4% [P less than .001], 4.6% vs. 0.9% [P = .02], respectively). Serious adverse events related to the procedure or device ranged from 3.9-5.9%.

Bottom line: PFO closure combined with antiplatelet therapy in patients aged 60 years or younger, particularly in those with significant right-to-left shunts and atrial septal aneurysms, reduced the risk of recurrent ischemic stroke compared to antiplatelet therapy alone.

Citation: Mas JL. Derumeaux B. Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377(11):1011-21.

Saver JL, Carroll JD, Thaler DE, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med. 2017;377(11):1022-32.

Søndergaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med. 2017;377(11):1033-42.

Background: Previous research on the use of PFO closure to prevent recurrent stroke has yielded mixed results.

Study design: Gore REDUCE, CLOSE, and RESPECT were all multicenter, randomized, open-label superiority trials, with blinded adjudication of endpoint events. RESPECT data reflected an exploratory analysis of an extended follow up period.

Setting: Gore REDUCE was a multinational study conducted at 63 sites in Europe and North America, from 2008-2015. CLOSE was conducted at 34 sites in France and Germany, from 2007 to 2016. RESPECT was conducted at 69 sites in the United States and Canada, from 2003 to 2011.

Synopsis: Three trials reexamined the impact of PFO closure with standard antiplatelet treatment, with a total of 2,307 patients between the ages of 16 and 60 years. CLOSE included only patients with a PFO and an associated atrial septal aneurysm or a large interatrial shunt. Gore REDUCE and RESPECT were both industry funded. All three trials found a statistically significant reduction in risk of recurrent ischemic stroke associated with PFO closure and antiplatelet therapy compared to antiplatelet therapy alone (CLOSE HR 0.03 [95% CI 0-0.26; P less than .001], RESPECT HR 0.55 [95% CI 0.31-0.999; P = .046], Gore REDUCE HR 0.23 [95% CI 0.09-0.62; P = .002]). Gore REDUCE and CLOSE identified increased rates of postprocedural atrial fibrillation or flutter (6.6% vs. 0.4% [P less than .001], 4.6% vs. 0.9% [P = .02], respectively). Serious adverse events related to the procedure or device ranged from 3.9-5.9%.

Bottom line: PFO closure combined with antiplatelet therapy in patients aged 60 years or younger, particularly in those with significant right-to-left shunts and atrial septal aneurysms, reduced the risk of recurrent ischemic stroke compared to antiplatelet therapy alone.

Citation: Mas JL. Derumeaux B. Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377(11):1011-21.

Saver JL, Carroll JD, Thaler DE, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med. 2017;377(11):1022-32.

Søndergaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med. 2017;377(11):1033-42.

Background: Previous research on the use of PFO closure to prevent recurrent stroke has yielded mixed results.

Study design: Gore REDUCE, CLOSE, and RESPECT were all multicenter, randomized, open-label superiority trials, with blinded adjudication of endpoint events. RESPECT data reflected an exploratory analysis of an extended follow up period.

Setting: Gore REDUCE was a multinational study conducted at 63 sites in Europe and North America, from 2008-2015. CLOSE was conducted at 34 sites in France and Germany, from 2007 to 2016. RESPECT was conducted at 69 sites in the United States and Canada, from 2003 to 2011.

Synopsis: Three trials reexamined the impact of PFO closure with standard antiplatelet treatment, with a total of 2,307 patients between the ages of 16 and 60 years. CLOSE included only patients with a PFO and an associated atrial septal aneurysm or a large interatrial shunt. Gore REDUCE and RESPECT were both industry funded. All three trials found a statistically significant reduction in risk of recurrent ischemic stroke associated with PFO closure and antiplatelet therapy compared to antiplatelet therapy alone (CLOSE HR 0.03 [95% CI 0-0.26; P less than .001], RESPECT HR 0.55 [95% CI 0.31-0.999; P = .046], Gore REDUCE HR 0.23 [95% CI 0.09-0.62; P = .002]). Gore REDUCE and CLOSE identified increased rates of postprocedural atrial fibrillation or flutter (6.6% vs. 0.4% [P less than .001], 4.6% vs. 0.9% [P = .02], respectively). Serious adverse events related to the procedure or device ranged from 3.9-5.9%.

Bottom line: PFO closure combined with antiplatelet therapy in patients aged 60 years or younger, particularly in those with significant right-to-left shunts and atrial septal aneurysms, reduced the risk of recurrent ischemic stroke compared to antiplatelet therapy alone.

Citation: Mas JL. Derumeaux B. Guillon B, et al. Patent foramen ovale closure or anticoagulation vs. antiplatelets after stroke. N Engl J Med. 2017;377(11):1011-21.

Saver JL, Carroll JD, Thaler DE, et al. Long-term outcomes of patent foramen ovale closure or medical therapy after stroke. N Engl J Med. 2017;377(11):1022-32.

Søndergaard L, Kasner SE, Rhodes JF, et al. Patent foramen ovale closure or antiplatelet therapy for cryptogenic stroke. N Engl J Med. 2017;377(11):1033-42.

Background: The association between platelet counts, risk of bleeding, and transfusions in patients with thrombocytopenia related to stem cell transplant (SCT) or chemotherapy is not clear, except at very low platelet counts.

Study design: Secondary analysis of a multicenter, randomized controlled trial, stratified by cause of thrombocytopenia: autologous or syngeneic SCT (AUTO), allogeneic SCT (ALLO), or chemotherapy for hematologic malignancy without SCT (CHEMO).

Setting: Twenty-six hospitals from 2004 to 2007.

Synopsis: The PLADO trial enrolled more than 1,200 patients aged 18 years and older expected to experience a period of hypoproliferative thrombocytopenia as a result of chemotherapy or SCT, and randomized them to low, medium, or high doses of prophylactic platelets. This secondary analysis assessed laboratory predictors of bleeding, and the effect of transfusion.

Of 1,077 patients who received platelet transfusions, there were no differences between dose groups for any bleeding outcomes. Over a wide range of platelet counts, the ALLO stratum had a higher risk of bleeding than other strata, with clinically significant bleeding on 21% of patient-days in the ALLO stratum, compared with 19% in the AUTO stratum and 11% in the CHEMO stratum (P less than .001). Risk for bleeding was significantly higher at platelet counts of equal to or less than 5x109/L compared with platelet counts greater than or equal to 81x109/L. Higher aPTT and INR were also associated with higher risk of clinically significant bleeding. In a multipredictor model, only hematocrit was significantly associated with more severe bleeding. Neither platelet transfusion nor RBC transfusion reduced the risk of bleeding on the following day, although the authors note some possibility of confounding by indication.

Bottom line: Predictors of overall increased risk for bleeding in patients with secondary hypoproliferative thrombocytopenia were treatment stratum, platelet counts less than or equal to 5x109/L, hematocrit less than 25%, INR greater than 1.2, and aPTT greater than 30 seconds. This study challenges the conventional wisdom that transfusions reduce bleeding risk in patients with secondary hypoproliferative thrombocytopenia.

Citation: Uhl L, Assmann SF, Hamza TH, et al. Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial. Blood. 2017;130(10):1247-58.

Background: The association between platelet counts, risk of bleeding, and transfusions in patients with thrombocytopenia related to stem cell transplant (SCT) or chemotherapy is not clear, except at very low platelet counts.

Study design: Secondary analysis of a multicenter, randomized controlled trial, stratified by cause of thrombocytopenia: autologous or syngeneic SCT (AUTO), allogeneic SCT (ALLO), or chemotherapy for hematologic malignancy without SCT (CHEMO).

Setting: Twenty-six hospitals from 2004 to 2007.

Synopsis: The PLADO trial enrolled more than 1,200 patients aged 18 years and older expected to experience a period of hypoproliferative thrombocytopenia as a result of chemotherapy or SCT, and randomized them to low, medium, or high doses of prophylactic platelets. This secondary analysis assessed laboratory predictors of bleeding, and the effect of transfusion.

Of 1,077 patients who received platelet transfusions, there were no differences between dose groups for any bleeding outcomes. Over a wide range of platelet counts, the ALLO stratum had a higher risk of bleeding than other strata, with clinically significant bleeding on 21% of patient-days in the ALLO stratum, compared with 19% in the AUTO stratum and 11% in the CHEMO stratum (P less than .001). Risk for bleeding was significantly higher at platelet counts of equal to or less than 5x109/L compared with platelet counts greater than or equal to 81x109/L. Higher aPTT and INR were also associated with higher risk of clinically significant bleeding. In a multipredictor model, only hematocrit was significantly associated with more severe bleeding. Neither platelet transfusion nor RBC transfusion reduced the risk of bleeding on the following day, although the authors note some possibility of confounding by indication.

Bottom line: Predictors of overall increased risk for bleeding in patients with secondary hypoproliferative thrombocytopenia were treatment stratum, platelet counts less than or equal to 5x109/L, hematocrit less than 25%, INR greater than 1.2, and aPTT greater than 30 seconds. This study challenges the conventional wisdom that transfusions reduce bleeding risk in patients with secondary hypoproliferative thrombocytopenia.

Citation: Uhl L, Assmann SF, Hamza TH, et al. Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial. Blood. 2017;130(10):1247-58.

Background: The association between platelet counts, risk of bleeding, and transfusions in patients with thrombocytopenia related to stem cell transplant (SCT) or chemotherapy is not clear, except at very low platelet counts.

Study design: Secondary analysis of a multicenter, randomized controlled trial, stratified by cause of thrombocytopenia: autologous or syngeneic SCT (AUTO), allogeneic SCT (ALLO), or chemotherapy for hematologic malignancy without SCT (CHEMO).

Setting: Twenty-six hospitals from 2004 to 2007.

Synopsis: The PLADO trial enrolled more than 1,200 patients aged 18 years and older expected to experience a period of hypoproliferative thrombocytopenia as a result of chemotherapy or SCT, and randomized them to low, medium, or high doses of prophylactic platelets. This secondary analysis assessed laboratory predictors of bleeding, and the effect of transfusion.

Of 1,077 patients who received platelet transfusions, there were no differences between dose groups for any bleeding outcomes. Over a wide range of platelet counts, the ALLO stratum had a higher risk of bleeding than other strata, with clinically significant bleeding on 21% of patient-days in the ALLO stratum, compared with 19% in the AUTO stratum and 11% in the CHEMO stratum (P less than .001). Risk for bleeding was significantly higher at platelet counts of equal to or less than 5x109/L compared with platelet counts greater than or equal to 81x109/L. Higher aPTT and INR were also associated with higher risk of clinically significant bleeding. In a multipredictor model, only hematocrit was significantly associated with more severe bleeding. Neither platelet transfusion nor RBC transfusion reduced the risk of bleeding on the following day, although the authors note some possibility of confounding by indication.

Bottom line: Predictors of overall increased risk for bleeding in patients with secondary hypoproliferative thrombocytopenia were treatment stratum, platelet counts less than or equal to 5x109/L, hematocrit less than 25%, INR greater than 1.2, and aPTT greater than 30 seconds. This study challenges the conventional wisdom that transfusions reduce bleeding risk in patients with secondary hypoproliferative thrombocytopenia.

Citation: Uhl L, Assmann SF, Hamza TH, et al. Laboratory predictors of bleeding and the effect of platelet and RBC transfusions on bleeding outcomes in the PLADO trial. Blood. 2017;130(10):1247-58.

Clinical question: Does a short, fixed duration of antibiotic therapy for complicated intra-abdominal infections lead to equivalent outcomes and less antibiotic exposure than the traditional approach?

Background: Published guidelines recommend appropriate antimicrobial agents for intra-abdominal infections, but the optimal duration of therapy remains unclear. Most practitioners continue to treat for 10–14 days and until all physiologic evidence of the systemic inflammatory response syndrome (SIRS) has resolved. More recently, small studies have suggested that a shorter course may lead to equivalent outcomes with decreased antibiotic exposure.

Study design: Open-label, multicenter, randomized control trial.

Setting: Twenty-three sites throughout the U.S. and Canada.

Synopsis: In the short-course group, 257 patients were randomized to receive antimicrobial therapy for four full days after their index source-control procedure; 260 patients in the control group received antimicrobial therapy until two days after resolution of the physiological abnormalities related to SIRS. The median duration of therapy was 4.0 days (interquartile range [IQR] 4.0–5.0) for the experimental group and 8.0 days (IQR 5.0–10.0) in the control group (95% CI, -4.7 to -3.3; P<0.001).

There was no significant difference in surgical site infection, recurrent intra-abdominal infection, or death between the experimental and control groups (21.8% vs. 22.3%, 95% CI, -7.0 to 8.0; P=0.92). In the experimental group, 47 patients did not adhere to the protocol, and all of those patients received a longer antimicrobial treatment course than specified in the protocol.

This trial excluded patients without adequate source control and included a small number of immunocompromised hosts. The rate of nonadherence to the protocol was high, at 18% of patients in the experimental group. The calculated sample size to assert equivalence between groups was not achieved, although the results are suggestive of equivalence.

Bottom line: A shorter course of antimicrobial therapy for complicated intra-abdominal infections might lead to equivalent outcomes with less antibiotic exposure compared with current practice; however, it is challenging for providers to stop antimicrobial therapy while patients continue to show physiologic evidence of SIRS.

Citation: Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection. NEJM. 2015;372(21):1996–2005.

Visit our website for more reviews of HM-focused research.

Clinical question: Does a short, fixed duration of antibiotic therapy for complicated intra-abdominal infections lead to equivalent outcomes and less antibiotic exposure than the traditional approach?

Background: Published guidelines recommend appropriate antimicrobial agents for intra-abdominal infections, but the optimal duration of therapy remains unclear. Most practitioners continue to treat for 10–14 days and until all physiologic evidence of the systemic inflammatory response syndrome (SIRS) has resolved. More recently, small studies have suggested that a shorter course may lead to equivalent outcomes with decreased antibiotic exposure.

Study design: Open-label, multicenter, randomized control trial.

Setting: Twenty-three sites throughout the U.S. and Canada.

Synopsis: In the short-course group, 257 patients were randomized to receive antimicrobial therapy for four full days after their index source-control procedure; 260 patients in the control group received antimicrobial therapy until two days after resolution of the physiological abnormalities related to SIRS. The median duration of therapy was 4.0 days (interquartile range [IQR] 4.0–5.0) for the experimental group and 8.0 days (IQR 5.0–10.0) in the control group (95% CI, -4.7 to -3.3; P<0.001).

There was no significant difference in surgical site infection, recurrent intra-abdominal infection, or death between the experimental and control groups (21.8% vs. 22.3%, 95% CI, -7.0 to 8.0; P=0.92). In the experimental group, 47 patients did not adhere to the protocol, and all of those patients received a longer antimicrobial treatment course than specified in the protocol.

This trial excluded patients without adequate source control and included a small number of immunocompromised hosts. The rate of nonadherence to the protocol was high, at 18% of patients in the experimental group. The calculated sample size to assert equivalence between groups was not achieved, although the results are suggestive of equivalence.

Bottom line: A shorter course of antimicrobial therapy for complicated intra-abdominal infections might lead to equivalent outcomes with less antibiotic exposure compared with current practice; however, it is challenging for providers to stop antimicrobial therapy while patients continue to show physiologic evidence of SIRS.

Citation: Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection. NEJM. 2015;372(21):1996–2005.

Visit our website for more reviews of HM-focused research.

Clinical question: Does a short, fixed duration of antibiotic therapy for complicated intra-abdominal infections lead to equivalent outcomes and less antibiotic exposure than the traditional approach?

Background: Published guidelines recommend appropriate antimicrobial agents for intra-abdominal infections, but the optimal duration of therapy remains unclear. Most practitioners continue to treat for 10–14 days and until all physiologic evidence of the systemic inflammatory response syndrome (SIRS) has resolved. More recently, small studies have suggested that a shorter course may lead to equivalent outcomes with decreased antibiotic exposure.

Study design: Open-label, multicenter, randomized control trial.

Setting: Twenty-three sites throughout the U.S. and Canada.

Synopsis: In the short-course group, 257 patients were randomized to receive antimicrobial therapy for four full days after their index source-control procedure; 260 patients in the control group received antimicrobial therapy until two days after resolution of the physiological abnormalities related to SIRS. The median duration of therapy was 4.0 days (interquartile range [IQR] 4.0–5.0) for the experimental group and 8.0 days (IQR 5.0–10.0) in the control group (95% CI, -4.7 to -3.3; P<0.001).

There was no significant difference in surgical site infection, recurrent intra-abdominal infection, or death between the experimental and control groups (21.8% vs. 22.3%, 95% CI, -7.0 to 8.0; P=0.92). In the experimental group, 47 patients did not adhere to the protocol, and all of those patients received a longer antimicrobial treatment course than specified in the protocol.

This trial excluded patients without adequate source control and included a small number of immunocompromised hosts. The rate of nonadherence to the protocol was high, at 18% of patients in the experimental group. The calculated sample size to assert equivalence between groups was not achieved, although the results are suggestive of equivalence.

Bottom line: A shorter course of antimicrobial therapy for complicated intra-abdominal infections might lead to equivalent outcomes with less antibiotic exposure compared with current practice; however, it is challenging for providers to stop antimicrobial therapy while patients continue to show physiologic evidence of SIRS.

Citation: Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection. NEJM. 2015;372(21):1996–2005.

Visit our website for more reviews of HM-focused research.

Clinical question: Is post-procedural bridging therapy necessary for secondary prevention of VTE?

Background: Bridging therapy has been studied to stratify peri-procedural risk for patients with atrial fibrillation and mechanical heart valves. Data examining the necessity of post-procedural bridging for secondary prevention of VTE are lacking.

Study design: Retrospective, cohort study.

Setting: Single-state, integrated, healthcare delivery system.

Synopsis: A retrospective analysis of patients treated with warfarin for VTE prior to undergoing an invasive procedure was conducted from January 2006 through March 2012 to evaluate the occurrence of post-procedural bleeding secondary to bridging therapy, as well as the occurrence of VTE if bridging therapy was withheld.

Nearly 19,000 procedures were evaluated, of which 1,812 were included in the study. Of note, 11,710 procedures were excluded because the indication for anticoagulation was not VTE. The primary outcome was post-procedure bleeding events at 30 days, while secondary outcomes included severe bleeding events, recurrent VTE, and 30-day mortality. Patient risk of recurrent VTE was stratified into low-, medium-, and high-risk categories based on AT9 current guidelines.

Clinically relevant bleeding events occurred in 2.7% (15/555) of bridged patients and in 0.2% (2/1257) of non-bridged patients (hazard ratio of 17.2). With respect to VTE recurrence, there were three events in the non-bridged group and zero in the bridged group, which was not statistically significant (P=0.56). No VTE events were seen in the high-risk group, and there was no mortality at 30 days across any group.

Bottom line: Peri-procedural bridging therapy for VTE is associated with higher risk of bleeding, but there is not a significant risk of recurrent VTE if bridging therapy is withheld.

Citation: Clark NP, Witt DM, Davies LE, et al. Bleeding, recurrent venous thromboembolism, and mortality risks during warfarin interruption for invasive procedures. JAMA Intern Med. 2015;175(7):1163-1168. doi:10.1001/jamainternmed.2015.1843.

Clinical question: Is post-procedural bridging therapy necessary for secondary prevention of VTE?

Background: Bridging therapy has been studied to stratify peri-procedural risk for patients with atrial fibrillation and mechanical heart valves. Data examining the necessity of post-procedural bridging for secondary prevention of VTE are lacking.

Study design: Retrospective, cohort study.

Setting: Single-state, integrated, healthcare delivery system.

Synopsis: A retrospective analysis of patients treated with warfarin for VTE prior to undergoing an invasive procedure was conducted from January 2006 through March 2012 to evaluate the occurrence of post-procedural bleeding secondary to bridging therapy, as well as the occurrence of VTE if bridging therapy was withheld.

Nearly 19,000 procedures were evaluated, of which 1,812 were included in the study. Of note, 11,710 procedures were excluded because the indication for anticoagulation was not VTE. The primary outcome was post-procedure bleeding events at 30 days, while secondary outcomes included severe bleeding events, recurrent VTE, and 30-day mortality. Patient risk of recurrent VTE was stratified into low-, medium-, and high-risk categories based on AT9 current guidelines.

Clinically relevant bleeding events occurred in 2.7% (15/555) of bridged patients and in 0.2% (2/1257) of non-bridged patients (hazard ratio of 17.2). With respect to VTE recurrence, there were three events in the non-bridged group and zero in the bridged group, which was not statistically significant (P=0.56). No VTE events were seen in the high-risk group, and there was no mortality at 30 days across any group.

Bottom line: Peri-procedural bridging therapy for VTE is associated with higher risk of bleeding, but there is not a significant risk of recurrent VTE if bridging therapy is withheld.

Citation: Clark NP, Witt DM, Davies LE, et al. Bleeding, recurrent venous thromboembolism, and mortality risks during warfarin interruption for invasive procedures. JAMA Intern Med. 2015;175(7):1163-1168. doi:10.1001/jamainternmed.2015.1843.

Clinical question: Is post-procedural bridging therapy necessary for secondary prevention of VTE?

Background: Bridging therapy has been studied to stratify peri-procedural risk for patients with atrial fibrillation and mechanical heart valves. Data examining the necessity of post-procedural bridging for secondary prevention of VTE are lacking.

Study design: Retrospective, cohort study.

Setting: Single-state, integrated, healthcare delivery system.

Synopsis: A retrospective analysis of patients treated with warfarin for VTE prior to undergoing an invasive procedure was conducted from January 2006 through March 2012 to evaluate the occurrence of post-procedural bleeding secondary to bridging therapy, as well as the occurrence of VTE if bridging therapy was withheld.

Nearly 19,000 procedures were evaluated, of which 1,812 were included in the study. Of note, 11,710 procedures were excluded because the indication for anticoagulation was not VTE. The primary outcome was post-procedure bleeding events at 30 days, while secondary outcomes included severe bleeding events, recurrent VTE, and 30-day mortality. Patient risk of recurrent VTE was stratified into low-, medium-, and high-risk categories based on AT9 current guidelines.

Clinically relevant bleeding events occurred in 2.7% (15/555) of bridged patients and in 0.2% (2/1257) of non-bridged patients (hazard ratio of 17.2). With respect to VTE recurrence, there were three events in the non-bridged group and zero in the bridged group, which was not statistically significant (P=0.56). No VTE events were seen in the high-risk group, and there was no mortality at 30 days across any group.

Bottom line: Peri-procedural bridging therapy for VTE is associated with higher risk of bleeding, but there is not a significant risk of recurrent VTE if bridging therapy is withheld.

Citation: Clark NP, Witt DM, Davies LE, et al. Bleeding, recurrent venous thromboembolism, and mortality risks during warfarin interruption for invasive procedures. JAMA Intern Med. 2015;175(7):1163-1168. doi:10.1001/jamainternmed.2015.1843.

Clinical question: Does a short, fixed duration of antibiotic therapy for complicated intraabdominal infections lead to equivalent outcomes and less antibiotic exposure than the traditional approach?

Background: Published guidelines recommend appropriate antimicrobial agents for intraabdominal infections, but the optimal duration of therapy remains unclear. Most practitioners continue to treat for 10-14 days and until all physiologic evidence of the systemic inflammatory response syndrome (SIRS) has resolved. More recently, small studies have suggested that a shorter course may lead to equivalent outcomes with decreased antibiotic exposure.

Study design: Open-label, multicenter, randomized control trial.

Setting: Twenty-three sites throughout the U.S. and Canada.

Synopsis: In the short-course group, 257 patients were randomized to receive antimicrobial therapy for four full days after their index source-control procedure; 260 patients in the control group received antimicrobial therapy until two days after resolution of the physiological abnormalities related to SIRS. The median duration of therapy was 4.0 days (interquartile range [IQR], 4.0-5.0) for the experimental group and 8.0 days (IQR 5.0-10.0) in the control group (95% CI, -4.7 to -3.3; P<0.001).

There was no significant difference in surgical site infection, recurrent intraabdominal infection, or death between the experimental and control groups (21.8% vs. 22.3%, 95% CI -7.0 to 8.0; P=0.92). In the experimental group, 47 patients did not adhere to the protocol, all of whom received a longer antimicrobial treatment course than specified in the protocol.

This trial excluded patients without adequate source control and included a small number of immunocompromised hosts. The rate of nonadherence to the protocol was high, at 18% of patients in the experimental group. The calculated sample size to assert equivalence between groups was not achieved, although the results are suggestive of equivalence.

Bottom line: A shorter course of antimicrobial therapy for complicated intraabdominal infections might lead to equivalent outcomes with less antibiotic exposure compared with current practice; however, it is challenging for providers to stop antimicrobial therapy while patients continue to show physiologic evidence of SIRS.

Citation: Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection. NEJM. 2015;372(21):1996-2005.

Clinical question: Does a short, fixed duration of antibiotic therapy for complicated intraabdominal infections lead to equivalent outcomes and less antibiotic exposure than the traditional approach?

Background: Published guidelines recommend appropriate antimicrobial agents for intraabdominal infections, but the optimal duration of therapy remains unclear. Most practitioners continue to treat for 10-14 days and until all physiologic evidence of the systemic inflammatory response syndrome (SIRS) has resolved. More recently, small studies have suggested that a shorter course may lead to equivalent outcomes with decreased antibiotic exposure.

Study design: Open-label, multicenter, randomized control trial.

Setting: Twenty-three sites throughout the U.S. and Canada.

Synopsis: In the short-course group, 257 patients were randomized to receive antimicrobial therapy for four full days after their index source-control procedure; 260 patients in the control group received antimicrobial therapy until two days after resolution of the physiological abnormalities related to SIRS. The median duration of therapy was 4.0 days (interquartile range [IQR], 4.0-5.0) for the experimental group and 8.0 days (IQR 5.0-10.0) in the control group (95% CI, -4.7 to -3.3; P<0.001).

There was no significant difference in surgical site infection, recurrent intraabdominal infection, or death between the experimental and control groups (21.8% vs. 22.3%, 95% CI -7.0 to 8.0; P=0.92). In the experimental group, 47 patients did not adhere to the protocol, all of whom received a longer antimicrobial treatment course than specified in the protocol.

This trial excluded patients without adequate source control and included a small number of immunocompromised hosts. The rate of nonadherence to the protocol was high, at 18% of patients in the experimental group. The calculated sample size to assert equivalence between groups was not achieved, although the results are suggestive of equivalence.

Bottom line: A shorter course of antimicrobial therapy for complicated intraabdominal infections might lead to equivalent outcomes with less antibiotic exposure compared with current practice; however, it is challenging for providers to stop antimicrobial therapy while patients continue to show physiologic evidence of SIRS.

Citation: Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection. NEJM. 2015;372(21):1996-2005.

Clinical question: Does a short, fixed duration of antibiotic therapy for complicated intraabdominal infections lead to equivalent outcomes and less antibiotic exposure than the traditional approach?

Background: Published guidelines recommend appropriate antimicrobial agents for intraabdominal infections, but the optimal duration of therapy remains unclear. Most practitioners continue to treat for 10-14 days and until all physiologic evidence of the systemic inflammatory response syndrome (SIRS) has resolved. More recently, small studies have suggested that a shorter course may lead to equivalent outcomes with decreased antibiotic exposure.

Study design: Open-label, multicenter, randomized control trial.

Setting: Twenty-three sites throughout the U.S. and Canada.

Synopsis: In the short-course group, 257 patients were randomized to receive antimicrobial therapy for four full days after their index source-control procedure; 260 patients in the control group received antimicrobial therapy until two days after resolution of the physiological abnormalities related to SIRS. The median duration of therapy was 4.0 days (interquartile range [IQR], 4.0-5.0) for the experimental group and 8.0 days (IQR 5.0-10.0) in the control group (95% CI, -4.7 to -3.3; P<0.001).

There was no significant difference in surgical site infection, recurrent intraabdominal infection, or death between the experimental and control groups (21.8% vs. 22.3%, 95% CI -7.0 to 8.0; P=0.92). In the experimental group, 47 patients did not adhere to the protocol, all of whom received a longer antimicrobial treatment course than specified in the protocol.

This trial excluded patients without adequate source control and included a small number of immunocompromised hosts. The rate of nonadherence to the protocol was high, at 18% of patients in the experimental group. The calculated sample size to assert equivalence between groups was not achieved, although the results are suggestive of equivalence.

Bottom line: A shorter course of antimicrobial therapy for complicated intraabdominal infections might lead to equivalent outcomes with less antibiotic exposure compared with current practice; however, it is challenging for providers to stop antimicrobial therapy while patients continue to show physiologic evidence of SIRS.

Citation: Sawyer RG, Claridge JA, Nathens AB, et al. Trial of short-course antimicrobial therapy for intraabdominal infection. NEJM. 2015;372(21):1996-2005.

Clinical question: In patients undergoing noncardiac surgery, are peri-operative beta blockers beneficial in those at high risk and harmful in those at low risk?

Background: Despite multiple RCTs, the exact utility of peri-operative beta-blockade remains unclear, especially in those patients considered low cardiac risk. While initial research prompted guidelines that encouraged the liberal use of peri-operative beta blockers, more recent studies have drawn attention to their potential adverse effects, prompting further investigation.

Study design: Retrospective, observational, cohort study.

Setting: One hundred nineteen Veterans Administration medical centers.

Synopsis: Through the modeling of data from 326,489 patients who underwent noncardiac surgery between 2008 and 2013, this study assessed the effects of beta blocker usage and cardiac risk factors on 30-day surgical mortality.

Analysis demonstrated a significant difference in the effect of beta blocker use on mortality based on the number of cardiac risk factors. For patients with no cardiac risk factors, those receiving beta blockers were at increased risk of death (odds ratio 1.19, 95% confidence interval 1.06-1.35). Among patients with three to four cardiac risk factors, however, those on beta blockers had a decreased risk of death (odds ratio 0.63, 95% confidence interval 0.43-0.93).

Bottom line: In noncardiac surgery, use of beta blockers may be beneficial for those at high cardiac risk and detrimental to those without cardiac risk factors.

Citation: Friedell ML, Van Way CW 3rd, Freyberg RW, Almenoff PL. Beta-blockade and operative mortality in noncardiac surgery: harmful or helpful? JAMA Surgery. 2015;150(7):658-664. doi:10.1001/jamasurg.2015.86.

Clinical question: In patients undergoing noncardiac surgery, are peri-operative beta blockers beneficial in those at high risk and harmful in those at low risk?

Background: Despite multiple RCTs, the exact utility of peri-operative beta-blockade remains unclear, especially in those patients considered low cardiac risk. While initial research prompted guidelines that encouraged the liberal use of peri-operative beta blockers, more recent studies have drawn attention to their potential adverse effects, prompting further investigation.

Study design: Retrospective, observational, cohort study.

Setting: One hundred nineteen Veterans Administration medical centers.

Synopsis: Through the modeling of data from 326,489 patients who underwent noncardiac surgery between 2008 and 2013, this study assessed the effects of beta blocker usage and cardiac risk factors on 30-day surgical mortality.

Analysis demonstrated a significant difference in the effect of beta blocker use on mortality based on the number of cardiac risk factors. For patients with no cardiac risk factors, those receiving beta blockers were at increased risk of death (odds ratio 1.19, 95% confidence interval 1.06-1.35). Among patients with three to four cardiac risk factors, however, those on beta blockers had a decreased risk of death (odds ratio 0.63, 95% confidence interval 0.43-0.93).

Bottom line: In noncardiac surgery, use of beta blockers may be beneficial for those at high cardiac risk and detrimental to those without cardiac risk factors.

Citation: Friedell ML, Van Way CW 3rd, Freyberg RW, Almenoff PL. Beta-blockade and operative mortality in noncardiac surgery: harmful or helpful? JAMA Surgery. 2015;150(7):658-664. doi:10.1001/jamasurg.2015.86.

Clinical question: In patients undergoing noncardiac surgery, are peri-operative beta blockers beneficial in those at high risk and harmful in those at low risk?

Background: Despite multiple RCTs, the exact utility of peri-operative beta-blockade remains unclear, especially in those patients considered low cardiac risk. While initial research prompted guidelines that encouraged the liberal use of peri-operative beta blockers, more recent studies have drawn attention to their potential adverse effects, prompting further investigation.

Study design: Retrospective, observational, cohort study.

Setting: One hundred nineteen Veterans Administration medical centers.

Synopsis: Through the modeling of data from 326,489 patients who underwent noncardiac surgery between 2008 and 2013, this study assessed the effects of beta blocker usage and cardiac risk factors on 30-day surgical mortality.

Analysis demonstrated a significant difference in the effect of beta blocker use on mortality based on the number of cardiac risk factors. For patients with no cardiac risk factors, those receiving beta blockers were at increased risk of death (odds ratio 1.19, 95% confidence interval 1.06-1.35). Among patients with three to four cardiac risk factors, however, those on beta blockers had a decreased risk of death (odds ratio 0.63, 95% confidence interval 0.43-0.93).

Bottom line: In noncardiac surgery, use of beta blockers may be beneficial for those at high cardiac risk and detrimental to those without cardiac risk factors.

Citation: Friedell ML, Van Way CW 3rd, Freyberg RW, Almenoff PL. Beta-blockade and operative mortality in noncardiac surgery: harmful or helpful? JAMA Surgery. 2015;150(7):658-664. doi:10.1001/jamasurg.2015.86.

Clinical question: Do stable, low-risk patients hospitalized for chest pain after negative ED evaluation experience adverse cardiac events in the hospital?

Background: Chest pain results in more than seven million ED visits annually, with a cost of over $11 billion to hospitalize these patients for closer monitoring. It is not well known to what extent these low-risk patients experience in-hospital adverse cardiac events after a negative ED evaluation.

Study design: Blinded data review from a prospectively collected, multicenter database.

Setting: Three community teaching hospitals in the U.S.

Synopsis: Researchers identified 11,230 patients, aged 18 and older, hospitalized with chest pain symptoms after negative serial troponin, from July 2008 through June 2013. Demographics included mean age 58 years, 55% female, with several co-morbid medical illnesses. One hundred ninety-seven patients met the primary outcomes of in-hospital life-threatening arrhythmia, ST segment elevation MI, cardiac or respiratory arrest, and death.

Blinded reviewers further stratified these patients and excluded any patients with initial abnormal vital signs, with ECG evidence of ischemia, or with an uninterpretable ECG. This resulted in four patients who experienced the primary outcome in hospital after presenting with chest pain, stable vital signs, and no evidence of ischemia. By verifying inclusion data from 5% of the primary cohort and extrapolating, they calculated a primary outcome incidence of 0.06% [95% CI, 0.02%-0.14%].

Results were in hospital only and were not time specific. Authors were unable to control for confounders, prevent data collection bias, or verify inclusion criteria for more than 5% of the initial sample.

Bottom line: Risk for in-hospital adverse cardiac events is low in patients hospitalized from the ED with chest pain and normal vital signs, negative serial troponin, and non-ischemic ECG.

Citation: Weinstock MB, Weingart S, Orth F, et al. Risk for clinically relevant adverse cardiac events in patients with chest pain at hospital admission. JAMA Intern Med. 2015;175(7):1207-1212. doi: 10.1001/jamainternmed.2015.1674.

Clinical question: Do stable, low-risk patients hospitalized for chest pain after negative ED evaluation experience adverse cardiac events in the hospital?

Background: Chest pain results in more than seven million ED visits annually, with a cost of over $11 billion to hospitalize these patients for closer monitoring. It is not well known to what extent these low-risk patients experience in-hospital adverse cardiac events after a negative ED evaluation.

Study design: Blinded data review from a prospectively collected, multicenter database.

Setting: Three community teaching hospitals in the U.S.

Synopsis: Researchers identified 11,230 patients, aged 18 and older, hospitalized with chest pain symptoms after negative serial troponin, from July 2008 through June 2013. Demographics included mean age 58 years, 55% female, with several co-morbid medical illnesses. One hundred ninety-seven patients met the primary outcomes of in-hospital life-threatening arrhythmia, ST segment elevation MI, cardiac or respiratory arrest, and death.

Blinded reviewers further stratified these patients and excluded any patients with initial abnormal vital signs, with ECG evidence of ischemia, or with an uninterpretable ECG. This resulted in four patients who experienced the primary outcome in hospital after presenting with chest pain, stable vital signs, and no evidence of ischemia. By verifying inclusion data from 5% of the primary cohort and extrapolating, they calculated a primary outcome incidence of 0.06% [95% CI, 0.02%-0.14%].

Results were in hospital only and were not time specific. Authors were unable to control for confounders, prevent data collection bias, or verify inclusion criteria for more than 5% of the initial sample.

Bottom line: Risk for in-hospital adverse cardiac events is low in patients hospitalized from the ED with chest pain and normal vital signs, negative serial troponin, and non-ischemic ECG.

Citation: Weinstock MB, Weingart S, Orth F, et al. Risk for clinically relevant adverse cardiac events in patients with chest pain at hospital admission. JAMA Intern Med. 2015;175(7):1207-1212. doi: 10.1001/jamainternmed.2015.1674.

Clinical question: Do stable, low-risk patients hospitalized for chest pain after negative ED evaluation experience adverse cardiac events in the hospital?

Background: Chest pain results in more than seven million ED visits annually, with a cost of over $11 billion to hospitalize these patients for closer monitoring. It is not well known to what extent these low-risk patients experience in-hospital adverse cardiac events after a negative ED evaluation.

Study design: Blinded data review from a prospectively collected, multicenter database.

Setting: Three community teaching hospitals in the U.S.

Synopsis: Researchers identified 11,230 patients, aged 18 and older, hospitalized with chest pain symptoms after negative serial troponin, from July 2008 through June 2013. Demographics included mean age 58 years, 55% female, with several co-morbid medical illnesses. One hundred ninety-seven patients met the primary outcomes of in-hospital life-threatening arrhythmia, ST segment elevation MI, cardiac or respiratory arrest, and death.

Blinded reviewers further stratified these patients and excluded any patients with initial abnormal vital signs, with ECG evidence of ischemia, or with an uninterpretable ECG. This resulted in four patients who experienced the primary outcome in hospital after presenting with chest pain, stable vital signs, and no evidence of ischemia. By verifying inclusion data from 5% of the primary cohort and extrapolating, they calculated a primary outcome incidence of 0.06% [95% CI, 0.02%-0.14%].

Results were in hospital only and were not time specific. Authors were unable to control for confounders, prevent data collection bias, or verify inclusion criteria for more than 5% of the initial sample.

Bottom line: Risk for in-hospital adverse cardiac events is low in patients hospitalized from the ED with chest pain and normal vital signs, negative serial troponin, and non-ischemic ECG.

Citation: Weinstock MB, Weingart S, Orth F, et al. Risk for clinically relevant adverse cardiac events in patients with chest pain at hospital admission. JAMA Intern Med. 2015;175(7):1207-1212. doi: 10.1001/jamainternmed.2015.1674.

Clinical question: Can a diagnostic strategy that utilizes a clinical prediction rule combined with an immunoassay appropriately guide management for patients with suspected heparin-induced thrombocytopenia (HIT)?

Background: The appropriate and timely diagnosis of HIT can decrease the risks of thromboembolic and major bleeding events. Unfortunately, the reference standard tests for diagnosing HIT (e.g. serotonin release assay) are time-intensive. Immunoassays such as PF4/H-PaGIA provide a faster diagnostic approach but have been limited by poor specificity.

Study design: Single-group prospective cohort trial.

Setting: Four hospitals in Ontario, Canada between 2008 and 2013.

Synopsis: In 526 patients with suspected HIT, the results of a diagnostic strategy that combined the 4Ts score system and a PF4/H-PaGIA assay were compared to a HIT reference standard. For the identification of patients with HIT, the use of (1) an intermediate 4Ts score and negative PF4/H-PaGIA or (2) a low 4Ts score regardless of PF4/H-PaGIA result incorrectly excluded patients with HIT in 1.1% of cases (95% confidence interval 0.2-2.1%). For patients with low and intermediate 4Ts scores, however, a negative PF4/H-PaGIA result did not result in any incorrect exclusion.

Bottom line: In patients with low or intermediate 4Ts scores, a negative PF4/H-PaGIA assay may be used to exclude HIT, but further research into how to approach patients with a low 4Ts score and a positive PF4/H-PaGIA assay is needed.

Citation: Linkins LA, Bates SM, Lee AY, Heddle NM, Wang G, Warkentin TE. Combination of 4Ts score and PF4/H-PaGIA for diagnosis and management of heparin-induced thrombocytopenia: prospective cohort study. Blood. 2015;126(5):597-603.

Clinical question: Can a diagnostic strategy that utilizes a clinical prediction rule combined with an immunoassay appropriately guide management for patients with suspected heparin-induced thrombocytopenia (HIT)?

Background: The appropriate and timely diagnosis of HIT can decrease the risks of thromboembolic and major bleeding events. Unfortunately, the reference standard tests for diagnosing HIT (e.g. serotonin release assay) are time-intensive. Immunoassays such as PF4/H-PaGIA provide a faster diagnostic approach but have been limited by poor specificity.

Study design: Single-group prospective cohort trial.

Setting: Four hospitals in Ontario, Canada between 2008 and 2013.

Synopsis: In 526 patients with suspected HIT, the results of a diagnostic strategy that combined the 4Ts score system and a PF4/H-PaGIA assay were compared to a HIT reference standard. For the identification of patients with HIT, the use of (1) an intermediate 4Ts score and negative PF4/H-PaGIA or (2) a low 4Ts score regardless of PF4/H-PaGIA result incorrectly excluded patients with HIT in 1.1% of cases (95% confidence interval 0.2-2.1%). For patients with low and intermediate 4Ts scores, however, a negative PF4/H-PaGIA result did not result in any incorrect exclusion.

Bottom line: In patients with low or intermediate 4Ts scores, a negative PF4/H-PaGIA assay may be used to exclude HIT, but further research into how to approach patients with a low 4Ts score and a positive PF4/H-PaGIA assay is needed.

Citation: Linkins LA, Bates SM, Lee AY, Heddle NM, Wang G, Warkentin TE. Combination of 4Ts score and PF4/H-PaGIA for diagnosis and management of heparin-induced thrombocytopenia: prospective cohort study. Blood. 2015;126(5):597-603.

Clinical question: Can a diagnostic strategy that utilizes a clinical prediction rule combined with an immunoassay appropriately guide management for patients with suspected heparin-induced thrombocytopenia (HIT)?

Background: The appropriate and timely diagnosis of HIT can decrease the risks of thromboembolic and major bleeding events. Unfortunately, the reference standard tests for diagnosing HIT (e.g. serotonin release assay) are time-intensive. Immunoassays such as PF4/H-PaGIA provide a faster diagnostic approach but have been limited by poor specificity.

Study design: Single-group prospective cohort trial.

Setting: Four hospitals in Ontario, Canada between 2008 and 2013.

Synopsis: In 526 patients with suspected HIT, the results of a diagnostic strategy that combined the 4Ts score system and a PF4/H-PaGIA assay were compared to a HIT reference standard. For the identification of patients with HIT, the use of (1) an intermediate 4Ts score and negative PF4/H-PaGIA or (2) a low 4Ts score regardless of PF4/H-PaGIA result incorrectly excluded patients with HIT in 1.1% of cases (95% confidence interval 0.2-2.1%). For patients with low and intermediate 4Ts scores, however, a negative PF4/H-PaGIA result did not result in any incorrect exclusion.

Bottom line: In patients with low or intermediate 4Ts scores, a negative PF4/H-PaGIA assay may be used to exclude HIT, but further research into how to approach patients with a low 4Ts score and a positive PF4/H-PaGIA assay is needed.

Citation: Linkins LA, Bates SM, Lee AY, Heddle NM, Wang G, Warkentin TE. Combination of 4Ts score and PF4/H-PaGIA for diagnosis and management of heparin-induced thrombocytopenia: prospective cohort study. Blood. 2015;126(5):597-603.

Clinical question: Can vasoactive medications be safely given in the ICU via peripheral intravenous (PIV) access instead of central venous access?

Background: Vasoactive medications are given to a variety of patients in shock to maintain hemodynamic function. These medications are given through central venous catheters, partly out of concern for extravasation and tissue injury from PIV access use; however, placement and use of central catheters are also associated with significant morbidity.

Study design: Single-arm, observational, consecutive patient study.

Setting: Single, 18-bed medical ICU.

Synopsis: Investigators identified 734 ICU patients who received vasoactive medications through PIV lines between September 2002 and June 2014. They were 54% male gender, with an average age of 72 years and a SAPS II score average of 75. Norepinephrine, dopamine, and phenylephrine were included in the study. The decision to use these medications was based on clinical judgment. A specific pre-approved protocol, involving PIV and vein size and location, use of ultrasound confirmation, and a maximum duration of 72 hours, was used to administer these medications via PIV. Extravasation was immediately treated with injected phentolamine and topical nitroglycerin.

The average duration of PIV vasoactive medication use was 49 hours. Of the study patients, 13% eventually required central catheters, 2% experienced peripheral extravasation of medication, and none experienced tissue injury as defined by the study group.

Because the study was observational, there was no control group, and outcomes/efficacy compared to central catheters could not be assessed. Patient characteristics and other variables were not controlled for, and its single-center design makes reproducibility uncertain.

Bottom line: Vasoactive medications can be safely and feasibly administered to ICU patients through PIV lines using adequate protocols.

Citation: Cardenas-Garcia J, Schaub KF, Belchikov YG, Narasimhan M, Koenig SJ, Mayo PH. Safety of peripheral intravenous administration of vasoactive medication [published online ahead of print May 26, 2015]. J Hosp Med. doi: 10.1002/jhm.2394.

Clinical question: Can vasoactive medications be safely given in the ICU via peripheral intravenous (PIV) access instead of central venous access?

Background: Vasoactive medications are given to a variety of patients in shock to maintain hemodynamic function. These medications are given through central venous catheters, partly out of concern for extravasation and tissue injury from PIV access use; however, placement and use of central catheters are also associated with significant morbidity.

Study design: Single-arm, observational, consecutive patient study.

Setting: Single, 18-bed medical ICU.

Synopsis: Investigators identified 734 ICU patients who received vasoactive medications through PIV lines between September 2002 and June 2014. They were 54% male gender, with an average age of 72 years and a SAPS II score average of 75. Norepinephrine, dopamine, and phenylephrine were included in the study. The decision to use these medications was based on clinical judgment. A specific pre-approved protocol, involving PIV and vein size and location, use of ultrasound confirmation, and a maximum duration of 72 hours, was used to administer these medications via PIV. Extravasation was immediately treated with injected phentolamine and topical nitroglycerin.

The average duration of PIV vasoactive medication use was 49 hours. Of the study patients, 13% eventually required central catheters, 2% experienced peripheral extravasation of medication, and none experienced tissue injury as defined by the study group.

Because the study was observational, there was no control group, and outcomes/efficacy compared to central catheters could not be assessed. Patient characteristics and other variables were not controlled for, and its single-center design makes reproducibility uncertain.

Bottom line: Vasoactive medications can be safely and feasibly administered to ICU patients through PIV lines using adequate protocols.

Citation: Cardenas-Garcia J, Schaub KF, Belchikov YG, Narasimhan M, Koenig SJ, Mayo PH. Safety of peripheral intravenous administration of vasoactive medication [published online ahead of print May 26, 2015]. J Hosp Med. doi: 10.1002/jhm.2394.

Clinical question: Can vasoactive medications be safely given in the ICU via peripheral intravenous (PIV) access instead of central venous access?

Background: Vasoactive medications are given to a variety of patients in shock to maintain hemodynamic function. These medications are given through central venous catheters, partly out of concern for extravasation and tissue injury from PIV access use; however, placement and use of central catheters are also associated with significant morbidity.

Study design: Single-arm, observational, consecutive patient study.

Setting: Single, 18-bed medical ICU.

Synopsis: Investigators identified 734 ICU patients who received vasoactive medications through PIV lines between September 2002 and June 2014. They were 54% male gender, with an average age of 72 years and a SAPS II score average of 75. Norepinephrine, dopamine, and phenylephrine were included in the study. The decision to use these medications was based on clinical judgment. A specific pre-approved protocol, involving PIV and vein size and location, use of ultrasound confirmation, and a maximum duration of 72 hours, was used to administer these medications via PIV. Extravasation was immediately treated with injected phentolamine and topical nitroglycerin.

The average duration of PIV vasoactive medication use was 49 hours. Of the study patients, 13% eventually required central catheters, 2% experienced peripheral extravasation of medication, and none experienced tissue injury as defined by the study group.

Because the study was observational, there was no control group, and outcomes/efficacy compared to central catheters could not be assessed. Patient characteristics and other variables were not controlled for, and its single-center design makes reproducibility uncertain.

Bottom line: Vasoactive medications can be safely and feasibly administered to ICU patients through PIV lines using adequate protocols.

Citation: Cardenas-Garcia J, Schaub KF, Belchikov YG, Narasimhan M, Koenig SJ, Mayo PH. Safety of peripheral intravenous administration of vasoactive medication [published online ahead of print May 26, 2015]. J Hosp Med. doi: 10.1002/jhm.2394.

Clinical question: What is the cost and frequency of ED revisits within three days and 30 days?

Background: ED revisits lead to a financial and resource utilization burden on the medical system. The costs and rates of these return visits are unknown and limited in characterization.

Study design: Observational study.

Setting: Six states, using Healthcare Cost and Utilization Project databases.

Synopsis: An observational study examined data from 2006-2010 across six states to determine cost and frequency of ED revisits within a 30-day period from initial ED treatment and discharge. The study examined revisit rates within the first three days of discharge, as well as the 30 days following discharge from the initial presentation.

Three-day revisit rates were 8.2%, with 29% resulting in admission; 32% of the revisits took place at a different institution.

The 30-day revisit rate was 19.9%, with 28% resulting in admission. The most common diagnoses were skin and soft tissue infections (23.9%) and abdominal pain (9.7%). The vast majority of revisits (89%) resulted in the same diagnosis as the first encounter.

Cost of the revisits was more difficult to assess, because only one of six states had full data (Florida); the cost data was extrapolated for the other states involved. In Florida, three-day revisit costs accounted for 30.3% of all primary visit costs. Thirty-day revisit costs were 118% of all primary ED visits costs within that time period.

There was not always an indication of whether the revisit was due to a planned revisit, worsening of symptoms, or inadequate initial treatment, however, leaving the evaluation of cost and revisit burden incomplete.

Bottom line: Initial evaluation of ED revisits shows that rates and cost are significant, though the nature of the revisits remains underevaluated. Preliminary data demonstrate that ED revisits are a significant cost to the healthcare system, though the number of preventable revisits remains unknown.

Citation: Duseja R, Bardach NS, Lin GA, et al. Revisit rates and associated costs after and emergency department encounter. Ann Intern Med. 2015;162(11):750-756.

Clinical question: What is the cost and frequency of ED revisits within three days and 30 days?

Background: ED revisits lead to a financial and resource utilization burden on the medical system. The costs and rates of these return visits are unknown and limited in characterization.

Study design: Observational study.

Setting: Six states, using Healthcare Cost and Utilization Project databases.

Synopsis: An observational study examined data from 2006-2010 across six states to determine cost and frequency of ED revisits within a 30-day period from initial ED treatment and discharge. The study examined revisit rates within the first three days of discharge, as well as the 30 days following discharge from the initial presentation.

Three-day revisit rates were 8.2%, with 29% resulting in admission; 32% of the revisits took place at a different institution.

The 30-day revisit rate was 19.9%, with 28% resulting in admission. The most common diagnoses were skin and soft tissue infections (23.9%) and abdominal pain (9.7%). The vast majority of revisits (89%) resulted in the same diagnosis as the first encounter.

Cost of the revisits was more difficult to assess, because only one of six states had full data (Florida); the cost data was extrapolated for the other states involved. In Florida, three-day revisit costs accounted for 30.3% of all primary visit costs. Thirty-day revisit costs were 118% of all primary ED visits costs within that time period.

There was not always an indication of whether the revisit was due to a planned revisit, worsening of symptoms, or inadequate initial treatment, however, leaving the evaluation of cost and revisit burden incomplete.

Bottom line: Initial evaluation of ED revisits shows that rates and cost are significant, though the nature of the revisits remains underevaluated. Preliminary data demonstrate that ED revisits are a significant cost to the healthcare system, though the number of preventable revisits remains unknown.

Citation: Duseja R, Bardach NS, Lin GA, et al. Revisit rates and associated costs after and emergency department encounter. Ann Intern Med. 2015;162(11):750-756.

Clinical question: What is the cost and frequency of ED revisits within three days and 30 days?

Background: ED revisits lead to a financial and resource utilization burden on the medical system. The costs and rates of these return visits are unknown and limited in characterization.

Study design: Observational study.

Setting: Six states, using Healthcare Cost and Utilization Project databases.

Synopsis: An observational study examined data from 2006-2010 across six states to determine cost and frequency of ED revisits within a 30-day period from initial ED treatment and discharge. The study examined revisit rates within the first three days of discharge, as well as the 30 days following discharge from the initial presentation.

Three-day revisit rates were 8.2%, with 29% resulting in admission; 32% of the revisits took place at a different institution.

The 30-day revisit rate was 19.9%, with 28% resulting in admission. The most common diagnoses were skin and soft tissue infections (23.9%) and abdominal pain (9.7%). The vast majority of revisits (89%) resulted in the same diagnosis as the first encounter.

Cost of the revisits was more difficult to assess, because only one of six states had full data (Florida); the cost data was extrapolated for the other states involved. In Florida, three-day revisit costs accounted for 30.3% of all primary visit costs. Thirty-day revisit costs were 118% of all primary ED visits costs within that time period.

There was not always an indication of whether the revisit was due to a planned revisit, worsening of symptoms, or inadequate initial treatment, however, leaving the evaluation of cost and revisit burden incomplete.

Bottom line: Initial evaluation of ED revisits shows that rates and cost are significant, though the nature of the revisits remains underevaluated. Preliminary data demonstrate that ED revisits are a significant cost to the healthcare system, though the number of preventable revisits remains unknown.

Citation: Duseja R, Bardach NS, Lin GA, et al. Revisit rates and associated costs after and emergency department encounter. Ann Intern Med. 2015;162(11):750-756.