NEW LNG IUS: GOOD FOR 5 YEARS

FOR MORE INFORMATION, VISIT:
https://hcp.kyleena-us.com/

EASIER LAPAROSCOPIC ACCESS

To use LapCap₂, says Life Care, center it over the umbilicus, attach a hose to the suction port, and apply negative pressure. The abdomen immediately rises for Veress needle insertion. Inert gas is then delivered to replace the negative pressure, and the procedure can continue.

FOR MORE INFORMATION, VISIT:
http://www.lcmd.com/products/lapcap2

NEW LNG IUS: GOOD FOR 5 YEARS

FOR MORE INFORMATION, VISIT:
https://hcp.kyleena-us.com/

EASIER LAPAROSCOPIC ACCESS

To use LapCap₂, says Life Care, center it over the umbilicus, attach a hose to the suction port, and apply negative pressure. The abdomen immediately rises for Veress needle insertion. Inert gas is then delivered to replace the negative pressure, and the procedure can continue.

FOR MORE INFORMATION, VISIT:
http://www.lcmd.com/products/lapcap2

NEW LNG IUS: GOOD FOR 5 YEARS

FOR MORE INFORMATION, VISIT:
https://hcp.kyleena-us.com/

EASIER LAPAROSCOPIC ACCESS

To use LapCap₂, says Life Care, center it over the umbilicus, attach a hose to the suction port, and apply negative pressure. The abdomen immediately rises for Veress needle insertion. Inert gas is then delivered to replace the negative pressure, and the procedure can continue.

FOR MORE INFORMATION, VISIT:
http://www.lcmd.com/products/lapcap2

Vasopressin is often used to reduce blood loss in gynecologic surgery. Results of randomized clinical trials indicate that its use reduces blood loss in many gynecologic surgery procedures, including hysterectomy, myomectomy, cervical conization, and second trimester pregnancy termination.¹⁻⁷ In contrast to the widespread use of dilute vasopressin injection in gynecology surgery, obstetricians in the United States seldom use vasopressin to reduce blood loss in difficult cesarean delivery surgery. Although there is very little direct evidence from clinical trials on the value of vasopressin in obstetric surgery, high-quality evidence from relevant gynecologic surgery and case reports from obstetricians support its use during difficult cesarean delivery surgery.

Biology of oxytocin and vasopressin

Oxytocin and vasopressin are fraternal twin nanopeptides that differ by only two amino acids and are secreted from the posterior pituitary. The human uterus contains both oxytocin and vasopressin receptors; stimulation of either receptor causes uterine contraction. Vasopressin receptor activation also causes vasoconstriction and platelet activation.

Given the similar biochemistry of oxytocin and vasopressin it is not surprising that each hormone is capable of binding to both oxytocin and vasopressin receptors. The affinity of oxytocin for the oxytocin and vasopressin receptors as expressed as an inhibition constant is 6.8 nM and 35 nM, respectively. Vasopressin’s affinity for the oxytocin and vasopressin V1a receptors is 48 nM and 1.4 nM, respectively.⁸

Administering vasopressin into the uterus will achieve a high concentration of the hormone, which stimulates both the oxytocin and vasopressin receptors, resulting in uterine contraction, vasoconstriction, and platelet activation. Of particular importance to obstetricians is that following a prolonged labor or administration of oxytocin, myometrial oxytocin receptors may be downregulated, but vasopressin receptors may remain functional.^9,10

Vasopressin regulates plasma volume, blood pressure, osmolality, and uterine contractility. The vasopressin V1a receptor is present on vascular smooth muscle cells, platelets, and uterine myocytes. Activating this receptor causes vasoconstriction, platelet activation, and uterine contraction.

Vasopressin reduces surgical blood loss in two ways. The first major mechanism is through vasoconstriction.¹¹ Second, in uterine surgery specifically, vasopressin stimulates uterine contraction. The hormone exerts its antidiuretic action through the V2 receptor in the kidney.

Optimal vasopressin dose

In gynecologic surgery, the vasopressin doses utilized to reduce blood loss range from 5 U to 20 U diluted in 20 mL to 200 mL of saline. Randomized trial results indicate that a vasopressin dose of 4 U is effective in reducing blood loss during second trimester pregnancy termination,⁷ and a dose of 3 U is effective in reducing blood loss during cervical conization.^5,6 There is insufficient obstetric literature to determine the optimal dose of vasopressin to reduce blood loss in difficult cesarean delivery sur- gery, but doses similar to those used in gynecologic surgery should be considered.

Possible effects of vasopressin overdosing. In gynecologic surgery, injection of vasopressin has been reported to cause bradycardia, hypotension, myocardial infarction, and cardiovascular collapse.¹² Given that multiple vasoactive medications may be given to a patient undergoing a complex cesarean delivery, including oxytocin, methergine, and ephedrine, it is important for the obstetrician to use the lowest effective dose of vasopressin necessary to facilitate control of blood loss. The obstetrician needs to communicate with the anesthesiologist and coordinate the use of dilute vasopressin with other vasoactive medications.

Avoid intravascular injection of vasopressin. I prefer to inject vasopressin in the subserosa of the uterus rather than to inject it in a highly vascular area such as the subendometrium or near the uterine artery and vein.

Vasopressin reduces blood loss during hysterectomy

One randomized trial has reported that the administration of 10 U of vasopressin diluted in saline into the lower uterine segment reduced blood loss at abdominal hysterectomy in nonpregnant women compared with an injection of saline alone (445 mL vs 748 mL of blood loss, respectively).¹ There are no clinical trials of the use of vasopressin in cesarean hysterectomy. However, abdominal hysterectomy procedures and cesarean hysterectomy are similar, and vasopressin likely helps to reduce blood loss at cesarean hysterectomy.

Vasopressin reduces blood loss during myomectomy

Authors of 3 small, randomized clinical trials in nonpregnant women have reported that the intramyometrial injection of dilute vasopressin reduces blood loss during myomectomy surgery.²⁻⁴ The vasopressin doses in the 3 trials ranged from 5 U of vasopressin in 100 mL of saline to 20 U of vasopressin in 20 mL of saline. A Cochrane meta-analyis of the 3 studies concluded that, at myomectomy, the intramyometrial injection of dilute vasopressin was associated with a significant reduction in blood loss compared with placebo (246 mL vs 483 mL, respectively).¹³

There are great similarities between myomectomy in the nonpregnant and pregnant uterus. Given the clinical trials data that support the use of vasopressin to reduce blood loss during myomectomy in the nonpregnant uterus, it is likely that vasopressin also would reduce blood loss during myomectomy performed at the time of a cesarean delivery.

At cesarean delivery, elective myomectomy of intramural fibroids is generally not recommended because of the risk of massive blood loss. Clinicians often remove large pedunculated fibroids because this surgery does not usually cause massive bleeding. However, on occasion it may be necessary to perform a myomectomy on intramural myoma(s) in order to close a hysterotomy incision.

For myomectomy surgery performed at the time of cesarean delivery, many techniques have been utilized to reduce blood loss, including:

• intravenous oxytocin infusion^14,15
• injection of oxytocin into the myoma pseudocapsule¹⁵
• electrosurgery¹⁶⁻¹⁸
• argon beam coagulator¹⁹
• uterine tourniquet²⁰
• premyomectomy placement of a uterine U stitch²¹ or purse string suture²²
• O’Leary sutures^23,24
• temporary balloon occlusion of pelvic arteries²⁵
• vasopressin injection.²⁶

Given the widespread use of vasopressin injection in gynecologic surgery to reduce blood loss at myomectomy, obstetricians should consider using vasopressin in their cesarean myomectomy surgery.

Use of vasopressin during cesarean delivery for placenta previa may reduce blood loss

Women with a complete placenta previa require a cesarean delivery to safely birth their baby. Cesarean deliveries performed for this indication are associated with an increased risk of hemorrhage. In one case series of 59 patients with placenta previa undergoing cesarean delivery, 4 U of vasopressin diluted in 20 mL of saline was injected into the placental implantation site to reduce blood loss. Among the patients receiving vasopressin in- jection, the blood loss was 1,149 mL. Among 50 women with placenta previa who did not receive vasopressin injection, the blood loss was 1,634 mL.²⁷

Obstetric surgery and vasopressin: The time has come

As obstetricians and gynecologists we constantly strive to improve the effectiveness of our surgical procedures and reduce adverse outcomes, including infection and blood loss. The use of vasopressin is widely accepted in gynecologic surgery as an adjuvant that reduces blood loss. The time has come to expand the use of vasopressin in difficult obstetric surgery.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Vasopressin is often used to reduce blood loss in gynecologic surgery. Results of randomized clinical trials indicate that its use reduces blood loss in many gynecologic surgery procedures, including hysterectomy, myomectomy, cervical conization, and second trimester pregnancy termination.¹⁻⁷ In contrast to the widespread use of dilute vasopressin injection in gynecology surgery, obstetricians in the United States seldom use vasopressin to reduce blood loss in difficult cesarean delivery surgery. Although there is very little direct evidence from clinical trials on the value of vasopressin in obstetric surgery, high-quality evidence from relevant gynecologic surgery and case reports from obstetricians support its use during difficult cesarean delivery surgery.

Biology of oxytocin and vasopressin

Oxytocin and vasopressin are fraternal twin nanopeptides that differ by only two amino acids and are secreted from the posterior pituitary. The human uterus contains both oxytocin and vasopressin receptors; stimulation of either receptor causes uterine contraction. Vasopressin receptor activation also causes vasoconstriction and platelet activation.

Given the similar biochemistry of oxytocin and vasopressin it is not surprising that each hormone is capable of binding to both oxytocin and vasopressin receptors. The affinity of oxytocin for the oxytocin and vasopressin receptors as expressed as an inhibition constant is 6.8 nM and 35 nM, respectively. Vasopressin’s affinity for the oxytocin and vasopressin V1a receptors is 48 nM and 1.4 nM, respectively.⁸

Administering vasopressin into the uterus will achieve a high concentration of the hormone, which stimulates both the oxytocin and vasopressin receptors, resulting in uterine contraction, vasoconstriction, and platelet activation. Of particular importance to obstetricians is that following a prolonged labor or administration of oxytocin, myometrial oxytocin receptors may be downregulated, but vasopressin receptors may remain functional.^9,10

Vasopressin regulates plasma volume, blood pressure, osmolality, and uterine contractility. The vasopressin V1a receptor is present on vascular smooth muscle cells, platelets, and uterine myocytes. Activating this receptor causes vasoconstriction, platelet activation, and uterine contraction.

Vasopressin reduces surgical blood loss in two ways. The first major mechanism is through vasoconstriction.¹¹ Second, in uterine surgery specifically, vasopressin stimulates uterine contraction. The hormone exerts its antidiuretic action through the V2 receptor in the kidney.

Optimal vasopressin dose

In gynecologic surgery, the vasopressin doses utilized to reduce blood loss range from 5 U to 20 U diluted in 20 mL to 200 mL of saline. Randomized trial results indicate that a vasopressin dose of 4 U is effective in reducing blood loss during second trimester pregnancy termination,⁷ and a dose of 3 U is effective in reducing blood loss during cervical conization.^5,6 There is insufficient obstetric literature to determine the optimal dose of vasopressin to reduce blood loss in difficult cesarean delivery sur- gery, but doses similar to those used in gynecologic surgery should be considered.

Possible effects of vasopressin overdosing. In gynecologic surgery, injection of vasopressin has been reported to cause bradycardia, hypotension, myocardial infarction, and cardiovascular collapse.¹² Given that multiple vasoactive medications may be given to a patient undergoing a complex cesarean delivery, including oxytocin, methergine, and ephedrine, it is important for the obstetrician to use the lowest effective dose of vasopressin necessary to facilitate control of blood loss. The obstetrician needs to communicate with the anesthesiologist and coordinate the use of dilute vasopressin with other vasoactive medications.

Avoid intravascular injection of vasopressin. I prefer to inject vasopressin in the subserosa of the uterus rather than to inject it in a highly vascular area such as the subendometrium or near the uterine artery and vein.

Vasopressin reduces blood loss during hysterectomy

One randomized trial has reported that the administration of 10 U of vasopressin diluted in saline into the lower uterine segment reduced blood loss at abdominal hysterectomy in nonpregnant women compared with an injection of saline alone (445 mL vs 748 mL of blood loss, respectively).¹ There are no clinical trials of the use of vasopressin in cesarean hysterectomy. However, abdominal hysterectomy procedures and cesarean hysterectomy are similar, and vasopressin likely helps to reduce blood loss at cesarean hysterectomy.

Vasopressin reduces blood loss during myomectomy

Authors of 3 small, randomized clinical trials in nonpregnant women have reported that the intramyometrial injection of dilute vasopressin reduces blood loss during myomectomy surgery.²⁻⁴ The vasopressin doses in the 3 trials ranged from 5 U of vasopressin in 100 mL of saline to 20 U of vasopressin in 20 mL of saline. A Cochrane meta-analyis of the 3 studies concluded that, at myomectomy, the intramyometrial injection of dilute vasopressin was associated with a significant reduction in blood loss compared with placebo (246 mL vs 483 mL, respectively).¹³

There are great similarities between myomectomy in the nonpregnant and pregnant uterus. Given the clinical trials data that support the use of vasopressin to reduce blood loss during myomectomy in the nonpregnant uterus, it is likely that vasopressin also would reduce blood loss during myomectomy performed at the time of a cesarean delivery.

At cesarean delivery, elective myomectomy of intramural fibroids is generally not recommended because of the risk of massive blood loss. Clinicians often remove large pedunculated fibroids because this surgery does not usually cause massive bleeding. However, on occasion it may be necessary to perform a myomectomy on intramural myoma(s) in order to close a hysterotomy incision.

For myomectomy surgery performed at the time of cesarean delivery, many techniques have been utilized to reduce blood loss, including:

• intravenous oxytocin infusion^14,15
• injection of oxytocin into the myoma pseudocapsule¹⁵
• electrosurgery¹⁶⁻¹⁸
• argon beam coagulator¹⁹
• uterine tourniquet²⁰
• premyomectomy placement of a uterine U stitch²¹ or purse string suture²²
• O’Leary sutures^23,24
• temporary balloon occlusion of pelvic arteries²⁵
• vasopressin injection.²⁶

Given the widespread use of vasopressin injection in gynecologic surgery to reduce blood loss at myomectomy, obstetricians should consider using vasopressin in their cesarean myomectomy surgery.

Use of vasopressin during cesarean delivery for placenta previa may reduce blood loss

Women with a complete placenta previa require a cesarean delivery to safely birth their baby. Cesarean deliveries performed for this indication are associated with an increased risk of hemorrhage. In one case series of 59 patients with placenta previa undergoing cesarean delivery, 4 U of vasopressin diluted in 20 mL of saline was injected into the placental implantation site to reduce blood loss. Among the patients receiving vasopressin in- jection, the blood loss was 1,149 mL. Among 50 women with placenta previa who did not receive vasopressin injection, the blood loss was 1,634 mL.²⁷

Obstetric surgery and vasopressin: The time has come

As obstetricians and gynecologists we constantly strive to improve the effectiveness of our surgical procedures and reduce adverse outcomes, including infection and blood loss. The use of vasopressin is widely accepted in gynecologic surgery as an adjuvant that reduces blood loss. The time has come to expand the use of vasopressin in difficult obstetric surgery.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Vasopressin is often used to reduce blood loss in gynecologic surgery. Results of randomized clinical trials indicate that its use reduces blood loss in many gynecologic surgery procedures, including hysterectomy, myomectomy, cervical conization, and second trimester pregnancy termination.¹⁻⁷ In contrast to the widespread use of dilute vasopressin injection in gynecology surgery, obstetricians in the United States seldom use vasopressin to reduce blood loss in difficult cesarean delivery surgery. Although there is very little direct evidence from clinical trials on the value of vasopressin in obstetric surgery, high-quality evidence from relevant gynecologic surgery and case reports from obstetricians support its use during difficult cesarean delivery surgery.

Biology of oxytocin and vasopressin

Oxytocin and vasopressin are fraternal twin nanopeptides that differ by only two amino acids and are secreted from the posterior pituitary. The human uterus contains both oxytocin and vasopressin receptors; stimulation of either receptor causes uterine contraction. Vasopressin receptor activation also causes vasoconstriction and platelet activation.

Given the similar biochemistry of oxytocin and vasopressin it is not surprising that each hormone is capable of binding to both oxytocin and vasopressin receptors. The affinity of oxytocin for the oxytocin and vasopressin receptors as expressed as an inhibition constant is 6.8 nM and 35 nM, respectively. Vasopressin’s affinity for the oxytocin and vasopressin V1a receptors is 48 nM and 1.4 nM, respectively.⁸

Administering vasopressin into the uterus will achieve a high concentration of the hormone, which stimulates both the oxytocin and vasopressin receptors, resulting in uterine contraction, vasoconstriction, and platelet activation. Of particular importance to obstetricians is that following a prolonged labor or administration of oxytocin, myometrial oxytocin receptors may be downregulated, but vasopressin receptors may remain functional.^9,10

Vasopressin regulates plasma volume, blood pressure, osmolality, and uterine contractility. The vasopressin V1a receptor is present on vascular smooth muscle cells, platelets, and uterine myocytes. Activating this receptor causes vasoconstriction, platelet activation, and uterine contraction.

Vasopressin reduces surgical blood loss in two ways. The first major mechanism is through vasoconstriction.¹¹ Second, in uterine surgery specifically, vasopressin stimulates uterine contraction. The hormone exerts its antidiuretic action through the V2 receptor in the kidney.

Optimal vasopressin dose

In gynecologic surgery, the vasopressin doses utilized to reduce blood loss range from 5 U to 20 U diluted in 20 mL to 200 mL of saline. Randomized trial results indicate that a vasopressin dose of 4 U is effective in reducing blood loss during second trimester pregnancy termination,⁷ and a dose of 3 U is effective in reducing blood loss during cervical conization.^5,6 There is insufficient obstetric literature to determine the optimal dose of vasopressin to reduce blood loss in difficult cesarean delivery sur- gery, but doses similar to those used in gynecologic surgery should be considered.

Possible effects of vasopressin overdosing. In gynecologic surgery, injection of vasopressin has been reported to cause bradycardia, hypotension, myocardial infarction, and cardiovascular collapse.¹² Given that multiple vasoactive medications may be given to a patient undergoing a complex cesarean delivery, including oxytocin, methergine, and ephedrine, it is important for the obstetrician to use the lowest effective dose of vasopressin necessary to facilitate control of blood loss. The obstetrician needs to communicate with the anesthesiologist and coordinate the use of dilute vasopressin with other vasoactive medications.

Avoid intravascular injection of vasopressin. I prefer to inject vasopressin in the subserosa of the uterus rather than to inject it in a highly vascular area such as the subendometrium or near the uterine artery and vein.

Vasopressin reduces blood loss during hysterectomy

One randomized trial has reported that the administration of 10 U of vasopressin diluted in saline into the lower uterine segment reduced blood loss at abdominal hysterectomy in nonpregnant women compared with an injection of saline alone (445 mL vs 748 mL of blood loss, respectively).¹ There are no clinical trials of the use of vasopressin in cesarean hysterectomy. However, abdominal hysterectomy procedures and cesarean hysterectomy are similar, and vasopressin likely helps to reduce blood loss at cesarean hysterectomy.

Vasopressin reduces blood loss during myomectomy

Authors of 3 small, randomized clinical trials in nonpregnant women have reported that the intramyometrial injection of dilute vasopressin reduces blood loss during myomectomy surgery.²⁻⁴ The vasopressin doses in the 3 trials ranged from 5 U of vasopressin in 100 mL of saline to 20 U of vasopressin in 20 mL of saline. A Cochrane meta-analyis of the 3 studies concluded that, at myomectomy, the intramyometrial injection of dilute vasopressin was associated with a significant reduction in blood loss compared with placebo (246 mL vs 483 mL, respectively).¹³

There are great similarities between myomectomy in the nonpregnant and pregnant uterus. Given the clinical trials data that support the use of vasopressin to reduce blood loss during myomectomy in the nonpregnant uterus, it is likely that vasopressin also would reduce blood loss during myomectomy performed at the time of a cesarean delivery.

At cesarean delivery, elective myomectomy of intramural fibroids is generally not recommended because of the risk of massive blood loss. Clinicians often remove large pedunculated fibroids because this surgery does not usually cause massive bleeding. However, on occasion it may be necessary to perform a myomectomy on intramural myoma(s) in order to close a hysterotomy incision.

For myomectomy surgery performed at the time of cesarean delivery, many techniques have been utilized to reduce blood loss, including:

• intravenous oxytocin infusion^14,15
• injection of oxytocin into the myoma pseudocapsule¹⁵
• electrosurgery¹⁶⁻¹⁸
• argon beam coagulator¹⁹
• uterine tourniquet²⁰
• premyomectomy placement of a uterine U stitch²¹ or purse string suture²²
• O’Leary sutures^23,24
• temporary balloon occlusion of pelvic arteries²⁵
• vasopressin injection.²⁶

Given the widespread use of vasopressin injection in gynecologic surgery to reduce blood loss at myomectomy, obstetricians should consider using vasopressin in their cesarean myomectomy surgery.

Use of vasopressin during cesarean delivery for placenta previa may reduce blood loss

Women with a complete placenta previa require a cesarean delivery to safely birth their baby. Cesarean deliveries performed for this indication are associated with an increased risk of hemorrhage. In one case series of 59 patients with placenta previa undergoing cesarean delivery, 4 U of vasopressin diluted in 20 mL of saline was injected into the placental implantation site to reduce blood loss. Among the patients receiving vasopressin in- jection, the blood loss was 1,149 mL. Among 50 women with placenta previa who did not receive vasopressin injection, the blood loss was 1,634 mL.²⁷

Obstetric surgery and vasopressin: The time has come

As obstetricians and gynecologists we constantly strive to improve the effectiveness of our surgical procedures and reduce adverse outcomes, including infection and blood loss. The use of vasopressin is widely accepted in gynecologic surgery as an adjuvant that reduces blood loss. The time has come to expand the use of vasopressin in difficult obstetric surgery.

Share your thoughts! Send your Letter to the Editor to rbarbieri@frontlinemedcom.com. Please include your name and the city and state in which you practice.

Percutaneous coronary intervention (PCI) using everolimus-eluting stents was found noninferior to coronary artery bypass grafting (CABG) with respect to the composite end point of death, stroke, or myocardial infarction at 3 years among patients with left main coronary artery disease and low or intermediate anatomical complexity, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the New England Journal of Medicine.

The rate of this composite outcome was lower with PCI than with CABG during the first 30 days following the procedure, but higher between day 30 and year 3. In addition, the 3-year rate of revascularization was slightly higher with PCI (23.1% vs 19.1%), but the rate of periprocedural MI and major adverse events was lower (8.1% vs 23.0%).

Taken together, these results “suggest that PCI with everolimus-eluting stents is an acceptable or perhaps preferred alternative to CABG in selected patients with left main CAD who are candidates for either procedure,” said Gregg W. Stone, MD, of Columbia University Medical Center, New York, and his associates in the EXCEL (Evaluation of XIENCE versus CABG for Effectiveness of Left Main Revascularization) trial.

This study was funded by Abbott Vascular, maker of the everolimus-eluting stent (the XIENCE). The company also participated in the design of the trial and in the selection and management of the treatment sites.

Until now, it was generally agreed that most patients with left main CAD would have better outcomes with CABG than with PCI, based on the results of earlier trials comparing the two approaches. But contemporary drug-eluting stents have better safety and efficacy profiles than first-generation stents, and surgical techniques have also improved over time, so a study comparing the current standards of care was warranted, Dr. Stone and his associates said (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMoa1610227).

They assessed 1,905 patients at 126 medical centers in 17 countries in the open-label noninferiority trial. Participants had left main coronary artery stenosis of 70% or more (estimated visually) or of 50%-70% (estimated by invasive or noninvasive testing) if the stenosis was judged to be hemodynamically significant. The study participants also were required to have low or intermediate anatomical complexity of the involved portion of the coronary artery, as defined by a SYNTAX score of 32 or lower. A total of 948 patients were randomly assigned to PCI and 957 to CABG.

The primary composite end point – the rate of death, stroke, or MI assessed at a median of 3 years of follow-up – was 15.4% with PCI and 14.7% with CABG, a nonsignificant difference (Hazard Ratio, 1.00) that demonstrates the noninferiority of PCI. This rate was consistently noninferior across all subgroups of patients, regardless of age, sex, and the presence or absence of diabetes or chronic kidney disease.

At 30 days, the rate of the composite end point was 4.9% with PCI and 7.9% with CABG, which also demonstrates the noninferiority of PCI. At 3 years, secondary end points including the rate of ischemia-driven revascularization also showed the noninferiority of PCI, as did each of the individual components of the primary composite end point.

The rate of death, stroke, or MI was lower at 30 days with PCI than with CABG, mainly because there were fewer MIs with PCI. But a post-hoc analysis showed that this rate was higher with PCI than with CABG after 30 days.

During follow-up, ischemia-driven revascularization was more common after PCI (12.6%) than after CABG (7.5%). However, symptomatic graft occlusion after CABG (5.4%) was more frequent than definite stent thrombosis after PCI (0.7%).

Periprocedural major adverse events developed in 8.1% of the PCI group and 23.0% of the CABG group, and the difference was attributed mainly to fewer arrhythmias, infections, and blood transfusions in the PCI group. Cardiovascular mortality was similar between the two study groups, though all-cause mortality was higher with PCI due to an excess of fatal infections and malignancies in that group.

The investigators noted several limitations with the EXCEL trial. First, treatment blinding wasn’t possible, so some degree of bias may have resulted.

Second, prerandomization SYNTAX scores estimating the anatomical complexity of the affected vessels weren’t always accurate, and 24% of the patients in this study proved to have complex lesions when their procedures were undertaken. However, the rate of the primary composite end point was the same in this subgroup of patients as in the overall patient population.

Third, long-term medications after PCI differ from those after CABG, and the investigators said further study is needed to determine how these differences may have contributed to patient outcomes. And finally, longer follow-up is needed to assess whether more differences between the two study groups emerge over time. Five-year follow-up of this study population is now under way.

Dr. Stone and his associates reported ties to numerous industry sources.

Percutaneous coronary intervention (PCI) using everolimus-eluting stents was found noninferior to coronary artery bypass grafting (CABG) with respect to the composite end point of death, stroke, or myocardial infarction at 3 years among patients with left main coronary artery disease and low or intermediate anatomical complexity, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the New England Journal of Medicine.

The rate of this composite outcome was lower with PCI than with CABG during the first 30 days following the procedure, but higher between day 30 and year 3. In addition, the 3-year rate of revascularization was slightly higher with PCI (23.1% vs 19.1%), but the rate of periprocedural MI and major adverse events was lower (8.1% vs 23.0%).

Taken together, these results “suggest that PCI with everolimus-eluting stents is an acceptable or perhaps preferred alternative to CABG in selected patients with left main CAD who are candidates for either procedure,” said Gregg W. Stone, MD, of Columbia University Medical Center, New York, and his associates in the EXCEL (Evaluation of XIENCE versus CABG for Effectiveness of Left Main Revascularization) trial.

This study was funded by Abbott Vascular, maker of the everolimus-eluting stent (the XIENCE). The company also participated in the design of the trial and in the selection and management of the treatment sites.

Until now, it was generally agreed that most patients with left main CAD would have better outcomes with CABG than with PCI, based on the results of earlier trials comparing the two approaches. But contemporary drug-eluting stents have better safety and efficacy profiles than first-generation stents, and surgical techniques have also improved over time, so a study comparing the current standards of care was warranted, Dr. Stone and his associates said (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMoa1610227).

They assessed 1,905 patients at 126 medical centers in 17 countries in the open-label noninferiority trial. Participants had left main coronary artery stenosis of 70% or more (estimated visually) or of 50%-70% (estimated by invasive or noninvasive testing) if the stenosis was judged to be hemodynamically significant. The study participants also were required to have low or intermediate anatomical complexity of the involved portion of the coronary artery, as defined by a SYNTAX score of 32 or lower. A total of 948 patients were randomly assigned to PCI and 957 to CABG.

The primary composite end point – the rate of death, stroke, or MI assessed at a median of 3 years of follow-up – was 15.4% with PCI and 14.7% with CABG, a nonsignificant difference (Hazard Ratio, 1.00) that demonstrates the noninferiority of PCI. This rate was consistently noninferior across all subgroups of patients, regardless of age, sex, and the presence or absence of diabetes or chronic kidney disease.

At 30 days, the rate of the composite end point was 4.9% with PCI and 7.9% with CABG, which also demonstrates the noninferiority of PCI. At 3 years, secondary end points including the rate of ischemia-driven revascularization also showed the noninferiority of PCI, as did each of the individual components of the primary composite end point.

The rate of death, stroke, or MI was lower at 30 days with PCI than with CABG, mainly because there were fewer MIs with PCI. But a post-hoc analysis showed that this rate was higher with PCI than with CABG after 30 days.

During follow-up, ischemia-driven revascularization was more common after PCI (12.6%) than after CABG (7.5%). However, symptomatic graft occlusion after CABG (5.4%) was more frequent than definite stent thrombosis after PCI (0.7%).

Periprocedural major adverse events developed in 8.1% of the PCI group and 23.0% of the CABG group, and the difference was attributed mainly to fewer arrhythmias, infections, and blood transfusions in the PCI group. Cardiovascular mortality was similar between the two study groups, though all-cause mortality was higher with PCI due to an excess of fatal infections and malignancies in that group.

The investigators noted several limitations with the EXCEL trial. First, treatment blinding wasn’t possible, so some degree of bias may have resulted.

Second, prerandomization SYNTAX scores estimating the anatomical complexity of the affected vessels weren’t always accurate, and 24% of the patients in this study proved to have complex lesions when their procedures were undertaken. However, the rate of the primary composite end point was the same in this subgroup of patients as in the overall patient population.

Third, long-term medications after PCI differ from those after CABG, and the investigators said further study is needed to determine how these differences may have contributed to patient outcomes. And finally, longer follow-up is needed to assess whether more differences between the two study groups emerge over time. Five-year follow-up of this study population is now under way.

Dr. Stone and his associates reported ties to numerous industry sources.

Percutaneous coronary intervention (PCI) using everolimus-eluting stents was found noninferior to coronary artery bypass grafting (CABG) with respect to the composite end point of death, stroke, or myocardial infarction at 3 years among patients with left main coronary artery disease and low or intermediate anatomical complexity, according to a report presented at the Transcatheter Cardiovascular Therapeutics annual meeting and published simultaneously in the New England Journal of Medicine.

The rate of this composite outcome was lower with PCI than with CABG during the first 30 days following the procedure, but higher between day 30 and year 3. In addition, the 3-year rate of revascularization was slightly higher with PCI (23.1% vs 19.1%), but the rate of periprocedural MI and major adverse events was lower (8.1% vs 23.0%).

Taken together, these results “suggest that PCI with everolimus-eluting stents is an acceptable or perhaps preferred alternative to CABG in selected patients with left main CAD who are candidates for either procedure,” said Gregg W. Stone, MD, of Columbia University Medical Center, New York, and his associates in the EXCEL (Evaluation of XIENCE versus CABG for Effectiveness of Left Main Revascularization) trial.

This study was funded by Abbott Vascular, maker of the everolimus-eluting stent (the XIENCE). The company also participated in the design of the trial and in the selection and management of the treatment sites.

Until now, it was generally agreed that most patients with left main CAD would have better outcomes with CABG than with PCI, based on the results of earlier trials comparing the two approaches. But contemporary drug-eluting stents have better safety and efficacy profiles than first-generation stents, and surgical techniques have also improved over time, so a study comparing the current standards of care was warranted, Dr. Stone and his associates said (New Engl J Med. 2016 Oct 31. doi:10.1056/NEJMoa1610227).

They assessed 1,905 patients at 126 medical centers in 17 countries in the open-label noninferiority trial. Participants had left main coronary artery stenosis of 70% or more (estimated visually) or of 50%-70% (estimated by invasive or noninvasive testing) if the stenosis was judged to be hemodynamically significant. The study participants also were required to have low or intermediate anatomical complexity of the involved portion of the coronary artery, as defined by a SYNTAX score of 32 or lower. A total of 948 patients were randomly assigned to PCI and 957 to CABG.

The primary composite end point – the rate of death, stroke, or MI assessed at a median of 3 years of follow-up – was 15.4% with PCI and 14.7% with CABG, a nonsignificant difference (Hazard Ratio, 1.00) that demonstrates the noninferiority of PCI. This rate was consistently noninferior across all subgroups of patients, regardless of age, sex, and the presence or absence of diabetes or chronic kidney disease.

At 30 days, the rate of the composite end point was 4.9% with PCI and 7.9% with CABG, which also demonstrates the noninferiority of PCI. At 3 years, secondary end points including the rate of ischemia-driven revascularization also showed the noninferiority of PCI, as did each of the individual components of the primary composite end point.

The rate of death, stroke, or MI was lower at 30 days with PCI than with CABG, mainly because there were fewer MIs with PCI. But a post-hoc analysis showed that this rate was higher with PCI than with CABG after 30 days.

During follow-up, ischemia-driven revascularization was more common after PCI (12.6%) than after CABG (7.5%). However, symptomatic graft occlusion after CABG (5.4%) was more frequent than definite stent thrombosis after PCI (0.7%).

Periprocedural major adverse events developed in 8.1% of the PCI group and 23.0% of the CABG group, and the difference was attributed mainly to fewer arrhythmias, infections, and blood transfusions in the PCI group. Cardiovascular mortality was similar between the two study groups, though all-cause mortality was higher with PCI due to an excess of fatal infections and malignancies in that group.

The investigators noted several limitations with the EXCEL trial. First, treatment blinding wasn’t possible, so some degree of bias may have resulted.

Second, prerandomization SYNTAX scores estimating the anatomical complexity of the affected vessels weren’t always accurate, and 24% of the patients in this study proved to have complex lesions when their procedures were undertaken. However, the rate of the primary composite end point was the same in this subgroup of patients as in the overall patient population.

Third, long-term medications after PCI differ from those after CABG, and the investigators said further study is needed to determine how these differences may have contributed to patient outcomes. And finally, longer follow-up is needed to assess whether more differences between the two study groups emerge over time. Five-year follow-up of this study population is now under way.

Dr. Stone and his associates reported ties to numerous industry sources.

One recent paper in Clinical Pediatrics, for example, chronicled low adherence to the 2011 National Heart, Lung, and Blood Institute lipid screening guidelines in primary-care settings.1 Another cautioned providers to “mind the (implementation) gap” in venous thromboembolism prevention guidelines for medical inpatients.2 A third found that lower adherence to guidelines issued by the American College of Cardiology/American Heart Association for acute coronary syndrome patients was significantly associated with higher bleeding and mortality rates.3

Both clinical trials and real-world studies have demonstrated that when guidelines are applied, patients do better, says William Lewis, MD, professor of medicine at Case Western Reserve University and director of the Heart & Vascular Center at MetroHealth in Cleveland. So why aren’t they followed more consistently?

Experts in both HM and other disciplines cite multiple obstacles. Lack of evidence, conflicting evidence, or lack of awareness about evidence can all conspire against the main goal of helping providers deliver consistent high-value care, says Christopher Moriates, MD, assistant clinical professor in the Division of Hospital Medicine at the University of California, San Francisco.

“In our day-to-day lives as hospitalists, for the vast majority probably of what we do there’s no clear guideline or there’s a guideline that doesn’t necessarily apply to the patient standing in front of me,” he says.

Even when a guideline is clear and relevant, other doctors say inadequate dissemination and implementation can still derail quality improvement efforts.

“A lot of what we do as physicians is what we learned in residency, and to incorporate the new data is difficult,” says Leonard Feldman, MD, SFHM, a hospitalist and associate professor of internal medicine and pediatrics at Johns Hopkins School of Medicine in Baltimore.

Dr. Feldman believes many doctors have yet to integrate recently revised hypertension and cholesterol guidelines into their practice, for example. Some guidelines have proven more complex or controversial, limiting their adoption.

“I know I struggle to keep up with all of the guidelines, and I’m in a big academic center where people are talking about them all the time, and I’m working with residents who are talking about them all the time,” Dr. Feldman says.

Despite the remaining gaps, however, many researchers agree that momentum has built steadily over the past two decades toward a more systematic approach to creating solid evidence-based guidelines and integrating them into real-world decision making.

Emphasis on Evidence and Transparency

The term “evidence-based medicine” was coined in 1990 by Gordon Guyatt, MD, MSc, FRCPC, distinguished professor of medicine and clinical epidemiology at McMaster University in Hamilton, Ontario. It’s played an active role in formulating guidelines for multiple organizations. The guideline-writing process, Dr. Guyatt says, once consisted of little more than self-selected clinicians sitting around a table.

“It used to be that a bunch of experts got together and decided and made the recommendations with very little in the way of a systematic process and certainly not evidence based,” he says.

Cincinnati Children’s Hospital Medical Center was among the pioneers pushing for a more systematic approach; the hospital began working on its own guidelines in 1995 and published the first of many the following year.

“We started evidence-based guidelines when the docs were still saying, ‘This is cookbook medicine. I don’t know if I want to do this or not,’” says Wendy Gerhardt, MSN, director of evidence-based decision making in the James M. Anderson Center for Health Systems Excellence at Cincinnati Children’s.

Some doctors also argued that clinical guidelines would stifle innovation, cramp their individual style, or intrude on their relationships with patients. Despite some lingering misgivings among clinicians, however, the process has gained considerable support. In 2000, an organization called the GRADE Working Group (Grading of Recommendations, Assessment, Development and Evaluation) began developing a new approach to raise the quality of evidence and strength of recommendations.

The group’s work led to a 2004 article in BMJ, and the journal subsequently published a six-part series about GRADE for clinicians.4 More recently, the Journal of Clinical Epidemiology also delved into the issue with a 15-part series detailing the GRADE methodology.5 Together, Dr. Guyatt says, the articles have become a go-to guide for guidelines and have helped solidify the focus on evidence.

Cincinnati Children’s and other institutions also have developed tools, and the Institute of Medicine has published guideline-writing standards.

“So it’s easier than it’s ever been to know whether or not you have a decent guideline in your hand,” Gerhardt says.

Likewise, medical organizations are more clearly explaining how they came up with different kinds of guidelines. Evidence-based and consensus guidelines aren’t necessarily mutually exclusive, though consensus building is often used in the absence of high-quality evidence. Some organizations have limited the pool of evidence for guidelines to randomized controlled trial data.

“Unfortunately, for us in the real world, we actually have to make decisions even when there’s not enough data,” Dr. Feldman says.

Sometimes, the best available evidence may be observational studies, and some committees still try to reach a consensus based on that evidence and on the panelists’ professional opinions.

Dr. Guyatt agrees that it’s “absolutely not” true that evidence-based guidelines require randomized controlled trials. “What you need for any recommendation is a thorough review and summary of the best available evidence,” he says.

As part of each final document, Cincinnati Children’s details how it created the guideline, when the literature searches occurred, how the committee reached a consensus, and which panelists participated in the deliberations. The information, Gerhardt says, allows anyone else to “make some sensible decisions about whether or not it’s a guideline you want to use.”

Guideline-crafting institutions are also focusing more on the proper makeup of their panels. In general, Dr. Guyatt says, a panel with more than 10 people can be unwieldy. Guidelines that include many specific recommendations, however, may require multiple subsections, each with its own committee.

Dr. Guyatt is careful to note that, like many other experts, he has multiple potential conflicts of interest, such as working on the anti-thrombotic guidelines issued by the American College of Chest Physicians. Committees, he says, have become increasingly aware of how properly handling conflicts (financial or otherwise) can be critical in building and maintaining trust among clinicians and patients. One technique is to ensure that a diversity of opinions is reflected among a committee whose experts have various conflicts. If one expert’s company makes drug A, for example, then the committee also includes experts involved with drugs B or C. As an alternative, some committees have explicitly barred anyone with a conflict of interest from participating at all.

But experts often provide crucial input, Dr. Guyatt says, and several committees have adopted variations of a middle-ground approach. In an approach that he favors, all guideline-formulating panelists are conflict-free but begin their work by meeting with a separate group of experts who may have some conflicts but can help point out the main issues. The panelists then deliberate and write a draft of the recommendations, after which they meet again with the experts to receive feedback before finalizing the draft.

In a related approach, experts sit on the panel and discuss the evidence, but those with conflicts recuse themselves before the group votes on any recommendations. Delineating between discussions of the evidence and discussions of recommendations can be tricky, though, increasing the risk that a conflict of interest may influence the outcome. Even so, Dr. Guyatt says the model is still preferable to other alternatives.

Getting the Word Out

Once guidelines have been crafted and vetted, how can hospitalists get up to speed on them? Dr. Feldman’s favorite go-to source is Guideline.gov, a national guideline clearinghouse that he calls one of the best compendiums of available information. Especially helpful, he adds, are details such as how the guidelines were created.

To help maximize his time, he also uses tools like NEJM Journal Watch, which sends daily emails on noteworthy articles and weekend roundups of the most important studies.

“It is a way of at least trying to keep up with what’s going on,” he says. Similarly, he adds, ACP Journal Club provides summaries of important new articles, The Hospitalist can help highlight important guidelines that affect HM, and CME meetings or online modules like SHMconsults.com can help doctors keep pace.

For the past decade, Dr. Guyatt has worked with another popular tool, a guideline-disseminating service called UpToDate. Many alternatives exist, such as DynaMed Plus.

“I think you just need to pick away,” Dr. Feldman says. “You need to decide that as a physician, as a lifelong learner, that you are going to do something that is going to keep you up-to-date. There are many ways of doing it. You just have to decide what you’re going to do and commit to it.”

Researchers are helping out by studying how to present new guidelines in ways that engage doctors and improve patient outcomes. Another trend is to make guidelines routinely accessible not only in electronic medical records but also on tablets and smartphones. Lisa Shieh, MD, PhD, FHM, a hospitalist and clinical professor of medicine at Stanford University Medical Center, has studied how best-practice alerts, or BPAs, impact adherence to guidelines covering the appropriate use of blood products. Dr. Shieh, who splits her time between quality improvement and hospital medicine, says getting new information and guidelines into clinicians’ hands can be a logistical challenge.

“At Stanford, we had a huge official campaign around the guidelines, and that did make some impact, but it wasn’t huge in improving appropriate blood use,” she says. When the medial center set up a BPA through the electronic medical record system, however, both overall and inappropriate blood use declined significantly. In fact, the percentage of providers ordering blood products for patients with a hemoglobin count above 8 g/dL dropped from 60% to 25%.6

One difference maker, Dr. Shieh says, was providing education at the moment a doctor actually ordered blood. To avoid alert fatigue, the “smart BPA” fires only if a doctor tries to order blood and the patient’s hemoglobin is greater than 7 or 8 g/dL, depending on the diagnosis. If the doctor still wants to transfuse, the system requests a clinical indication for the exception.

Despite the clear improvement in appropriate use, the team wanted to understand why 25% of providers were still ordering blood products for patients with a hemoglobin count greater than 8 despite the triggered BPA and whether additional interventions could yield further improvements. Through their study, the researchers documented several reasons for the continued ordering. In some cases, the system failed to properly document actual or potential bleeding as an indicator. In other cases, the ordering reflected a lack of consensus on the guidelines in fields like hematology and oncology.

One of the most intriguing reasons, though, was that residents often did the ordering at the behest of an attending who might have never seen the BPA.

“It’s not actually reaching the audience making the decision; it might be reaching the audience that’s just carrying out the order,” Dr. Shieh says.

The insight, she says, may provide an opportunity to talk with attending physicians who may not have completely bought into the guidelines and to involve the entire team in the decision-making process.

Hospitalists, she says, can play a vital role in guideline development and implementation, especially for strategies that include BPAs.

“I think they’re the perfect group to help use this technology wisely because they are at the front lines taking care of patients so they’ll know the best workflow of when these alerts fire and maybe which ones happen the most often,” Dr. Shieh says. “I think this is a fantastic opportunity to get more hospitalists involved in designing these alerts and collaborating with the IT folks.”

Even with widespread buy-in from providers, guidelines may not reach their full potential without a careful consideration of patients’ values and concerns. Experts say joint deliberations and discussions are especially important for guidelines that are complicated, controversial, or carrying potential risks that must be weighed against the benefits.

Some of the conversations are easy, with well-defined risks and benefits and clear patient preferences, but others must traverse vast tracts of gray area. Fortunately, Dr. Feldman says, more tools also are becoming available for this kind of shared decision making. Some use pictorial representations to help patients understand the potential outcomes of alternative courses of action or inaction.

“Sometimes, that pictorial representation is worth the 1,000 words that we wouldn’t be able to adequately describe otherwise,” he says.

Similarly, Cincinnati Children’s has developed tools to help to ease the shared decision-making process.

“We look where there’s equivocal evidence or no evidence and have developed tools that help the clinician have that conversation with the family and then have them informed enough that they can actually weigh in on what they want,” Gerhardt says. One end product is a card or trifold pamphlet that might help parents understand the benefits and side effects of alternate strategies.

“Typically, in medicine, we’re used to telling people what needs to be done,” she says. “So shared decision making is kind of a different thing for clinicians to engage in.” TH

Bryn Nelson, PhD, is a freelance writer in Seattle.

References

1. Valle CW, Binns HJ, Quadri-Sheriff M, Benuck I, Patel A. Physicians’ lack of adherence to National Heart, Lung, and Blood Institute guidelines for pediatric lipid screening. Clin Pediatr. 2015;54(12):1200-1205.
2. Maynard G, Jenkins IH, Merli GJ. Venous thromboembolism prevention guidelines for medical inpatients: mind the (implementation) gap. J Hosp Med. 2013;8(10):582-588.
3. Mehta RH, Chen AY, Alexander KP, Ohman EM, Roe MT, Peterson ED. Doing the right things and doing them the right way: association between hospital guideline adherence, dosing safety, and outcomes among patients with acute coronary syndrome. Circulation. 2015;131(11):980-987.
4. GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ. 2004;328:1490
5. Andrews JC, Schünemann HJ, Oxman AD, et al. GRADE guidelines: 15. Going from evidence to recommendation—determinants of a recommendation’s direction and strength. J Clin Epidemiol. 2013;66(7):726-735.
6. 6. Chen JH, Fang DZ, Tim Goodnough L, Evans KH, Lee Porter M, Shieh L. Why providers transfuse blood products outside recommended guidelines in spite of integrated electronic best practice alerts. J Hosp Med. 2015;10(1):1-7.

One recent paper in Clinical Pediatrics, for example, chronicled low adherence to the 2011 National Heart, Lung, and Blood Institute lipid screening guidelines in primary-care settings.1 Another cautioned providers to “mind the (implementation) gap” in venous thromboembolism prevention guidelines for medical inpatients.2 A third found that lower adherence to guidelines issued by the American College of Cardiology/American Heart Association for acute coronary syndrome patients was significantly associated with higher bleeding and mortality rates.3

Both clinical trials and real-world studies have demonstrated that when guidelines are applied, patients do better, says William Lewis, MD, professor of medicine at Case Western Reserve University and director of the Heart & Vascular Center at MetroHealth in Cleveland. So why aren’t they followed more consistently?

Experts in both HM and other disciplines cite multiple obstacles. Lack of evidence, conflicting evidence, or lack of awareness about evidence can all conspire against the main goal of helping providers deliver consistent high-value care, says Christopher Moriates, MD, assistant clinical professor in the Division of Hospital Medicine at the University of California, San Francisco.

“In our day-to-day lives as hospitalists, for the vast majority probably of what we do there’s no clear guideline or there’s a guideline that doesn’t necessarily apply to the patient standing in front of me,” he says.

Even when a guideline is clear and relevant, other doctors say inadequate dissemination and implementation can still derail quality improvement efforts.

“A lot of what we do as physicians is what we learned in residency, and to incorporate the new data is difficult,” says Leonard Feldman, MD, SFHM, a hospitalist and associate professor of internal medicine and pediatrics at Johns Hopkins School of Medicine in Baltimore.

Dr. Feldman believes many doctors have yet to integrate recently revised hypertension and cholesterol guidelines into their practice, for example. Some guidelines have proven more complex or controversial, limiting their adoption.

“I know I struggle to keep up with all of the guidelines, and I’m in a big academic center where people are talking about them all the time, and I’m working with residents who are talking about them all the time,” Dr. Feldman says.

Despite the remaining gaps, however, many researchers agree that momentum has built steadily over the past two decades toward a more systematic approach to creating solid evidence-based guidelines and integrating them into real-world decision making.

Emphasis on Evidence and Transparency

The term “evidence-based medicine” was coined in 1990 by Gordon Guyatt, MD, MSc, FRCPC, distinguished professor of medicine and clinical epidemiology at McMaster University in Hamilton, Ontario. It’s played an active role in formulating guidelines for multiple organizations. The guideline-writing process, Dr. Guyatt says, once consisted of little more than self-selected clinicians sitting around a table.

“It used to be that a bunch of experts got together and decided and made the recommendations with very little in the way of a systematic process and certainly not evidence based,” he says.

Cincinnati Children’s Hospital Medical Center was among the pioneers pushing for a more systematic approach; the hospital began working on its own guidelines in 1995 and published the first of many the following year.

“We started evidence-based guidelines when the docs were still saying, ‘This is cookbook medicine. I don’t know if I want to do this or not,’” says Wendy Gerhardt, MSN, director of evidence-based decision making in the James M. Anderson Center for Health Systems Excellence at Cincinnati Children’s.

Some doctors also argued that clinical guidelines would stifle innovation, cramp their individual style, or intrude on their relationships with patients. Despite some lingering misgivings among clinicians, however, the process has gained considerable support. In 2000, an organization called the GRADE Working Group (Grading of Recommendations, Assessment, Development and Evaluation) began developing a new approach to raise the quality of evidence and strength of recommendations.

The group’s work led to a 2004 article in BMJ, and the journal subsequently published a six-part series about GRADE for clinicians.4 More recently, the Journal of Clinical Epidemiology also delved into the issue with a 15-part series detailing the GRADE methodology.5 Together, Dr. Guyatt says, the articles have become a go-to guide for guidelines and have helped solidify the focus on evidence.

Cincinnati Children’s and other institutions also have developed tools, and the Institute of Medicine has published guideline-writing standards.

“So it’s easier than it’s ever been to know whether or not you have a decent guideline in your hand,” Gerhardt says.

Likewise, medical organizations are more clearly explaining how they came up with different kinds of guidelines. Evidence-based and consensus guidelines aren’t necessarily mutually exclusive, though consensus building is often used in the absence of high-quality evidence. Some organizations have limited the pool of evidence for guidelines to randomized controlled trial data.

“Unfortunately, for us in the real world, we actually have to make decisions even when there’s not enough data,” Dr. Feldman says.

Sometimes, the best available evidence may be observational studies, and some committees still try to reach a consensus based on that evidence and on the panelists’ professional opinions.

Dr. Guyatt agrees that it’s “absolutely not” true that evidence-based guidelines require randomized controlled trials. “What you need for any recommendation is a thorough review and summary of the best available evidence,” he says.

As part of each final document, Cincinnati Children’s details how it created the guideline, when the literature searches occurred, how the committee reached a consensus, and which panelists participated in the deliberations. The information, Gerhardt says, allows anyone else to “make some sensible decisions about whether or not it’s a guideline you want to use.”

Guideline-crafting institutions are also focusing more on the proper makeup of their panels. In general, Dr. Guyatt says, a panel with more than 10 people can be unwieldy. Guidelines that include many specific recommendations, however, may require multiple subsections, each with its own committee.

Dr. Guyatt is careful to note that, like many other experts, he has multiple potential conflicts of interest, such as working on the anti-thrombotic guidelines issued by the American College of Chest Physicians. Committees, he says, have become increasingly aware of how properly handling conflicts (financial or otherwise) can be critical in building and maintaining trust among clinicians and patients. One technique is to ensure that a diversity of opinions is reflected among a committee whose experts have various conflicts. If one expert’s company makes drug A, for example, then the committee also includes experts involved with drugs B or C. As an alternative, some committees have explicitly barred anyone with a conflict of interest from participating at all.

But experts often provide crucial input, Dr. Guyatt says, and several committees have adopted variations of a middle-ground approach. In an approach that he favors, all guideline-formulating panelists are conflict-free but begin their work by meeting with a separate group of experts who may have some conflicts but can help point out the main issues. The panelists then deliberate and write a draft of the recommendations, after which they meet again with the experts to receive feedback before finalizing the draft.

In a related approach, experts sit on the panel and discuss the evidence, but those with conflicts recuse themselves before the group votes on any recommendations. Delineating between discussions of the evidence and discussions of recommendations can be tricky, though, increasing the risk that a conflict of interest may influence the outcome. Even so, Dr. Guyatt says the model is still preferable to other alternatives.

Getting the Word Out

Once guidelines have been crafted and vetted, how can hospitalists get up to speed on them? Dr. Feldman’s favorite go-to source is Guideline.gov, a national guideline clearinghouse that he calls one of the best compendiums of available information. Especially helpful, he adds, are details such as how the guidelines were created.

To help maximize his time, he also uses tools like NEJM Journal Watch, which sends daily emails on noteworthy articles and weekend roundups of the most important studies.

“It is a way of at least trying to keep up with what’s going on,” he says. Similarly, he adds, ACP Journal Club provides summaries of important new articles, The Hospitalist can help highlight important guidelines that affect HM, and CME meetings or online modules like SHMconsults.com can help doctors keep pace.

For the past decade, Dr. Guyatt has worked with another popular tool, a guideline-disseminating service called UpToDate. Many alternatives exist, such as DynaMed Plus.

“I think you just need to pick away,” Dr. Feldman says. “You need to decide that as a physician, as a lifelong learner, that you are going to do something that is going to keep you up-to-date. There are many ways of doing it. You just have to decide what you’re going to do and commit to it.”

Researchers are helping out by studying how to present new guidelines in ways that engage doctors and improve patient outcomes. Another trend is to make guidelines routinely accessible not only in electronic medical records but also on tablets and smartphones. Lisa Shieh, MD, PhD, FHM, a hospitalist and clinical professor of medicine at Stanford University Medical Center, has studied how best-practice alerts, or BPAs, impact adherence to guidelines covering the appropriate use of blood products. Dr. Shieh, who splits her time between quality improvement and hospital medicine, says getting new information and guidelines into clinicians’ hands can be a logistical challenge.

“At Stanford, we had a huge official campaign around the guidelines, and that did make some impact, but it wasn’t huge in improving appropriate blood use,” she says. When the medial center set up a BPA through the electronic medical record system, however, both overall and inappropriate blood use declined significantly. In fact, the percentage of providers ordering blood products for patients with a hemoglobin count above 8 g/dL dropped from 60% to 25%.6

One difference maker, Dr. Shieh says, was providing education at the moment a doctor actually ordered blood. To avoid alert fatigue, the “smart BPA” fires only if a doctor tries to order blood and the patient’s hemoglobin is greater than 7 or 8 g/dL, depending on the diagnosis. If the doctor still wants to transfuse, the system requests a clinical indication for the exception.

Despite the clear improvement in appropriate use, the team wanted to understand why 25% of providers were still ordering blood products for patients with a hemoglobin count greater than 8 despite the triggered BPA and whether additional interventions could yield further improvements. Through their study, the researchers documented several reasons for the continued ordering. In some cases, the system failed to properly document actual or potential bleeding as an indicator. In other cases, the ordering reflected a lack of consensus on the guidelines in fields like hematology and oncology.

One of the most intriguing reasons, though, was that residents often did the ordering at the behest of an attending who might have never seen the BPA.

“It’s not actually reaching the audience making the decision; it might be reaching the audience that’s just carrying out the order,” Dr. Shieh says.

The insight, she says, may provide an opportunity to talk with attending physicians who may not have completely bought into the guidelines and to involve the entire team in the decision-making process.

Hospitalists, she says, can play a vital role in guideline development and implementation, especially for strategies that include BPAs.

“I think they’re the perfect group to help use this technology wisely because they are at the front lines taking care of patients so they’ll know the best workflow of when these alerts fire and maybe which ones happen the most often,” Dr. Shieh says. “I think this is a fantastic opportunity to get more hospitalists involved in designing these alerts and collaborating with the IT folks.”

Even with widespread buy-in from providers, guidelines may not reach their full potential without a careful consideration of patients’ values and concerns. Experts say joint deliberations and discussions are especially important for guidelines that are complicated, controversial, or carrying potential risks that must be weighed against the benefits.

Some of the conversations are easy, with well-defined risks and benefits and clear patient preferences, but others must traverse vast tracts of gray area. Fortunately, Dr. Feldman says, more tools also are becoming available for this kind of shared decision making. Some use pictorial representations to help patients understand the potential outcomes of alternative courses of action or inaction.

“Sometimes, that pictorial representation is worth the 1,000 words that we wouldn’t be able to adequately describe otherwise,” he says.

Similarly, Cincinnati Children’s has developed tools to help to ease the shared decision-making process.

“We look where there’s equivocal evidence or no evidence and have developed tools that help the clinician have that conversation with the family and then have them informed enough that they can actually weigh in on what they want,” Gerhardt says. One end product is a card or trifold pamphlet that might help parents understand the benefits and side effects of alternate strategies.

“Typically, in medicine, we’re used to telling people what needs to be done,” she says. “So shared decision making is kind of a different thing for clinicians to engage in.” TH

Bryn Nelson, PhD, is a freelance writer in Seattle.

References

1. Valle CW, Binns HJ, Quadri-Sheriff M, Benuck I, Patel A. Physicians’ lack of adherence to National Heart, Lung, and Blood Institute guidelines for pediatric lipid screening. Clin Pediatr. 2015;54(12):1200-1205.
2. Maynard G, Jenkins IH, Merli GJ. Venous thromboembolism prevention guidelines for medical inpatients: mind the (implementation) gap. J Hosp Med. 2013;8(10):582-588.
3. Mehta RH, Chen AY, Alexander KP, Ohman EM, Roe MT, Peterson ED. Doing the right things and doing them the right way: association between hospital guideline adherence, dosing safety, and outcomes among patients with acute coronary syndrome. Circulation. 2015;131(11):980-987.
4. GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ. 2004;328:1490
5. Andrews JC, Schünemann HJ, Oxman AD, et al. GRADE guidelines: 15. Going from evidence to recommendation—determinants of a recommendation’s direction and strength. J Clin Epidemiol. 2013;66(7):726-735.
6. 6. Chen JH, Fang DZ, Tim Goodnough L, Evans KH, Lee Porter M, Shieh L. Why providers transfuse blood products outside recommended guidelines in spite of integrated electronic best practice alerts. J Hosp Med. 2015;10(1):1-7.

One recent paper in Clinical Pediatrics, for example, chronicled low adherence to the 2011 National Heart, Lung, and Blood Institute lipid screening guidelines in primary-care settings.1 Another cautioned providers to “mind the (implementation) gap” in venous thromboembolism prevention guidelines for medical inpatients.2 A third found that lower adherence to guidelines issued by the American College of Cardiology/American Heart Association for acute coronary syndrome patients was significantly associated with higher bleeding and mortality rates.3

Both clinical trials and real-world studies have demonstrated that when guidelines are applied, patients do better, says William Lewis, MD, professor of medicine at Case Western Reserve University and director of the Heart & Vascular Center at MetroHealth in Cleveland. So why aren’t they followed more consistently?

Experts in both HM and other disciplines cite multiple obstacles. Lack of evidence, conflicting evidence, or lack of awareness about evidence can all conspire against the main goal of helping providers deliver consistent high-value care, says Christopher Moriates, MD, assistant clinical professor in the Division of Hospital Medicine at the University of California, San Francisco.

“In our day-to-day lives as hospitalists, for the vast majority probably of what we do there’s no clear guideline or there’s a guideline that doesn’t necessarily apply to the patient standing in front of me,” he says.

Even when a guideline is clear and relevant, other doctors say inadequate dissemination and implementation can still derail quality improvement efforts.

“A lot of what we do as physicians is what we learned in residency, and to incorporate the new data is difficult,” says Leonard Feldman, MD, SFHM, a hospitalist and associate professor of internal medicine and pediatrics at Johns Hopkins School of Medicine in Baltimore.

Dr. Feldman believes many doctors have yet to integrate recently revised hypertension and cholesterol guidelines into their practice, for example. Some guidelines have proven more complex or controversial, limiting their adoption.

“I know I struggle to keep up with all of the guidelines, and I’m in a big academic center where people are talking about them all the time, and I’m working with residents who are talking about them all the time,” Dr. Feldman says.

Despite the remaining gaps, however, many researchers agree that momentum has built steadily over the past two decades toward a more systematic approach to creating solid evidence-based guidelines and integrating them into real-world decision making.

Emphasis on Evidence and Transparency

The term “evidence-based medicine” was coined in 1990 by Gordon Guyatt, MD, MSc, FRCPC, distinguished professor of medicine and clinical epidemiology at McMaster University in Hamilton, Ontario. It’s played an active role in formulating guidelines for multiple organizations. The guideline-writing process, Dr. Guyatt says, once consisted of little more than self-selected clinicians sitting around a table.

“It used to be that a bunch of experts got together and decided and made the recommendations with very little in the way of a systematic process and certainly not evidence based,” he says.

Cincinnati Children’s Hospital Medical Center was among the pioneers pushing for a more systematic approach; the hospital began working on its own guidelines in 1995 and published the first of many the following year.

“We started evidence-based guidelines when the docs were still saying, ‘This is cookbook medicine. I don’t know if I want to do this or not,’” says Wendy Gerhardt, MSN, director of evidence-based decision making in the James M. Anderson Center for Health Systems Excellence at Cincinnati Children’s.

Some doctors also argued that clinical guidelines would stifle innovation, cramp their individual style, or intrude on their relationships with patients. Despite some lingering misgivings among clinicians, however, the process has gained considerable support. In 2000, an organization called the GRADE Working Group (Grading of Recommendations, Assessment, Development and Evaluation) began developing a new approach to raise the quality of evidence and strength of recommendations.

The group’s work led to a 2004 article in BMJ, and the journal subsequently published a six-part series about GRADE for clinicians.4 More recently, the Journal of Clinical Epidemiology also delved into the issue with a 15-part series detailing the GRADE methodology.5 Together, Dr. Guyatt says, the articles have become a go-to guide for guidelines and have helped solidify the focus on evidence.

Cincinnati Children’s and other institutions also have developed tools, and the Institute of Medicine has published guideline-writing standards.

“So it’s easier than it’s ever been to know whether or not you have a decent guideline in your hand,” Gerhardt says.

Likewise, medical organizations are more clearly explaining how they came up with different kinds of guidelines. Evidence-based and consensus guidelines aren’t necessarily mutually exclusive, though consensus building is often used in the absence of high-quality evidence. Some organizations have limited the pool of evidence for guidelines to randomized controlled trial data.

“Unfortunately, for us in the real world, we actually have to make decisions even when there’s not enough data,” Dr. Feldman says.

Sometimes, the best available evidence may be observational studies, and some committees still try to reach a consensus based on that evidence and on the panelists’ professional opinions.

Dr. Guyatt agrees that it’s “absolutely not” true that evidence-based guidelines require randomized controlled trials. “What you need for any recommendation is a thorough review and summary of the best available evidence,” he says.

As part of each final document, Cincinnati Children’s details how it created the guideline, when the literature searches occurred, how the committee reached a consensus, and which panelists participated in the deliberations. The information, Gerhardt says, allows anyone else to “make some sensible decisions about whether or not it’s a guideline you want to use.”

Guideline-crafting institutions are also focusing more on the proper makeup of their panels. In general, Dr. Guyatt says, a panel with more than 10 people can be unwieldy. Guidelines that include many specific recommendations, however, may require multiple subsections, each with its own committee.

Dr. Guyatt is careful to note that, like many other experts, he has multiple potential conflicts of interest, such as working on the anti-thrombotic guidelines issued by the American College of Chest Physicians. Committees, he says, have become increasingly aware of how properly handling conflicts (financial or otherwise) can be critical in building and maintaining trust among clinicians and patients. One technique is to ensure that a diversity of opinions is reflected among a committee whose experts have various conflicts. If one expert’s company makes drug A, for example, then the committee also includes experts involved with drugs B or C. As an alternative, some committees have explicitly barred anyone with a conflict of interest from participating at all.

But experts often provide crucial input, Dr. Guyatt says, and several committees have adopted variations of a middle-ground approach. In an approach that he favors, all guideline-formulating panelists are conflict-free but begin their work by meeting with a separate group of experts who may have some conflicts but can help point out the main issues. The panelists then deliberate and write a draft of the recommendations, after which they meet again with the experts to receive feedback before finalizing the draft.

In a related approach, experts sit on the panel and discuss the evidence, but those with conflicts recuse themselves before the group votes on any recommendations. Delineating between discussions of the evidence and discussions of recommendations can be tricky, though, increasing the risk that a conflict of interest may influence the outcome. Even so, Dr. Guyatt says the model is still preferable to other alternatives.

Getting the Word Out

Once guidelines have been crafted and vetted, how can hospitalists get up to speed on them? Dr. Feldman’s favorite go-to source is Guideline.gov, a national guideline clearinghouse that he calls one of the best compendiums of available information. Especially helpful, he adds, are details such as how the guidelines were created.

To help maximize his time, he also uses tools like NEJM Journal Watch, which sends daily emails on noteworthy articles and weekend roundups of the most important studies.

“It is a way of at least trying to keep up with what’s going on,” he says. Similarly, he adds, ACP Journal Club provides summaries of important new articles, The Hospitalist can help highlight important guidelines that affect HM, and CME meetings or online modules like SHMconsults.com can help doctors keep pace.

For the past decade, Dr. Guyatt has worked with another popular tool, a guideline-disseminating service called UpToDate. Many alternatives exist, such as DynaMed Plus.

“I think you just need to pick away,” Dr. Feldman says. “You need to decide that as a physician, as a lifelong learner, that you are going to do something that is going to keep you up-to-date. There are many ways of doing it. You just have to decide what you’re going to do and commit to it.”

Researchers are helping out by studying how to present new guidelines in ways that engage doctors and improve patient outcomes. Another trend is to make guidelines routinely accessible not only in electronic medical records but also on tablets and smartphones. Lisa Shieh, MD, PhD, FHM, a hospitalist and clinical professor of medicine at Stanford University Medical Center, has studied how best-practice alerts, or BPAs, impact adherence to guidelines covering the appropriate use of blood products. Dr. Shieh, who splits her time between quality improvement and hospital medicine, says getting new information and guidelines into clinicians’ hands can be a logistical challenge.

“At Stanford, we had a huge official campaign around the guidelines, and that did make some impact, but it wasn’t huge in improving appropriate blood use,” she says. When the medial center set up a BPA through the electronic medical record system, however, both overall and inappropriate blood use declined significantly. In fact, the percentage of providers ordering blood products for patients with a hemoglobin count above 8 g/dL dropped from 60% to 25%.6

One difference maker, Dr. Shieh says, was providing education at the moment a doctor actually ordered blood. To avoid alert fatigue, the “smart BPA” fires only if a doctor tries to order blood and the patient’s hemoglobin is greater than 7 or 8 g/dL, depending on the diagnosis. If the doctor still wants to transfuse, the system requests a clinical indication for the exception.

Despite the clear improvement in appropriate use, the team wanted to understand why 25% of providers were still ordering blood products for patients with a hemoglobin count greater than 8 despite the triggered BPA and whether additional interventions could yield further improvements. Through their study, the researchers documented several reasons for the continued ordering. In some cases, the system failed to properly document actual or potential bleeding as an indicator. In other cases, the ordering reflected a lack of consensus on the guidelines in fields like hematology and oncology.

One of the most intriguing reasons, though, was that residents often did the ordering at the behest of an attending who might have never seen the BPA.

“It’s not actually reaching the audience making the decision; it might be reaching the audience that’s just carrying out the order,” Dr. Shieh says.

The insight, she says, may provide an opportunity to talk with attending physicians who may not have completely bought into the guidelines and to involve the entire team in the decision-making process.

Hospitalists, she says, can play a vital role in guideline development and implementation, especially for strategies that include BPAs.

“I think they’re the perfect group to help use this technology wisely because they are at the front lines taking care of patients so they’ll know the best workflow of when these alerts fire and maybe which ones happen the most often,” Dr. Shieh says. “I think this is a fantastic opportunity to get more hospitalists involved in designing these alerts and collaborating with the IT folks.”

Even with widespread buy-in from providers, guidelines may not reach their full potential without a careful consideration of patients’ values and concerns. Experts say joint deliberations and discussions are especially important for guidelines that are complicated, controversial, or carrying potential risks that must be weighed against the benefits.

Some of the conversations are easy, with well-defined risks and benefits and clear patient preferences, but others must traverse vast tracts of gray area. Fortunately, Dr. Feldman says, more tools also are becoming available for this kind of shared decision making. Some use pictorial representations to help patients understand the potential outcomes of alternative courses of action or inaction.

“Sometimes, that pictorial representation is worth the 1,000 words that we wouldn’t be able to adequately describe otherwise,” he says.

Similarly, Cincinnati Children’s has developed tools to help to ease the shared decision-making process.

“We look where there’s equivocal evidence or no evidence and have developed tools that help the clinician have that conversation with the family and then have them informed enough that they can actually weigh in on what they want,” Gerhardt says. One end product is a card or trifold pamphlet that might help parents understand the benefits and side effects of alternate strategies.

“Typically, in medicine, we’re used to telling people what needs to be done,” she says. “So shared decision making is kind of a different thing for clinicians to engage in.” TH

Bryn Nelson, PhD, is a freelance writer in Seattle.

References

1. Valle CW, Binns HJ, Quadri-Sheriff M, Benuck I, Patel A. Physicians’ lack of adherence to National Heart, Lung, and Blood Institute guidelines for pediatric lipid screening. Clin Pediatr. 2015;54(12):1200-1205.
2. Maynard G, Jenkins IH, Merli GJ. Venous thromboembolism prevention guidelines for medical inpatients: mind the (implementation) gap. J Hosp Med. 2013;8(10):582-588.
3. Mehta RH, Chen AY, Alexander KP, Ohman EM, Roe MT, Peterson ED. Doing the right things and doing them the right way: association between hospital guideline adherence, dosing safety, and outcomes among patients with acute coronary syndrome. Circulation. 2015;131(11):980-987.
4. GRADE Working Group. Grading quality of evidence and strength of recommendations. BMJ. 2004;328:1490
5. Andrews JC, Schünemann HJ, Oxman AD, et al. GRADE guidelines: 15. Going from evidence to recommendation—determinants of a recommendation’s direction and strength. J Clin Epidemiol. 2013;66(7):726-735.
6. 6. Chen JH, Fang DZ, Tim Goodnough L, Evans KH, Lee Porter M, Shieh L. Why providers transfuse blood products outside recommended guidelines in spite of integrated electronic best practice alerts. J Hosp Med. 2015;10(1):1-7.

Malignant plasma cells

NEW YORK—As the number of therapeutic options for multiple myeloma (MM) increases, so too does the need to reassess prognostic markers for the disease, according to a speaker at Lymphoma & Myeloma 2016.

“A good prognosticator for one patient may have little meaning for another patient,” said Scott Ely, MD, of Weill Cornell Medicine in New York, New York.

“It’s really important before doing any testing to ask, ‘Will the result of this test affect patient care?’”

To answer this question, Dr Ely reviewed the different testing methods used in MM patients and explained the advantages of each.

“[I]t’s really important to understand that a lot of methods are really great for research but don’t work or are not feasible for real-life diagnostic purposes,” he added.

Dr Ely also said it’s important to consider who wants the data, how much the test costs, and who will pay for it, keeping in mind that, these days, the patient’s share of the bill is increasing.

Dr Ely stressed that, until more precise targets or a better understanding of drug mechanisms exist, clinical features—patient age, performance status or frailty, renal function, and disease stage—remain the most important prognosticators.

“But still, 2 patients in the same box based on clinical features will often have very different outcomes,”  he said. “So in addition to clinical factors, we need prognosticators for tumor cell behavior. We need to know how fast they are growing and how they will respond to treatment.”

Methods to assess myeloma cell proliferation

Cytogenetics (FISH), gene array technology, and genomics using next-generation sequencing can provide some information, but they are not necessarily good methods to assess proliferation, Dr Ely explained.

To determine the proliferation rate of a patient’s cancer, you can look at tens of thousands of genes by gene array, he said, “or you can just look at one thing, which is Ki67.”

If the cell has Ki67, it’s proliferating, and if it doesn’t have Ki67, it’s not.

“Often, looking at all the other upstream molecules can be confusing and even misleading,” he noted. “So Ki67 is the best way to look for proliferation when it comes to myeloma.”

Other methods include the plasma cell labeling index (PCLI), gene expression profiling, flow cytometry, and multiplex immunohistochemistry (mIHC).

Dr Ely, as a hematopathologist, has found IHC to be the best method to determine proliferation, most likely because the other methods use bone marrow aspirate and IHC uses core biopsy of histologic sections.

It’s the gold standard, he said, for determining the percentage of plasma cells because core biopsy takes a “complete, intact piece of marrow that’s truly representative of what’s going on in the patient.”

In a study of more than 350 bone marrow samples comparing core biopsy with aspirate smears, plasma cells were under-represented in approximately half the aspirate specimens by about 20%.

In addition, Dr Ely noted that myeloma cells die very quickly once they are removed from the stroma.

“So if you take myeloma cells out as an aspirate,” he said, “myeloma cells die and others survive.”

And if the aspirate is sent overnight to the lab, the number of plasma cells in the specimen will already be reduced when the lab gets it.

Aspirates are best for leukemia and myelodysplastic syndromes, Dr Ely said, while core biopsies are best for lymphoma and myeloma.

Plasma cell proliferation indices

Proliferation is a myeloma-defining criterion, Dr Ely said. It predicts an 80% probability of progression in 2 years.

And PCLI has shown conclusively that plasma cell proliferation is a good prognosticator in all types of myeloma patients. However, it is not really feasible to use or easy to perform.

On the other hand, core biopsy combined with IHC is a feasible way of measuring plasma cell proliferation for routine clinical use.

Using standard IHC, it’s difficult to distinguish proliferating from non-proliferating cells, Dr Ely said.

“The solution to this problem is multiplex IHC,” he said, using 3 stains—red for CD138 (the plasma cell marker), brown for Ki67 (the proliferation marker), and blue as a negative nuclear counter stain.

A red membrane around the stained cell indicates a myeloma cell. Non-proliferating MM cells have blue nuclei, and proliferating MM cells have brown nuclei.

This assay is called the plasma cell proliferation index (PCPI).

“[A]ny lab that can do standard IHC can do multiplex IHC,” Dr Ely added.

It uses the same machines, the same reagents, the same expertise, and it’s easy to set up.

Validation studies

Dr Ely and his colleagues performed extensive laboratory validation to make sure the new PCPI correlated with the old PCLI.

They also performed 3 clinical validation studies, the first in bone marrow transplant patients. The investigators followed the patients for 12 years and found the PCPI correlated with survival.

The investigators performed a second clinical validation in 151 newly diagnosed patients. On multivariate analysis, the team found PCPI to be an independent prognostic indicator.

Each 1% increase in PCPI was associated with a 3% increased risk of disease progression (hazard ratio=1.03, 95% CI, 1.01-1.05, P=0.02).

The third clinical validation the investigators conducted was a retrospective cohort study in which they evaluated the effect of rising PCPI at relapse in 37 patients. The team defined rising PCPI as a 5% or greater increase in plasma cells.

Nineteen patients had a rising PCPI, and 17 patients had stable or decreased PCPI.

Patients with a rising PCPI at relapse had a shorter median overall survival than patients with stable or decreased PCPI—72 months and not reached, respectively (P=0.0069).

Patients with a rising PCPI also had a shorter median progression-free survival on first post-relapse treatment compared to patients with stable or decreased PCPI—25 months and 47 months, respectively (P=0.036).

“It’s also important to note that if you’re getting high-risk by PCPI plus β2-microglobulin albumin, I’d advise that, for all high-risk patients, getting the cytogenetics doesn’t really help,” Dr Ely said

Three patients considered high-risk by cytogenetics were standard-risk by PCPI plus β2 microglobulin.

“So we found that cytogenetics isn’t really adding anything except the cost,” Dr Ely asserted.

Other labs are now using PCPI for prognostication, he noted, adding, “We hope PCPI will be incorporated into the International Myeloma Working Group diagnosis of MM.”

Malignant plasma cells

NEW YORK—As the number of therapeutic options for multiple myeloma (MM) increases, so too does the need to reassess prognostic markers for the disease, according to a speaker at Lymphoma & Myeloma 2016.

“A good prognosticator for one patient may have little meaning for another patient,” said Scott Ely, MD, of Weill Cornell Medicine in New York, New York.

“It’s really important before doing any testing to ask, ‘Will the result of this test affect patient care?’”

To answer this question, Dr Ely reviewed the different testing methods used in MM patients and explained the advantages of each.

“[I]t’s really important to understand that a lot of methods are really great for research but don’t work or are not feasible for real-life diagnostic purposes,” he added.

Dr Ely also said it’s important to consider who wants the data, how much the test costs, and who will pay for it, keeping in mind that, these days, the patient’s share of the bill is increasing.

Dr Ely stressed that, until more precise targets or a better understanding of drug mechanisms exist, clinical features—patient age, performance status or frailty, renal function, and disease stage—remain the most important prognosticators.

“But still, 2 patients in the same box based on clinical features will often have very different outcomes,”  he said. “So in addition to clinical factors, we need prognosticators for tumor cell behavior. We need to know how fast they are growing and how they will respond to treatment.”

Methods to assess myeloma cell proliferation

Cytogenetics (FISH), gene array technology, and genomics using next-generation sequencing can provide some information, but they are not necessarily good methods to assess proliferation, Dr Ely explained.

To determine the proliferation rate of a patient’s cancer, you can look at tens of thousands of genes by gene array, he said, “or you can just look at one thing, which is Ki67.”

If the cell has Ki67, it’s proliferating, and if it doesn’t have Ki67, it’s not.

“Often, looking at all the other upstream molecules can be confusing and even misleading,” he noted. “So Ki67 is the best way to look for proliferation when it comes to myeloma.”

Other methods include the plasma cell labeling index (PCLI), gene expression profiling, flow cytometry, and multiplex immunohistochemistry (mIHC).

Dr Ely, as a hematopathologist, has found IHC to be the best method to determine proliferation, most likely because the other methods use bone marrow aspirate and IHC uses core biopsy of histologic sections.

It’s the gold standard, he said, for determining the percentage of plasma cells because core biopsy takes a “complete, intact piece of marrow that’s truly representative of what’s going on in the patient.”

In a study of more than 350 bone marrow samples comparing core biopsy with aspirate smears, plasma cells were under-represented in approximately half the aspirate specimens by about 20%.

In addition, Dr Ely noted that myeloma cells die very quickly once they are removed from the stroma.

“So if you take myeloma cells out as an aspirate,” he said, “myeloma cells die and others survive.”

And if the aspirate is sent overnight to the lab, the number of plasma cells in the specimen will already be reduced when the lab gets it.

Aspirates are best for leukemia and myelodysplastic syndromes, Dr Ely said, while core biopsies are best for lymphoma and myeloma.

Plasma cell proliferation indices

Proliferation is a myeloma-defining criterion, Dr Ely said. It predicts an 80% probability of progression in 2 years.

And PCLI has shown conclusively that plasma cell proliferation is a good prognosticator in all types of myeloma patients. However, it is not really feasible to use or easy to perform.

On the other hand, core biopsy combined with IHC is a feasible way of measuring plasma cell proliferation for routine clinical use.

Using standard IHC, it’s difficult to distinguish proliferating from non-proliferating cells, Dr Ely said.

“The solution to this problem is multiplex IHC,” he said, using 3 stains—red for CD138 (the plasma cell marker), brown for Ki67 (the proliferation marker), and blue as a negative nuclear counter stain.

A red membrane around the stained cell indicates a myeloma cell. Non-proliferating MM cells have blue nuclei, and proliferating MM cells have brown nuclei.

This assay is called the plasma cell proliferation index (PCPI).

“[A]ny lab that can do standard IHC can do multiplex IHC,” Dr Ely added.

It uses the same machines, the same reagents, the same expertise, and it’s easy to set up.

Validation studies

Dr Ely and his colleagues performed extensive laboratory validation to make sure the new PCPI correlated with the old PCLI.

They also performed 3 clinical validation studies, the first in bone marrow transplant patients. The investigators followed the patients for 12 years and found the PCPI correlated with survival.

The investigators performed a second clinical validation in 151 newly diagnosed patients. On multivariate analysis, the team found PCPI to be an independent prognostic indicator.

Each 1% increase in PCPI was associated with a 3% increased risk of disease progression (hazard ratio=1.03, 95% CI, 1.01-1.05, P=0.02).

The third clinical validation the investigators conducted was a retrospective cohort study in which they evaluated the effect of rising PCPI at relapse in 37 patients. The team defined rising PCPI as a 5% or greater increase in plasma cells.

Nineteen patients had a rising PCPI, and 17 patients had stable or decreased PCPI.

Patients with a rising PCPI at relapse had a shorter median overall survival than patients with stable or decreased PCPI—72 months and not reached, respectively (P=0.0069).

Patients with a rising PCPI also had a shorter median progression-free survival on first post-relapse treatment compared to patients with stable or decreased PCPI—25 months and 47 months, respectively (P=0.036).

“It’s also important to note that if you’re getting high-risk by PCPI plus β2-microglobulin albumin, I’d advise that, for all high-risk patients, getting the cytogenetics doesn’t really help,” Dr Ely said

Three patients considered high-risk by cytogenetics were standard-risk by PCPI plus β2 microglobulin.

“So we found that cytogenetics isn’t really adding anything except the cost,” Dr Ely asserted.

Other labs are now using PCPI for prognostication, he noted, adding, “We hope PCPI will be incorporated into the International Myeloma Working Group diagnosis of MM.”

Malignant plasma cells

NEW YORK—As the number of therapeutic options for multiple myeloma (MM) increases, so too does the need to reassess prognostic markers for the disease, according to a speaker at Lymphoma & Myeloma 2016.

“A good prognosticator for one patient may have little meaning for another patient,” said Scott Ely, MD, of Weill Cornell Medicine in New York, New York.

“It’s really important before doing any testing to ask, ‘Will the result of this test affect patient care?’”

To answer this question, Dr Ely reviewed the different testing methods used in MM patients and explained the advantages of each.

“[I]t’s really important to understand that a lot of methods are really great for research but don’t work or are not feasible for real-life diagnostic purposes,” he added.

Dr Ely also said it’s important to consider who wants the data, how much the test costs, and who will pay for it, keeping in mind that, these days, the patient’s share of the bill is increasing.

Dr Ely stressed that, until more precise targets or a better understanding of drug mechanisms exist, clinical features—patient age, performance status or frailty, renal function, and disease stage—remain the most important prognosticators.

“But still, 2 patients in the same box based on clinical features will often have very different outcomes,”  he said. “So in addition to clinical factors, we need prognosticators for tumor cell behavior. We need to know how fast they are growing and how they will respond to treatment.”

Methods to assess myeloma cell proliferation

Cytogenetics (FISH), gene array technology, and genomics using next-generation sequencing can provide some information, but they are not necessarily good methods to assess proliferation, Dr Ely explained.

To determine the proliferation rate of a patient’s cancer, you can look at tens of thousands of genes by gene array, he said, “or you can just look at one thing, which is Ki67.”

If the cell has Ki67, it’s proliferating, and if it doesn’t have Ki67, it’s not.

“Often, looking at all the other upstream molecules can be confusing and even misleading,” he noted. “So Ki67 is the best way to look for proliferation when it comes to myeloma.”

Other methods include the plasma cell labeling index (PCLI), gene expression profiling, flow cytometry, and multiplex immunohistochemistry (mIHC).

Dr Ely, as a hematopathologist, has found IHC to be the best method to determine proliferation, most likely because the other methods use bone marrow aspirate and IHC uses core biopsy of histologic sections.

It’s the gold standard, he said, for determining the percentage of plasma cells because core biopsy takes a “complete, intact piece of marrow that’s truly representative of what’s going on in the patient.”

In a study of more than 350 bone marrow samples comparing core biopsy with aspirate smears, plasma cells were under-represented in approximately half the aspirate specimens by about 20%.

In addition, Dr Ely noted that myeloma cells die very quickly once they are removed from the stroma.

“So if you take myeloma cells out as an aspirate,” he said, “myeloma cells die and others survive.”

And if the aspirate is sent overnight to the lab, the number of plasma cells in the specimen will already be reduced when the lab gets it.

Aspirates are best for leukemia and myelodysplastic syndromes, Dr Ely said, while core biopsies are best for lymphoma and myeloma.

Plasma cell proliferation indices

Proliferation is a myeloma-defining criterion, Dr Ely said. It predicts an 80% probability of progression in 2 years.

And PCLI has shown conclusively that plasma cell proliferation is a good prognosticator in all types of myeloma patients. However, it is not really feasible to use or easy to perform.

On the other hand, core biopsy combined with IHC is a feasible way of measuring plasma cell proliferation for routine clinical use.

Using standard IHC, it’s difficult to distinguish proliferating from non-proliferating cells, Dr Ely said.

“The solution to this problem is multiplex IHC,” he said, using 3 stains—red for CD138 (the plasma cell marker), brown for Ki67 (the proliferation marker), and blue as a negative nuclear counter stain.

A red membrane around the stained cell indicates a myeloma cell. Non-proliferating MM cells have blue nuclei, and proliferating MM cells have brown nuclei.

This assay is called the plasma cell proliferation index (PCPI).

“[A]ny lab that can do standard IHC can do multiplex IHC,” Dr Ely added.

It uses the same machines, the same reagents, the same expertise, and it’s easy to set up.

Validation studies

Dr Ely and his colleagues performed extensive laboratory validation to make sure the new PCPI correlated with the old PCLI.

They also performed 3 clinical validation studies, the first in bone marrow transplant patients. The investigators followed the patients for 12 years and found the PCPI correlated with survival.

The investigators performed a second clinical validation in 151 newly diagnosed patients. On multivariate analysis, the team found PCPI to be an independent prognostic indicator.

Each 1% increase in PCPI was associated with a 3% increased risk of disease progression (hazard ratio=1.03, 95% CI, 1.01-1.05, P=0.02).

The third clinical validation the investigators conducted was a retrospective cohort study in which they evaluated the effect of rising PCPI at relapse in 37 patients. The team defined rising PCPI as a 5% or greater increase in plasma cells.

Nineteen patients had a rising PCPI, and 17 patients had stable or decreased PCPI.

Patients with a rising PCPI at relapse had a shorter median overall survival than patients with stable or decreased PCPI—72 months and not reached, respectively (P=0.0069).

Patients with a rising PCPI also had a shorter median progression-free survival on first post-relapse treatment compared to patients with stable or decreased PCPI—25 months and 47 months, respectively (P=0.036).

“It’s also important to note that if you’re getting high-risk by PCPI plus β2-microglobulin albumin, I’d advise that, for all high-risk patients, getting the cytogenetics doesn’t really help,” Dr Ely said

Three patients considered high-risk by cytogenetics were standard-risk by PCPI plus β2 microglobulin.

“So we found that cytogenetics isn’t really adding anything except the cost,” Dr Ely asserted.

Other labs are now using PCPI for prognostication, he noted, adding, “We hope PCPI will be incorporated into the International Myeloma Working Group diagnosis of MM.”

Micrograph showing T-cell

acute lymphoblastic leukemia

Image by Hind Medyou

Preclinical research suggests that 2 investigational drugs synergize to kill T-cell acute lymphoblastic leukemia (T-ALL) cells while having a minimal impact on normal blood cells.

Both drugs—the CK2 inhibitor CX-4945 and the BET inhibitor JQ1—have already been tested as single agents in clinical trials of hematologic malignancies and solid tumors.

However, the effects of the drugs in combination were not known until now.

“Previous studies provided us a rationale to test the combination of CX-4945 and JQ1 on refractory/relapsed T-cell leukemia,” said Hui Feng, MD, PhD, of Boston University School of Medicine in Massachusetts.

“Our findings suggest that the combination treatment of CX-4945 and JQ1 could be an effective strategy to target refractory/relapsed T-cell leukemia.”

Dr Feng and her colleagues reported these findings in Haematologica.

The researchers noted that targeting MYC-mediated transcriptional programs using JQ1 produces anti-leukemic activity in vitro and in vivo. However, global repression of transcription is likely to cause toxicities.

Therefore, the team theorized that finding drugs that synergize with JQ1 might allow them to reduce the dose of JQ1 and therefore decrease the risk of toxicity while enhancing the efficacy of treatment.

For this, the researchers looked to CX-4945, which is currently being investigated in clinical trials of breast cancer and multiple myeloma.

The team said CX-4945 has been shown to significantly reduce the growth and survival of human T-ALL cells on its own.

In a series of experiments, Dr Feng and her colleagues were able to show that CX-4945 destabilizes NOTCH1 and synergizes with JQ1 to induce apoptosis in human T-ALL cells.

The researchers also assessed the effects of JQ1 and CX-4946, alone and in combination, on normal peripheral blood monocytes (PBMs).

PBMs proved less sensitive than ALL-SIL T-ALL cells to each drug alone and to the drugs in combination. In fact, the combination had an antagonistic effect in PBMs.

Dr Feng and her colleagues said this research suggests JQ1 and CX-4946 in combination may be a feasible treatment option for relapsed/refractory T-ALL and other cancers involving CK2 and NOTCH1/MYC.

Micrograph showing T-cell

acute lymphoblastic leukemia

Image by Hind Medyou

Preclinical research suggests that 2 investigational drugs synergize to kill T-cell acute lymphoblastic leukemia (T-ALL) cells while having a minimal impact on normal blood cells.

Both drugs—the CK2 inhibitor CX-4945 and the BET inhibitor JQ1—have already been tested as single agents in clinical trials of hematologic malignancies and solid tumors.

However, the effects of the drugs in combination were not known until now.

“Previous studies provided us a rationale to test the combination of CX-4945 and JQ1 on refractory/relapsed T-cell leukemia,” said Hui Feng, MD, PhD, of Boston University School of Medicine in Massachusetts.

“Our findings suggest that the combination treatment of CX-4945 and JQ1 could be an effective strategy to target refractory/relapsed T-cell leukemia.”

Dr Feng and her colleagues reported these findings in Haematologica.

The researchers noted that targeting MYC-mediated transcriptional programs using JQ1 produces anti-leukemic activity in vitro and in vivo. However, global repression of transcription is likely to cause toxicities.

Therefore, the team theorized that finding drugs that synergize with JQ1 might allow them to reduce the dose of JQ1 and therefore decrease the risk of toxicity while enhancing the efficacy of treatment.

For this, the researchers looked to CX-4945, which is currently being investigated in clinical trials of breast cancer and multiple myeloma.

The team said CX-4945 has been shown to significantly reduce the growth and survival of human T-ALL cells on its own.

In a series of experiments, Dr Feng and her colleagues were able to show that CX-4945 destabilizes NOTCH1 and synergizes with JQ1 to induce apoptosis in human T-ALL cells.

The researchers also assessed the effects of JQ1 and CX-4946, alone and in combination, on normal peripheral blood monocytes (PBMs).

PBMs proved less sensitive than ALL-SIL T-ALL cells to each drug alone and to the drugs in combination. In fact, the combination had an antagonistic effect in PBMs.

Dr Feng and her colleagues said this research suggests JQ1 and CX-4946 in combination may be a feasible treatment option for relapsed/refractory T-ALL and other cancers involving CK2 and NOTCH1/MYC.

Micrograph showing T-cell

acute lymphoblastic leukemia

Image by Hind Medyou

Preclinical research suggests that 2 investigational drugs synergize to kill T-cell acute lymphoblastic leukemia (T-ALL) cells while having a minimal impact on normal blood cells.

Both drugs—the CK2 inhibitor CX-4945 and the BET inhibitor JQ1—have already been tested as single agents in clinical trials of hematologic malignancies and solid tumors.

However, the effects of the drugs in combination were not known until now.

“Previous studies provided us a rationale to test the combination of CX-4945 and JQ1 on refractory/relapsed T-cell leukemia,” said Hui Feng, MD, PhD, of Boston University School of Medicine in Massachusetts.

“Our findings suggest that the combination treatment of CX-4945 and JQ1 could be an effective strategy to target refractory/relapsed T-cell leukemia.”

Dr Feng and her colleagues reported these findings in Haematologica.

The researchers noted that targeting MYC-mediated transcriptional programs using JQ1 produces anti-leukemic activity in vitro and in vivo. However, global repression of transcription is likely to cause toxicities.

Therefore, the team theorized that finding drugs that synergize with JQ1 might allow them to reduce the dose of JQ1 and therefore decrease the risk of toxicity while enhancing the efficacy of treatment.

For this, the researchers looked to CX-4945, which is currently being investigated in clinical trials of breast cancer and multiple myeloma.

The team said CX-4945 has been shown to significantly reduce the growth and survival of human T-ALL cells on its own.

In a series of experiments, Dr Feng and her colleagues were able to show that CX-4945 destabilizes NOTCH1 and synergizes with JQ1 to induce apoptosis in human T-ALL cells.

The researchers also assessed the effects of JQ1 and CX-4946, alone and in combination, on normal peripheral blood monocytes (PBMs).

PBMs proved less sensitive than ALL-SIL T-ALL cells to each drug alone and to the drugs in combination. In fact, the combination had an antagonistic effect in PBMs.

Dr Feng and her colleagues said this research suggests JQ1 and CX-4946 in combination may be a feasible treatment option for relapsed/refractory T-ALL and other cancers involving CK2 and NOTCH1/MYC.

Absolute humidity and temperature are the most important environmental drivers of global influenza, despite differences in outbreak patterns between tropical and temperate countries, according to a new analysis by U.S.-based researchers.

Using convergent cross-mapping and an empirical dynamic modeling approach on data collected by the World Health Organization, investigators led by George Sugihara, PhD, of the Scripps Institution of Oceanography at the University of California, San Diego, confirmed a hypothetical U-shaped relationship between influenza outbreaks and absolute humidity. At low latitudes in the tropics, absolute humidity has a positive effect, increasing the likelihood of influenza as humidity rises but at higher latitudes in temperate countries, absolute humidity has a negative effect, making influenza more likely when absolute humidity is low.

While absolute humidity was the most important factor in the likelihood of influenza outbreaks, the U-shaped relationship was dictated by average temperature. An average temperature below 70 °F had little effect on the negative relationship between absolute humidity and influenza at that range of temperatures, but if the temperature was between 75 °F and 85 °F, the effect was positive. Above 85 °F, aerosol transmission of influenza is blocked, the investigators noted.

“Augmented with further laboratory testing, these population-level results could help set the stage for public health initiatives such as placing humidifiers in schools and hospitals during cold, dry, temperate winter, and in the tropics, perhaps using dehumidifiers or air conditioners set above 75 °F to dry air in public buildings,” Dr. Sugihara and his colleagues wrote.

Find the full study in Proceedings of the National Academy of Sciences of the United States of America (doi: 10.1073/pnas.1607747113).
 

lfranki@frontlinemedcom.com

Absolute humidity and temperature are the most important environmental drivers of global influenza, despite differences in outbreak patterns between tropical and temperate countries, according to a new analysis by U.S.-based researchers.

Using convergent cross-mapping and an empirical dynamic modeling approach on data collected by the World Health Organization, investigators led by George Sugihara, PhD, of the Scripps Institution of Oceanography at the University of California, San Diego, confirmed a hypothetical U-shaped relationship between influenza outbreaks and absolute humidity. At low latitudes in the tropics, absolute humidity has a positive effect, increasing the likelihood of influenza as humidity rises but at higher latitudes in temperate countries, absolute humidity has a negative effect, making influenza more likely when absolute humidity is low.

While absolute humidity was the most important factor in the likelihood of influenza outbreaks, the U-shaped relationship was dictated by average temperature. An average temperature below 70 °F had little effect on the negative relationship between absolute humidity and influenza at that range of temperatures, but if the temperature was between 75 °F and 85 °F, the effect was positive. Above 85 °F, aerosol transmission of influenza is blocked, the investigators noted.

“Augmented with further laboratory testing, these population-level results could help set the stage for public health initiatives such as placing humidifiers in schools and hospitals during cold, dry, temperate winter, and in the tropics, perhaps using dehumidifiers or air conditioners set above 75 °F to dry air in public buildings,” Dr. Sugihara and his colleagues wrote.

Find the full study in Proceedings of the National Academy of Sciences of the United States of America (doi: 10.1073/pnas.1607747113).
 

lfranki@frontlinemedcom.com

Absolute humidity and temperature are the most important environmental drivers of global influenza, despite differences in outbreak patterns between tropical and temperate countries, according to a new analysis by U.S.-based researchers.

Using convergent cross-mapping and an empirical dynamic modeling approach on data collected by the World Health Organization, investigators led by George Sugihara, PhD, of the Scripps Institution of Oceanography at the University of California, San Diego, confirmed a hypothetical U-shaped relationship between influenza outbreaks and absolute humidity. At low latitudes in the tropics, absolute humidity has a positive effect, increasing the likelihood of influenza as humidity rises but at higher latitudes in temperate countries, absolute humidity has a negative effect, making influenza more likely when absolute humidity is low.

While absolute humidity was the most important factor in the likelihood of influenza outbreaks, the U-shaped relationship was dictated by average temperature. An average temperature below 70 °F had little effect on the negative relationship between absolute humidity and influenza at that range of temperatures, but if the temperature was between 75 °F and 85 °F, the effect was positive. Above 85 °F, aerosol transmission of influenza is blocked, the investigators noted.

“Augmented with further laboratory testing, these population-level results could help set the stage for public health initiatives such as placing humidifiers in schools and hospitals during cold, dry, temperate winter, and in the tropics, perhaps using dehumidifiers or air conditioners set above 75 °F to dry air in public buildings,” Dr. Sugihara and his colleagues wrote.

Find the full study in Proceedings of the National Academy of Sciences of the United States of America (doi: 10.1073/pnas.1607747113).
 

lfranki@frontlinemedcom.com

Help us celebrate the AATS Centennial. Experience activities, events, historical artifacts and memorabilia commemorating the 100th anniversary of the American Association for Thoracic Surgery and the field of cardiothoracic surgery.

April 29 – May 3, 2017
Boston Hynes Convention Center
Boston, MA

A unique aspect of this year’s meeting is our collaboration with the American Society of Extracorporeal Technology (AmSECT). During the didactic portion of the program, the two organizations will be conducting joint panel sessions of interest to all members of the team.

AATS President & Annual Meeting Chair
Thoralf M. Sundt, III

AATS Annual Meeting Co-Chairs
Robert D. Jaquiss & Bryan F. Meyers

AmSECT President
Kenneth Shann

AmSECT International Conference Co-Chairs
Emily Saulitis & Larissa M.V. Teresi

More Information

Saturday Courses 

Adult Cardiac Skills Chairs
Volkmar Falk, David Fitzgerald, Kenton Zehr

Congenital Skills Chairs
Ron Angona, David Bichell, Bohdan Maruszewski

General Thoracic Skills Chairs
Virginia Litle, Kazuhiro Yasufuku

Cardiothoracic Transplant and Mechanical Circulatory Support of Heart and Lung Failure Chairs
Matthew Bacchetta, Carmelo Milano, Rich Walczak

Surgical Ethics Forum Chairs
Bill DeBois, Martin McKneally, Robert Sade

Sunday Symposia

AATS/STS Adult Cardiac Surgery Symposium  Chairs
David Fitzgerald, Hitoshi Ognio, Vinod Thourani 

AATS/STS Congenital Heart Disease Symposium Chairs
Ron Angona, Michael Mitchell, Giovanni Stellin 

AATS/STS General Thoracic Surgery Symposium Chairs
 Seth Force, Moishe Liberman

Interprofessional Cardiothoracic Team Symposium Chairs
Steven Gottesfeld, Katherine Hoercher, Bruce Searles, Glenn Whitman

Saturday Course/Sunday Symposia Program

Share:

Help us celebrate the AATS Centennial. Experience activities, events, historical artifacts and memorabilia commemorating the 100th anniversary of the American Association for Thoracic Surgery and the field of cardiothoracic surgery.

April 29 – May 3, 2017
Boston Hynes Convention Center
Boston, MA

A unique aspect of this year’s meeting is our collaboration with the American Society of Extracorporeal Technology (AmSECT). During the didactic portion of the program, the two organizations will be conducting joint panel sessions of interest to all members of the team.

AATS President & Annual Meeting Chair
Thoralf M. Sundt, III

AATS Annual Meeting Co-Chairs
Robert D. Jaquiss & Bryan F. Meyers

AmSECT President
Kenneth Shann

AmSECT International Conference Co-Chairs
Emily Saulitis & Larissa M.V. Teresi

More Information

Saturday Courses 

Adult Cardiac Skills Chairs
Volkmar Falk, David Fitzgerald, Kenton Zehr

Congenital Skills Chairs
Ron Angona, David Bichell, Bohdan Maruszewski

General Thoracic Skills Chairs
Virginia Litle, Kazuhiro Yasufuku

Cardiothoracic Transplant and Mechanical Circulatory Support of Heart and Lung Failure Chairs
Matthew Bacchetta, Carmelo Milano, Rich Walczak

Surgical Ethics Forum Chairs
Bill DeBois, Martin McKneally, Robert Sade

Sunday Symposia

AATS/STS Adult Cardiac Surgery Symposium  Chairs
David Fitzgerald, Hitoshi Ognio, Vinod Thourani 

AATS/STS Congenital Heart Disease Symposium Chairs
Ron Angona, Michael Mitchell, Giovanni Stellin 

AATS/STS General Thoracic Surgery Symposium Chairs
 Seth Force, Moishe Liberman

Interprofessional Cardiothoracic Team Symposium Chairs
Steven Gottesfeld, Katherine Hoercher, Bruce Searles, Glenn Whitman

Saturday Course/Sunday Symposia Program

Share:

Help us celebrate the AATS Centennial. Experience activities, events, historical artifacts and memorabilia commemorating the 100th anniversary of the American Association for Thoracic Surgery and the field of cardiothoracic surgery.

April 29 – May 3, 2017
Boston Hynes Convention Center
Boston, MA

A unique aspect of this year’s meeting is our collaboration with the American Society of Extracorporeal Technology (AmSECT). During the didactic portion of the program, the two organizations will be conducting joint panel sessions of interest to all members of the team.

AATS President & Annual Meeting Chair
Thoralf M. Sundt, III

AATS Annual Meeting Co-Chairs
Robert D. Jaquiss & Bryan F. Meyers

AmSECT President
Kenneth Shann

AmSECT International Conference Co-Chairs
Emily Saulitis & Larissa M.V. Teresi

More Information

Saturday Courses 

Adult Cardiac Skills Chairs
Volkmar Falk, David Fitzgerald, Kenton Zehr

Congenital Skills Chairs
Ron Angona, David Bichell, Bohdan Maruszewski

General Thoracic Skills Chairs
Virginia Litle, Kazuhiro Yasufuku

Cardiothoracic Transplant and Mechanical Circulatory Support of Heart and Lung Failure Chairs
Matthew Bacchetta, Carmelo Milano, Rich Walczak

Surgical Ethics Forum Chairs
Bill DeBois, Martin McKneally, Robert Sade

Sunday Symposia

AATS/STS Adult Cardiac Surgery Symposium  Chairs
David Fitzgerald, Hitoshi Ognio, Vinod Thourani 

AATS/STS Congenital Heart Disease Symposium Chairs
Ron Angona, Michael Mitchell, Giovanni Stellin 

AATS/STS General Thoracic Surgery Symposium Chairs
 Seth Force, Moishe Liberman

Interprofessional Cardiothoracic Team Symposium Chairs
Steven Gottesfeld, Katherine Hoercher, Bruce Searles, Glenn Whitman

Saturday Course/Sunday Symposia Program

Share:

The 2014-2015 influenza vaccines offered little protection against the predominant influenza A/H3N2 virus, but were effective against influenza B, according to the vaccine effectiveness estimates provided by the U.S. Flu Vaccine Effectiveness Network.

Preferential use of the live attenuated influenza vaccine (LAIV) among young children, a recommendation previously published by the Advisory Committee on Immunization Practices, was not supported.

During the 2014-2015 influenza season, a total of 9,710 patients seeking outpatient medical treatment for acute respiratory infection with cough were enrolled into the U.S. Flu Vaccine Effectiveness study, reported Richard Zimmerman, MD, of the University of Pittsburgh, and his colleagues (Clin Infect Dis. 2016 Oct 4. doi: 10.1093/cid/ciw635).

Of these, 9,311 participants had complete data, and 7,078 (76%) tested negative for influenza. A total of 1,840 participants tested positive for influenza A – 99% of these cases were strain A/H3N2 – and 395 participants tested positive for influenza B.

Of the 4,360 vaccinated participants with known vaccine type, 39.7% received standard dose trivalent, 1.6% received high dose trivalent, 46.8% received standard dose quadrivalent, and 11.9% received quadrivalent live-attenuated vaccines.

©luiscar/Thinkstockphotos

The study was supported by the Centers for Disease Control and Prevention and the National Institutes of Health. Dr. Zimmerman and four other investigators reported receiving research funding from several pharmaceutical companies.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

The 2014-2015 influenza vaccines offered little protection against the predominant influenza A/H3N2 virus, but were effective against influenza B, according to the vaccine effectiveness estimates provided by the U.S. Flu Vaccine Effectiveness Network.

Preferential use of the live attenuated influenza vaccine (LAIV) among young children, a recommendation previously published by the Advisory Committee on Immunization Practices, was not supported.

During the 2014-2015 influenza season, a total of 9,710 patients seeking outpatient medical treatment for acute respiratory infection with cough were enrolled into the U.S. Flu Vaccine Effectiveness study, reported Richard Zimmerman, MD, of the University of Pittsburgh, and his colleagues (Clin Infect Dis. 2016 Oct 4. doi: 10.1093/cid/ciw635).

Of these, 9,311 participants had complete data, and 7,078 (76%) tested negative for influenza. A total of 1,840 participants tested positive for influenza A – 99% of these cases were strain A/H3N2 – and 395 participants tested positive for influenza B.

Of the 4,360 vaccinated participants with known vaccine type, 39.7% received standard dose trivalent, 1.6% received high dose trivalent, 46.8% received standard dose quadrivalent, and 11.9% received quadrivalent live-attenuated vaccines.

©luiscar/Thinkstockphotos

The study was supported by the Centers for Disease Control and Prevention and the National Institutes of Health. Dr. Zimmerman and four other investigators reported receiving research funding from several pharmaceutical companies.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig

The 2014-2015 influenza vaccines offered little protection against the predominant influenza A/H3N2 virus, but were effective against influenza B, according to the vaccine effectiveness estimates provided by the U.S. Flu Vaccine Effectiveness Network.

Preferential use of the live attenuated influenza vaccine (LAIV) among young children, a recommendation previously published by the Advisory Committee on Immunization Practices, was not supported.

During the 2014-2015 influenza season, a total of 9,710 patients seeking outpatient medical treatment for acute respiratory infection with cough were enrolled into the U.S. Flu Vaccine Effectiveness study, reported Richard Zimmerman, MD, of the University of Pittsburgh, and his colleagues (Clin Infect Dis. 2016 Oct 4. doi: 10.1093/cid/ciw635).

Of these, 9,311 participants had complete data, and 7,078 (76%) tested negative for influenza. A total of 1,840 participants tested positive for influenza A – 99% of these cases were strain A/H3N2 – and 395 participants tested positive for influenza B.

Of the 4,360 vaccinated participants with known vaccine type, 39.7% received standard dose trivalent, 1.6% received high dose trivalent, 46.8% received standard dose quadrivalent, and 11.9% received quadrivalent live-attenuated vaccines.

©luiscar/Thinkstockphotos

The study was supported by the Centers for Disease Control and Prevention and the National Institutes of Health. Dr. Zimmerman and four other investigators reported receiving research funding from several pharmaceutical companies.

jcraig@frontlinemedcom.com

On Twitter @jessnicolecraig