Debate exists regarding the optimal method of evaluation of the urinary tract at the time of hysterectomy and the circumstances under which it should be performed. Procedures directed at prolapse and incontinence have rates of genitourinary injury as high as 11%-38%, and national guidelines affirm the importance of cystoscopy in these patients.¹ However, for patients undergoing hysterectomy in the absence of these procedures, the optimal strategy is debated. One approach that has been advanced is a policy of universal cystoscopy at the time of hysterectomy. This policy, by which all women undergoing hysterectomy would undergo cystoscopy, aims to prevent the occurrence of an unrecognized genitourinary injury by diagnosing and treating the injury intraoperatively. However, cystoscopy is not the only method that can be used to evaluate the urinary tract. Retroperitoneal dissection also can be used to visually identify the pertinent structures and has been performed with high fidelity by generations of experienced and skilled pelvic surgeons.

Injuries that are not identified intraoperatively at the time of surgery, so-called delayed genitourinary tract injuries, are associated with serious postoperative consequences for patients and high costs for institutions. As surgeons strive to decrease complications and improve the quality of gynecologic surgery, the question of whether cystoscopy should routinely be performed at the time of hysterectomy for benign indications remains unanswered. Proponents argue that cystoscopy is a low-cost assessment and that 75% of genitourinary injuries occur in women without identifiable risk factors.² Opponents point out that cystoscopy is not an entirely benign intervention; it is associated with increased rates of urinary tract infection, bladder and ureteral trauma, and additional operating room time. Furthermore, it is unclear that the use of cystoscopy will reduce the incidence of delayed genitourinary tract injury in clinical practice.

Ultimately, cystoscopy after hysterectomy is being used as a screening test for genitourinary injury, and this lens can be applied to provide more information about its usefulness. For screening tests, the sensitivity and false negative rate are of paramount importance. High sensitivity and resultant few false negatives are the characteristics of a robust screening test which has a low likelihood of missing a diagnosis. Unfortunately, the sensitivity of cystoscopy is not 100% for genitourinary tract injury; it ranges from 60% to 85% and can be as low as 43% for ureteral injury.^3,4 This means that cystoscopy will falsely reassure the surgeon with normal results in greater than 50% of the cases in which the patient actually has a ureteral injury.

Some larger series call into question the usefulness of cystoscopy as a screening tool, finding that this evaluation is not associated with a decreased rate of delayed genitourinary injury. A recent publication by our group of a series of 39,529 women who underwent benign hysterectomy without procedures directed at incontinence and prolapse recorded in the National Surgical Quality Improvement Program (NSQIP) database between 2015 and 2017 found no difference in the rate of delayed genitourinary injury among women exposed to diagnostic cystoscopy and those who were not.⁵ These results are consistent with those of the largest systematic review and meta-analysis of 79 studies capturing 41,482 hysterectomies which found universal cystoscopy was not associated with a decreased rate of delayed genitourinary tract injury.⁶

Another consideration with the use of universal cystoscopy is cost. Although cystoscopy is typically a short procedure, the false positive rate is approximately 2%,² often leading to additional interventions to evaluate the urinary tract which can be time consuming. In the limited available data regarding operative time, patients who underwent cystoscopy had a median operative time that was 17 minutes longer than it was among patients who did not.⁵ Moreover, there may be risks associated with this additional bladder instrumentation, evidenced by an increased incidence of urinary tract infection among women undergoing cystoscopy. In a recent cost-effectiveness analysis of cystoscopy at the time of benign hysterectomy, universal cystoscopy was found to add $51.39-$57.86 per case, and the risk of bladder injury would need to exceed 21%-47% and ureteral injury 27%-38% to be cost saving, compared with selective cystoscopy.⁷ A prior cost-effectiveness analysis concluded that universal cystoscopy is cost effective when the incidence of ureteral injury at the time of hysterectomy exceeds 1.5%-2.0%.⁸ Given these high thresholds, with a contemporary composite lower–genitourinary tract injury incidence of 0.24%-0.27%, it is unlikely that universal cystoscopy could be considered a cost-saving strategy in the majority of clinical settings.

Potential explanations for these results are many. Intraoperative cystoscopy is likely to be normal in the setting of nonobstructive and thermal injuries, which in the current era of minimally invasive surgery may be more prevalent mechanisms of injury. False positives can occur leading to unnecessary interventions, as well as overdiagnosis of asymptomatic urinary tract injuries that may have resolved spontaneously.⁹ It has been observed that cystoscopy is performed less frequently when hysterectomy is completed by a high-volume surgeon, which suggests that surgeon skill and experience play a significant role in the usefulness of this evaluation.⁹

Given these data, what is the best way forward regarding evaluation of the urinary tract at the time of benign hysterectomy? Ultimately, this is a clinical question that should be individualized, taking into account patient and surgical complexity, as well as surgeon training and individual rates of genitourinary injuries.⁹ Given its low sensitivity, caution should be exercised regarding the routine use of cystoscopy alone for evaluation of the urinary tract because false negatives occur with significant frequency. Benefits of cystoscopy in a given clinical scenario should be weighed against the risks of longer operative time, increased costs, and increased rate of urinary tract infection. In the absence of clinical scenarios with high rates of genitourinary injury (greater than 5%), selective rather than universal cystoscopy is the preferred strategy.⁷ Cystoscopy is fundamentally a form of secondary prevention that aims to mitigate damage that has already been done, and is no substitute for primary prevention of genitourinary tract injury itself through thorough knowledge of pelvic anatomy, comfort with retroperitoneal dissection, and awareness of the ureter and bladder at all times.

Dr. Polan is a resident in obstetrics and gynecology at Northwestern University, Chicago. Dr. Barber is an assistant professor of obstetrics and gynecology, specializing in gynecologic oncology, at the university. Neither of them have relevant financial disclosures. Email Dr. Polan and Dr. Barber at obnews@mdedge.com.

References

1. Am J Obstet Gynecol. 2018 Jul;219(1):75-7.

2. Obstet Gynecol. 2009 Jan;113(1):6-10.

3. Obstet Gynecol. 2016 Feb;127(2):369-75.

4. J Minim Invasive Gynecol. 2015 Nov-Dec;22(7):1278-86.

5. Obstet Gynecol. 2019 May;133(5):888-95.

6. Obstet Gynecol. 2015 Dec;126(6):1161-9.

7. Am J Obstet Gynecol. 2019 Apr;220(4):369.e1-7.

8. Obstet Gynecol. 2001 May;97(5 Pt 1):685-92.

9. Obstet Gynecol. 2012 Dec;120(6):1363-70.

Debate exists regarding the optimal method of evaluation of the urinary tract at the time of hysterectomy and the circumstances under which it should be performed. Procedures directed at prolapse and incontinence have rates of genitourinary injury as high as 11%-38%, and national guidelines affirm the importance of cystoscopy in these patients.¹ However, for patients undergoing hysterectomy in the absence of these procedures, the optimal strategy is debated. One approach that has been advanced is a policy of universal cystoscopy at the time of hysterectomy. This policy, by which all women undergoing hysterectomy would undergo cystoscopy, aims to prevent the occurrence of an unrecognized genitourinary injury by diagnosing and treating the injury intraoperatively. However, cystoscopy is not the only method that can be used to evaluate the urinary tract. Retroperitoneal dissection also can be used to visually identify the pertinent structures and has been performed with high fidelity by generations of experienced and skilled pelvic surgeons.

Injuries that are not identified intraoperatively at the time of surgery, so-called delayed genitourinary tract injuries, are associated with serious postoperative consequences for patients and high costs for institutions. As surgeons strive to decrease complications and improve the quality of gynecologic surgery, the question of whether cystoscopy should routinely be performed at the time of hysterectomy for benign indications remains unanswered. Proponents argue that cystoscopy is a low-cost assessment and that 75% of genitourinary injuries occur in women without identifiable risk factors.² Opponents point out that cystoscopy is not an entirely benign intervention; it is associated with increased rates of urinary tract infection, bladder and ureteral trauma, and additional operating room time. Furthermore, it is unclear that the use of cystoscopy will reduce the incidence of delayed genitourinary tract injury in clinical practice.

Ultimately, cystoscopy after hysterectomy is being used as a screening test for genitourinary injury, and this lens can be applied to provide more information about its usefulness. For screening tests, the sensitivity and false negative rate are of paramount importance. High sensitivity and resultant few false negatives are the characteristics of a robust screening test which has a low likelihood of missing a diagnosis. Unfortunately, the sensitivity of cystoscopy is not 100% for genitourinary tract injury; it ranges from 60% to 85% and can be as low as 43% for ureteral injury.^3,4 This means that cystoscopy will falsely reassure the surgeon with normal results in greater than 50% of the cases in which the patient actually has a ureteral injury.

Some larger series call into question the usefulness of cystoscopy as a screening tool, finding that this evaluation is not associated with a decreased rate of delayed genitourinary injury. A recent publication by our group of a series of 39,529 women who underwent benign hysterectomy without procedures directed at incontinence and prolapse recorded in the National Surgical Quality Improvement Program (NSQIP) database between 2015 and 2017 found no difference in the rate of delayed genitourinary injury among women exposed to diagnostic cystoscopy and those who were not.⁵ These results are consistent with those of the largest systematic review and meta-analysis of 79 studies capturing 41,482 hysterectomies which found universal cystoscopy was not associated with a decreased rate of delayed genitourinary tract injury.⁶

Another consideration with the use of universal cystoscopy is cost. Although cystoscopy is typically a short procedure, the false positive rate is approximately 2%,² often leading to additional interventions to evaluate the urinary tract which can be time consuming. In the limited available data regarding operative time, patients who underwent cystoscopy had a median operative time that was 17 minutes longer than it was among patients who did not.⁵ Moreover, there may be risks associated with this additional bladder instrumentation, evidenced by an increased incidence of urinary tract infection among women undergoing cystoscopy. In a recent cost-effectiveness analysis of cystoscopy at the time of benign hysterectomy, universal cystoscopy was found to add $51.39-$57.86 per case, and the risk of bladder injury would need to exceed 21%-47% and ureteral injury 27%-38% to be cost saving, compared with selective cystoscopy.⁷ A prior cost-effectiveness analysis concluded that universal cystoscopy is cost effective when the incidence of ureteral injury at the time of hysterectomy exceeds 1.5%-2.0%.⁸ Given these high thresholds, with a contemporary composite lower–genitourinary tract injury incidence of 0.24%-0.27%, it is unlikely that universal cystoscopy could be considered a cost-saving strategy in the majority of clinical settings.

Potential explanations for these results are many. Intraoperative cystoscopy is likely to be normal in the setting of nonobstructive and thermal injuries, which in the current era of minimally invasive surgery may be more prevalent mechanisms of injury. False positives can occur leading to unnecessary interventions, as well as overdiagnosis of asymptomatic urinary tract injuries that may have resolved spontaneously.⁹ It has been observed that cystoscopy is performed less frequently when hysterectomy is completed by a high-volume surgeon, which suggests that surgeon skill and experience play a significant role in the usefulness of this evaluation.⁹

Given these data, what is the best way forward regarding evaluation of the urinary tract at the time of benign hysterectomy? Ultimately, this is a clinical question that should be individualized, taking into account patient and surgical complexity, as well as surgeon training and individual rates of genitourinary injuries.⁹ Given its low sensitivity, caution should be exercised regarding the routine use of cystoscopy alone for evaluation of the urinary tract because false negatives occur with significant frequency. Benefits of cystoscopy in a given clinical scenario should be weighed against the risks of longer operative time, increased costs, and increased rate of urinary tract infection. In the absence of clinical scenarios with high rates of genitourinary injury (greater than 5%), selective rather than universal cystoscopy is the preferred strategy.⁷ Cystoscopy is fundamentally a form of secondary prevention that aims to mitigate damage that has already been done, and is no substitute for primary prevention of genitourinary tract injury itself through thorough knowledge of pelvic anatomy, comfort with retroperitoneal dissection, and awareness of the ureter and bladder at all times.

Dr. Polan is a resident in obstetrics and gynecology at Northwestern University, Chicago. Dr. Barber is an assistant professor of obstetrics and gynecology, specializing in gynecologic oncology, at the university. Neither of them have relevant financial disclosures. Email Dr. Polan and Dr. Barber at obnews@mdedge.com.

References

1. Am J Obstet Gynecol. 2018 Jul;219(1):75-7.

2. Obstet Gynecol. 2009 Jan;113(1):6-10.

3. Obstet Gynecol. 2016 Feb;127(2):369-75.

4. J Minim Invasive Gynecol. 2015 Nov-Dec;22(7):1278-86.

5. Obstet Gynecol. 2019 May;133(5):888-95.

6. Obstet Gynecol. 2015 Dec;126(6):1161-9.

7. Am J Obstet Gynecol. 2019 Apr;220(4):369.e1-7.

8. Obstet Gynecol. 2001 May;97(5 Pt 1):685-92.

9. Obstet Gynecol. 2012 Dec;120(6):1363-70.

Debate exists regarding the optimal method of evaluation of the urinary tract at the time of hysterectomy and the circumstances under which it should be performed. Procedures directed at prolapse and incontinence have rates of genitourinary injury as high as 11%-38%, and national guidelines affirm the importance of cystoscopy in these patients.¹ However, for patients undergoing hysterectomy in the absence of these procedures, the optimal strategy is debated. One approach that has been advanced is a policy of universal cystoscopy at the time of hysterectomy. This policy, by which all women undergoing hysterectomy would undergo cystoscopy, aims to prevent the occurrence of an unrecognized genitourinary injury by diagnosing and treating the injury intraoperatively. However, cystoscopy is not the only method that can be used to evaluate the urinary tract. Retroperitoneal dissection also can be used to visually identify the pertinent structures and has been performed with high fidelity by generations of experienced and skilled pelvic surgeons.

Injuries that are not identified intraoperatively at the time of surgery, so-called delayed genitourinary tract injuries, are associated with serious postoperative consequences for patients and high costs for institutions. As surgeons strive to decrease complications and improve the quality of gynecologic surgery, the question of whether cystoscopy should routinely be performed at the time of hysterectomy for benign indications remains unanswered. Proponents argue that cystoscopy is a low-cost assessment and that 75% of genitourinary injuries occur in women without identifiable risk factors.² Opponents point out that cystoscopy is not an entirely benign intervention; it is associated with increased rates of urinary tract infection, bladder and ureteral trauma, and additional operating room time. Furthermore, it is unclear that the use of cystoscopy will reduce the incidence of delayed genitourinary tract injury in clinical practice.

Ultimately, cystoscopy after hysterectomy is being used as a screening test for genitourinary injury, and this lens can be applied to provide more information about its usefulness. For screening tests, the sensitivity and false negative rate are of paramount importance. High sensitivity and resultant few false negatives are the characteristics of a robust screening test which has a low likelihood of missing a diagnosis. Unfortunately, the sensitivity of cystoscopy is not 100% for genitourinary tract injury; it ranges from 60% to 85% and can be as low as 43% for ureteral injury.^3,4 This means that cystoscopy will falsely reassure the surgeon with normal results in greater than 50% of the cases in which the patient actually has a ureteral injury.

Some larger series call into question the usefulness of cystoscopy as a screening tool, finding that this evaluation is not associated with a decreased rate of delayed genitourinary injury. A recent publication by our group of a series of 39,529 women who underwent benign hysterectomy without procedures directed at incontinence and prolapse recorded in the National Surgical Quality Improvement Program (NSQIP) database between 2015 and 2017 found no difference in the rate of delayed genitourinary injury among women exposed to diagnostic cystoscopy and those who were not.⁵ These results are consistent with those of the largest systematic review and meta-analysis of 79 studies capturing 41,482 hysterectomies which found universal cystoscopy was not associated with a decreased rate of delayed genitourinary tract injury.⁶

Another consideration with the use of universal cystoscopy is cost. Although cystoscopy is typically a short procedure, the false positive rate is approximately 2%,² often leading to additional interventions to evaluate the urinary tract which can be time consuming. In the limited available data regarding operative time, patients who underwent cystoscopy had a median operative time that was 17 minutes longer than it was among patients who did not.⁵ Moreover, there may be risks associated with this additional bladder instrumentation, evidenced by an increased incidence of urinary tract infection among women undergoing cystoscopy. In a recent cost-effectiveness analysis of cystoscopy at the time of benign hysterectomy, universal cystoscopy was found to add $51.39-$57.86 per case, and the risk of bladder injury would need to exceed 21%-47% and ureteral injury 27%-38% to be cost saving, compared with selective cystoscopy.⁷ A prior cost-effectiveness analysis concluded that universal cystoscopy is cost effective when the incidence of ureteral injury at the time of hysterectomy exceeds 1.5%-2.0%.⁸ Given these high thresholds, with a contemporary composite lower–genitourinary tract injury incidence of 0.24%-0.27%, it is unlikely that universal cystoscopy could be considered a cost-saving strategy in the majority of clinical settings.

Potential explanations for these results are many. Intraoperative cystoscopy is likely to be normal in the setting of nonobstructive and thermal injuries, which in the current era of minimally invasive surgery may be more prevalent mechanisms of injury. False positives can occur leading to unnecessary interventions, as well as overdiagnosis of asymptomatic urinary tract injuries that may have resolved spontaneously.⁹ It has been observed that cystoscopy is performed less frequently when hysterectomy is completed by a high-volume surgeon, which suggests that surgeon skill and experience play a significant role in the usefulness of this evaluation.⁹

Given these data, what is the best way forward regarding evaluation of the urinary tract at the time of benign hysterectomy? Ultimately, this is a clinical question that should be individualized, taking into account patient and surgical complexity, as well as surgeon training and individual rates of genitourinary injuries.⁹ Given its low sensitivity, caution should be exercised regarding the routine use of cystoscopy alone for evaluation of the urinary tract because false negatives occur with significant frequency. Benefits of cystoscopy in a given clinical scenario should be weighed against the risks of longer operative time, increased costs, and increased rate of urinary tract infection. In the absence of clinical scenarios with high rates of genitourinary injury (greater than 5%), selective rather than universal cystoscopy is the preferred strategy.⁷ Cystoscopy is fundamentally a form of secondary prevention that aims to mitigate damage that has already been done, and is no substitute for primary prevention of genitourinary tract injury itself through thorough knowledge of pelvic anatomy, comfort with retroperitoneal dissection, and awareness of the ureter and bladder at all times.

Dr. Polan is a resident in obstetrics and gynecology at Northwestern University, Chicago. Dr. Barber is an assistant professor of obstetrics and gynecology, specializing in gynecologic oncology, at the university. Neither of them have relevant financial disclosures. Email Dr. Polan and Dr. Barber at obnews@mdedge.com.

References

1. Am J Obstet Gynecol. 2018 Jul;219(1):75-7.

2. Obstet Gynecol. 2009 Jan;113(1):6-10.

3. Obstet Gynecol. 2016 Feb;127(2):369-75.

4. J Minim Invasive Gynecol. 2015 Nov-Dec;22(7):1278-86.

5. Obstet Gynecol. 2019 May;133(5):888-95.

6. Obstet Gynecol. 2015 Dec;126(6):1161-9.

7. Am J Obstet Gynecol. 2019 Apr;220(4):369.e1-7.

8. Obstet Gynecol. 2001 May;97(5 Pt 1):685-92.

9. Obstet Gynecol. 2012 Dec;120(6):1363-70.

Entrectinib demonstrated “very promising” antitumor activity in children and adolescents with recurrent or refractory solid tumors, according to an investigator involved in a phase 1/1b trial.

Twelve of 29 patients enrolled in the trial have responded to entrectinib. All responders had fusions in genes targeted by the drug – NTRK1/2/3 (TRKA/B/C), ROS1, or ALK – or an ALK mutation.

Details of this study are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Giles W. Robinson, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., discussed the study during a press briefing in advance of the meeting.

“Entrectinib is an oral and potent inhibitor of the TRKA/B/C, ROS1, and ALK proteins, but it also penetrates into the brain to reach tumors in the brain and spine, which can be a hard area to get drugs to,” Dr. Robinson explained.

“Promising clinical activity was initially seen in the adult solid tumor patients with target rearrangements, and it was encouraging to see these patients also had responses when the tumors were located in their brains. And what got us really excited as pediatric oncologists was that a variety of pediatric cancers harbor these fusions and mutations within certain tumors.”

With this in mind, Dr. Robinson and colleagues conducted a phase 1/1b study (NCT02650401) of entrectinib in 29 patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors.

The patients’ median age was 7 years (range, 0-20 years), and roughly half of them were male (n = 15). Patients were diagnosed with neuroblastoma (n = 16), high-grade glioma (n = 5), inflammatory myofibroblastic tumors (n = 3), infantile fibrosarcoma (n = 2), CNS embryonal tumor (n = 1), melanoma (n = 1), and synovial sarcoma (n = 1).

In the dose-finding portion of the trial, patients received entrectinib at 250 mg/m² (n = 3), 400 mg/m² (n = 3), 550 mg/m² (n = 7), or 750 mg/m² (n = 3).

In the phase 1b portion, patients received entrectinib at 550 mg/m² (n = 7) – the recommended dose – or 400 mg/m² (n = 6) if they were unable to swallow intact capsules.

Dr. Robinson said entrectinib was “quite well tolerated” overall, but he did not present any data on adverse events. He did say dose-limiting toxicities included fatigue, elevated creatinine levels, dysgeusia resulting in loss of taste, weight gain, and, in one patient, pulmonary edema.

“Entrectinib produced striking, rapid, and durable responses in all children with refractory CNS and solid tumors that actually harbored these fusions in NTRK1/2/3, ROS1, or ALK,” Dr. Robinson said. “It also produced a significant response in one ALK-mutated neuroblastoma patient. [N]o responses were seen in tumors lacking aberrations in the target kinases.”

In all, 12 patients responded. The three complete responders had an ALK F1174L mutation, an ALK fusion, and an NTRK fusion, respectively. Five partial responders had NTRK fusions, three had ROS1 fusions, and one had an ALK fusion.

Three responders discontinued treatment. Ten patients were still receiving entrectinib at last follow-up, and 11 patients had died.

Progression-free survival was significantly longer among patients who had fusions than among those who did not (P less than .0001).

“To sum up, entrectinib really is very promising,” Dr. Robinson said. “It has very promising antitumor activity and progression-free survival but [only] in patients with target gene fusions.”

Dr. Robinson said this trial is ongoing, but it is now limited to patients with fusions targeted by entrectinib.

The trial is sponsored by Hoffman-La Roche Ltd. and supported by Alex’s Lemonade Stand Center of Excellence. Dr. Robinson has relationships with Lilly, Genentech/Roche, and Novartis.

jensmith@mdedge.com

SOURCE: Robinson GW et al. ASCO 2019. Abstract 10009.

Entrectinib demonstrated “very promising” antitumor activity in children and adolescents with recurrent or refractory solid tumors, according to an investigator involved in a phase 1/1b trial.

Twelve of 29 patients enrolled in the trial have responded to entrectinib. All responders had fusions in genes targeted by the drug – NTRK1/2/3 (TRKA/B/C), ROS1, or ALK – or an ALK mutation.

Details of this study are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Giles W. Robinson, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., discussed the study during a press briefing in advance of the meeting.

“Entrectinib is an oral and potent inhibitor of the TRKA/B/C, ROS1, and ALK proteins, but it also penetrates into the brain to reach tumors in the brain and spine, which can be a hard area to get drugs to,” Dr. Robinson explained.

“Promising clinical activity was initially seen in the adult solid tumor patients with target rearrangements, and it was encouraging to see these patients also had responses when the tumors were located in their brains. And what got us really excited as pediatric oncologists was that a variety of pediatric cancers harbor these fusions and mutations within certain tumors.”

With this in mind, Dr. Robinson and colleagues conducted a phase 1/1b study (NCT02650401) of entrectinib in 29 patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors.

The patients’ median age was 7 years (range, 0-20 years), and roughly half of them were male (n = 15). Patients were diagnosed with neuroblastoma (n = 16), high-grade glioma (n = 5), inflammatory myofibroblastic tumors (n = 3), infantile fibrosarcoma (n = 2), CNS embryonal tumor (n = 1), melanoma (n = 1), and synovial sarcoma (n = 1).

In the dose-finding portion of the trial, patients received entrectinib at 250 mg/m² (n = 3), 400 mg/m² (n = 3), 550 mg/m² (n = 7), or 750 mg/m² (n = 3).

In the phase 1b portion, patients received entrectinib at 550 mg/m² (n = 7) – the recommended dose – or 400 mg/m² (n = 6) if they were unable to swallow intact capsules.

Dr. Robinson said entrectinib was “quite well tolerated” overall, but he did not present any data on adverse events. He did say dose-limiting toxicities included fatigue, elevated creatinine levels, dysgeusia resulting in loss of taste, weight gain, and, in one patient, pulmonary edema.

“Entrectinib produced striking, rapid, and durable responses in all children with refractory CNS and solid tumors that actually harbored these fusions in NTRK1/2/3, ROS1, or ALK,” Dr. Robinson said. “It also produced a significant response in one ALK-mutated neuroblastoma patient. [N]o responses were seen in tumors lacking aberrations in the target kinases.”

In all, 12 patients responded. The three complete responders had an ALK F1174L mutation, an ALK fusion, and an NTRK fusion, respectively. Five partial responders had NTRK fusions, three had ROS1 fusions, and one had an ALK fusion.

Three responders discontinued treatment. Ten patients were still receiving entrectinib at last follow-up, and 11 patients had died.

Progression-free survival was significantly longer among patients who had fusions than among those who did not (P less than .0001).

“To sum up, entrectinib really is very promising,” Dr. Robinson said. “It has very promising antitumor activity and progression-free survival but [only] in patients with target gene fusions.”

Dr. Robinson said this trial is ongoing, but it is now limited to patients with fusions targeted by entrectinib.

The trial is sponsored by Hoffman-La Roche Ltd. and supported by Alex’s Lemonade Stand Center of Excellence. Dr. Robinson has relationships with Lilly, Genentech/Roche, and Novartis.

jensmith@mdedge.com

SOURCE: Robinson GW et al. ASCO 2019. Abstract 10009.

Entrectinib demonstrated “very promising” antitumor activity in children and adolescents with recurrent or refractory solid tumors, according to an investigator involved in a phase 1/1b trial.

Twelve of 29 patients enrolled in the trial have responded to entrectinib. All responders had fusions in genes targeted by the drug – NTRK1/2/3 (TRKA/B/C), ROS1, or ALK – or an ALK mutation.

Details of this study are scheduled to be presented at the annual meeting of the American Society of Clinical Oncology.

Giles W. Robinson, MD, of St. Jude Children’s Research Hospital in Memphis, Tenn., discussed the study during a press briefing in advance of the meeting.

“Entrectinib is an oral and potent inhibitor of the TRKA/B/C, ROS1, and ALK proteins, but it also penetrates into the brain to reach tumors in the brain and spine, which can be a hard area to get drugs to,” Dr. Robinson explained.

“Promising clinical activity was initially seen in the adult solid tumor patients with target rearrangements, and it was encouraging to see these patients also had responses when the tumors were located in their brains. And what got us really excited as pediatric oncologists was that a variety of pediatric cancers harbor these fusions and mutations within certain tumors.”

With this in mind, Dr. Robinson and colleagues conducted a phase 1/1b study (NCT02650401) of entrectinib in 29 patients with recurrent or refractory solid tumors, including central nervous system (CNS) tumors.

The patients’ median age was 7 years (range, 0-20 years), and roughly half of them were male (n = 15). Patients were diagnosed with neuroblastoma (n = 16), high-grade glioma (n = 5), inflammatory myofibroblastic tumors (n = 3), infantile fibrosarcoma (n = 2), CNS embryonal tumor (n = 1), melanoma (n = 1), and synovial sarcoma (n = 1).

In the dose-finding portion of the trial, patients received entrectinib at 250 mg/m² (n = 3), 400 mg/m² (n = 3), 550 mg/m² (n = 7), or 750 mg/m² (n = 3).

In the phase 1b portion, patients received entrectinib at 550 mg/m² (n = 7) – the recommended dose – or 400 mg/m² (n = 6) if they were unable to swallow intact capsules.

Dr. Robinson said entrectinib was “quite well tolerated” overall, but he did not present any data on adverse events. He did say dose-limiting toxicities included fatigue, elevated creatinine levels, dysgeusia resulting in loss of taste, weight gain, and, in one patient, pulmonary edema.

“Entrectinib produced striking, rapid, and durable responses in all children with refractory CNS and solid tumors that actually harbored these fusions in NTRK1/2/3, ROS1, or ALK,” Dr. Robinson said. “It also produced a significant response in one ALK-mutated neuroblastoma patient. [N]o responses were seen in tumors lacking aberrations in the target kinases.”

In all, 12 patients responded. The three complete responders had an ALK F1174L mutation, an ALK fusion, and an NTRK fusion, respectively. Five partial responders had NTRK fusions, three had ROS1 fusions, and one had an ALK fusion.

Three responders discontinued treatment. Ten patients were still receiving entrectinib at last follow-up, and 11 patients had died.

Progression-free survival was significantly longer among patients who had fusions than among those who did not (P less than .0001).

“To sum up, entrectinib really is very promising,” Dr. Robinson said. “It has very promising antitumor activity and progression-free survival but [only] in patients with target gene fusions.”

Dr. Robinson said this trial is ongoing, but it is now limited to patients with fusions targeted by entrectinib.

The trial is sponsored by Hoffman-La Roche Ltd. and supported by Alex’s Lemonade Stand Center of Excellence. Dr. Robinson has relationships with Lilly, Genentech/Roche, and Novartis.

jensmith@mdedge.com

SOURCE: Robinson GW et al. ASCO 2019. Abstract 10009.

Women experiencing syncope during pregnancy and their offspring have elevated rates of adverse outcomes that may warrant closer follow-up, a retrospective population-based cohort study finds. Risks appeared highest with first-trimester syncope.

“There are very limited data on the frequency of fainting during pregnancy,” Padma Kaul, Ph.D., senior study author and professor of medicine at the University of Alberta, Edmonton, said in a statement. “In our study, fainting during pregnancy occurred in about 1%, or 10 per 1,000 pregnancies, but appears to be increasing by 5% each year.”

“Fainting during pregnancy has previously been thought to follow a relatively benign course,” Dr. Kaul said. “The findings of our study suggest that timing of fainting during pregnancy may be important. When the faint happens early during pregnancy or multiple times during pregnancy, it may be associated with both short- and long-term health issues for the baby and the mother.”

First authors Safia Chatur, MD, of the University of Calgary (Alta.) and Sunjidatul Islam, MBBS, of the Canadian Vigour Centre, Edmonton, Alta., and associates analyzed 481,930 pregnancies occurring during 2005-2014 in the province.

Study results, reported in the Journal of the American Heart Association, showed that syncope occurred in almost 1% of pregnancies (9.7 episodes per 1,000 pregnancies) overall. Incidence increased by 5% per year during the study period.

Syncope episodes were distributed across the first trimester (32%), second trimester (44%), and third trimester (24%). Eight percent of pregnancies had more than one episode.

Compared with unaffected peers, women who experienced syncope were younger (age younger than 25 years, 35% vs. 21%; P less than .001) and more often primiparous (52% vs. 42%; P less than .001).

The rate of preterm birth was 18%, 16%, and 14% in pregnancies with an initial syncope episode during the first, second, and third trimester, respectively, compared with 15% in pregnancies without syncope (P less than .01 across groups).

With a median follow-up of about 5 years, compared with peers of syncope-free pregnancies, children of pregnancies complicated by syncope had a higher incidence of congenital anomalies (3.1% vs. 2.6%; P = .023). Incidence was highest in pregnancies with multiple episodes of syncope (5% vs. 3%; P less than .01).

In adjusted analyses that accounted for multiple pregnancies in individual women, relative to counterparts with no syncope during pregnancy, women who experienced syncope during the first trimester had higher odds of giving birth preterm (odds ratio, 1.3; P = .001) and of having an infant small for gestational age (OR, 1.2; P = .04) or with congenital anomalies (OR, 1.4; P = .036). Women with multiple syncope episodes versus none were twice as likely to have offspring with congenital anomalies (OR, 2.0; P = .003).

Relative to peers who did not experience syncope in pregnancy, women who did had higher incidences of cardiac arrhythmias (0.8% vs. 0.2%; P less than .01) and syncope episodes (1.4% vs. 0.2%; P less than .01) in the first year after delivery.

“Our data suggest that syncope during pregnancy may not be a benign occurrence,” Dr. Chatur and associates said. “More detailed clinical data are needed to identify potential causes for the observed increase in syncope during pregnancy in our study.“Whether women who experience syncope during pregnancy may benefit from closer monitoring during the obstetric and postpartum periods requires further study,” they concluded.

The investigators disclosed no relevant conflicts of interest. This study was funded by a grant from the Cardiac Arrhythmia Network of Canada.

SOURCE: Chatur S et al. J Am Heart Assoc. 2019;8:e011608.

Women experiencing syncope during pregnancy and their offspring have elevated rates of adverse outcomes that may warrant closer follow-up, a retrospective population-based cohort study finds. Risks appeared highest with first-trimester syncope.

“There are very limited data on the frequency of fainting during pregnancy,” Padma Kaul, Ph.D., senior study author and professor of medicine at the University of Alberta, Edmonton, said in a statement. “In our study, fainting during pregnancy occurred in about 1%, or 10 per 1,000 pregnancies, but appears to be increasing by 5% each year.”

“Fainting during pregnancy has previously been thought to follow a relatively benign course,” Dr. Kaul said. “The findings of our study suggest that timing of fainting during pregnancy may be important. When the faint happens early during pregnancy or multiple times during pregnancy, it may be associated with both short- and long-term health issues for the baby and the mother.”

First authors Safia Chatur, MD, of the University of Calgary (Alta.) and Sunjidatul Islam, MBBS, of the Canadian Vigour Centre, Edmonton, Alta., and associates analyzed 481,930 pregnancies occurring during 2005-2014 in the province.

Study results, reported in the Journal of the American Heart Association, showed that syncope occurred in almost 1% of pregnancies (9.7 episodes per 1,000 pregnancies) overall. Incidence increased by 5% per year during the study period.

Syncope episodes were distributed across the first trimester (32%), second trimester (44%), and third trimester (24%). Eight percent of pregnancies had more than one episode.

Compared with unaffected peers, women who experienced syncope were younger (age younger than 25 years, 35% vs. 21%; P less than .001) and more often primiparous (52% vs. 42%; P less than .001).

The rate of preterm birth was 18%, 16%, and 14% in pregnancies with an initial syncope episode during the first, second, and third trimester, respectively, compared with 15% in pregnancies without syncope (P less than .01 across groups).

With a median follow-up of about 5 years, compared with peers of syncope-free pregnancies, children of pregnancies complicated by syncope had a higher incidence of congenital anomalies (3.1% vs. 2.6%; P = .023). Incidence was highest in pregnancies with multiple episodes of syncope (5% vs. 3%; P less than .01).

In adjusted analyses that accounted for multiple pregnancies in individual women, relative to counterparts with no syncope during pregnancy, women who experienced syncope during the first trimester had higher odds of giving birth preterm (odds ratio, 1.3; P = .001) and of having an infant small for gestational age (OR, 1.2; P = .04) or with congenital anomalies (OR, 1.4; P = .036). Women with multiple syncope episodes versus none were twice as likely to have offspring with congenital anomalies (OR, 2.0; P = .003).

Relative to peers who did not experience syncope in pregnancy, women who did had higher incidences of cardiac arrhythmias (0.8% vs. 0.2%; P less than .01) and syncope episodes (1.4% vs. 0.2%; P less than .01) in the first year after delivery.

“Our data suggest that syncope during pregnancy may not be a benign occurrence,” Dr. Chatur and associates said. “More detailed clinical data are needed to identify potential causes for the observed increase in syncope during pregnancy in our study.“Whether women who experience syncope during pregnancy may benefit from closer monitoring during the obstetric and postpartum periods requires further study,” they concluded.

The investigators disclosed no relevant conflicts of interest. This study was funded by a grant from the Cardiac Arrhythmia Network of Canada.

SOURCE: Chatur S et al. J Am Heart Assoc. 2019;8:e011608.

Women experiencing syncope during pregnancy and their offspring have elevated rates of adverse outcomes that may warrant closer follow-up, a retrospective population-based cohort study finds. Risks appeared highest with first-trimester syncope.

“There are very limited data on the frequency of fainting during pregnancy,” Padma Kaul, Ph.D., senior study author and professor of medicine at the University of Alberta, Edmonton, said in a statement. “In our study, fainting during pregnancy occurred in about 1%, or 10 per 1,000 pregnancies, but appears to be increasing by 5% each year.”

“Fainting during pregnancy has previously been thought to follow a relatively benign course,” Dr. Kaul said. “The findings of our study suggest that timing of fainting during pregnancy may be important. When the faint happens early during pregnancy or multiple times during pregnancy, it may be associated with both short- and long-term health issues for the baby and the mother.”

First authors Safia Chatur, MD, of the University of Calgary (Alta.) and Sunjidatul Islam, MBBS, of the Canadian Vigour Centre, Edmonton, Alta., and associates analyzed 481,930 pregnancies occurring during 2005-2014 in the province.

Study results, reported in the Journal of the American Heart Association, showed that syncope occurred in almost 1% of pregnancies (9.7 episodes per 1,000 pregnancies) overall. Incidence increased by 5% per year during the study period.

Syncope episodes were distributed across the first trimester (32%), second trimester (44%), and third trimester (24%). Eight percent of pregnancies had more than one episode.

Compared with unaffected peers, women who experienced syncope were younger (age younger than 25 years, 35% vs. 21%; P less than .001) and more often primiparous (52% vs. 42%; P less than .001).

The rate of preterm birth was 18%, 16%, and 14% in pregnancies with an initial syncope episode during the first, second, and third trimester, respectively, compared with 15% in pregnancies without syncope (P less than .01 across groups).

With a median follow-up of about 5 years, compared with peers of syncope-free pregnancies, children of pregnancies complicated by syncope had a higher incidence of congenital anomalies (3.1% vs. 2.6%; P = .023). Incidence was highest in pregnancies with multiple episodes of syncope (5% vs. 3%; P less than .01).

In adjusted analyses that accounted for multiple pregnancies in individual women, relative to counterparts with no syncope during pregnancy, women who experienced syncope during the first trimester had higher odds of giving birth preterm (odds ratio, 1.3; P = .001) and of having an infant small for gestational age (OR, 1.2; P = .04) or with congenital anomalies (OR, 1.4; P = .036). Women with multiple syncope episodes versus none were twice as likely to have offspring with congenital anomalies (OR, 2.0; P = .003).

Relative to peers who did not experience syncope in pregnancy, women who did had higher incidences of cardiac arrhythmias (0.8% vs. 0.2%; P less than .01) and syncope episodes (1.4% vs. 0.2%; P less than .01) in the first year after delivery.

“Our data suggest that syncope during pregnancy may not be a benign occurrence,” Dr. Chatur and associates said. “More detailed clinical data are needed to identify potential causes for the observed increase in syncope during pregnancy in our study.“Whether women who experience syncope during pregnancy may benefit from closer monitoring during the obstetric and postpartum periods requires further study,” they concluded.

The investigators disclosed no relevant conflicts of interest. This study was funded by a grant from the Cardiac Arrhythmia Network of Canada.

SOURCE: Chatur S et al. J Am Heart Assoc. 2019;8:e011608.

I previously shared my concerns about the compromises some physicians are making when they consent to practicing in a telemedicine arrangement in which the system’s technical limitations prevents them from obtaining information critical to making an accurate diagnosis. In the scenarios that I described, a physician would have great difficulty being a good steward of antibiotic usage if he were willing to make a diagnosis of otitis media or strep throat without access to tympanic membrane visualization or the results of a rapid strep test.

AJ_Watt/E+

In response to my observation, I received an email from Dr. Kenneth McConnochie, a name out of my deep past from when we were teammates in college. Now a professor of pediatrics at University of Rochester (N.Y.) Medical Center, Dr. McConnochie has studied telemedicine in primary care extensively. He has thought a lot about telemedicine and more specifically about how it relates to quality. As he pointed out to me, before we can start discussing quality, we must clear up the confusion engendered by the term “telemedicine.”

I suspect that like me, whenever you look at an article or study that has “telemedicine” in its title or headline, you are never sure what you’re going to be reading about. Is it going to be a discussion of telephone triaging in a suburban primary practice or will the article describe how a pediatric cardiologist in Anchorage can follow his little patients in the Aleutians via an audio/video hookup that provides him with the ability to auscultate and review electrocardiograms and radiographic images? Dr. McConnochie suggests that by using the broader term “connected care” for care that is delivered at a distance, and by clearly specifying different types or levels, we will be one big step closer to a more meaningful way to understand the usefulness of that care.

In the conceptual framework he proposes, level 1 is text-only care because it offers the physician the least capacity for the acquisition of (1) diagnostically relevant information and (2) interpersonal connection. Phone care can provide more and videoconferencing still more. Level 4 would be what Dr. McConnochie labels “information rich” care providing the most abundant capacity. Here, think of an arrangement in which someone at the patient’s end of the connection has been trained to use an electronic otoscope that can capture an image of the child’s tympanic membrane, an electronic stethoscope that can record heart and breath sounds, and a high resolution camera to capture images of the patient’s skin, throat, and eyes, then transmit them to the child’s electronic health record (EHR) in real time. Someone in the school or day care center where the child spends his day has been taught how to obtain and process a rapid strep test. The physician who has instant access to the child’s EHR can communicate “face to face” via teleconferencing with the day care providers and with the parent who is at work to discuss the diagnosis, treatment plan, and follow-up. If any of the parties feels the exchange of information is insufficiently robust, a traditional office visit can be arranged.

The challenge of assigning value to each level care still remains. Is the level 4 scenario I just described as valuable as a face to face traditional office visit? In some situations, it is likely to be more valuable than a visit with a physician in an urgent care clinic or emergency department who has never seen the patient and/or lacks access to the EHR because her computer doesn’t interface with the primary care physician’s EHR. It certainly may be more convenient for the family.

But who is going to assign value? A connected visit may be more efficient for the patient and the parent, but will it be more costly? And who is going to pay? Dr. McConnochie’s observations should be taken seriously by those folks who assign value and pay.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

I previously shared my concerns about the compromises some physicians are making when they consent to practicing in a telemedicine arrangement in which the system’s technical limitations prevents them from obtaining information critical to making an accurate diagnosis. In the scenarios that I described, a physician would have great difficulty being a good steward of antibiotic usage if he were willing to make a diagnosis of otitis media or strep throat without access to tympanic membrane visualization or the results of a rapid strep test.

AJ_Watt/E+

In response to my observation, I received an email from Dr. Kenneth McConnochie, a name out of my deep past from when we were teammates in college. Now a professor of pediatrics at University of Rochester (N.Y.) Medical Center, Dr. McConnochie has studied telemedicine in primary care extensively. He has thought a lot about telemedicine and more specifically about how it relates to quality. As he pointed out to me, before we can start discussing quality, we must clear up the confusion engendered by the term “telemedicine.”

I suspect that like me, whenever you look at an article or study that has “telemedicine” in its title or headline, you are never sure what you’re going to be reading about. Is it going to be a discussion of telephone triaging in a suburban primary practice or will the article describe how a pediatric cardiologist in Anchorage can follow his little patients in the Aleutians via an audio/video hookup that provides him with the ability to auscultate and review electrocardiograms and radiographic images? Dr. McConnochie suggests that by using the broader term “connected care” for care that is delivered at a distance, and by clearly specifying different types or levels, we will be one big step closer to a more meaningful way to understand the usefulness of that care.

In the conceptual framework he proposes, level 1 is text-only care because it offers the physician the least capacity for the acquisition of (1) diagnostically relevant information and (2) interpersonal connection. Phone care can provide more and videoconferencing still more. Level 4 would be what Dr. McConnochie labels “information rich” care providing the most abundant capacity. Here, think of an arrangement in which someone at the patient’s end of the connection has been trained to use an electronic otoscope that can capture an image of the child’s tympanic membrane, an electronic stethoscope that can record heart and breath sounds, and a high resolution camera to capture images of the patient’s skin, throat, and eyes, then transmit them to the child’s electronic health record (EHR) in real time. Someone in the school or day care center where the child spends his day has been taught how to obtain and process a rapid strep test. The physician who has instant access to the child’s EHR can communicate “face to face” via teleconferencing with the day care providers and with the parent who is at work to discuss the diagnosis, treatment plan, and follow-up. If any of the parties feels the exchange of information is insufficiently robust, a traditional office visit can be arranged.

The challenge of assigning value to each level care still remains. Is the level 4 scenario I just described as valuable as a face to face traditional office visit? In some situations, it is likely to be more valuable than a visit with a physician in an urgent care clinic or emergency department who has never seen the patient and/or lacks access to the EHR because her computer doesn’t interface with the primary care physician’s EHR. It certainly may be more convenient for the family.

But who is going to assign value? A connected visit may be more efficient for the patient and the parent, but will it be more costly? And who is going to pay? Dr. McConnochie’s observations should be taken seriously by those folks who assign value and pay.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

I previously shared my concerns about the compromises some physicians are making when they consent to practicing in a telemedicine arrangement in which the system’s technical limitations prevents them from obtaining information critical to making an accurate diagnosis. In the scenarios that I described, a physician would have great difficulty being a good steward of antibiotic usage if he were willing to make a diagnosis of otitis media or strep throat without access to tympanic membrane visualization or the results of a rapid strep test.

AJ_Watt/E+

In response to my observation, I received an email from Dr. Kenneth McConnochie, a name out of my deep past from when we were teammates in college. Now a professor of pediatrics at University of Rochester (N.Y.) Medical Center, Dr. McConnochie has studied telemedicine in primary care extensively. He has thought a lot about telemedicine and more specifically about how it relates to quality. As he pointed out to me, before we can start discussing quality, we must clear up the confusion engendered by the term “telemedicine.”

I suspect that like me, whenever you look at an article or study that has “telemedicine” in its title or headline, you are never sure what you’re going to be reading about. Is it going to be a discussion of telephone triaging in a suburban primary practice or will the article describe how a pediatric cardiologist in Anchorage can follow his little patients in the Aleutians via an audio/video hookup that provides him with the ability to auscultate and review electrocardiograms and radiographic images? Dr. McConnochie suggests that by using the broader term “connected care” for care that is delivered at a distance, and by clearly specifying different types or levels, we will be one big step closer to a more meaningful way to understand the usefulness of that care.

In the conceptual framework he proposes, level 1 is text-only care because it offers the physician the least capacity for the acquisition of (1) diagnostically relevant information and (2) interpersonal connection. Phone care can provide more and videoconferencing still more. Level 4 would be what Dr. McConnochie labels “information rich” care providing the most abundant capacity. Here, think of an arrangement in which someone at the patient’s end of the connection has been trained to use an electronic otoscope that can capture an image of the child’s tympanic membrane, an electronic stethoscope that can record heart and breath sounds, and a high resolution camera to capture images of the patient’s skin, throat, and eyes, then transmit them to the child’s electronic health record (EHR) in real time. Someone in the school or day care center where the child spends his day has been taught how to obtain and process a rapid strep test. The physician who has instant access to the child’s EHR can communicate “face to face” via teleconferencing with the day care providers and with the parent who is at work to discuss the diagnosis, treatment plan, and follow-up. If any of the parties feels the exchange of information is insufficiently robust, a traditional office visit can be arranged.

The challenge of assigning value to each level care still remains. Is the level 4 scenario I just described as valuable as a face to face traditional office visit? In some situations, it is likely to be more valuable than a visit with a physician in an urgent care clinic or emergency department who has never seen the patient and/or lacks access to the EHR because her computer doesn’t interface with the primary care physician’s EHR. It certainly may be more convenient for the family.

But who is going to assign value? A connected visit may be more efficient for the patient and the parent, but will it be more costly? And who is going to pay? Dr. McConnochie’s observations should be taken seriously by those folks who assign value and pay.

Dr. Wilkoff practiced primary care pediatrics in Brunswick, Maine for nearly 40 years. He has authored several books on behavioral pediatrics, including “How to Say No to Your Toddler.” Email him at pdnews@mdedge.com.

WASHINGTON – Implementing an alert on electronic medical records to reinforce a change in public policy appears to be having a positive effect on opioid prescriptions.

Gregory Twachtman/MDedge News

Researchers looked at prescribing patterns of doctors in the Penn Medicine health system, which straddles both the Philadelphia area and southern New Jersey, following the implementation of prescribing limits in New Jersey.

The law in question is a 5-day limit on new opioid prescriptions, which was passed in February 2017 and implemented in May 2017. Penn Medicine implemented an EMR alert in their New Jersey locations to alert physicians within the Penn Medicine system of the change in their state law 2 months after the law went into effect. Researchers looked at prescribing patterns before passage, during the transition between passage and the implementation of the EMR alert and following implementation of the EMR alert, as well as secondary outcomes such as rate of refills, telephone calls, and utilization.

“The implementation of the prescribing limit and EMR alert was associated with a decrease in the volume of opioids prescribed in acute prescriptions without changes in the rates of refills, telephone calls or utilization,” Margaret Lowenstein, MD, of the University of Pennsylvania, Philadelphia, said at the annual meeting of the Society of General Internal Medicine.

“This combination of the policy and the EMR alert may be an effective strategy to influence prescriber behavior,” she added.

Researchers compared outcomes before and after the implementation of the law in New Jersey, using prescribing patterns in Pennsylvania as the control. The cohort of patients was those with a new opioid prescription within Penn Medicine ambulatory nonteaching practices. It excluded specialties not represented in both states as well as patients with cancer, those in hospice and palliative care and those in treatment for opioid use disorder, since the law does not apply to those groups.

In New Jersey, there were 434 patients receiving new prescriptions in the 12 months prior to the implementation of the law, with 234 patients receiving new prescriptions in the 9 months after the EMR alert was implemented in New Jersey. In Pennsylvania, the cohort included 2,961 patients prior to the law going into effect and 1,677 after the EMR intervention went live in New Jersey.

For New Jersey, the morphine milligram equivalent (MME) per prescription was steady at about 350 during the period prior to the law’s implementation, but dropped to nearly 250 by the end of the postintervention period examined. In Pennsylvania, the prelaw implementation period had an MME per prescription a little higher than 200, which leveled off at around 200 during the postintervention period.

“In New Jersey, there is a significantly higher MME than in Pennsylvania and this difference persists in the transition period but what you see in the post period is a significantly greater decline in the MME per prescription in New Jersey as compared to the rate of change in Pa.,” Dr. Lowenstein said. “That difference was statistically significant.”

She said similar results were seen regarding the quantity of tablets prescribed. In New Jersey before the law’s passage, the number of tablets per prescription was close to 50, dropping down to about 35 post period. Pennsylvania saw a slight decrease from about 35 pills per prescription to about 33 during the same period.

No significant changes occurred in the other outcomes measured following implementation of the EMR alert.

Dr. Lowenstein noted that, because the transition period between the law going into effect and the implementation of the EMR alert was so short, whether the greater decreases in opioid prescriptions in New Jersey relative to Pennsylvania was because of the law alone, the EMR alert alone, or both changes is unclear.

Based on the limited amount of change in prescribing patterns during the transition period, it appears that the EMR intervention may be driving the change, “but we weren’t powered to make that determination,” she added.

Dr. Lowenstein and her colleagues reported no disclosures.

gtwachtman@mdedge.com

WASHINGTON – Implementing an alert on electronic medical records to reinforce a change in public policy appears to be having a positive effect on opioid prescriptions.

Gregory Twachtman/MDedge News

Researchers looked at prescribing patterns of doctors in the Penn Medicine health system, which straddles both the Philadelphia area and southern New Jersey, following the implementation of prescribing limits in New Jersey.

The law in question is a 5-day limit on new opioid prescriptions, which was passed in February 2017 and implemented in May 2017. Penn Medicine implemented an EMR alert in their New Jersey locations to alert physicians within the Penn Medicine system of the change in their state law 2 months after the law went into effect. Researchers looked at prescribing patterns before passage, during the transition between passage and the implementation of the EMR alert and following implementation of the EMR alert, as well as secondary outcomes such as rate of refills, telephone calls, and utilization.

“The implementation of the prescribing limit and EMR alert was associated with a decrease in the volume of opioids prescribed in acute prescriptions without changes in the rates of refills, telephone calls or utilization,” Margaret Lowenstein, MD, of the University of Pennsylvania, Philadelphia, said at the annual meeting of the Society of General Internal Medicine.

“This combination of the policy and the EMR alert may be an effective strategy to influence prescriber behavior,” she added.

Researchers compared outcomes before and after the implementation of the law in New Jersey, using prescribing patterns in Pennsylvania as the control. The cohort of patients was those with a new opioid prescription within Penn Medicine ambulatory nonteaching practices. It excluded specialties not represented in both states as well as patients with cancer, those in hospice and palliative care and those in treatment for opioid use disorder, since the law does not apply to those groups.

In New Jersey, there were 434 patients receiving new prescriptions in the 12 months prior to the implementation of the law, with 234 patients receiving new prescriptions in the 9 months after the EMR alert was implemented in New Jersey. In Pennsylvania, the cohort included 2,961 patients prior to the law going into effect and 1,677 after the EMR intervention went live in New Jersey.

For New Jersey, the morphine milligram equivalent (MME) per prescription was steady at about 350 during the period prior to the law’s implementation, but dropped to nearly 250 by the end of the postintervention period examined. In Pennsylvania, the prelaw implementation period had an MME per prescription a little higher than 200, which leveled off at around 200 during the postintervention period.

“In New Jersey, there is a significantly higher MME than in Pennsylvania and this difference persists in the transition period but what you see in the post period is a significantly greater decline in the MME per prescription in New Jersey as compared to the rate of change in Pa.,” Dr. Lowenstein said. “That difference was statistically significant.”

She said similar results were seen regarding the quantity of tablets prescribed. In New Jersey before the law’s passage, the number of tablets per prescription was close to 50, dropping down to about 35 post period. Pennsylvania saw a slight decrease from about 35 pills per prescription to about 33 during the same period.

No significant changes occurred in the other outcomes measured following implementation of the EMR alert.

Dr. Lowenstein noted that, because the transition period between the law going into effect and the implementation of the EMR alert was so short, whether the greater decreases in opioid prescriptions in New Jersey relative to Pennsylvania was because of the law alone, the EMR alert alone, or both changes is unclear.

Based on the limited amount of change in prescribing patterns during the transition period, it appears that the EMR intervention may be driving the change, “but we weren’t powered to make that determination,” she added.

Dr. Lowenstein and her colleagues reported no disclosures.

gtwachtman@mdedge.com

WASHINGTON – Implementing an alert on electronic medical records to reinforce a change in public policy appears to be having a positive effect on opioid prescriptions.

Gregory Twachtman/MDedge News

Researchers looked at prescribing patterns of doctors in the Penn Medicine health system, which straddles both the Philadelphia area and southern New Jersey, following the implementation of prescribing limits in New Jersey.

The law in question is a 5-day limit on new opioid prescriptions, which was passed in February 2017 and implemented in May 2017. Penn Medicine implemented an EMR alert in their New Jersey locations to alert physicians within the Penn Medicine system of the change in their state law 2 months after the law went into effect. Researchers looked at prescribing patterns before passage, during the transition between passage and the implementation of the EMR alert and following implementation of the EMR alert, as well as secondary outcomes such as rate of refills, telephone calls, and utilization.

“The implementation of the prescribing limit and EMR alert was associated with a decrease in the volume of opioids prescribed in acute prescriptions without changes in the rates of refills, telephone calls or utilization,” Margaret Lowenstein, MD, of the University of Pennsylvania, Philadelphia, said at the annual meeting of the Society of General Internal Medicine.

“This combination of the policy and the EMR alert may be an effective strategy to influence prescriber behavior,” she added.

Researchers compared outcomes before and after the implementation of the law in New Jersey, using prescribing patterns in Pennsylvania as the control. The cohort of patients was those with a new opioid prescription within Penn Medicine ambulatory nonteaching practices. It excluded specialties not represented in both states as well as patients with cancer, those in hospice and palliative care and those in treatment for opioid use disorder, since the law does not apply to those groups.

In New Jersey, there were 434 patients receiving new prescriptions in the 12 months prior to the implementation of the law, with 234 patients receiving new prescriptions in the 9 months after the EMR alert was implemented in New Jersey. In Pennsylvania, the cohort included 2,961 patients prior to the law going into effect and 1,677 after the EMR intervention went live in New Jersey.

For New Jersey, the morphine milligram equivalent (MME) per prescription was steady at about 350 during the period prior to the law’s implementation, but dropped to nearly 250 by the end of the postintervention period examined. In Pennsylvania, the prelaw implementation period had an MME per prescription a little higher than 200, which leveled off at around 200 during the postintervention period.

“In New Jersey, there is a significantly higher MME than in Pennsylvania and this difference persists in the transition period but what you see in the post period is a significantly greater decline in the MME per prescription in New Jersey as compared to the rate of change in Pa.,” Dr. Lowenstein said. “That difference was statistically significant.”

She said similar results were seen regarding the quantity of tablets prescribed. In New Jersey before the law’s passage, the number of tablets per prescription was close to 50, dropping down to about 35 post period. Pennsylvania saw a slight decrease from about 35 pills per prescription to about 33 during the same period.

No significant changes occurred in the other outcomes measured following implementation of the EMR alert.

Dr. Lowenstein noted that, because the transition period between the law going into effect and the implementation of the EMR alert was so short, whether the greater decreases in opioid prescriptions in New Jersey relative to Pennsylvania was because of the law alone, the EMR alert alone, or both changes is unclear.

Based on the limited amount of change in prescribing patterns during the transition period, it appears that the EMR intervention may be driving the change, “but we weren’t powered to make that determination,” she added.

Dr. Lowenstein and her colleagues reported no disclosures.

gtwachtman@mdedge.com

Kailah is a 13-year-old cisgender female with two working parents, two younger siblings, and a history of mild asthma and overweight who recently presented for a problem-focused visit related to increasing anxiety. An interview of Kailah and her parents led to a diagnosis of generalized anxiety disorder, and she was referred for cognitive-behavioral therapy (CBT) and started on a low-dose SSRI. She now presents 3 months later with decreased anxiety and is compliant with the SSRI and CBT. What next?

Positive psychology and psychiatry have emerged as scientific disciplines since Seligman et al.¹ charged the field of psychology with reclaiming its stake in helping everyday people to thrive, as well as cultivating strengths and talents at each level of society – individual, family, institutional, and beyond. This call to action revealed the shift over time from mental health care toward a focus only on mental illness. And study after study confirmed that being “not depressed,” “not anxious” and so on was not the same as flourishing.²

Returning to Kailah, from a mental-health-as-usual approach, your job may be done. Her symptoms have responded to first-line treatments. Perhaps you even tracked her symptoms with a freely available standardized assessment tool like the Screen for Child Anxiety Related Disorders (SCARED)³ and noted a significant drop in her generalized anxiety score. But how to be sure she is not just less anxious, but also experiencing well-being?

After a couple decades of research, the science of well-being has led to some consistent findings that can be translated into office practice with children and families. As with any new science, the first steps to building well-being are defining and measuring what we are talking about. I recommend the Flourishing Scale⁴ for its brevity, availability, and ease of use. It covers the domains included in Seligman’s formula for thriving: PERMA. This acronym represents a consolidation of the first decades of research on well-being, and stands for Positive Emotions, Engagement, (Positive) Relationships, Meaning, and Accomplishments. For a readable but deeper look at the science behind this, check out Seligman’s “Flourish.”⁵

With the Flourishing Scale total score as a starting point, the acronym PERMA itself can be a good rubric to guide assessment and treatment planning in the office. You can query each of the elements to understand a youth’s current status and areas for building strengths. What brings positive emotions? What activities bring a sense of harmonious engagement without self-consciousness or awareness of time (such as a flow state)? What supportive relationships exist? Where does the youth find meaning or purpose – connection to something larger than themselves (family, work, community, teams, religion, and so on)? And where does the youth derive a sense of competence or self-esteem – something they are good at (accomplishment)?

Your clinical recommendations can flow from this assessment discussion, melding the patient’s and family’s strengths and priorities with evidence-based interventions. “The Resilience Drive,” by Alexia Michiels,⁶ is a good source for the latter – each chapter has segments relating research to straightforward happiness practices. The Growing Happy card deck (available online) also has brief and usable recommendations suitable for many young people. You can use these during office visits, loan out cards, gift them to families, or recommend families purchase a deck.

Dr. Andrew J. Rosenfeld is an assistant professor in the departments of psychiatry and pediatrics at the University of Vermont Medical Center, Burlington. He said he has no relevant disclosures. Email him at pdnews@mdedge.com.

References

1. Am Psychol. 2000;55(1):5-14.

2. Am Psychol. 2007 Feb-Mar;62(2):95-108.

3. J Am Acad Child Adolesc Psychiatry. 1999 Oct;38(10):1230-6.

4. Soc Indic Res. 2009; 39:247-66.

5. “Flourish: A visionary new understanding of happiness and well-being” (New York: Free Press, 2011).

6. “The Resilience Drive” (Switzerland: Favre, 2017).

7. Am Psychol. 2005 Jul-Aug;60(5):410-21.

Kailah is a 13-year-old cisgender female with two working parents, two younger siblings, and a history of mild asthma and overweight who recently presented for a problem-focused visit related to increasing anxiety. An interview of Kailah and her parents led to a diagnosis of generalized anxiety disorder, and she was referred for cognitive-behavioral therapy (CBT) and started on a low-dose SSRI. She now presents 3 months later with decreased anxiety and is compliant with the SSRI and CBT. What next?

Positive psychology and psychiatry have emerged as scientific disciplines since Seligman et al.¹ charged the field of psychology with reclaiming its stake in helping everyday people to thrive, as well as cultivating strengths and talents at each level of society – individual, family, institutional, and beyond. This call to action revealed the shift over time from mental health care toward a focus only on mental illness. And study after study confirmed that being “not depressed,” “not anxious” and so on was not the same as flourishing.²

Returning to Kailah, from a mental-health-as-usual approach, your job may be done. Her symptoms have responded to first-line treatments. Perhaps you even tracked her symptoms with a freely available standardized assessment tool like the Screen for Child Anxiety Related Disorders (SCARED)³ and noted a significant drop in her generalized anxiety score. But how to be sure she is not just less anxious, but also experiencing well-being?

After a couple decades of research, the science of well-being has led to some consistent findings that can be translated into office practice with children and families. As with any new science, the first steps to building well-being are defining and measuring what we are talking about. I recommend the Flourishing Scale⁴ for its brevity, availability, and ease of use. It covers the domains included in Seligman’s formula for thriving: PERMA. This acronym represents a consolidation of the first decades of research on well-being, and stands for Positive Emotions, Engagement, (Positive) Relationships, Meaning, and Accomplishments. For a readable but deeper look at the science behind this, check out Seligman’s “Flourish.”⁵

With the Flourishing Scale total score as a starting point, the acronym PERMA itself can be a good rubric to guide assessment and treatment planning in the office. You can query each of the elements to understand a youth’s current status and areas for building strengths. What brings positive emotions? What activities bring a sense of harmonious engagement without self-consciousness or awareness of time (such as a flow state)? What supportive relationships exist? Where does the youth find meaning or purpose – connection to something larger than themselves (family, work, community, teams, religion, and so on)? And where does the youth derive a sense of competence or self-esteem – something they are good at (accomplishment)?

Your clinical recommendations can flow from this assessment discussion, melding the patient’s and family’s strengths and priorities with evidence-based interventions. “The Resilience Drive,” by Alexia Michiels,⁶ is a good source for the latter – each chapter has segments relating research to straightforward happiness practices. The Growing Happy card deck (available online) also has brief and usable recommendations suitable for many young people. You can use these during office visits, loan out cards, gift them to families, or recommend families purchase a deck.

Dr. Andrew J. Rosenfeld is an assistant professor in the departments of psychiatry and pediatrics at the University of Vermont Medical Center, Burlington. He said he has no relevant disclosures. Email him at pdnews@mdedge.com.

References

1. Am Psychol. 2000;55(1):5-14.

2. Am Psychol. 2007 Feb-Mar;62(2):95-108.

3. J Am Acad Child Adolesc Psychiatry. 1999 Oct;38(10):1230-6.

4. Soc Indic Res. 2009; 39:247-66.

5. “Flourish: A visionary new understanding of happiness and well-being” (New York: Free Press, 2011).

6. “The Resilience Drive” (Switzerland: Favre, 2017).

7. Am Psychol. 2005 Jul-Aug;60(5):410-21.

Kailah is a 13-year-old cisgender female with two working parents, two younger siblings, and a history of mild asthma and overweight who recently presented for a problem-focused visit related to increasing anxiety. An interview of Kailah and her parents led to a diagnosis of generalized anxiety disorder, and she was referred for cognitive-behavioral therapy (CBT) and started on a low-dose SSRI. She now presents 3 months later with decreased anxiety and is compliant with the SSRI and CBT. What next?

Positive psychology and psychiatry have emerged as scientific disciplines since Seligman et al.¹ charged the field of psychology with reclaiming its stake in helping everyday people to thrive, as well as cultivating strengths and talents at each level of society – individual, family, institutional, and beyond. This call to action revealed the shift over time from mental health care toward a focus only on mental illness. And study after study confirmed that being “not depressed,” “not anxious” and so on was not the same as flourishing.²

Returning to Kailah, from a mental-health-as-usual approach, your job may be done. Her symptoms have responded to first-line treatments. Perhaps you even tracked her symptoms with a freely available standardized assessment tool like the Screen for Child Anxiety Related Disorders (SCARED)³ and noted a significant drop in her generalized anxiety score. But how to be sure she is not just less anxious, but also experiencing well-being?

After a couple decades of research, the science of well-being has led to some consistent findings that can be translated into office practice with children and families. As with any new science, the first steps to building well-being are defining and measuring what we are talking about. I recommend the Flourishing Scale⁴ for its brevity, availability, and ease of use. It covers the domains included in Seligman’s formula for thriving: PERMA. This acronym represents a consolidation of the first decades of research on well-being, and stands for Positive Emotions, Engagement, (Positive) Relationships, Meaning, and Accomplishments. For a readable but deeper look at the science behind this, check out Seligman’s “Flourish.”⁵

With the Flourishing Scale total score as a starting point, the acronym PERMA itself can be a good rubric to guide assessment and treatment planning in the office. You can query each of the elements to understand a youth’s current status and areas for building strengths. What brings positive emotions? What activities bring a sense of harmonious engagement without self-consciousness or awareness of time (such as a flow state)? What supportive relationships exist? Where does the youth find meaning or purpose – connection to something larger than themselves (family, work, community, teams, religion, and so on)? And where does the youth derive a sense of competence or self-esteem – something they are good at (accomplishment)?

Your clinical recommendations can flow from this assessment discussion, melding the patient’s and family’s strengths and priorities with evidence-based interventions. “The Resilience Drive,” by Alexia Michiels,⁶ is a good source for the latter – each chapter has segments relating research to straightforward happiness practices. The Growing Happy card deck (available online) also has brief and usable recommendations suitable for many young people. You can use these during office visits, loan out cards, gift them to families, or recommend families purchase a deck.

Dr. Andrew J. Rosenfeld is an assistant professor in the departments of psychiatry and pediatrics at the University of Vermont Medical Center, Burlington. He said he has no relevant disclosures. Email him at pdnews@mdedge.com.

References

1. Am Psychol. 2000;55(1):5-14.

2. Am Psychol. 2007 Feb-Mar;62(2):95-108.

3. J Am Acad Child Adolesc Psychiatry. 1999 Oct;38(10):1230-6.

4. Soc Indic Res. 2009; 39:247-66.

5. “Flourish: A visionary new understanding of happiness and well-being” (New York: Free Press, 2011).

6. “The Resilience Drive” (Switzerland: Favre, 2017).

7. Am Psychol. 2005 Jul-Aug;60(5):410-21.

Children of parents with extensive exposure to prescription opioids appear to be nearly two times more likely to attempt suicide than children of control parents, according to an evaluation of a medical claims database from which a sample of more than 200,00 privately insured parents was evaluated.

StHelena/Getty Images

Based on data collected between the years 2010 and 2016, the study raises the possibility that rising rates of opioid prescriptions and rising rates of suicide in adolescents and children are linked, said David A. Brent, of the University of Pittsburgh, and associates.

The relationship was considered sufficiently strong that the authors recommended clinicians consider mental health screening of children whose parents are known to have had extensive opioid exposure.

Addressing both opioid use in parents and the mental health in their children “may help, at least in part, to reverse the current upward trend in mortality due to the twin epidemics of suicide and opioid overdose,” said Dr. Brent and associates, whose findings were published in JAMA Psychiatry.

From a pool of more than 1 million parents aged 30-50 years in the claims database, 121,306 parents with extensive opioid use – defined as receiving opioid prescriptions for more than 365 days between 2010 and 2016 – were matched with 121,306 controls in the same age range. Children aged 10-19 years in both groups were compared for suicide attempts.

Overall, the rate of prescription opioid use as defined for inclusion in this study was 5% in the target parent population evaluated in this claims database.

Of the 184,142 children with parents exposed to opioids, 678 (0.37%) attempted suicide versus 212 (0.14%) of the 148,395 children from the nonopioid group. Expressed as a rate per 10,000 person years, the figures were 11.7 and 5.9 for the opioid and nonopioid groups, respectively.

When translated into an odds ratio (OR), the increased risk of suicide was found to be almost twice as high (OR 1.99) among children with parents meeting the study criteria for prescription opioid use. The OR was only slightly reduced (OR 1.85) after adjustment for sex and age.

Suicide attempts overall were higher in daughters than sons and in older children (15 years of age or older) than younger (ages 10 to less than 15 years) whether or not parents were taking opioids, but the relative risk remained consistently higher across all these subgroups when comparing those whose parents were taking prescription opioids with those whose parents were not.

As in past studies, children were more likely to make a suicide attempt if they had a parent who had a history of attempting suicide. However, the authors reported a significantly elevated risk of a suicide attempt for children of prescription opioid users after adjustment for this factor as well as for child depression, parental depression, and parental substance use disorder (OR, 1.45).

The OR of a suicide attempt was not significantly higher for a suicide attempt among those children with both parents taking prescription opioids relative to opioid use in only one parent (OR 1.05).

Dr. Brent and associates acknowledged that these data do not confirm that the rising rate of prescription opioid use is linked to the recent parallel rise in suicide attempts among children. However, they did conclude that children of parents using opioid prescriptions are at risk and might be an appropriate target for suicide prevention.

“Recognition and treatment of patients with opioid use disorder, attendance to comorbid conditions in affected parents, and screening and appropriate referral of their children may help” address both major public health issues, they maintained.

The study was supported by a National Institutes of Health grant. Dr Brent reported receiving royalties from Guilford Press, eRT, and UpToDate. Dr. Gibbons has served as an expert witness in cases related to suicide involving pharmaceutical companies, such as Pfizer and GlaxoSmithKline.

SOURCE: Brent DA et al. JAMA Psychiatry. 2019 May 22 doi: 10.1001/jamapsychiatry.2019.0940.

Children of parents with extensive exposure to prescription opioids appear to be nearly two times more likely to attempt suicide than children of control parents, according to an evaluation of a medical claims database from which a sample of more than 200,00 privately insured parents was evaluated.

StHelena/Getty Images

Based on data collected between the years 2010 and 2016, the study raises the possibility that rising rates of opioid prescriptions and rising rates of suicide in adolescents and children are linked, said David A. Brent, of the University of Pittsburgh, and associates.

The relationship was considered sufficiently strong that the authors recommended clinicians consider mental health screening of children whose parents are known to have had extensive opioid exposure.

Addressing both opioid use in parents and the mental health in their children “may help, at least in part, to reverse the current upward trend in mortality due to the twin epidemics of suicide and opioid overdose,” said Dr. Brent and associates, whose findings were published in JAMA Psychiatry.

From a pool of more than 1 million parents aged 30-50 years in the claims database, 121,306 parents with extensive opioid use – defined as receiving opioid prescriptions for more than 365 days between 2010 and 2016 – were matched with 121,306 controls in the same age range. Children aged 10-19 years in both groups were compared for suicide attempts.

Overall, the rate of prescription opioid use as defined for inclusion in this study was 5% in the target parent population evaluated in this claims database.

Of the 184,142 children with parents exposed to opioids, 678 (0.37%) attempted suicide versus 212 (0.14%) of the 148,395 children from the nonopioid group. Expressed as a rate per 10,000 person years, the figures were 11.7 and 5.9 for the opioid and nonopioid groups, respectively.

When translated into an odds ratio (OR), the increased risk of suicide was found to be almost twice as high (OR 1.99) among children with parents meeting the study criteria for prescription opioid use. The OR was only slightly reduced (OR 1.85) after adjustment for sex and age.

Suicide attempts overall were higher in daughters than sons and in older children (15 years of age or older) than younger (ages 10 to less than 15 years) whether or not parents were taking opioids, but the relative risk remained consistently higher across all these subgroups when comparing those whose parents were taking prescription opioids with those whose parents were not.

As in past studies, children were more likely to make a suicide attempt if they had a parent who had a history of attempting suicide. However, the authors reported a significantly elevated risk of a suicide attempt for children of prescription opioid users after adjustment for this factor as well as for child depression, parental depression, and parental substance use disorder (OR, 1.45).

The OR of a suicide attempt was not significantly higher for a suicide attempt among those children with both parents taking prescription opioids relative to opioid use in only one parent (OR 1.05).

Dr. Brent and associates acknowledged that these data do not confirm that the rising rate of prescription opioid use is linked to the recent parallel rise in suicide attempts among children. However, they did conclude that children of parents using opioid prescriptions are at risk and might be an appropriate target for suicide prevention.

“Recognition and treatment of patients with opioid use disorder, attendance to comorbid conditions in affected parents, and screening and appropriate referral of their children may help” address both major public health issues, they maintained.

The study was supported by a National Institutes of Health grant. Dr Brent reported receiving royalties from Guilford Press, eRT, and UpToDate. Dr. Gibbons has served as an expert witness in cases related to suicide involving pharmaceutical companies, such as Pfizer and GlaxoSmithKline.

SOURCE: Brent DA et al. JAMA Psychiatry. 2019 May 22 doi: 10.1001/jamapsychiatry.2019.0940.

Children of parents with extensive exposure to prescription opioids appear to be nearly two times more likely to attempt suicide than children of control parents, according to an evaluation of a medical claims database from which a sample of more than 200,00 privately insured parents was evaluated.

StHelena/Getty Images

Based on data collected between the years 2010 and 2016, the study raises the possibility that rising rates of opioid prescriptions and rising rates of suicide in adolescents and children are linked, said David A. Brent, of the University of Pittsburgh, and associates.

The relationship was considered sufficiently strong that the authors recommended clinicians consider mental health screening of children whose parents are known to have had extensive opioid exposure.

Addressing both opioid use in parents and the mental health in their children “may help, at least in part, to reverse the current upward trend in mortality due to the twin epidemics of suicide and opioid overdose,” said Dr. Brent and associates, whose findings were published in JAMA Psychiatry.

From a pool of more than 1 million parents aged 30-50 years in the claims database, 121,306 parents with extensive opioid use – defined as receiving opioid prescriptions for more than 365 days between 2010 and 2016 – were matched with 121,306 controls in the same age range. Children aged 10-19 years in both groups were compared for suicide attempts.

Overall, the rate of prescription opioid use as defined for inclusion in this study was 5% in the target parent population evaluated in this claims database.

Of the 184,142 children with parents exposed to opioids, 678 (0.37%) attempted suicide versus 212 (0.14%) of the 148,395 children from the nonopioid group. Expressed as a rate per 10,000 person years, the figures were 11.7 and 5.9 for the opioid and nonopioid groups, respectively.

When translated into an odds ratio (OR), the increased risk of suicide was found to be almost twice as high (OR 1.99) among children with parents meeting the study criteria for prescription opioid use. The OR was only slightly reduced (OR 1.85) after adjustment for sex and age.

Suicide attempts overall were higher in daughters than sons and in older children (15 years of age or older) than younger (ages 10 to less than 15 years) whether or not parents were taking opioids, but the relative risk remained consistently higher across all these subgroups when comparing those whose parents were taking prescription opioids with those whose parents were not.

As in past studies, children were more likely to make a suicide attempt if they had a parent who had a history of attempting suicide. However, the authors reported a significantly elevated risk of a suicide attempt for children of prescription opioid users after adjustment for this factor as well as for child depression, parental depression, and parental substance use disorder (OR, 1.45).

The OR of a suicide attempt was not significantly higher for a suicide attempt among those children with both parents taking prescription opioids relative to opioid use in only one parent (OR 1.05).

Dr. Brent and associates acknowledged that these data do not confirm that the rising rate of prescription opioid use is linked to the recent parallel rise in suicide attempts among children. However, they did conclude that children of parents using opioid prescriptions are at risk and might be an appropriate target for suicide prevention.

“Recognition and treatment of patients with opioid use disorder, attendance to comorbid conditions in affected parents, and screening and appropriate referral of their children may help” address both major public health issues, they maintained.

The study was supported by a National Institutes of Health grant. Dr Brent reported receiving royalties from Guilford Press, eRT, and UpToDate. Dr. Gibbons has served as an expert witness in cases related to suicide involving pharmaceutical companies, such as Pfizer and GlaxoSmithKline.

SOURCE: Brent DA et al. JAMA Psychiatry. 2019 May 22 doi: 10.1001/jamapsychiatry.2019.0940.

Danish researchers have linked multiple factors to higher risk of first-time diabetic foot ulcers (DFUs) in patients with type 1 and type 2 diabetes, although some of the factors – older age, smoking, history of cardiovascular disease, and longer duration of diabetes – seem to indicate increased risk only in type 1 disease, according to the new study findings.

The authors suggest that since clinical information gathered from patients during routine follow-up visits often includes mention of the risk factors for first-time DFU, it could form the basis of a risk stratification process for first-time DFU that can be integrated into the electronic record system and easily incorporated into routine care.

DFU is a significant complication for both type 1 and type 2 diabetes, but no previous research has stratified the risk factors for first-time DFUs by type of diabetes, emphasized the study authors, led by Sine Hangaard, MSc, of Steno Diabetes Center Copenhagen.

For the new study, the researchers tracked 5,588 patients with type 1 diabetes and 7,113 with type 2, all of whom were treated at a hospital clinic in Denmark between 2001 and 2015. The authors noted that the patients with type 2 disease who were treated at the center were clinically more complicated and had a longer disease duration than average type 2 patients, whereas the patients with type 1 diabetes did not differ from average type 1 patients.

Several factors boosted the risk of first-time DFU in both types of disease, including high or low levels of albumin excretion, advanced diabetic retinopathy, limited or nonexistent vibration sense, symptoms of neuropathy, and absence of foot pulses per univariable regression (all P less than .01). The researchers linked the neuropathy and absences of foot pulses to especially high spikes in risk.

Female gender was protective for type 1 and type 2 disease (hazard ratios, 0.7 and 0.5, respectively; P = .0000). Various body mass index levels seemed to have no impact on risk.

Three factors that posed a higher risk for first-time DFU in type 1 disease, but not type 2, were: smoking (HR, 1.4 vs. no smoking, P = .0220), age of 60-79 years (HR, 1.7 vs. age 40-59; P = .0000), cardiovascular disease (HR, 2.2 vs. no cardiovascular disease; P = .0000), and diabetes duration of between 5 and 20 years (HR, 2.2 vs. less than 5 years; P = .0027) or 20 years or more (HR, 5.2 vs. less than 5 years; P = .0000).

The authors noted that “25% of all patients with diabetes develop DFU during their lifetime, and DFUs precede 80% of all lower leg amputations in patients with diabetes.” In addition, DFU often occurs in feet already compromised by neuropathy or peripheral vascular disease, and is therefore associated with greater risk for infection, poorer outcomes, recurrent ulceration, amputation, and increased mortality. These risks underscore the need for the earliest-possible identification of first-time DFU and timely adoption of effective, preventative strategies, they wrote.

The study was not funded. Several of the authors reported that they own shares in Novo Nordisk.

SOURCE: Hangaard S et al. Diabetes Res Clin Pract. 2019 Apr 18;151:177-86.

Danish researchers have linked multiple factors to higher risk of first-time diabetic foot ulcers (DFUs) in patients with type 1 and type 2 diabetes, although some of the factors – older age, smoking, history of cardiovascular disease, and longer duration of diabetes – seem to indicate increased risk only in type 1 disease, according to the new study findings.

The authors suggest that since clinical information gathered from patients during routine follow-up visits often includes mention of the risk factors for first-time DFU, it could form the basis of a risk stratification process for first-time DFU that can be integrated into the electronic record system and easily incorporated into routine care.

DFU is a significant complication for both type 1 and type 2 diabetes, but no previous research has stratified the risk factors for first-time DFUs by type of diabetes, emphasized the study authors, led by Sine Hangaard, MSc, of Steno Diabetes Center Copenhagen.

For the new study, the researchers tracked 5,588 patients with type 1 diabetes and 7,113 with type 2, all of whom were treated at a hospital clinic in Denmark between 2001 and 2015. The authors noted that the patients with type 2 disease who were treated at the center were clinically more complicated and had a longer disease duration than average type 2 patients, whereas the patients with type 1 diabetes did not differ from average type 1 patients.

Several factors boosted the risk of first-time DFU in both types of disease, including high or low levels of albumin excretion, advanced diabetic retinopathy, limited or nonexistent vibration sense, symptoms of neuropathy, and absence of foot pulses per univariable regression (all P less than .01). The researchers linked the neuropathy and absences of foot pulses to especially high spikes in risk.

Female gender was protective for type 1 and type 2 disease (hazard ratios, 0.7 and 0.5, respectively; P = .0000). Various body mass index levels seemed to have no impact on risk.

Three factors that posed a higher risk for first-time DFU in type 1 disease, but not type 2, were: smoking (HR, 1.4 vs. no smoking, P = .0220), age of 60-79 years (HR, 1.7 vs. age 40-59; P = .0000), cardiovascular disease (HR, 2.2 vs. no cardiovascular disease; P = .0000), and diabetes duration of between 5 and 20 years (HR, 2.2 vs. less than 5 years; P = .0027) or 20 years or more (HR, 5.2 vs. less than 5 years; P = .0000).

The authors noted that “25% of all patients with diabetes develop DFU during their lifetime, and DFUs precede 80% of all lower leg amputations in patients with diabetes.” In addition, DFU often occurs in feet already compromised by neuropathy or peripheral vascular disease, and is therefore associated with greater risk for infection, poorer outcomes, recurrent ulceration, amputation, and increased mortality. These risks underscore the need for the earliest-possible identification of first-time DFU and timely adoption of effective, preventative strategies, they wrote.

The study was not funded. Several of the authors reported that they own shares in Novo Nordisk.

SOURCE: Hangaard S et al. Diabetes Res Clin Pract. 2019 Apr 18;151:177-86.

Danish researchers have linked multiple factors to higher risk of first-time diabetic foot ulcers (DFUs) in patients with type 1 and type 2 diabetes, although some of the factors – older age, smoking, history of cardiovascular disease, and longer duration of diabetes – seem to indicate increased risk only in type 1 disease, according to the new study findings.

The authors suggest that since clinical information gathered from patients during routine follow-up visits often includes mention of the risk factors for first-time DFU, it could form the basis of a risk stratification process for first-time DFU that can be integrated into the electronic record system and easily incorporated into routine care.

DFU is a significant complication for both type 1 and type 2 diabetes, but no previous research has stratified the risk factors for first-time DFUs by type of diabetes, emphasized the study authors, led by Sine Hangaard, MSc, of Steno Diabetes Center Copenhagen.

For the new study, the researchers tracked 5,588 patients with type 1 diabetes and 7,113 with type 2, all of whom were treated at a hospital clinic in Denmark between 2001 and 2015. The authors noted that the patients with type 2 disease who were treated at the center were clinically more complicated and had a longer disease duration than average type 2 patients, whereas the patients with type 1 diabetes did not differ from average type 1 patients.

Several factors boosted the risk of first-time DFU in both types of disease, including high or low levels of albumin excretion, advanced diabetic retinopathy, limited or nonexistent vibration sense, symptoms of neuropathy, and absence of foot pulses per univariable regression (all P less than .01). The researchers linked the neuropathy and absences of foot pulses to especially high spikes in risk.

Female gender was protective for type 1 and type 2 disease (hazard ratios, 0.7 and 0.5, respectively; P = .0000). Various body mass index levels seemed to have no impact on risk.

Three factors that posed a higher risk for first-time DFU in type 1 disease, but not type 2, were: smoking (HR, 1.4 vs. no smoking, P = .0220), age of 60-79 years (HR, 1.7 vs. age 40-59; P = .0000), cardiovascular disease (HR, 2.2 vs. no cardiovascular disease; P = .0000), and diabetes duration of between 5 and 20 years (HR, 2.2 vs. less than 5 years; P = .0027) or 20 years or more (HR, 5.2 vs. less than 5 years; P = .0000).

The authors noted that “25% of all patients with diabetes develop DFU during their lifetime, and DFUs precede 80% of all lower leg amputations in patients with diabetes.” In addition, DFU often occurs in feet already compromised by neuropathy or peripheral vascular disease, and is therefore associated with greater risk for infection, poorer outcomes, recurrent ulceration, amputation, and increased mortality. These risks underscore the need for the earliest-possible identification of first-time DFU and timely adoption of effective, preventative strategies, they wrote.

The study was not funded. Several of the authors reported that they own shares in Novo Nordisk.

SOURCE: Hangaard S et al. Diabetes Res Clin Pract. 2019 Apr 18;151:177-86.

SAN FRANCISCO – The recent Food and Drug Administration approval of intranasal esketamine for treatment-resistant depression has prompted interest in using this class of drugs in other conditions, including obsessive-compulsive disorder.

“OCD is severe, and one in seven people with OCD will attempt suicide in their lifetime,” said Carolyn Rodriguez, MD, PhD, associate professor of psychiatry and behavioral sciences at Stanford (Calif.) University.

Dr. Rodriguez presented some of her research on the mechanism of action of ketamine and its potential benefits for OCD during a session at the annual meeting of the American Psychiatric Association.

OCD patients experience a lengthy delay between treatment initiation and clinical benefit, sometimes 2 to 3 months, and most don’t achieve complete symptom remission, according to Dr. Rodriguez. “To help patients, I wanted to look at therapies that could be rapid acting, and given the converging lines of evidence that glutamate may play a role as an excitatory chemical messenger that helps neurons communicate, I looked at ketamine, which blocks the glutamate receptor,” she said.

A small study published in 2013 by her group was the first randomized, clinical trial of ketamine in OCD. It included 15 adults who experienced near-constant obsessions. A single dose given over 40 minutes led to a dramatic decrease in intrusive thoughts. One week after the infusion, four of eight patients who received ketamine met the criteria for a treatment response (35% or more reduction in Yale-Brown Obsessive Compulsive Scale scores), compared with none of the seven patients in the placebo group.

Dr. Rodriguez is now preparing to conduct a new trial comparing ketamine with midazolam as an active placebo, with the intent of looking at the drug’s effects on the circuits involved in OCD. “We need a large study to see if this is something that can be replicated, and we don’t know how long the effects persist. We’re just at the tip of the iceberg with OCD. In depression, there are these large studies that have been replicated, and in OCD, at least for randomized studies, it’s just this one study (from 2013) and the one that we have coming,” Dr. Rodriguez said.

Given the severity of OCD, ketamine and esketamine have generated some excitement, especially as a bridge to other therapies, such as cognitive-behavioral therapy or selective serotonin reuptake inhibitors.

The FDA’s approval of esketamine in March further boosted interest, but Dr. Rodriguez cautions that more research needs to be done. There is also at least one potential twist to use of an inhaled version of the drug. Contamination OCD patients may be unwilling to use a spray. In fact, Dr. Rodriguez’s team had to cancel a study looking at an inhaled form of racemic ketamine in OCD because they couldn’t recruit enough subjects. “There are variants [in OCD], and that’s why it’s important to study all populations and not assume that depression studies will cover the whole spectrum of our patients,” she said.

Dr. Rodriguez has consulted for Epiodyne, Allergan, BlackThorn, and Rugen.

SAN FRANCISCO – The recent Food and Drug Administration approval of intranasal esketamine for treatment-resistant depression has prompted interest in using this class of drugs in other conditions, including obsessive-compulsive disorder.

“OCD is severe, and one in seven people with OCD will attempt suicide in their lifetime,” said Carolyn Rodriguez, MD, PhD, associate professor of psychiatry and behavioral sciences at Stanford (Calif.) University.

Dr. Rodriguez presented some of her research on the mechanism of action of ketamine and its potential benefits for OCD during a session at the annual meeting of the American Psychiatric Association.

OCD patients experience a lengthy delay between treatment initiation and clinical benefit, sometimes 2 to 3 months, and most don’t achieve complete symptom remission, according to Dr. Rodriguez. “To help patients, I wanted to look at therapies that could be rapid acting, and given the converging lines of evidence that glutamate may play a role as an excitatory chemical messenger that helps neurons communicate, I looked at ketamine, which blocks the glutamate receptor,” she said.

A small study published in 2013 by her group was the first randomized, clinical trial of ketamine in OCD. It included 15 adults who experienced near-constant obsessions. A single dose given over 40 minutes led to a dramatic decrease in intrusive thoughts. One week after the infusion, four of eight patients who received ketamine met the criteria for a treatment response (35% or more reduction in Yale-Brown Obsessive Compulsive Scale scores), compared with none of the seven patients in the placebo group.

Dr. Rodriguez is now preparing to conduct a new trial comparing ketamine with midazolam as an active placebo, with the intent of looking at the drug’s effects on the circuits involved in OCD. “We need a large study to see if this is something that can be replicated, and we don’t know how long the effects persist. We’re just at the tip of the iceberg with OCD. In depression, there are these large studies that have been replicated, and in OCD, at least for randomized studies, it’s just this one study (from 2013) and the one that we have coming,” Dr. Rodriguez said.

Given the severity of OCD, ketamine and esketamine have generated some excitement, especially as a bridge to other therapies, such as cognitive-behavioral therapy or selective serotonin reuptake inhibitors.

The FDA’s approval of esketamine in March further boosted interest, but Dr. Rodriguez cautions that more research needs to be done. There is also at least one potential twist to use of an inhaled version of the drug. Contamination OCD patients may be unwilling to use a spray. In fact, Dr. Rodriguez’s team had to cancel a study looking at an inhaled form of racemic ketamine in OCD because they couldn’t recruit enough subjects. “There are variants [in OCD], and that’s why it’s important to study all populations and not assume that depression studies will cover the whole spectrum of our patients,” she said.

Dr. Rodriguez has consulted for Epiodyne, Allergan, BlackThorn, and Rugen.

SAN FRANCISCO – The recent Food and Drug Administration approval of intranasal esketamine for treatment-resistant depression has prompted interest in using this class of drugs in other conditions, including obsessive-compulsive disorder.

“OCD is severe, and one in seven people with OCD will attempt suicide in their lifetime,” said Carolyn Rodriguez, MD, PhD, associate professor of psychiatry and behavioral sciences at Stanford (Calif.) University.

Dr. Rodriguez presented some of her research on the mechanism of action of ketamine and its potential benefits for OCD during a session at the annual meeting of the American Psychiatric Association.

OCD patients experience a lengthy delay between treatment initiation and clinical benefit, sometimes 2 to 3 months, and most don’t achieve complete symptom remission, according to Dr. Rodriguez. “To help patients, I wanted to look at therapies that could be rapid acting, and given the converging lines of evidence that glutamate may play a role as an excitatory chemical messenger that helps neurons communicate, I looked at ketamine, which blocks the glutamate receptor,” she said.

A small study published in 2013 by her group was the first randomized, clinical trial of ketamine in OCD. It included 15 adults who experienced near-constant obsessions. A single dose given over 40 minutes led to a dramatic decrease in intrusive thoughts. One week after the infusion, four of eight patients who received ketamine met the criteria for a treatment response (35% or more reduction in Yale-Brown Obsessive Compulsive Scale scores), compared with none of the seven patients in the placebo group.

Dr. Rodriguez is now preparing to conduct a new trial comparing ketamine with midazolam as an active placebo, with the intent of looking at the drug’s effects on the circuits involved in OCD. “We need a large study to see if this is something that can be replicated, and we don’t know how long the effects persist. We’re just at the tip of the iceberg with OCD. In depression, there are these large studies that have been replicated, and in OCD, at least for randomized studies, it’s just this one study (from 2013) and the one that we have coming,” Dr. Rodriguez said.

Given the severity of OCD, ketamine and esketamine have generated some excitement, especially as a bridge to other therapies, such as cognitive-behavioral therapy or selective serotonin reuptake inhibitors.

The FDA’s approval of esketamine in March further boosted interest, but Dr. Rodriguez cautions that more research needs to be done. There is also at least one potential twist to use of an inhaled version of the drug. Contamination OCD patients may be unwilling to use a spray. In fact, Dr. Rodriguez’s team had to cancel a study looking at an inhaled form of racemic ketamine in OCD because they couldn’t recruit enough subjects. “There are variants [in OCD], and that’s why it’s important to study all populations and not assume that depression studies will cover the whole spectrum of our patients,” she said.

Dr. Rodriguez has consulted for Epiodyne, Allergan, BlackThorn, and Rugen.

LAS VEGAS – A novel protocol for acute management of patients in cardiogenic shock secondary to an acute MI that started hemodynamic support prior to coronary revascularization produced an unprecedented in-hospital survival rate of 72% in 171 patients treated at any of 35 U.S. centers.

The 72% acute survival compares with historical rates of roughly 50% starting with the landmark SHOCK trial from 1999 (N Engl J Med. 1999 Aug 26;341[9]:625-34) and continuing in much more recent reports (J Am Coll Cardiol. 2017 Jan 24;69[3]:278-87)

“This is a first step toward reducing the futility in treating a disease where management has not changed for more than 20 years,” Mir B. Basir, D.O., said at the annual scientific sessions of the Society for Cardiovascular Angiography and Interventions. While Dr. Basir acknowledged that the new protocol needs further testing, as well as further improvement, a need exists to immediately implement changes in the routine management of cardiogenic shock caused by an acute MI because “50% in-hospital survival is no longer acceptable,” said Dr. Basir, an interventional cardiologist at the Henry Ford Health System in Detroit.

The National Cardiogenic Shock Initiative operates as a single-arm study with no control group. The novel management protocol used by the Initiative in the current study included the following five key best-practice steps, Dr. Basir said in a video interview:

1. Begin hemodynamic support before increasing dosages of vasopressors or inotropes.

2. Use right-heart catheterization to monitor the patient’s hemodynamics, which shows the efficacy of the hemodynamic support and guides tapering down of vasopressor and inotrope drugs.

3. Apply hemodynamic support before starting percutaneous coronary intervention (PCI).

4. Act fast, with a goal of less than 90 minutes from door to hemodynamic support. In the 171 patients that Dr. Basir reviewed, the average door-to-support time was 85 minutes.

5. Mitigate complications from the devices and vascular access.

This protocol started at four hospitals in the Detroit region, and then expanded to the National Cardiogenic Shock Initiative that now includes 68 U.S. sites and more than 200 patients treated, with another 23 U.S. hospitals about to join. The 68 active sites include 26 academic centers and 42 community hospitals. The initiative has enrolled patients who match the enrollment criteria of the SHOCK trial so that historical comparisons are possible. The initiative’s patients would be classified as class C, D, or E patients based on the society’s newly published cardiogenic shock classification scheme (Catheter Cardiovasc Interv. 2019 May 19. doi: 10.1002/ccd.28329).

“The numbers that Dr. Basir has reported are very encouraging and provocative,” commented Chandanreddy M. Devireddy, MD, an interventional cardiologist at Emory Healthcare in Atlanta. “In light of the fact that we have had few solutions for these patients, this will accelerate the discussion.”

Several barriers exist for widespread adoption of the initiative’s protocol, Dr. Basir said. The protocol requires a lot of resources and the ability to deliver this care 24/7. Currently, hemodynamic support is “greatly underused,” and right-heart catheterization is not standard of care for these patients at many U.S. centers, he noted.

A few weeks before Dr. Basir’s report at the meeting, his data from the National Cardiogenic Shock Initiative appeared in an article published online (Catheter Cardiovasc Interv. 2019 Apr 25. doi: 10.1002/ccd.28307).

mzoler@mdedge.com

LAS VEGAS – A novel protocol for acute management of patients in cardiogenic shock secondary to an acute MI that started hemodynamic support prior to coronary revascularization produced an unprecedented in-hospital survival rate of 72% in 171 patients treated at any of 35 U.S. centers.

The 72% acute survival compares with historical rates of roughly 50% starting with the landmark SHOCK trial from 1999 (N Engl J Med. 1999 Aug 26;341[9]:625-34) and continuing in much more recent reports (J Am Coll Cardiol. 2017 Jan 24;69[3]:278-87)

“This is a first step toward reducing the futility in treating a disease where management has not changed for more than 20 years,” Mir B. Basir, D.O., said at the annual scientific sessions of the Society for Cardiovascular Angiography and Interventions. While Dr. Basir acknowledged that the new protocol needs further testing, as well as further improvement, a need exists to immediately implement changes in the routine management of cardiogenic shock caused by an acute MI because “50% in-hospital survival is no longer acceptable,” said Dr. Basir, an interventional cardiologist at the Henry Ford Health System in Detroit.

The National Cardiogenic Shock Initiative operates as a single-arm study with no control group. The novel management protocol used by the Initiative in the current study included the following five key best-practice steps, Dr. Basir said in a video interview:

1. Begin hemodynamic support before increasing dosages of vasopressors or inotropes.

2. Use right-heart catheterization to monitor the patient’s hemodynamics, which shows the efficacy of the hemodynamic support and guides tapering down of vasopressor and inotrope drugs.

3. Apply hemodynamic support before starting percutaneous coronary intervention (PCI).

4. Act fast, with a goal of less than 90 minutes from door to hemodynamic support. In the 171 patients that Dr. Basir reviewed, the average door-to-support time was 85 minutes.

5. Mitigate complications from the devices and vascular access.

This protocol started at four hospitals in the Detroit region, and then expanded to the National Cardiogenic Shock Initiative that now includes 68 U.S. sites and more than 200 patients treated, with another 23 U.S. hospitals about to join. The 68 active sites include 26 academic centers and 42 community hospitals. The initiative has enrolled patients who match the enrollment criteria of the SHOCK trial so that historical comparisons are possible. The initiative’s patients would be classified as class C, D, or E patients based on the society’s newly published cardiogenic shock classification scheme (Catheter Cardiovasc Interv. 2019 May 19. doi: 10.1002/ccd.28329).

“The numbers that Dr. Basir has reported are very encouraging and provocative,” commented Chandanreddy M. Devireddy, MD, an interventional cardiologist at Emory Healthcare in Atlanta. “In light of the fact that we have had few solutions for these patients, this will accelerate the discussion.”

Several barriers exist for widespread adoption of the initiative’s protocol, Dr. Basir said. The protocol requires a lot of resources and the ability to deliver this care 24/7. Currently, hemodynamic support is “greatly underused,” and right-heart catheterization is not standard of care for these patients at many U.S. centers, he noted.

A few weeks before Dr. Basir’s report at the meeting, his data from the National Cardiogenic Shock Initiative appeared in an article published online (Catheter Cardiovasc Interv. 2019 Apr 25. doi: 10.1002/ccd.28307).

mzoler@mdedge.com

LAS VEGAS – A novel protocol for acute management of patients in cardiogenic shock secondary to an acute MI that started hemodynamic support prior to coronary revascularization produced an unprecedented in-hospital survival rate of 72% in 171 patients treated at any of 35 U.S. centers.

The 72% acute survival compares with historical rates of roughly 50% starting with the landmark SHOCK trial from 1999 (N Engl J Med. 1999 Aug 26;341[9]:625-34) and continuing in much more recent reports (J Am Coll Cardiol. 2017 Jan 24;69[3]:278-87)

“This is a first step toward reducing the futility in treating a disease where management has not changed for more than 20 years,” Mir B. Basir, D.O., said at the annual scientific sessions of the Society for Cardiovascular Angiography and Interventions. While Dr. Basir acknowledged that the new protocol needs further testing, as well as further improvement, a need exists to immediately implement changes in the routine management of cardiogenic shock caused by an acute MI because “50% in-hospital survival is no longer acceptable,” said Dr. Basir, an interventional cardiologist at the Henry Ford Health System in Detroit.

The National Cardiogenic Shock Initiative operates as a single-arm study with no control group. The novel management protocol used by the Initiative in the current study included the following five key best-practice steps, Dr. Basir said in a video interview:

1. Begin hemodynamic support before increasing dosages of vasopressors or inotropes.

2. Use right-heart catheterization to monitor the patient’s hemodynamics, which shows the efficacy of the hemodynamic support and guides tapering down of vasopressor and inotrope drugs.

3. Apply hemodynamic support before starting percutaneous coronary intervention (PCI).

4. Act fast, with a goal of less than 90 minutes from door to hemodynamic support. In the 171 patients that Dr. Basir reviewed, the average door-to-support time was 85 minutes.

5. Mitigate complications from the devices and vascular access.

This protocol started at four hospitals in the Detroit region, and then expanded to the National Cardiogenic Shock Initiative that now includes 68 U.S. sites and more than 200 patients treated, with another 23 U.S. hospitals about to join. The 68 active sites include 26 academic centers and 42 community hospitals. The initiative has enrolled patients who match the enrollment criteria of the SHOCK trial so that historical comparisons are possible. The initiative’s patients would be classified as class C, D, or E patients based on the society’s newly published cardiogenic shock classification scheme (Catheter Cardiovasc Interv. 2019 May 19. doi: 10.1002/ccd.28329).

“The numbers that Dr. Basir has reported are very encouraging and provocative,” commented Chandanreddy M. Devireddy, MD, an interventional cardiologist at Emory Healthcare in Atlanta. “In light of the fact that we have had few solutions for these patients, this will accelerate the discussion.”

Several barriers exist for widespread adoption of the initiative’s protocol, Dr. Basir said. The protocol requires a lot of resources and the ability to deliver this care 24/7. Currently, hemodynamic support is “greatly underused,” and right-heart catheterization is not standard of care for these patients at many U.S. centers, he noted.

A few weeks before Dr. Basir’s report at the meeting, his data from the National Cardiogenic Shock Initiative appeared in an article published online (Catheter Cardiovasc Interv. 2019 Apr 25. doi: 10.1002/ccd.28307).

mzoler@mdedge.com