The continued use of perioperative clopidogrel is appropriate

Surgeons have always worried about bleeding risks for procedures we do. Complex vascular procedures are further complicated by the myriad of available antiplatelet agents designed to reduce ischemic events from cardiovascular disease burden at the expense of potential bleeding complications if antiplatelet medications are continued. Rather than relying on anecdotal reports by historical vignettes, let’s look at the evidence.

There probably is no other drug available in our vascular toolbox which has been studied more in the last 20 years than clopidogrel. Multiple randomized and double blinded studies such as CASPAR¹ and CHARISMA² have amplified what was known since the early CAPRIE trial in the 1990’s and that is that clopidogrel is safe when used as a single medication or as a dual agent with aspirin (duel antiplatelet therapy [DAPT]).

But not all our patients need DAPT. There is no level 1 evidence demonstrating the need for any antiplatelet therapy in the primary prevention of cardiovascular events for patients deemed at low or moderate risk of cardiovascular disease from a large meta-analysis review of six primary prevention trials encompassing over 95,000 patients.³

If our patients do present with vascular disease, current ACCP guidelines recommend single-agent antiplatelet medication (either ASA or clopidogrel) for symptomatic peripheral arterial disease (PAD) whether planning LE revascularization with bypass or via endovascular means with grade 1A evidence.⁴ This works fine for single-focus vascular disease and each antiplatelet agent have proponents but either works well.

That’s great, but what about all those sick cardiac patients we see the most of? First, CHARISMA subgroup analysis of patients with preexisting coronary and/or cerebrovascular disease demonstrate a 7.1% risk reduction in MI, cerebrovascular events, and cardiac ischemic deaths when continuing DAPT over aspirin alone, and similar risk reduction is found in PAD patients for endpoints of MI and ischemic cardiovascular events. Second, there was no significant difference in severe, fatal, or moderate bleeding in those receiving DAPT vs. aspirin alone with only minor bleeding increased using DAPT. Third, real-life practice echoes multiple trial experiences such as the Vascular Study Group of New England study group confirmed in reviewing 16 centers and 66 surgeons with more than 10,000 patients. Approximately 39% underwent major aortic or lower extremity bypass operations.

No statistical difference could be found for reoperation (P = .74), transfusion (P = .1) or operative type between DAPT or aspirin use alone.⁵ This is rediscovered once again by Saadeh and Sfeir in their prospective study of 647 major arterial procedures over 7 years finding no significant difference in reoperation for bleeding or bleeding mortality between DAPT vs. aspirin alone.⁶

So can we stop bashing clopidogrel as an evil agent of bleeding as Dr. Dalsing wishes to do? After all, he has been on record as stating, “I don’t know if our bleeding risk is worse or better … something we have to do to keep our grafts going.” Evidence tells us the benefits for continuing DAPT as seen in risk reduction in primary cardiovascular outcomes far outweigh the risk of minor bleeding associated with continued use.

Let the science dictate practice. Patients with low or moderate risk for cardiovascular disease need no antiplatelet medication unless undergoing PAD treatment where a single agent, either aspirin or clopidogrel alone, is sufficient. In those patients having a large cardiovascular burden of disease, combination of aspirin and clopidogrel improves survival benefit and reduces ischemic events without a significant risk of reoperation, transfusion, or bleeding-related mortality. As many of our patients require DAPT for drug eluting coronary stents, withholding clopidogrel preoperatively increases overall risk beyond acceptable limits. Improving surgical skills and paying attention to hemostasis during the operation will allow naysayers to achieve improved patient survival without fear of bleeding when continuing best medical therapy such as DAPT.

Gary Lemmon, MD, is professor of vascular surgery at Indiana University, Indianapolis, and chief, vascular surgery, Indianapolis VA Medical Center. He reported no relevant conflicts.

References

1. J Vasc Surg. 2010;52:825-33

2. Eur Heart J. 2009;30:192-201

3. Lancet. 2009;373:1849-604. Chest. 2012;141:e669s-90s

5. J Vasc Surg. 2011;54: 779-84

6. J Vasc Surg. 2013;58: 1586-92

The continued use of perioperative clopidogrel is debatable!

There are cases in which clopidogrel should not be discontinued for a needed vascular intervention. Delaying operation or maintaining clopidogrel during operation if your patient required a recent coronary stent is warranted unless you are willing to accept an acute coronary thrombosis.

However, in other cases, for example infrainguinal grafts, the risk of potential increased bleeding when adding clopidogrel to aspirin may outweigh potential improvements in graft patency. This is especially true of below-knee vein bypass grafts where data do not support improved patency. However, in the CASPAR trial, prosthetic graft patency did appear to be beneficial, but only in subgroup analysis.¹

It is true that severe bleeding was not increased (intracranial hemorrhage, or hemodynamic compromise: 1 vs 2.7%, P = NS) but moderate bleeding (transfusion required: 0.7 vs 3.7%, P = .012) and mild bleeding (5.4 vs 12.1%, P = .004) was increased when this agent was used especially in vein graft surgery. This risk of bleeding was present even when clopidogrel was begun 2 or more days after surgery.¹

To complicate this decision, a Cochrane review did not consider subgroup analysis as statistically valid and so the authors considered infrainguinal graft patency as not improved with clopidogrel but bleeding risk was increased. One might even question the use of acetylsalicylic acid (ASA) for vein graft bypasses based on the results of this metanalysis.2 Carotid endarterectomy is a common vascular surgery procedure in which antiplatelet use has been evaluated in the real-world situation and with large cohorts. As is always the case when dealing with patient issues, the addition of one agent does not tell the entire story and patient demographics can have a significant influence on the outcome. A report from the Vascular Quality Initiative (VQI) database controlled for patient differences by propensity matching with more than 4,500 patients in each of the two groups; ASA vs. ASA + clopidogrel; demonstrated that major bleeding, defined as return to the OR for bleeding, was statistically more common with dual therapy (1.3% vs. 0.7%, P = .004).³

The addition of clopidogrel did statistically decrease the risk of ipsilateral TIA or stroke (0.8% vs. 1.2%, P = .02) but not the risk of death (0.2% vs. 0.3%, P = .3) or postoperative MI (1% vs. 0.8%, P = .4). Reoperation for bleeding is not inconsequential since in patients requiring this intervention, there is a significantly worse outcome in regard to stroke (3.7% vs. 0.8%, P = .001), MI (6.2% vs. 0.8%, P = .001), and death (2.5% vs. 0.2%,P = .001). Further drill down involving propensity score–matched analysis stratified by symptom status (asymptomatic vs. symptomatic) was quite interesting in that in only asymptomatic patients did the addition of clopidogrel actually demonstrate a statistically significant reduction in TIA or stroke, any stroke, or composite stroke/death. Symptomatic patients taking dual therapy demonstrated a slight reduction in TIA or stroke (1.4% vs. 1.7%, P = .6), any stroke (1.1% vs. 1.2%, P = .9) and composite stroke/death (1.2% vs. 1.5%, P = .5) but in no instance was statistical significance reached. The use of protamine did help to decrease the risk of bleeding.

Regarding the use of dual therapy during open aortic operations, an earlier report of the VQI database demonstrated no significant difference in bleeding risk statistically, but if one delves deeper the data indicate something different. In the majority of cases, vascular surgeons do not feel comfortable preforming this extensive dissection on dual therapy. Of the cases reported, 1,074 were preformed either free of either drug or only on ASA while 42 were on dual therapy and only 12 on clopidogrel only. In fact, in the conclusions, the authors note that they do not believe that conclusions regarding clopidogrel use in patient undergoing open abdominal aortic aneurysm repair can be drawn based on their results since the potential for a type II error was too great.⁴

It may be that our current level of sophistication is not sufficiently mature to determine the actual effect that clopidogrel is having on our patients. Clopidogrel, a thienopyridine, inhibits platelet activation by blocking the ADP-binding site for the P2Y12 receptor. Over 85% of ingested drug is metabolized into inactive metabolites while 15% is metabolized by the liver via a two-step oxidative process into the active thiol metabolite. Inter-individual variability in the antiplatelet response to thienopyridines is noted and partially caused by genetic mutations in the CP isoenzymes. Platelet reactivity testing is possible but most of the work has been conducted for those patients requiring coronary artery revascularization. Results of tailoring intervention to maximize therapeutic benefit and decrease the risk of bleeding have been inconsistent but, in some studies, appear to be promising.⁵ This approach may ultimately be found superior to determining how effective clopidogrel actually is in a particular case with some insight into the bleeding risk as well. With this determination, whether or not to hold clopidogrel perioperatively can be made with some science behind the decision.

Clearly, a blanket statement that the risk of bleeding should be accepted or ignored because of the demonstrated benefits of clopidogrel in patients requiring vascular surgery is not accurate. In some cases, there is no clear benefit, so eliminating the bleeding risk may well be the appropriate decision. The astute vascular surgeon understands the details of the written word in order to make an educated decision and understands that new information such as determining platelet reactivity may provide more clarity to such decisions in the future.

Michael C. Dalsing, MD, is chief of vascular surgery at Indiana University, Indianapolis. He reported no relevant conflicts.

References

1. J Vasc Surg. 2010;52:825-33

2. Cochrane Database Syst Rev. 2015, Issue 2. Art. No.: CD000535

3. J Vasc Surg. 2016;63:1262-70

4.J Vasc Surg. 2011;54:779-84

5. Vascul Pharmacol. 2016;77:19-27

The continued use of perioperative clopidogrel is appropriate

Surgeons have always worried about bleeding risks for procedures we do. Complex vascular procedures are further complicated by the myriad of available antiplatelet agents designed to reduce ischemic events from cardiovascular disease burden at the expense of potential bleeding complications if antiplatelet medications are continued. Rather than relying on anecdotal reports by historical vignettes, let’s look at the evidence.

There probably is no other drug available in our vascular toolbox which has been studied more in the last 20 years than clopidogrel. Multiple randomized and double blinded studies such as CASPAR¹ and CHARISMA² have amplified what was known since the early CAPRIE trial in the 1990’s and that is that clopidogrel is safe when used as a single medication or as a dual agent with aspirin (duel antiplatelet therapy [DAPT]).

But not all our patients need DAPT. There is no level 1 evidence demonstrating the need for any antiplatelet therapy in the primary prevention of cardiovascular events for patients deemed at low or moderate risk of cardiovascular disease from a large meta-analysis review of six primary prevention trials encompassing over 95,000 patients.³

If our patients do present with vascular disease, current ACCP guidelines recommend single-agent antiplatelet medication (either ASA or clopidogrel) for symptomatic peripheral arterial disease (PAD) whether planning LE revascularization with bypass or via endovascular means with grade 1A evidence.⁴ This works fine for single-focus vascular disease and each antiplatelet agent have proponents but either works well.

That’s great, but what about all those sick cardiac patients we see the most of? First, CHARISMA subgroup analysis of patients with preexisting coronary and/or cerebrovascular disease demonstrate a 7.1% risk reduction in MI, cerebrovascular events, and cardiac ischemic deaths when continuing DAPT over aspirin alone, and similar risk reduction is found in PAD patients for endpoints of MI and ischemic cardiovascular events. Second, there was no significant difference in severe, fatal, or moderate bleeding in those receiving DAPT vs. aspirin alone with only minor bleeding increased using DAPT. Third, real-life practice echoes multiple trial experiences such as the Vascular Study Group of New England study group confirmed in reviewing 16 centers and 66 surgeons with more than 10,000 patients. Approximately 39% underwent major aortic or lower extremity bypass operations.

No statistical difference could be found for reoperation (P = .74), transfusion (P = .1) or operative type between DAPT or aspirin use alone.⁵ This is rediscovered once again by Saadeh and Sfeir in their prospective study of 647 major arterial procedures over 7 years finding no significant difference in reoperation for bleeding or bleeding mortality between DAPT vs. aspirin alone.⁶

So can we stop bashing clopidogrel as an evil agent of bleeding as Dr. Dalsing wishes to do? After all, he has been on record as stating, “I don’t know if our bleeding risk is worse or better … something we have to do to keep our grafts going.” Evidence tells us the benefits for continuing DAPT as seen in risk reduction in primary cardiovascular outcomes far outweigh the risk of minor bleeding associated with continued use.

Let the science dictate practice. Patients with low or moderate risk for cardiovascular disease need no antiplatelet medication unless undergoing PAD treatment where a single agent, either aspirin or clopidogrel alone, is sufficient. In those patients having a large cardiovascular burden of disease, combination of aspirin and clopidogrel improves survival benefit and reduces ischemic events without a significant risk of reoperation, transfusion, or bleeding-related mortality. As many of our patients require DAPT for drug eluting coronary stents, withholding clopidogrel preoperatively increases overall risk beyond acceptable limits. Improving surgical skills and paying attention to hemostasis during the operation will allow naysayers to achieve improved patient survival without fear of bleeding when continuing best medical therapy such as DAPT.

Gary Lemmon, MD, is professor of vascular surgery at Indiana University, Indianapolis, and chief, vascular surgery, Indianapolis VA Medical Center. He reported no relevant conflicts.

References

1. J Vasc Surg. 2010;52:825-33

2. Eur Heart J. 2009;30:192-201

3. Lancet. 2009;373:1849-604. Chest. 2012;141:e669s-90s

5. J Vasc Surg. 2011;54: 779-84

6. J Vasc Surg. 2013;58: 1586-92

The continued use of perioperative clopidogrel is debatable!

There are cases in which clopidogrel should not be discontinued for a needed vascular intervention. Delaying operation or maintaining clopidogrel during operation if your patient required a recent coronary stent is warranted unless you are willing to accept an acute coronary thrombosis.

However, in other cases, for example infrainguinal grafts, the risk of potential increased bleeding when adding clopidogrel to aspirin may outweigh potential improvements in graft patency. This is especially true of below-knee vein bypass grafts where data do not support improved patency. However, in the CASPAR trial, prosthetic graft patency did appear to be beneficial, but only in subgroup analysis.¹

It is true that severe bleeding was not increased (intracranial hemorrhage, or hemodynamic compromise: 1 vs 2.7%, P = NS) but moderate bleeding (transfusion required: 0.7 vs 3.7%, P = .012) and mild bleeding (5.4 vs 12.1%, P = .004) was increased when this agent was used especially in vein graft surgery. This risk of bleeding was present even when clopidogrel was begun 2 or more days after surgery.¹

To complicate this decision, a Cochrane review did not consider subgroup analysis as statistically valid and so the authors considered infrainguinal graft patency as not improved with clopidogrel but bleeding risk was increased. One might even question the use of acetylsalicylic acid (ASA) for vein graft bypasses based on the results of this metanalysis.2 Carotid endarterectomy is a common vascular surgery procedure in which antiplatelet use has been evaluated in the real-world situation and with large cohorts. As is always the case when dealing with patient issues, the addition of one agent does not tell the entire story and patient demographics can have a significant influence on the outcome. A report from the Vascular Quality Initiative (VQI) database controlled for patient differences by propensity matching with more than 4,500 patients in each of the two groups; ASA vs. ASA + clopidogrel; demonstrated that major bleeding, defined as return to the OR for bleeding, was statistically more common with dual therapy (1.3% vs. 0.7%, P = .004).³

The addition of clopidogrel did statistically decrease the risk of ipsilateral TIA or stroke (0.8% vs. 1.2%, P = .02) but not the risk of death (0.2% vs. 0.3%, P = .3) or postoperative MI (1% vs. 0.8%, P = .4). Reoperation for bleeding is not inconsequential since in patients requiring this intervention, there is a significantly worse outcome in regard to stroke (3.7% vs. 0.8%, P = .001), MI (6.2% vs. 0.8%, P = .001), and death (2.5% vs. 0.2%,P = .001). Further drill down involving propensity score–matched analysis stratified by symptom status (asymptomatic vs. symptomatic) was quite interesting in that in only asymptomatic patients did the addition of clopidogrel actually demonstrate a statistically significant reduction in TIA or stroke, any stroke, or composite stroke/death. Symptomatic patients taking dual therapy demonstrated a slight reduction in TIA or stroke (1.4% vs. 1.7%, P = .6), any stroke (1.1% vs. 1.2%, P = .9) and composite stroke/death (1.2% vs. 1.5%, P = .5) but in no instance was statistical significance reached. The use of protamine did help to decrease the risk of bleeding.

Regarding the use of dual therapy during open aortic operations, an earlier report of the VQI database demonstrated no significant difference in bleeding risk statistically, but if one delves deeper the data indicate something different. In the majority of cases, vascular surgeons do not feel comfortable preforming this extensive dissection on dual therapy. Of the cases reported, 1,074 were preformed either free of either drug or only on ASA while 42 were on dual therapy and only 12 on clopidogrel only. In fact, in the conclusions, the authors note that they do not believe that conclusions regarding clopidogrel use in patient undergoing open abdominal aortic aneurysm repair can be drawn based on their results since the potential for a type II error was too great.⁴

It may be that our current level of sophistication is not sufficiently mature to determine the actual effect that clopidogrel is having on our patients. Clopidogrel, a thienopyridine, inhibits platelet activation by blocking the ADP-binding site for the P2Y12 receptor. Over 85% of ingested drug is metabolized into inactive metabolites while 15% is metabolized by the liver via a two-step oxidative process into the active thiol metabolite. Inter-individual variability in the antiplatelet response to thienopyridines is noted and partially caused by genetic mutations in the CP isoenzymes. Platelet reactivity testing is possible but most of the work has been conducted for those patients requiring coronary artery revascularization. Results of tailoring intervention to maximize therapeutic benefit and decrease the risk of bleeding have been inconsistent but, in some studies, appear to be promising.⁵ This approach may ultimately be found superior to determining how effective clopidogrel actually is in a particular case with some insight into the bleeding risk as well. With this determination, whether or not to hold clopidogrel perioperatively can be made with some science behind the decision.

Clearly, a blanket statement that the risk of bleeding should be accepted or ignored because of the demonstrated benefits of clopidogrel in patients requiring vascular surgery is not accurate. In some cases, there is no clear benefit, so eliminating the bleeding risk may well be the appropriate decision. The astute vascular surgeon understands the details of the written word in order to make an educated decision and understands that new information such as determining platelet reactivity may provide more clarity to such decisions in the future.

Michael C. Dalsing, MD, is chief of vascular surgery at Indiana University, Indianapolis. He reported no relevant conflicts.

References

1. J Vasc Surg. 2010;52:825-33

2. Cochrane Database Syst Rev. 2015, Issue 2. Art. No.: CD000535

3. J Vasc Surg. 2016;63:1262-70

4.J Vasc Surg. 2011;54:779-84

5. Vascul Pharmacol. 2016;77:19-27

The continued use of perioperative clopidogrel is appropriate

Surgeons have always worried about bleeding risks for procedures we do. Complex vascular procedures are further complicated by the myriad of available antiplatelet agents designed to reduce ischemic events from cardiovascular disease burden at the expense of potential bleeding complications if antiplatelet medications are continued. Rather than relying on anecdotal reports by historical vignettes, let’s look at the evidence.

There probably is no other drug available in our vascular toolbox which has been studied more in the last 20 years than clopidogrel. Multiple randomized and double blinded studies such as CASPAR¹ and CHARISMA² have amplified what was known since the early CAPRIE trial in the 1990’s and that is that clopidogrel is safe when used as a single medication or as a dual agent with aspirin (duel antiplatelet therapy [DAPT]).

But not all our patients need DAPT. There is no level 1 evidence demonstrating the need for any antiplatelet therapy in the primary prevention of cardiovascular events for patients deemed at low or moderate risk of cardiovascular disease from a large meta-analysis review of six primary prevention trials encompassing over 95,000 patients.³

If our patients do present with vascular disease, current ACCP guidelines recommend single-agent antiplatelet medication (either ASA or clopidogrel) for symptomatic peripheral arterial disease (PAD) whether planning LE revascularization with bypass or via endovascular means with grade 1A evidence.⁴ This works fine for single-focus vascular disease and each antiplatelet agent have proponents but either works well.

That’s great, but what about all those sick cardiac patients we see the most of? First, CHARISMA subgroup analysis of patients with preexisting coronary and/or cerebrovascular disease demonstrate a 7.1% risk reduction in MI, cerebrovascular events, and cardiac ischemic deaths when continuing DAPT over aspirin alone, and similar risk reduction is found in PAD patients for endpoints of MI and ischemic cardiovascular events. Second, there was no significant difference in severe, fatal, or moderate bleeding in those receiving DAPT vs. aspirin alone with only minor bleeding increased using DAPT. Third, real-life practice echoes multiple trial experiences such as the Vascular Study Group of New England study group confirmed in reviewing 16 centers and 66 surgeons with more than 10,000 patients. Approximately 39% underwent major aortic or lower extremity bypass operations.

No statistical difference could be found for reoperation (P = .74), transfusion (P = .1) or operative type between DAPT or aspirin use alone.⁵ This is rediscovered once again by Saadeh and Sfeir in their prospective study of 647 major arterial procedures over 7 years finding no significant difference in reoperation for bleeding or bleeding mortality between DAPT vs. aspirin alone.⁶

So can we stop bashing clopidogrel as an evil agent of bleeding as Dr. Dalsing wishes to do? After all, he has been on record as stating, “I don’t know if our bleeding risk is worse or better … something we have to do to keep our grafts going.” Evidence tells us the benefits for continuing DAPT as seen in risk reduction in primary cardiovascular outcomes far outweigh the risk of minor bleeding associated with continued use.

Let the science dictate practice. Patients with low or moderate risk for cardiovascular disease need no antiplatelet medication unless undergoing PAD treatment where a single agent, either aspirin or clopidogrel alone, is sufficient. In those patients having a large cardiovascular burden of disease, combination of aspirin and clopidogrel improves survival benefit and reduces ischemic events without a significant risk of reoperation, transfusion, or bleeding-related mortality. As many of our patients require DAPT for drug eluting coronary stents, withholding clopidogrel preoperatively increases overall risk beyond acceptable limits. Improving surgical skills and paying attention to hemostasis during the operation will allow naysayers to achieve improved patient survival without fear of bleeding when continuing best medical therapy such as DAPT.

Gary Lemmon, MD, is professor of vascular surgery at Indiana University, Indianapolis, and chief, vascular surgery, Indianapolis VA Medical Center. He reported no relevant conflicts.

References

1. J Vasc Surg. 2010;52:825-33

2. Eur Heart J. 2009;30:192-201

3. Lancet. 2009;373:1849-604. Chest. 2012;141:e669s-90s

5. J Vasc Surg. 2011;54: 779-84

6. J Vasc Surg. 2013;58: 1586-92

The continued use of perioperative clopidogrel is debatable!

There are cases in which clopidogrel should not be discontinued for a needed vascular intervention. Delaying operation or maintaining clopidogrel during operation if your patient required a recent coronary stent is warranted unless you are willing to accept an acute coronary thrombosis.

However, in other cases, for example infrainguinal grafts, the risk of potential increased bleeding when adding clopidogrel to aspirin may outweigh potential improvements in graft patency. This is especially true of below-knee vein bypass grafts where data do not support improved patency. However, in the CASPAR trial, prosthetic graft patency did appear to be beneficial, but only in subgroup analysis.¹

It is true that severe bleeding was not increased (intracranial hemorrhage, or hemodynamic compromise: 1 vs 2.7%, P = NS) but moderate bleeding (transfusion required: 0.7 vs 3.7%, P = .012) and mild bleeding (5.4 vs 12.1%, P = .004) was increased when this agent was used especially in vein graft surgery. This risk of bleeding was present even when clopidogrel was begun 2 or more days after surgery.¹

To complicate this decision, a Cochrane review did not consider subgroup analysis as statistically valid and so the authors considered infrainguinal graft patency as not improved with clopidogrel but bleeding risk was increased. One might even question the use of acetylsalicylic acid (ASA) for vein graft bypasses based on the results of this metanalysis.2 Carotid endarterectomy is a common vascular surgery procedure in which antiplatelet use has been evaluated in the real-world situation and with large cohorts. As is always the case when dealing with patient issues, the addition of one agent does not tell the entire story and patient demographics can have a significant influence on the outcome. A report from the Vascular Quality Initiative (VQI) database controlled for patient differences by propensity matching with more than 4,500 patients in each of the two groups; ASA vs. ASA + clopidogrel; demonstrated that major bleeding, defined as return to the OR for bleeding, was statistically more common with dual therapy (1.3% vs. 0.7%, P = .004).³

The addition of clopidogrel did statistically decrease the risk of ipsilateral TIA or stroke (0.8% vs. 1.2%, P = .02) but not the risk of death (0.2% vs. 0.3%, P = .3) or postoperative MI (1% vs. 0.8%, P = .4). Reoperation for bleeding is not inconsequential since in patients requiring this intervention, there is a significantly worse outcome in regard to stroke (3.7% vs. 0.8%, P = .001), MI (6.2% vs. 0.8%, P = .001), and death (2.5% vs. 0.2%,P = .001). Further drill down involving propensity score–matched analysis stratified by symptom status (asymptomatic vs. symptomatic) was quite interesting in that in only asymptomatic patients did the addition of clopidogrel actually demonstrate a statistically significant reduction in TIA or stroke, any stroke, or composite stroke/death. Symptomatic patients taking dual therapy demonstrated a slight reduction in TIA or stroke (1.4% vs. 1.7%, P = .6), any stroke (1.1% vs. 1.2%, P = .9) and composite stroke/death (1.2% vs. 1.5%, P = .5) but in no instance was statistical significance reached. The use of protamine did help to decrease the risk of bleeding.

Regarding the use of dual therapy during open aortic operations, an earlier report of the VQI database demonstrated no significant difference in bleeding risk statistically, but if one delves deeper the data indicate something different. In the majority of cases, vascular surgeons do not feel comfortable preforming this extensive dissection on dual therapy. Of the cases reported, 1,074 were preformed either free of either drug or only on ASA while 42 were on dual therapy and only 12 on clopidogrel only. In fact, in the conclusions, the authors note that they do not believe that conclusions regarding clopidogrel use in patient undergoing open abdominal aortic aneurysm repair can be drawn based on their results since the potential for a type II error was too great.⁴

It may be that our current level of sophistication is not sufficiently mature to determine the actual effect that clopidogrel is having on our patients. Clopidogrel, a thienopyridine, inhibits platelet activation by blocking the ADP-binding site for the P2Y12 receptor. Over 85% of ingested drug is metabolized into inactive metabolites while 15% is metabolized by the liver via a two-step oxidative process into the active thiol metabolite. Inter-individual variability in the antiplatelet response to thienopyridines is noted and partially caused by genetic mutations in the CP isoenzymes. Platelet reactivity testing is possible but most of the work has been conducted for those patients requiring coronary artery revascularization. Results of tailoring intervention to maximize therapeutic benefit and decrease the risk of bleeding have been inconsistent but, in some studies, appear to be promising.⁵ This approach may ultimately be found superior to determining how effective clopidogrel actually is in a particular case with some insight into the bleeding risk as well. With this determination, whether or not to hold clopidogrel perioperatively can be made with some science behind the decision.

Clearly, a blanket statement that the risk of bleeding should be accepted or ignored because of the demonstrated benefits of clopidogrel in patients requiring vascular surgery is not accurate. In some cases, there is no clear benefit, so eliminating the bleeding risk may well be the appropriate decision. The astute vascular surgeon understands the details of the written word in order to make an educated decision and understands that new information such as determining platelet reactivity may provide more clarity to such decisions in the future.

Michael C. Dalsing, MD, is chief of vascular surgery at Indiana University, Indianapolis. He reported no relevant conflicts.

References

1. J Vasc Surg. 2010;52:825-33

2. Cochrane Database Syst Rev. 2015, Issue 2. Art. No.: CD000535

3. J Vasc Surg. 2016;63:1262-70

4.J Vasc Surg. 2011;54:779-84

5. Vascul Pharmacol. 2016;77:19-27

The Diagnosis: Blue Toe Syndrome

The clinical manifestation suggested blue toe syndrome. A variety of causes for blue toe syndrome are known such as embolism, thrombosis, vasoconstrictive disorders, infectious and noninfectious inflammation, extensive venous thrombosis, and abnormal circulating blood.¹ Among them, only emboli from atherosclerotic plaques give rise to typical cholesterol clefts on skin biopsy (Figure 1). Such atheroemboli often are an iatrogenic complication, especially those caused by invasive percutaneous procedures or damage to the arterial walls from vascular surgery. However, spontaneous plaque hemorrhage or shearing forces of the circulating blood can disrupt atheromatous plaques and cause embolization of the cholesterol crystals, which was likely to be the case in our patient because no preceding trigger events were noted.

Other clinical features also are seen in atheroembolism. Approximately half of patients with atheroembolism develop clinical kidney disease.² Almost all iatrogenic cases have acute or subacute reduction in glomerular filtration rate of at least to 50% level, whereas the spontaneous cases present as stable chronic renal failure.³ Approximately 20% of patients with atheroembolism also have involvement of digestive organs.^4,5 Abdominal pain, diarrhea, and gastrointestinal blood loss are common features; bowel infarction and perforation occasionally occur.⁵ Pancreatitis is another common complication, and serum amylase levels are raised in approximately 50% of patients.6 Atheroemboli may reach the eyes and brain. They occasionally can cause loss of vision,⁷ as well as transient ischemic attacks, strokes, and gradual deterioration in cerebral function.³ Blood eosinophilia, which occurs in approximately 60% of patients, is an important finding.^3,8

Although there is no specific therapy for atheroembolism, the use of antiplatelet agents is considered reasonable because they are beneficial in preventing myocardial infarction in patients with atherosclerosis.⁹ In our case, the livedo reticularis cleared, as did the coldness on the affected toes after 2 weeks of sarpogrelate hydrochloride administration; however, development of necrotic change was noted (Figure 2). Necrotic change on the hallux disappeared after 2 weeks.

The Diagnosis: Blue Toe Syndrome

The clinical manifestation suggested blue toe syndrome. A variety of causes for blue toe syndrome are known such as embolism, thrombosis, vasoconstrictive disorders, infectious and noninfectious inflammation, extensive venous thrombosis, and abnormal circulating blood.¹ Among them, only emboli from atherosclerotic plaques give rise to typical cholesterol clefts on skin biopsy (Figure 1). Such atheroemboli often are an iatrogenic complication, especially those caused by invasive percutaneous procedures or damage to the arterial walls from vascular surgery. However, spontaneous plaque hemorrhage or shearing forces of the circulating blood can disrupt atheromatous plaques and cause embolization of the cholesterol crystals, which was likely to be the case in our patient because no preceding trigger events were noted.

Other clinical features also are seen in atheroembolism. Approximately half of patients with atheroembolism develop clinical kidney disease.² Almost all iatrogenic cases have acute or subacute reduction in glomerular filtration rate of at least to 50% level, whereas the spontaneous cases present as stable chronic renal failure.³ Approximately 20% of patients with atheroembolism also have involvement of digestive organs.^4,5 Abdominal pain, diarrhea, and gastrointestinal blood loss are common features; bowel infarction and perforation occasionally occur.⁵ Pancreatitis is another common complication, and serum amylase levels are raised in approximately 50% of patients.6 Atheroemboli may reach the eyes and brain. They occasionally can cause loss of vision,⁷ as well as transient ischemic attacks, strokes, and gradual deterioration in cerebral function.³ Blood eosinophilia, which occurs in approximately 60% of patients, is an important finding.^3,8

Although there is no specific therapy for atheroembolism, the use of antiplatelet agents is considered reasonable because they are beneficial in preventing myocardial infarction in patients with atherosclerosis.⁹ In our case, the livedo reticularis cleared, as did the coldness on the affected toes after 2 weeks of sarpogrelate hydrochloride administration; however, development of necrotic change was noted (Figure 2). Necrotic change on the hallux disappeared after 2 weeks.

The Diagnosis: Blue Toe Syndrome

The clinical manifestation suggested blue toe syndrome. A variety of causes for blue toe syndrome are known such as embolism, thrombosis, vasoconstrictive disorders, infectious and noninfectious inflammation, extensive venous thrombosis, and abnormal circulating blood.¹ Among them, only emboli from atherosclerotic plaques give rise to typical cholesterol clefts on skin biopsy (Figure 1). Such atheroemboli often are an iatrogenic complication, especially those caused by invasive percutaneous procedures or damage to the arterial walls from vascular surgery. However, spontaneous plaque hemorrhage or shearing forces of the circulating blood can disrupt atheromatous plaques and cause embolization of the cholesterol crystals, which was likely to be the case in our patient because no preceding trigger events were noted.

Other clinical features also are seen in atheroembolism. Approximately half of patients with atheroembolism develop clinical kidney disease.² Almost all iatrogenic cases have acute or subacute reduction in glomerular filtration rate of at least to 50% level, whereas the spontaneous cases present as stable chronic renal failure.³ Approximately 20% of patients with atheroembolism also have involvement of digestive organs.^4,5 Abdominal pain, diarrhea, and gastrointestinal blood loss are common features; bowel infarction and perforation occasionally occur.⁵ Pancreatitis is another common complication, and serum amylase levels are raised in approximately 50% of patients.6 Atheroemboli may reach the eyes and brain. They occasionally can cause loss of vision,⁷ as well as transient ischemic attacks, strokes, and gradual deterioration in cerebral function.³ Blood eosinophilia, which occurs in approximately 60% of patients, is an important finding.^3,8

Although there is no specific therapy for atheroembolism, the use of antiplatelet agents is considered reasonable because they are beneficial in preventing myocardial infarction in patients with atherosclerosis.⁹ In our case, the livedo reticularis cleared, as did the coldness on the affected toes after 2 weeks of sarpogrelate hydrochloride administration; however, development of necrotic change was noted (Figure 2). Necrotic change on the hallux disappeared after 2 weeks.

The diagnosis

Histologic analysis was consistent with a fibrolamellar-hepatocellular carcinoma (HCC). The patient developed decerebrate posturing without cerebral edema on CT of the head. The patient was treated with mannitol, hyperventilation, and therapeutic hypothermia, as well as lactulose, rifaximin, hemodialysis, and “empiric” sodium benzoate/sodium phenylacetate (Ammonul, Ucyclyd Pharma, Scottsdale, Ariz.) for the possibility of a urea cycle disorder. In hopes of decreasing blood flow to the tumor, the patient underwent embolization of the right hepatic artery with no clinical improvement. Given the persistently elevated ammonia level, a work-up for an underlying urea cycle disorder was performed, revealing trace citrulline and increased urine orotic acids and uracil, suggesting an ornithine transcarbamylase (OTC) deficiency. She was started on parenteral nutrition with arginine supplementation, after which her ammonia level normalized with subsequent improvement in her mental status.

Fibrolamellar-HCC is a rare, malignant, primary liver tumor predominantly affecting young adults with no underlying liver disease. This hypervascular tumor is radiographically characterized by a central scar.¹ Most patients experience vague abdominal pain, weight loss, and fatigue. Fibrolamellar-HCC carries a better prognosis than HCC; in surgically resectable cases, the 5-year survival rates range between 37% and 76% vs. 12-14 months in nonresectable cases.² Systemic chemotherapy has been used in case reports and the role of sorafenib remains unexplored and ill defined.

This is the second reported case of metastatic fibrolamellar-HCC with hyperammonemia.³ Although urea cycle disorders are more commonly diagnosed in newborns and infants, patients with partial enzyme deficiencies may present later in life and manifest in the setting of metabolic decompensation or stress. Our patient’s initial evaluation was consistent with a urea cycle deficiency, but OTC sequencing from the blood was negative. We hypothesize that the patient exhibited a “functional” OTC deficiency as a result of a combination of the massive tumor burden and portal vein thrombus, leading to a decreased expression of the OTC gene and insufficient enzyme production. The patient is doing well 3 months post resection and is being considered for a phase I clinical trial with a telomerase inhibitor, imetelstat.

References

1. Ichikawa, T., Federle, M.P., Grazioli, L., et al. Fibrolamellar hepatocellular carcinoma: Imaging and pathologic findings in 31 recent cases. Radiology. 1999;213(2):352-61.

2. Ward, S.C. Waxman, S. Fibrolamellar carcinoma: A review with focus on genetics and comparison to other malignant primary liver tumors. Semin Liver Dis. 2011;31(1):61-70.

3. Sethi, S., Tageja, N., Singh, J., et al. Hyperammonemic encephalopathy: A rare presentation of fibrolamellar hepatocellular carcinoma. Am J Med Sci. 2009;338(6):522-4.

The diagnosis

Histologic analysis was consistent with a fibrolamellar-hepatocellular carcinoma (HCC). The patient developed decerebrate posturing without cerebral edema on CT of the head. The patient was treated with mannitol, hyperventilation, and therapeutic hypothermia, as well as lactulose, rifaximin, hemodialysis, and “empiric” sodium benzoate/sodium phenylacetate (Ammonul, Ucyclyd Pharma, Scottsdale, Ariz.) for the possibility of a urea cycle disorder. In hopes of decreasing blood flow to the tumor, the patient underwent embolization of the right hepatic artery with no clinical improvement. Given the persistently elevated ammonia level, a work-up for an underlying urea cycle disorder was performed, revealing trace citrulline and increased urine orotic acids and uracil, suggesting an ornithine transcarbamylase (OTC) deficiency. She was started on parenteral nutrition with arginine supplementation, after which her ammonia level normalized with subsequent improvement in her mental status.

Fibrolamellar-HCC is a rare, malignant, primary liver tumor predominantly affecting young adults with no underlying liver disease. This hypervascular tumor is radiographically characterized by a central scar.¹ Most patients experience vague abdominal pain, weight loss, and fatigue. Fibrolamellar-HCC carries a better prognosis than HCC; in surgically resectable cases, the 5-year survival rates range between 37% and 76% vs. 12-14 months in nonresectable cases.² Systemic chemotherapy has been used in case reports and the role of sorafenib remains unexplored and ill defined.

This is the second reported case of metastatic fibrolamellar-HCC with hyperammonemia.³ Although urea cycle disorders are more commonly diagnosed in newborns and infants, patients with partial enzyme deficiencies may present later in life and manifest in the setting of metabolic decompensation or stress. Our patient’s initial evaluation was consistent with a urea cycle deficiency, but OTC sequencing from the blood was negative. We hypothesize that the patient exhibited a “functional” OTC deficiency as a result of a combination of the massive tumor burden and portal vein thrombus, leading to a decreased expression of the OTC gene and insufficient enzyme production. The patient is doing well 3 months post resection and is being considered for a phase I clinical trial with a telomerase inhibitor, imetelstat.

References

1. Ichikawa, T., Federle, M.P., Grazioli, L., et al. Fibrolamellar hepatocellular carcinoma: Imaging and pathologic findings in 31 recent cases. Radiology. 1999;213(2):352-61.

2. Ward, S.C. Waxman, S. Fibrolamellar carcinoma: A review with focus on genetics and comparison to other malignant primary liver tumors. Semin Liver Dis. 2011;31(1):61-70.

3. Sethi, S., Tageja, N., Singh, J., et al. Hyperammonemic encephalopathy: A rare presentation of fibrolamellar hepatocellular carcinoma. Am J Med Sci. 2009;338(6):522-4.

The diagnosis

Histologic analysis was consistent with a fibrolamellar-hepatocellular carcinoma (HCC). The patient developed decerebrate posturing without cerebral edema on CT of the head. The patient was treated with mannitol, hyperventilation, and therapeutic hypothermia, as well as lactulose, rifaximin, hemodialysis, and “empiric” sodium benzoate/sodium phenylacetate (Ammonul, Ucyclyd Pharma, Scottsdale, Ariz.) for the possibility of a urea cycle disorder. In hopes of decreasing blood flow to the tumor, the patient underwent embolization of the right hepatic artery with no clinical improvement. Given the persistently elevated ammonia level, a work-up for an underlying urea cycle disorder was performed, revealing trace citrulline and increased urine orotic acids and uracil, suggesting an ornithine transcarbamylase (OTC) deficiency. She was started on parenteral nutrition with arginine supplementation, after which her ammonia level normalized with subsequent improvement in her mental status.

Fibrolamellar-HCC is a rare, malignant, primary liver tumor predominantly affecting young adults with no underlying liver disease. This hypervascular tumor is radiographically characterized by a central scar.¹ Most patients experience vague abdominal pain, weight loss, and fatigue. Fibrolamellar-HCC carries a better prognosis than HCC; in surgically resectable cases, the 5-year survival rates range between 37% and 76% vs. 12-14 months in nonresectable cases.² Systemic chemotherapy has been used in case reports and the role of sorafenib remains unexplored and ill defined.

This is the second reported case of metastatic fibrolamellar-HCC with hyperammonemia.³ Although urea cycle disorders are more commonly diagnosed in newborns and infants, patients with partial enzyme deficiencies may present later in life and manifest in the setting of metabolic decompensation or stress. Our patient’s initial evaluation was consistent with a urea cycle deficiency, but OTC sequencing from the blood was negative. We hypothesize that the patient exhibited a “functional” OTC deficiency as a result of a combination of the massive tumor burden and portal vein thrombus, leading to a decreased expression of the OTC gene and insufficient enzyme production. The patient is doing well 3 months post resection and is being considered for a phase I clinical trial with a telomerase inhibitor, imetelstat.

References

1. Ichikawa, T., Federle, M.P., Grazioli, L., et al. Fibrolamellar hepatocellular carcinoma: Imaging and pathologic findings in 31 recent cases. Radiology. 1999;213(2):352-61.

2. Ward, S.C. Waxman, S. Fibrolamellar carcinoma: A review with focus on genetics and comparison to other malignant primary liver tumors. Semin Liver Dis. 2011;31(1):61-70.

3. Sethi, S., Tageja, N., Singh, J., et al. Hyperammonemic encephalopathy: A rare presentation of fibrolamellar hepatocellular carcinoma. Am J Med Sci. 2009;338(6):522-4.

Federal Practitioner  welcomes submission of manuscripts on subjects pertinent to physicians, clinical pharmacists, physician assistants, advanced practice nurses, and medical center administrators currently working within the VA, the DoD, IHS, and the PHS. Authored features include clinical review articles, original research, case reports, evidence-based treatment protocols, and program profiles. The journal also publishes bylined editorials and columns. Manuscript submissions will be considered for publication only if the author has certified that the work is original, has not been published previously, and is not under consideration for publication elsewhere. All manuscripts are subject to peer review.

Click here for more information.

Federal Practitioner  welcomes submission of manuscripts on subjects pertinent to physicians, clinical pharmacists, physician assistants, advanced practice nurses, and medical center administrators currently working within the VA, the DoD, IHS, and the PHS. Authored features include clinical review articles, original research, case reports, evidence-based treatment protocols, and program profiles. The journal also publishes bylined editorials and columns. Manuscript submissions will be considered for publication only if the author has certified that the work is original, has not been published previously, and is not under consideration for publication elsewhere. All manuscripts are subject to peer review.

Click here for more information.

Federal Practitioner  welcomes submission of manuscripts on subjects pertinent to physicians, clinical pharmacists, physician assistants, advanced practice nurses, and medical center administrators currently working within the VA, the DoD, IHS, and the PHS. Authored features include clinical review articles, original research, case reports, evidence-based treatment protocols, and program profiles. The journal also publishes bylined editorials and columns. Manuscript submissions will be considered for publication only if the author has certified that the work is original, has not been published previously, and is not under consideration for publication elsewhere. All manuscripts are subject to peer review.

Click here for more information.

Kathryn Hutchins

©ASCO/Todd Buchanan 2016

SAN FRANCISCO—Patients may face challenges when trying to access palliative and supportive care services at cancer centers, a new study suggests.

Researchers took a “mystery shopper” approach and placed calls to cancer centers inquiring about palliative and supportive care services for a family member.

The callers sometimes had difficulty obtaining information about these services, even though all of the centers offer them.

“It’s sobering to hear that such services are not readily accessible at many centers,” said study investigator Kathryn Hutchins, a medical student at Duke University in Durham, North Carolina.

“However, it provides an opportunity for cancer centers to empower their front-line staff, as well as the oncology care team, through education and training so that the entire enterprise has a common understanding of palliative care and how to access it.”

Hutchins and her colleagues presented this research at the 2016 Palliative Care in Oncology Symposium (abstract 122).

The researchers placed 160 calls to 40 major cancer centers. The team chose to focus on National Cancer Institute-designated cancer centers because they all provide palliative care services along with other supportive care services.

The researchers used the same script for every call, asking about services for a 58-year-old female who was recently diagnosed with inoperable liver cancer. The team called each center 4 times on different days.

In 38.2% of the calls, the researchers were not able to receive complete information about supportive care services.

In 9.5% of calls, cancer center staff gave an answer other than “yes” regarding the availability of palliative care services, even though such services were available.

The answers varied and included responses such as:

• Palliative care was for end-of-life patients only (n=2)
• No physicians specialized in symptom management (n=3)
• A medical record review would be needed first (n=2).

In addition, 10 staff members said they were unsure about the availability of palliative care, and 2 were unfamiliar with the term.

Overall, 37.6% of the callers were told that all 7 supportive care services they inquired about were offered.

“As oncologists, we like to believe that, when we refer patients to our institution’s helpline, they will get connected to the services they need, but that doesn’t always happen,” said study investigator Arif Kamal, MD, of Duke Cancer Institute.

“It’s important for oncologists to be aware of these barriers and to work to eliminate them.”

Kathryn Hutchins

©ASCO/Todd Buchanan 2016

SAN FRANCISCO—Patients may face challenges when trying to access palliative and supportive care services at cancer centers, a new study suggests.

Researchers took a “mystery shopper” approach and placed calls to cancer centers inquiring about palliative and supportive care services for a family member.

The callers sometimes had difficulty obtaining information about these services, even though all of the centers offer them.

“It’s sobering to hear that such services are not readily accessible at many centers,” said study investigator Kathryn Hutchins, a medical student at Duke University in Durham, North Carolina.

“However, it provides an opportunity for cancer centers to empower their front-line staff, as well as the oncology care team, through education and training so that the entire enterprise has a common understanding of palliative care and how to access it.”

Hutchins and her colleagues presented this research at the 2016 Palliative Care in Oncology Symposium (abstract 122).

The researchers placed 160 calls to 40 major cancer centers. The team chose to focus on National Cancer Institute-designated cancer centers because they all provide palliative care services along with other supportive care services.

The researchers used the same script for every call, asking about services for a 58-year-old female who was recently diagnosed with inoperable liver cancer. The team called each center 4 times on different days.

In 38.2% of the calls, the researchers were not able to receive complete information about supportive care services.

In 9.5% of calls, cancer center staff gave an answer other than “yes” regarding the availability of palliative care services, even though such services were available.

The answers varied and included responses such as:

• Palliative care was for end-of-life patients only (n=2)
• No physicians specialized in symptom management (n=3)
• A medical record review would be needed first (n=2).

In addition, 10 staff members said they were unsure about the availability of palliative care, and 2 were unfamiliar with the term.

Overall, 37.6% of the callers were told that all 7 supportive care services they inquired about were offered.

“As oncologists, we like to believe that, when we refer patients to our institution’s helpline, they will get connected to the services they need, but that doesn’t always happen,” said study investigator Arif Kamal, MD, of Duke Cancer Institute.

“It’s important for oncologists to be aware of these barriers and to work to eliminate them.”

Kathryn Hutchins

©ASCO/Todd Buchanan 2016

SAN FRANCISCO—Patients may face challenges when trying to access palliative and supportive care services at cancer centers, a new study suggests.

Researchers took a “mystery shopper” approach and placed calls to cancer centers inquiring about palliative and supportive care services for a family member.

The callers sometimes had difficulty obtaining information about these services, even though all of the centers offer them.

“It’s sobering to hear that such services are not readily accessible at many centers,” said study investigator Kathryn Hutchins, a medical student at Duke University in Durham, North Carolina.

“However, it provides an opportunity for cancer centers to empower their front-line staff, as well as the oncology care team, through education and training so that the entire enterprise has a common understanding of palliative care and how to access it.”

Hutchins and her colleagues presented this research at the 2016 Palliative Care in Oncology Symposium (abstract 122).

The researchers placed 160 calls to 40 major cancer centers. The team chose to focus on National Cancer Institute-designated cancer centers because they all provide palliative care services along with other supportive care services.

The researchers used the same script for every call, asking about services for a 58-year-old female who was recently diagnosed with inoperable liver cancer. The team called each center 4 times on different days.

In 38.2% of the calls, the researchers were not able to receive complete information about supportive care services.

In 9.5% of calls, cancer center staff gave an answer other than “yes” regarding the availability of palliative care services, even though such services were available.

The answers varied and included responses such as:

• Palliative care was for end-of-life patients only (n=2)
• No physicians specialized in symptom management (n=3)
• A medical record review would be needed first (n=2).

In addition, 10 staff members said they were unsure about the availability of palliative care, and 2 were unfamiliar with the term.

Overall, 37.6% of the callers were told that all 7 supportive care services they inquired about were offered.

“As oncologists, we like to believe that, when we refer patients to our institution’s helpline, they will get connected to the services they need, but that doesn’t always happen,” said study investigator Arif Kamal, MD, of Duke Cancer Institute.

“It’s important for oncologists to be aware of these barriers and to work to eliminate them.”

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

Many adolescent females are not being screened for pregnancy before beginning chemotherapy or undergoing computed tomography (CT) scans, according to research published in Cancer.

In this study, pregnancy screening was underused in adolescents with acute lymphoblastic leukemia (ALL), those with acute myeloid leukemia (AML), and those who received CT scans of the abdomen or pelvis during visits to the emergency room (ER).

“We found that adolescent girls are not adequately screened for pregnancy prior to receiving chemotherapy or CT scans that could harm a developing fetus,” said study author Pooja Rao, MD, of Penn State Health’s Milton S. Hershey Medical Center in Hershey, Pennsylvania.

“Adolescents with ALL, the most common childhood cancer, had the lowest rates of pregnancy screening of the patients we studied.”

Dr Rao and her colleagues examined pregnancy screening patterns among adolescent females newly diagnosed with ALL or AML, as well as adolescent females who visited the ER and received CT scans of the abdomen or pelvis. (In emergency medicine, pregnancy screening protocols exist for adolescents prior to receiving radiation due to the known teratogenic risks of radiation.)

The analysis included patients ages 10 to 18 who were admitted to hospitals across the US from 1999 to 2011. There were a total of 35,650 patient visits—127 for AML patients, 889 for ALL patients, and 34,634 ER admissions with CT scans of the abdomen/pelvis.

The proportion of visits with an appropriately timed pregnancy test was 35% for the ALL patients, 64% for the AML patients, and 58% in the ER group.

The researchers noted that ALL patients tended to be younger than the AML patients and the ER patients, and there was substantial variation in pregnancy screening patterns among the different hospitals.

However, in a generalized estimating equation (GEE) model adjusted for hospital clustering and patient age, patients with ALL were significantly less likely to have an appropriately timed pregnancy test when compared to patients in the ER cohort. The adjusted prevalence ratio was 0.71 (95% CI, 0.65-0.78).

And in a GEE model adjusted for hospital clustering, patients with AML were more likely to have an appropriately timed pregnancy test than patients in the ER cohort, but this difference was not statistically significant. The adjusted prevalence ratio was 1.12 (95% CI, 0.99-1.27).

The researchers also found that pregnancy screening continued to increase over time in the ALL cohort but remained “relatively stable” from 2008 onward in the AML and ER cohorts.

“Since nearly all chemotherapy agents used for childhood/adolescent acute leukemia can cause potential harm to a developing fetus, our findings indicate a need for standardized pregnancy screening practices for adolescent patients being treated for cancer,” Dr Rao said.

She also noted that the low rates of pregnancy screening observed in this study may indicate a reluctance on the part of pediatric oncologists to discuss sexual health practices with adolescent patients.

“While sexual health discussions and education may traditionally be thought to be the responsibility of the patient’s primary care provider, adolescents with cancer will often see their oncologist frequently over the course of their cancer treatment and afterwards,” Dr Rao said. “Oncologists therefore are well-positioned to initiate discussions about sexual health with their patients.”

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

Many adolescent females are not being screened for pregnancy before beginning chemotherapy or undergoing computed tomography (CT) scans, according to research published in Cancer.

In this study, pregnancy screening was underused in adolescents with acute lymphoblastic leukemia (ALL), those with acute myeloid leukemia (AML), and those who received CT scans of the abdomen or pelvis during visits to the emergency room (ER).

“We found that adolescent girls are not adequately screened for pregnancy prior to receiving chemotherapy or CT scans that could harm a developing fetus,” said study author Pooja Rao, MD, of Penn State Health’s Milton S. Hershey Medical Center in Hershey, Pennsylvania.

“Adolescents with ALL, the most common childhood cancer, had the lowest rates of pregnancy screening of the patients we studied.”

Dr Rao and her colleagues examined pregnancy screening patterns among adolescent females newly diagnosed with ALL or AML, as well as adolescent females who visited the ER and received CT scans of the abdomen or pelvis. (In emergency medicine, pregnancy screening protocols exist for adolescents prior to receiving radiation due to the known teratogenic risks of radiation.)

The analysis included patients ages 10 to 18 who were admitted to hospitals across the US from 1999 to 2011. There were a total of 35,650 patient visits—127 for AML patients, 889 for ALL patients, and 34,634 ER admissions with CT scans of the abdomen/pelvis.

The proportion of visits with an appropriately timed pregnancy test was 35% for the ALL patients, 64% for the AML patients, and 58% in the ER group.

The researchers noted that ALL patients tended to be younger than the AML patients and the ER patients, and there was substantial variation in pregnancy screening patterns among the different hospitals.

However, in a generalized estimating equation (GEE) model adjusted for hospital clustering and patient age, patients with ALL were significantly less likely to have an appropriately timed pregnancy test when compared to patients in the ER cohort. The adjusted prevalence ratio was 0.71 (95% CI, 0.65-0.78).

And in a GEE model adjusted for hospital clustering, patients with AML were more likely to have an appropriately timed pregnancy test than patients in the ER cohort, but this difference was not statistically significant. The adjusted prevalence ratio was 1.12 (95% CI, 0.99-1.27).

The researchers also found that pregnancy screening continued to increase over time in the ALL cohort but remained “relatively stable” from 2008 onward in the AML and ER cohorts.

“Since nearly all chemotherapy agents used for childhood/adolescent acute leukemia can cause potential harm to a developing fetus, our findings indicate a need for standardized pregnancy screening practices for adolescent patients being treated for cancer,” Dr Rao said.

She also noted that the low rates of pregnancy screening observed in this study may indicate a reluctance on the part of pediatric oncologists to discuss sexual health practices with adolescent patients.

“While sexual health discussions and education may traditionally be thought to be the responsibility of the patient’s primary care provider, adolescents with cancer will often see their oncologist frequently over the course of their cancer treatment and afterwards,” Dr Rao said. “Oncologists therefore are well-positioned to initiate discussions about sexual health with their patients.”

Doctor consults with cancer

patient and her father

Photo by Rhoda Baer

Many adolescent females are not being screened for pregnancy before beginning chemotherapy or undergoing computed tomography (CT) scans, according to research published in Cancer.

In this study, pregnancy screening was underused in adolescents with acute lymphoblastic leukemia (ALL), those with acute myeloid leukemia (AML), and those who received CT scans of the abdomen or pelvis during visits to the emergency room (ER).

“We found that adolescent girls are not adequately screened for pregnancy prior to receiving chemotherapy or CT scans that could harm a developing fetus,” said study author Pooja Rao, MD, of Penn State Health’s Milton S. Hershey Medical Center in Hershey, Pennsylvania.

“Adolescents with ALL, the most common childhood cancer, had the lowest rates of pregnancy screening of the patients we studied.”

Dr Rao and her colleagues examined pregnancy screening patterns among adolescent females newly diagnosed with ALL or AML, as well as adolescent females who visited the ER and received CT scans of the abdomen or pelvis. (In emergency medicine, pregnancy screening protocols exist for adolescents prior to receiving radiation due to the known teratogenic risks of radiation.)

The analysis included patients ages 10 to 18 who were admitted to hospitals across the US from 1999 to 2011. There were a total of 35,650 patient visits—127 for AML patients, 889 for ALL patients, and 34,634 ER admissions with CT scans of the abdomen/pelvis.

The proportion of visits with an appropriately timed pregnancy test was 35% for the ALL patients, 64% for the AML patients, and 58% in the ER group.

The researchers noted that ALL patients tended to be younger than the AML patients and the ER patients, and there was substantial variation in pregnancy screening patterns among the different hospitals.

However, in a generalized estimating equation (GEE) model adjusted for hospital clustering and patient age, patients with ALL were significantly less likely to have an appropriately timed pregnancy test when compared to patients in the ER cohort. The adjusted prevalence ratio was 0.71 (95% CI, 0.65-0.78).

And in a GEE model adjusted for hospital clustering, patients with AML were more likely to have an appropriately timed pregnancy test than patients in the ER cohort, but this difference was not statistically significant. The adjusted prevalence ratio was 1.12 (95% CI, 0.99-1.27).

The researchers also found that pregnancy screening continued to increase over time in the ALL cohort but remained “relatively stable” from 2008 onward in the AML and ER cohorts.

“Since nearly all chemotherapy agents used for childhood/adolescent acute leukemia can cause potential harm to a developing fetus, our findings indicate a need for standardized pregnancy screening practices for adolescent patients being treated for cancer,” Dr Rao said.

She also noted that the low rates of pregnancy screening observed in this study may indicate a reluctance on the part of pediatric oncologists to discuss sexual health practices with adolescent patients.

“While sexual health discussions and education may traditionally be thought to be the responsibility of the patient’s primary care provider, adolescents with cancer will often see their oncologist frequently over the course of their cancer treatment and afterwards,” Dr Rao said. “Oncologists therefore are well-positioned to initiate discussions about sexual health with their patients.”

The rate of soccer injuries treated at U.S. emergency departments among patients aged 7-17 years rose by 111%, and that of soccer-related concussions and closed-head injuries increased by 1,595%, during the last 25 years, according to a report published online Sept. 12 in Pediatrics.

These increases underscore the need to improve injury prevention in this patient population. In particular, concussion prevention should focus on reducing player-to-player contact, especially during illegal moves. “Education of players, coaches, referees or officials, and parents about the importance of following the rules of the game, and enforcement of those rules, are critical first steps,” said Nicholas A. Smith of the Center for Injury Research and Policy, the Research Institute at Nationwide Children’s Hospital, Columbus, and his associates.

©James Boulette/iStockphoto.com

In what they described as the first study to comprehensively examine the epidemiology of U.S. youth soccer-related injuries treated at EDs, the investigators analyzed data from a nationally representative injury surveillance system between 1990 and 2014. Almost 3 million children were treated during that period for concussions/closed-head injuries, fractures, dislocations, sprains or strains, soft-tissue injuries such as abrasions or hematomas, lacerations, nondental avulsions, or punctures sustained during soccer practice or games.

The annual rate of soccer-related injury per 10,000 participants rose by 111%, and the annual number of such injuries rose by 78%. Much of this increase was attributed to a 1,595% rise in the annual rate of concussions/closed-head injuries and a 1,332% rise in the number of concussions/closed-head injuries. Patients with head injuries were twice as likely to be admitted to the hospital as were those with other types of injury, highlighting the severity of head injuries, the investigators noted.

The majority of injuries (73%) occurred in older children aged 12-17 years; their injury rate was more than three times higher than that in younger children, “probably because of the more aggressive play and the higher-energy impacts associated with the older age group,” Mr. Smith and his associates wrote (Pediatrics. 2016 Sep 12. doi: 10.1542/peds.2016-0346).

The increase in soccer-related injuries was much greater among girls than among boys, paralleling the much larger increase in soccer participation among girls than among boys during the study period.

This study underestimates the actual number of soccer-related injuries because it didn’t include patients who were treated in health care settings other than the ED and patients who were not treated at all, the investigators added.

The rate of soccer injuries treated at U.S. emergency departments among patients aged 7-17 years rose by 111%, and that of soccer-related concussions and closed-head injuries increased by 1,595%, during the last 25 years, according to a report published online Sept. 12 in Pediatrics.

These increases underscore the need to improve injury prevention in this patient population. In particular, concussion prevention should focus on reducing player-to-player contact, especially during illegal moves. “Education of players, coaches, referees or officials, and parents about the importance of following the rules of the game, and enforcement of those rules, are critical first steps,” said Nicholas A. Smith of the Center for Injury Research and Policy, the Research Institute at Nationwide Children’s Hospital, Columbus, and his associates.

©James Boulette/iStockphoto.com

In what they described as the first study to comprehensively examine the epidemiology of U.S. youth soccer-related injuries treated at EDs, the investigators analyzed data from a nationally representative injury surveillance system between 1990 and 2014. Almost 3 million children were treated during that period for concussions/closed-head injuries, fractures, dislocations, sprains or strains, soft-tissue injuries such as abrasions or hematomas, lacerations, nondental avulsions, or punctures sustained during soccer practice or games.

The annual rate of soccer-related injury per 10,000 participants rose by 111%, and the annual number of such injuries rose by 78%. Much of this increase was attributed to a 1,595% rise in the annual rate of concussions/closed-head injuries and a 1,332% rise in the number of concussions/closed-head injuries. Patients with head injuries were twice as likely to be admitted to the hospital as were those with other types of injury, highlighting the severity of head injuries, the investigators noted.

The majority of injuries (73%) occurred in older children aged 12-17 years; their injury rate was more than three times higher than that in younger children, “probably because of the more aggressive play and the higher-energy impacts associated with the older age group,” Mr. Smith and his associates wrote (Pediatrics. 2016 Sep 12. doi: 10.1542/peds.2016-0346).

The increase in soccer-related injuries was much greater among girls than among boys, paralleling the much larger increase in soccer participation among girls than among boys during the study period.

This study underestimates the actual number of soccer-related injuries because it didn’t include patients who were treated in health care settings other than the ED and patients who were not treated at all, the investigators added.

The rate of soccer injuries treated at U.S. emergency departments among patients aged 7-17 years rose by 111%, and that of soccer-related concussions and closed-head injuries increased by 1,595%, during the last 25 years, according to a report published online Sept. 12 in Pediatrics.

These increases underscore the need to improve injury prevention in this patient population. In particular, concussion prevention should focus on reducing player-to-player contact, especially during illegal moves. “Education of players, coaches, referees or officials, and parents about the importance of following the rules of the game, and enforcement of those rules, are critical first steps,” said Nicholas A. Smith of the Center for Injury Research and Policy, the Research Institute at Nationwide Children’s Hospital, Columbus, and his associates.

©James Boulette/iStockphoto.com

In what they described as the first study to comprehensively examine the epidemiology of U.S. youth soccer-related injuries treated at EDs, the investigators analyzed data from a nationally representative injury surveillance system between 1990 and 2014. Almost 3 million children were treated during that period for concussions/closed-head injuries, fractures, dislocations, sprains or strains, soft-tissue injuries such as abrasions or hematomas, lacerations, nondental avulsions, or punctures sustained during soccer practice or games.

The annual rate of soccer-related injury per 10,000 participants rose by 111%, and the annual number of such injuries rose by 78%. Much of this increase was attributed to a 1,595% rise in the annual rate of concussions/closed-head injuries and a 1,332% rise in the number of concussions/closed-head injuries. Patients with head injuries were twice as likely to be admitted to the hospital as were those with other types of injury, highlighting the severity of head injuries, the investigators noted.

The majority of injuries (73%) occurred in older children aged 12-17 years; their injury rate was more than three times higher than that in younger children, “probably because of the more aggressive play and the higher-energy impacts associated with the older age group,” Mr. Smith and his associates wrote (Pediatrics. 2016 Sep 12. doi: 10.1542/peds.2016-0346).

The increase in soccer-related injuries was much greater among girls than among boys, paralleling the much larger increase in soccer participation among girls than among boys during the study period.

This study underestimates the actual number of soccer-related injuries because it didn’t include patients who were treated in health care settings other than the ED and patients who were not treated at all, the investigators added.

Nearly one-third of hospital newborn nurseries and neonatal ICUs do not have an antibiotic stewardship program, according to a survey of 146 hospital nursery centers across all 50 states.

Researchers randomly selected a level III NICU in each state using the 2014 American Hospital Association annual survey, then selected a level I and level II nursery in the same city. They collected data on the hospital, nursery, and antibiotic stewardship program characteristics and interviewed staff pharmacists and infectious diseases physicians (J Pediatric Infect Dis Soc. 2016 Jul 15. doi: 10.1093/jpids/piw040).

©luchschen/Thinkstock

A total of 104 (71%) of responding hospitals had an antibiotic stewardship program in place for their nurseries. Hospitals with a nursery-based antibiotic stewardship programs tended to be larger, have more full-time equivalent staff dedicated to the antibiotic stewardship program, have higher level nurses, and be affiliated with a university, according to Joseph B. Cantey, MD, and his colleagues from the Texas A&M Health Science Center in Temple.

Geographic region and core stewardship strategies did not influence the likelihood of a nursery-based antibiotic stewardship program in place.

From the interviews, the researchers identified several barriers to implementation of antibiotic stewardship programs, and themes such as unwanted coverage, unnecessary coverage, and need for communication.

“Many [antibiotic stewardship program] and nursery representatives stated that nursery [antibiotic stewardship program] coverage was not important, either because antibiotic consumption was perceived as low (theme 1), narrow-spectrum (theme 2), or both,” the authors wrote.

Some nursery providers also argued that participating in stewardship programs was time consuming and not valuable, which the authors said was often related to a lack of pediatric expertise in the program providers. Some of those interviewed also spoke of issues relating to jurisdiction and responsibility for the programs, and there was also a common perception that antibiotic stewardship programs were more concerned with cost savings than patient care.

“Barriers to effective nursery stewardship are exacerbated by lack of communication between stewardship providers and their nursery counterparts,” the authors reported.

No conflicts of interest were declared.

Nearly one-third of hospital newborn nurseries and neonatal ICUs do not have an antibiotic stewardship program, according to a survey of 146 hospital nursery centers across all 50 states.

Researchers randomly selected a level III NICU in each state using the 2014 American Hospital Association annual survey, then selected a level I and level II nursery in the same city. They collected data on the hospital, nursery, and antibiotic stewardship program characteristics and interviewed staff pharmacists and infectious diseases physicians (J Pediatric Infect Dis Soc. 2016 Jul 15. doi: 10.1093/jpids/piw040).

©luchschen/Thinkstock

A total of 104 (71%) of responding hospitals had an antibiotic stewardship program in place for their nurseries. Hospitals with a nursery-based antibiotic stewardship programs tended to be larger, have more full-time equivalent staff dedicated to the antibiotic stewardship program, have higher level nurses, and be affiliated with a university, according to Joseph B. Cantey, MD, and his colleagues from the Texas A&M Health Science Center in Temple.

Geographic region and core stewardship strategies did not influence the likelihood of a nursery-based antibiotic stewardship program in place.

From the interviews, the researchers identified several barriers to implementation of antibiotic stewardship programs, and themes such as unwanted coverage, unnecessary coverage, and need for communication.

“Many [antibiotic stewardship program] and nursery representatives stated that nursery [antibiotic stewardship program] coverage was not important, either because antibiotic consumption was perceived as low (theme 1), narrow-spectrum (theme 2), or both,” the authors wrote.

Some nursery providers also argued that participating in stewardship programs was time consuming and not valuable, which the authors said was often related to a lack of pediatric expertise in the program providers. Some of those interviewed also spoke of issues relating to jurisdiction and responsibility for the programs, and there was also a common perception that antibiotic stewardship programs were more concerned with cost savings than patient care.

“Barriers to effective nursery stewardship are exacerbated by lack of communication between stewardship providers and their nursery counterparts,” the authors reported.

No conflicts of interest were declared.

Nearly one-third of hospital newborn nurseries and neonatal ICUs do not have an antibiotic stewardship program, according to a survey of 146 hospital nursery centers across all 50 states.

Researchers randomly selected a level III NICU in each state using the 2014 American Hospital Association annual survey, then selected a level I and level II nursery in the same city. They collected data on the hospital, nursery, and antibiotic stewardship program characteristics and interviewed staff pharmacists and infectious diseases physicians (J Pediatric Infect Dis Soc. 2016 Jul 15. doi: 10.1093/jpids/piw040).

©luchschen/Thinkstock

A total of 104 (71%) of responding hospitals had an antibiotic stewardship program in place for their nurseries. Hospitals with a nursery-based antibiotic stewardship programs tended to be larger, have more full-time equivalent staff dedicated to the antibiotic stewardship program, have higher level nurses, and be affiliated with a university, according to Joseph B. Cantey, MD, and his colleagues from the Texas A&M Health Science Center in Temple.

Geographic region and core stewardship strategies did not influence the likelihood of a nursery-based antibiotic stewardship program in place.

From the interviews, the researchers identified several barriers to implementation of antibiotic stewardship programs, and themes such as unwanted coverage, unnecessary coverage, and need for communication.

“Many [antibiotic stewardship program] and nursery representatives stated that nursery [antibiotic stewardship program] coverage was not important, either because antibiotic consumption was perceived as low (theme 1), narrow-spectrum (theme 2), or both,” the authors wrote.

Some nursery providers also argued that participating in stewardship programs was time consuming and not valuable, which the authors said was often related to a lack of pediatric expertise in the program providers. Some of those interviewed also spoke of issues relating to jurisdiction and responsibility for the programs, and there was also a common perception that antibiotic stewardship programs were more concerned with cost savings than patient care.

“Barriers to effective nursery stewardship are exacerbated by lack of communication between stewardship providers and their nursery counterparts,” the authors reported.

No conflicts of interest were declared.

NEWPORT BEACH, CALIF. – As the spread of Zika virus continues to garner attention in the national spotlight, two other mosquito-borne viral infections pose a potential threat to the United States: dengue fever and chikungunya.

At the annual meeting of the Pacific Dermatologic Association, Iris Z. Ahronowitz, MD, shared tips on how to spot and diagnose patients with these viral infections.

“You really need to use all the data at your disposal, including a thorough symptom history, a thorough exposure history, and of course, our most important tool in all of this: our eyes,” said Dr. Ahronowitz, a dermatologist at the University of Southern California, Los Angeles. Reaching a diagnosis involves asking about epidemiologic exposure, symptoms, morphology, and performing confirmatory testing by PCR and/or ELISA. “Unfortunately we are not getting these results very quickly,” she said. “Sometimes the turn-around time can be 3 weeks or longer.”

She discussed the case of a 32-year-old woman who had returned from travel to Central Mexico (J Am Acad Dermatol. 2008;58[2]:308-16). Two days later, she developed fever, fatigue, and retro-orbital headache, as well as flushing macular erythema over the chest. Three days later, she developed a generalized morbilliform eruption. Her white blood cell count was 1.5, platelets were 37, aspartate aminotransferase was 124 and alanine aminotransferase was 87.

The differential diagnosis for morbilliform eruption plus fever in a returning traveler is extensive, Dr. Ahronowitz said, including measles, chikungunya, West Nile virus, O’nyong-nyong fever, Mayaro virus, Sindbis virus, Ross river disease, Ebola/Marburg, dengue, and Zika. Bacterial/rickettsial possibilities include typhoid fever, typhus, and leptospirosis.

© World Health Organization

The patient was ultimately diagnosed with dengue virus, a mosquito-borne flavivirus. Five serotypes have been identified, the most recent in 2013. According to Dr. Ahronowitz, dengue ranks as the most common febrile illness in travelers returning from the Caribbean, South American, and Southeast Asia. “There are up to 100 million cases every year, 40% of the world population is at risk, and an estimated 80% of people are asymptomatic carriers, which is facilitating the spread of this disease,” she said. The most common vector is Aedes aegypti, a daytime biting mosquito that is endemic to the tropics and subtropics. But a new vector is emerging, A. albopictus, which is common in temperate areas. “Both types of mosquitoes are in the United States, and they’re spreading rapidly,” she said. “This is probably due to a combination of climate change and international travel.”

Dengue classically presents with sudden onset of fevers, headaches, and particularly retro-orbital pain, severe myalgia; 50%-82% of cases develop a distinctive rash. “While most viruses have nonspecific lab abnormalities, one that can be very helpful to you with suspected dengue is thrombocytopenia,” she said. “The incubation period ranges from 3 to 14 days.”

Rashes associated with dengue are classically biphasic and sequential. The initial rash occurs within 24-48 hours of symptom onset and is often mistaken for sunburn, with a flushing erythema of the face, neck, and chest. Three to five days later, a subsequent rash develops that starts out as a generalized morbilliform eruption but becomes confluent with petechiae and islands of sparing. “It’s been described as white islands in a sea of red,” Dr. Ahronowitz said.

A more severe form of the disease, dengue hemorrhagic fever, is characterized by extensive purpura and bleeding from mucosa, GI tract, and injection sites. “The patients who get this have prior immunity to a different serotype,” she said. “This is thought to be due to a phenomenon called antibody-dependent enhancement whereby the presence of preexisting antibodies facilitates entry of the virus and produces a more robust inflammatory response. Most of these patients, even the ones with severe dengue, recover fully. The most common long-term sequela we’re seeing is chronic fatigue.”

The diagnosis is made with viral PCR from serum less than 7 days from onset of symptoms, or IgM ELISA more than 4 days from onset of symptoms. The treatment is supportive care with fluid resuscitation and analgesia; there’s no specific treatment. “Do not give NSAIDs, which can potentiate hemorrhage; give acetaminophen for pain and fevers,” she advised. “A tetravalent vaccine is now available for dengue. Prevention is so important because there is no treatment.”

Next, Dr. Ahronowitz discussed the case of a 38-year-old man who returned from travel to Bangladesh (Int J Dermatol. 2008;47[1]:1148-52). Two days after returning he developed fever to 104 degrees, headaches, and cervical lymphadenopathy. Three days after returning, he developed severe pain in the wrist, knees, and ankles, and a rash. “This rash was not specific, it was a morbilliform eruption primarily on the chest,” she said.

James Gathany/CDC

The patient was ultimately diagnosed with chikungunya, a single-strand RNA mosquito-borne virus with the same vectors as dengue. “This has been wreaking havoc across the Caribbean in the past few years,” Dr. Ahronowitz said. “Chikungunya was first identified in the Americas in 2013, and there have been hundreds of thousands of cases in the Caribbean.” The first case acquired in the United States occurred in Florida in the summer of 2014. As of January 2016 there were 679 imported cases of the infection in the United States. “Fortunately, this most recent epidemic is slowing down a bit, but it’s important to be aware of,” she said.

Clinical presentation of chikungunya includes an incubation period of 3-7 days, acute onset of high fevers, chills, and myalgia. Nonspecific exanthem around 3 days occurs in 40%-75% of cases, and symmetric polyarthralgias are common in the fingers, wrists, and ankles. Labs may reveal lymphopenia, AKI, and elevated AST/ALT. Acute symptoms resolve within 7-10 days.

Besides the rash, other cutaneous signs of the disease include aphthous-like ulcers and anogenital ulcers, particularly around the scrotum. Other patients may present with controfacial hyperpigmentation, also known as “brownie nose,” that appears with the rash. In babies, bullous lesions can occur. More than 20% of patients who acquire chikungunya still have severe joint pain 1 year after initial presentation. “This can be really debilitating,” she said. “A subset of patients will develop an inflammatory seronegative rheumatoid-like arthritis. It’s generally not a fatal condition except in the extremes of age and in people with a lot of comorbidities. Most people recover fully.”

As in dengue, clinicians can diagnose chikungunya by viral culture in the first 3 days of illness, and by RT-PCR in the first 8 days of illness. On serology, IgM is positive by 5 days of symptom onset.

“If testing is not available locally, contact the [Centers for Disease Control and Prevention],” Dr. Ahronowitz said. “Treatment is supportive. Evaluate for and treat potential coinfections, including dengue, malaria, and bacterial infections. If dengue is in the differential diagnosis, avoid NSAIDs.” A new vaccine for chikungunya is currently in phase II trials.

Dr. Ahronowitz reported having no relevant disclosures.

dbrunk@frontlinemedcom.com

NEWPORT BEACH, CALIF. – As the spread of Zika virus continues to garner attention in the national spotlight, two other mosquito-borne viral infections pose a potential threat to the United States: dengue fever and chikungunya.

At the annual meeting of the Pacific Dermatologic Association, Iris Z. Ahronowitz, MD, shared tips on how to spot and diagnose patients with these viral infections.

“You really need to use all the data at your disposal, including a thorough symptom history, a thorough exposure history, and of course, our most important tool in all of this: our eyes,” said Dr. Ahronowitz, a dermatologist at the University of Southern California, Los Angeles. Reaching a diagnosis involves asking about epidemiologic exposure, symptoms, morphology, and performing confirmatory testing by PCR and/or ELISA. “Unfortunately we are not getting these results very quickly,” she said. “Sometimes the turn-around time can be 3 weeks or longer.”

She discussed the case of a 32-year-old woman who had returned from travel to Central Mexico (J Am Acad Dermatol. 2008;58[2]:308-16). Two days later, she developed fever, fatigue, and retro-orbital headache, as well as flushing macular erythema over the chest. Three days later, she developed a generalized morbilliform eruption. Her white blood cell count was 1.5, platelets were 37, aspartate aminotransferase was 124 and alanine aminotransferase was 87.

The differential diagnosis for morbilliform eruption plus fever in a returning traveler is extensive, Dr. Ahronowitz said, including measles, chikungunya, West Nile virus, O’nyong-nyong fever, Mayaro virus, Sindbis virus, Ross river disease, Ebola/Marburg, dengue, and Zika. Bacterial/rickettsial possibilities include typhoid fever, typhus, and leptospirosis.

© World Health Organization

The patient was ultimately diagnosed with dengue virus, a mosquito-borne flavivirus. Five serotypes have been identified, the most recent in 2013. According to Dr. Ahronowitz, dengue ranks as the most common febrile illness in travelers returning from the Caribbean, South American, and Southeast Asia. “There are up to 100 million cases every year, 40% of the world population is at risk, and an estimated 80% of people are asymptomatic carriers, which is facilitating the spread of this disease,” she said. The most common vector is Aedes aegypti, a daytime biting mosquito that is endemic to the tropics and subtropics. But a new vector is emerging, A. albopictus, which is common in temperate areas. “Both types of mosquitoes are in the United States, and they’re spreading rapidly,” she said. “This is probably due to a combination of climate change and international travel.”

Dengue classically presents with sudden onset of fevers, headaches, and particularly retro-orbital pain, severe myalgia; 50%-82% of cases develop a distinctive rash. “While most viruses have nonspecific lab abnormalities, one that can be very helpful to you with suspected dengue is thrombocytopenia,” she said. “The incubation period ranges from 3 to 14 days.”

Rashes associated with dengue are classically biphasic and sequential. The initial rash occurs within 24-48 hours of symptom onset and is often mistaken for sunburn, with a flushing erythema of the face, neck, and chest. Three to five days later, a subsequent rash develops that starts out as a generalized morbilliform eruption but becomes confluent with petechiae and islands of sparing. “It’s been described as white islands in a sea of red,” Dr. Ahronowitz said.

A more severe form of the disease, dengue hemorrhagic fever, is characterized by extensive purpura and bleeding from mucosa, GI tract, and injection sites. “The patients who get this have prior immunity to a different serotype,” she said. “This is thought to be due to a phenomenon called antibody-dependent enhancement whereby the presence of preexisting antibodies facilitates entry of the virus and produces a more robust inflammatory response. Most of these patients, even the ones with severe dengue, recover fully. The most common long-term sequela we’re seeing is chronic fatigue.”

The diagnosis is made with viral PCR from serum less than 7 days from onset of symptoms, or IgM ELISA more than 4 days from onset of symptoms. The treatment is supportive care with fluid resuscitation and analgesia; there’s no specific treatment. “Do not give NSAIDs, which can potentiate hemorrhage; give acetaminophen for pain and fevers,” she advised. “A tetravalent vaccine is now available for dengue. Prevention is so important because there is no treatment.”

Next, Dr. Ahronowitz discussed the case of a 38-year-old man who returned from travel to Bangladesh (Int J Dermatol. 2008;47[1]:1148-52). Two days after returning he developed fever to 104 degrees, headaches, and cervical lymphadenopathy. Three days after returning, he developed severe pain in the wrist, knees, and ankles, and a rash. “This rash was not specific, it was a morbilliform eruption primarily on the chest,” she said.

James Gathany/CDC

The patient was ultimately diagnosed with chikungunya, a single-strand RNA mosquito-borne virus with the same vectors as dengue. “This has been wreaking havoc across the Caribbean in the past few years,” Dr. Ahronowitz said. “Chikungunya was first identified in the Americas in 2013, and there have been hundreds of thousands of cases in the Caribbean.” The first case acquired in the United States occurred in Florida in the summer of 2014. As of January 2016 there were 679 imported cases of the infection in the United States. “Fortunately, this most recent epidemic is slowing down a bit, but it’s important to be aware of,” she said.

Clinical presentation of chikungunya includes an incubation period of 3-7 days, acute onset of high fevers, chills, and myalgia. Nonspecific exanthem around 3 days occurs in 40%-75% of cases, and symmetric polyarthralgias are common in the fingers, wrists, and ankles. Labs may reveal lymphopenia, AKI, and elevated AST/ALT. Acute symptoms resolve within 7-10 days.

Besides the rash, other cutaneous signs of the disease include aphthous-like ulcers and anogenital ulcers, particularly around the scrotum. Other patients may present with controfacial hyperpigmentation, also known as “brownie nose,” that appears with the rash. In babies, bullous lesions can occur. More than 20% of patients who acquire chikungunya still have severe joint pain 1 year after initial presentation. “This can be really debilitating,” she said. “A subset of patients will develop an inflammatory seronegative rheumatoid-like arthritis. It’s generally not a fatal condition except in the extremes of age and in people with a lot of comorbidities. Most people recover fully.”

As in dengue, clinicians can diagnose chikungunya by viral culture in the first 3 days of illness, and by RT-PCR in the first 8 days of illness. On serology, IgM is positive by 5 days of symptom onset.

“If testing is not available locally, contact the [Centers for Disease Control and Prevention],” Dr. Ahronowitz said. “Treatment is supportive. Evaluate for and treat potential coinfections, including dengue, malaria, and bacterial infections. If dengue is in the differential diagnosis, avoid NSAIDs.” A new vaccine for chikungunya is currently in phase II trials.

Dr. Ahronowitz reported having no relevant disclosures.

dbrunk@frontlinemedcom.com

NEWPORT BEACH, CALIF. – As the spread of Zika virus continues to garner attention in the national spotlight, two other mosquito-borne viral infections pose a potential threat to the United States: dengue fever and chikungunya.

At the annual meeting of the Pacific Dermatologic Association, Iris Z. Ahronowitz, MD, shared tips on how to spot and diagnose patients with these viral infections.

“You really need to use all the data at your disposal, including a thorough symptom history, a thorough exposure history, and of course, our most important tool in all of this: our eyes,” said Dr. Ahronowitz, a dermatologist at the University of Southern California, Los Angeles. Reaching a diagnosis involves asking about epidemiologic exposure, symptoms, morphology, and performing confirmatory testing by PCR and/or ELISA. “Unfortunately we are not getting these results very quickly,” she said. “Sometimes the turn-around time can be 3 weeks or longer.”

She discussed the case of a 32-year-old woman who had returned from travel to Central Mexico (J Am Acad Dermatol. 2008;58[2]:308-16). Two days later, she developed fever, fatigue, and retro-orbital headache, as well as flushing macular erythema over the chest. Three days later, she developed a generalized morbilliform eruption. Her white blood cell count was 1.5, platelets were 37, aspartate aminotransferase was 124 and alanine aminotransferase was 87.

The differential diagnosis for morbilliform eruption plus fever in a returning traveler is extensive, Dr. Ahronowitz said, including measles, chikungunya, West Nile virus, O’nyong-nyong fever, Mayaro virus, Sindbis virus, Ross river disease, Ebola/Marburg, dengue, and Zika. Bacterial/rickettsial possibilities include typhoid fever, typhus, and leptospirosis.

© World Health Organization

The patient was ultimately diagnosed with dengue virus, a mosquito-borne flavivirus. Five serotypes have been identified, the most recent in 2013. According to Dr. Ahronowitz, dengue ranks as the most common febrile illness in travelers returning from the Caribbean, South American, and Southeast Asia. “There are up to 100 million cases every year, 40% of the world population is at risk, and an estimated 80% of people are asymptomatic carriers, which is facilitating the spread of this disease,” she said. The most common vector is Aedes aegypti, a daytime biting mosquito that is endemic to the tropics and subtropics. But a new vector is emerging, A. albopictus, which is common in temperate areas. “Both types of mosquitoes are in the United States, and they’re spreading rapidly,” she said. “This is probably due to a combination of climate change and international travel.”

Dengue classically presents with sudden onset of fevers, headaches, and particularly retro-orbital pain, severe myalgia; 50%-82% of cases develop a distinctive rash. “While most viruses have nonspecific lab abnormalities, one that can be very helpful to you with suspected dengue is thrombocytopenia,” she said. “The incubation period ranges from 3 to 14 days.”

Rashes associated with dengue are classically biphasic and sequential. The initial rash occurs within 24-48 hours of symptom onset and is often mistaken for sunburn, with a flushing erythema of the face, neck, and chest. Three to five days later, a subsequent rash develops that starts out as a generalized morbilliform eruption but becomes confluent with petechiae and islands of sparing. “It’s been described as white islands in a sea of red,” Dr. Ahronowitz said.

A more severe form of the disease, dengue hemorrhagic fever, is characterized by extensive purpura and bleeding from mucosa, GI tract, and injection sites. “The patients who get this have prior immunity to a different serotype,” she said. “This is thought to be due to a phenomenon called antibody-dependent enhancement whereby the presence of preexisting antibodies facilitates entry of the virus and produces a more robust inflammatory response. Most of these patients, even the ones with severe dengue, recover fully. The most common long-term sequela we’re seeing is chronic fatigue.”

The diagnosis is made with viral PCR from serum less than 7 days from onset of symptoms, or IgM ELISA more than 4 days from onset of symptoms. The treatment is supportive care with fluid resuscitation and analgesia; there’s no specific treatment. “Do not give NSAIDs, which can potentiate hemorrhage; give acetaminophen for pain and fevers,” she advised. “A tetravalent vaccine is now available for dengue. Prevention is so important because there is no treatment.”

Next, Dr. Ahronowitz discussed the case of a 38-year-old man who returned from travel to Bangladesh (Int J Dermatol. 2008;47[1]:1148-52). Two days after returning he developed fever to 104 degrees, headaches, and cervical lymphadenopathy. Three days after returning, he developed severe pain in the wrist, knees, and ankles, and a rash. “This rash was not specific, it was a morbilliform eruption primarily on the chest,” she said.

James Gathany/CDC

The patient was ultimately diagnosed with chikungunya, a single-strand RNA mosquito-borne virus with the same vectors as dengue. “This has been wreaking havoc across the Caribbean in the past few years,” Dr. Ahronowitz said. “Chikungunya was first identified in the Americas in 2013, and there have been hundreds of thousands of cases in the Caribbean.” The first case acquired in the United States occurred in Florida in the summer of 2014. As of January 2016 there were 679 imported cases of the infection in the United States. “Fortunately, this most recent epidemic is slowing down a bit, but it’s important to be aware of,” she said.

Clinical presentation of chikungunya includes an incubation period of 3-7 days, acute onset of high fevers, chills, and myalgia. Nonspecific exanthem around 3 days occurs in 40%-75% of cases, and symmetric polyarthralgias are common in the fingers, wrists, and ankles. Labs may reveal lymphopenia, AKI, and elevated AST/ALT. Acute symptoms resolve within 7-10 days.

Besides the rash, other cutaneous signs of the disease include aphthous-like ulcers and anogenital ulcers, particularly around the scrotum. Other patients may present with controfacial hyperpigmentation, also known as “brownie nose,” that appears with the rash. In babies, bullous lesions can occur. More than 20% of patients who acquire chikungunya still have severe joint pain 1 year after initial presentation. “This can be really debilitating,” she said. “A subset of patients will develop an inflammatory seronegative rheumatoid-like arthritis. It’s generally not a fatal condition except in the extremes of age and in people with a lot of comorbidities. Most people recover fully.”

As in dengue, clinicians can diagnose chikungunya by viral culture in the first 3 days of illness, and by RT-PCR in the first 8 days of illness. On serology, IgM is positive by 5 days of symptom onset.

“If testing is not available locally, contact the [Centers for Disease Control and Prevention],” Dr. Ahronowitz said. “Treatment is supportive. Evaluate for and treat potential coinfections, including dengue, malaria, and bacterial infections. If dengue is in the differential diagnosis, avoid NSAIDs.” A new vaccine for chikungunya is currently in phase II trials.

Dr. Ahronowitz reported having no relevant disclosures.

dbrunk@frontlinemedcom.com

No marketed screening test has been clinically proven to accurately diagnose ovarian cancer, according to a MedWatch announcement from the Food and Drug Administration.

Despite extensive research and published studies, there are currently no screening tests for ovarian cancer that are sensitive enough to reliably screen for ovarian cancer without a high number of inaccurate results,” FDA officials said in a statement.

Officials with the American Congress of Obstetricians and Gynecologists echoed the FDA’s concern, pointing out that several ovarian cancer screening tests, including the CA-125 test and the Risk of Ovarian Cancer Algorithm test, are currently available and claim to detect ovarian cancer before symptoms occur. These claims are “not based on data,” ACOG president Thomas Gellhaus, MD, said in a statement.

The FDA and ACOG both expressed concern that the use of these tests could delay treatment for asymptomatic women with early-stage ovarian cancer and also may result in unnecessary medical procedures for women who receive positive test results even though no cancer is present.

“Using unproven ovarian cancer screening tests also may be harmful for women with increased risk for developing ovarian cancer,” the FDA wrote and added that “women at high risk for developing ovarian cancer should not use any currently offered test that claims to screen for ovarian cancer.”

Instead, women at high risk of developing ovarian cancer, including those with BRCA mutations, should be referred to a genetic counselor, gynecologic oncologist, or other appropriate health care provider for more specialized care, the FDA recommended. “Currently, it appears that the best way to detect ovarian cancer is for both the patient and her clinician to have a high index of suspicion of the diagnosis in symptomatic women. Persistent and progressive symptoms, such as an increase in bloating, pelvic or abdominal pain, or difficulty eating or feeling full quickly, should be evaluated,” Dr. Gellhaus added.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

No marketed screening test has been clinically proven to accurately diagnose ovarian cancer, according to a MedWatch announcement from the Food and Drug Administration.

Despite extensive research and published studies, there are currently no screening tests for ovarian cancer that are sensitive enough to reliably screen for ovarian cancer without a high number of inaccurate results,” FDA officials said in a statement.

Officials with the American Congress of Obstetricians and Gynecologists echoed the FDA’s concern, pointing out that several ovarian cancer screening tests, including the CA-125 test and the Risk of Ovarian Cancer Algorithm test, are currently available and claim to detect ovarian cancer before symptoms occur. These claims are “not based on data,” ACOG president Thomas Gellhaus, MD, said in a statement.

The FDA and ACOG both expressed concern that the use of these tests could delay treatment for asymptomatic women with early-stage ovarian cancer and also may result in unnecessary medical procedures for women who receive positive test results even though no cancer is present.

“Using unproven ovarian cancer screening tests also may be harmful for women with increased risk for developing ovarian cancer,” the FDA wrote and added that “women at high risk for developing ovarian cancer should not use any currently offered test that claims to screen for ovarian cancer.”

Instead, women at high risk of developing ovarian cancer, including those with BRCA mutations, should be referred to a genetic counselor, gynecologic oncologist, or other appropriate health care provider for more specialized care, the FDA recommended. “Currently, it appears that the best way to detect ovarian cancer is for both the patient and her clinician to have a high index of suspicion of the diagnosis in symptomatic women. Persistent and progressive symptoms, such as an increase in bloating, pelvic or abdominal pain, or difficulty eating or feeling full quickly, should be evaluated,” Dr. Gellhaus added.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

No marketed screening test has been clinically proven to accurately diagnose ovarian cancer, according to a MedWatch announcement from the Food and Drug Administration.

Despite extensive research and published studies, there are currently no screening tests for ovarian cancer that are sensitive enough to reliably screen for ovarian cancer without a high number of inaccurate results,” FDA officials said in a statement.

Officials with the American Congress of Obstetricians and Gynecologists echoed the FDA’s concern, pointing out that several ovarian cancer screening tests, including the CA-125 test and the Risk of Ovarian Cancer Algorithm test, are currently available and claim to detect ovarian cancer before symptoms occur. These claims are “not based on data,” ACOG president Thomas Gellhaus, MD, said in a statement.

The FDA and ACOG both expressed concern that the use of these tests could delay treatment for asymptomatic women with early-stage ovarian cancer and also may result in unnecessary medical procedures for women who receive positive test results even though no cancer is present.

“Using unproven ovarian cancer screening tests also may be harmful for women with increased risk for developing ovarian cancer,” the FDA wrote and added that “women at high risk for developing ovarian cancer should not use any currently offered test that claims to screen for ovarian cancer.”

Instead, women at high risk of developing ovarian cancer, including those with BRCA mutations, should be referred to a genetic counselor, gynecologic oncologist, or other appropriate health care provider for more specialized care, the FDA recommended. “Currently, it appears that the best way to detect ovarian cancer is for both the patient and her clinician to have a high index of suspicion of the diagnosis in symptomatic women. Persistent and progressive symptoms, such as an increase in bloating, pelvic or abdominal pain, or difficulty eating or feeling full quickly, should be evaluated,” Dr. Gellhaus added.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig