Pneumonia shot? Check. Flu shot? Got it.

What do asking about these two immunizations mean in a neurology history? Absolutely nothing, for most cases.

But that doesn’t stop me and other neurologists from asking about them. Why? Because they’re part of the Physician Quality Reporting System (PQRS) measures, of course! None of us want to be penalized by Medicare for failing to document them. Along with medications (Measure 130: drug, dose, and route of administration), counseling for women of childbearing potential with epilepsy (Measure 268), tobacco status (Measure 226), and blood pressure at visit (Measure 317).

My colleagues in orthopedics tell me they’re now documenting a female patient’s most recent mammogram for the same reasons. While it’s unlikely to affect why they need a new knee, it’s what they have to do to avoid penalties.

How much time does this take? About 30-60 seconds per Medicare patient in my practice. That’s not a huge amount of time, but when you see about 1,000 Medicare visits per year, that adds up to 8-16 hours spent on extraneous documentation.

Do I do it to improve patient care? No. Checking off boxes that have no relation to the case at hand makes no difference at all. I doubt you’ll find a practicing physician who believes otherwise. It simply comes down to playing by the rules, no matter how irrelevant they are.

That’s part of the problem in health care today. In documentation, quantity has replaced quality as a measure of care. The concise, pointed, summary has been eclipsed by long notes that document a large amount of unimportant data. Attaching the PQRS data (a 2-page form in my office) to the bill I submit, and noting it in my chart, only wastes time and paper.

Obviously, documenting blood pressure, tobacco status, and medications are important ... but I’ve always done those. I don’t know any neurologist who doesn’t check those things regularly, since they can directly affect our care.

But the rest is just fluff, which, sadly, seems to be more important these days than actually doing something to help the patient, at least in the eyes of Medicare.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Pneumonia shot? Check. Flu shot? Got it.

What do asking about these two immunizations mean in a neurology history? Absolutely nothing, for most cases.

But that doesn’t stop me and other neurologists from asking about them. Why? Because they’re part of the Physician Quality Reporting System (PQRS) measures, of course! None of us want to be penalized by Medicare for failing to document them. Along with medications (Measure 130: drug, dose, and route of administration), counseling for women of childbearing potential with epilepsy (Measure 268), tobacco status (Measure 226), and blood pressure at visit (Measure 317).

My colleagues in orthopedics tell me they’re now documenting a female patient’s most recent mammogram for the same reasons. While it’s unlikely to affect why they need a new knee, it’s what they have to do to avoid penalties.

How much time does this take? About 30-60 seconds per Medicare patient in my practice. That’s not a huge amount of time, but when you see about 1,000 Medicare visits per year, that adds up to 8-16 hours spent on extraneous documentation.

Do I do it to improve patient care? No. Checking off boxes that have no relation to the case at hand makes no difference at all. I doubt you’ll find a practicing physician who believes otherwise. It simply comes down to playing by the rules, no matter how irrelevant they are.

That’s part of the problem in health care today. In documentation, quantity has replaced quality as a measure of care. The concise, pointed, summary has been eclipsed by long notes that document a large amount of unimportant data. Attaching the PQRS data (a 2-page form in my office) to the bill I submit, and noting it in my chart, only wastes time and paper.

Obviously, documenting blood pressure, tobacco status, and medications are important ... but I’ve always done those. I don’t know any neurologist who doesn’t check those things regularly, since they can directly affect our care.

But the rest is just fluff, which, sadly, seems to be more important these days than actually doing something to help the patient, at least in the eyes of Medicare.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Pneumonia shot? Check. Flu shot? Got it.

What do asking about these two immunizations mean in a neurology history? Absolutely nothing, for most cases.

But that doesn’t stop me and other neurologists from asking about them. Why? Because they’re part of the Physician Quality Reporting System (PQRS) measures, of course! None of us want to be penalized by Medicare for failing to document them. Along with medications (Measure 130: drug, dose, and route of administration), counseling for women of childbearing potential with epilepsy (Measure 268), tobacco status (Measure 226), and blood pressure at visit (Measure 317).

My colleagues in orthopedics tell me they’re now documenting a female patient’s most recent mammogram for the same reasons. While it’s unlikely to affect why they need a new knee, it’s what they have to do to avoid penalties.

How much time does this take? About 30-60 seconds per Medicare patient in my practice. That’s not a huge amount of time, but when you see about 1,000 Medicare visits per year, that adds up to 8-16 hours spent on extraneous documentation.

Do I do it to improve patient care? No. Checking off boxes that have no relation to the case at hand makes no difference at all. I doubt you’ll find a practicing physician who believes otherwise. It simply comes down to playing by the rules, no matter how irrelevant they are.

That’s part of the problem in health care today. In documentation, quantity has replaced quality as a measure of care. The concise, pointed, summary has been eclipsed by long notes that document a large amount of unimportant data. Attaching the PQRS data (a 2-page form in my office) to the bill I submit, and noting it in my chart, only wastes time and paper.

Obviously, documenting blood pressure, tobacco status, and medications are important ... but I’ve always done those. I don’t know any neurologist who doesn’t check those things regularly, since they can directly affect our care.

But the rest is just fluff, which, sadly, seems to be more important these days than actually doing something to help the patient, at least in the eyes of Medicare.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

The mean income for ObGyns rose by 2% in 2014 over 2013 to $249,000, according to the 2015 Medscape Compensation Report.¹ This slight rise continues a gradual increase over the past few years ($242,000 in 2012; $220,000 in 2011).^1–4 The 2015 report took into account survey responses from 19,657 physicians across 26 specialties, 5% (982) of whom were ObGyns.

The highest earners among all physician specialties were orthopedists ($421,000), cardiologists, and gastroenterologists. The lowest earners were pediatricians, family physicians, endocrinologists, and internists ($196,000).  The highest ObGyn earners lived in the Northwest ($289,000) and Great Lakes ($268,000) regions; the lowest earners lived in the Mid-Atlantic ($230,000) and Northeast ($235,000) areas.¹

Survey findings
Career satisfaction for ObGyns is dipping
In 2011, 69%, 53%, and 48% of ObGyns indicated they would choose a career in medicine again, select the same specialty, and pick the same practice setting, respectively.⁴ In the 2015 survey, 67% of ObGyns reported that they would still choose medicine; however, only 40% would pick obstetrics and gynecology as their specialty, and only 22% would select the same practice setting.¹

Employment over private practice: Who feels best compensated?
Overall, 63% of all physicians are now employed, with only 23% reporting to be in private practice. Employment appears to be more popular for women: 59% of men and 72% of women responded that they work for a salary. Slightly more than a third (36%) of men and about a quarter (23%) of women are self-employed.⁵

The gender picture. Half of all ObGyns are women, and almost half of medical school graduates are women, yet male ObGyns continue to make more money than their female counterparts.^1,5,6 The 9% difference between compensation rates for self-employed male and female ObGyns ($265,000 vs $242,000, respectively) is less than the 14% difference between their employed colleagues ($266,000 vs $229,000, respectively).¹ Women tend to work shorter hours, fewer weeks, and see fewer patients than men, which could account for the lower compensation rate for female ObGyns. Studies suggest that greater schedule flexibility and fewer hours are key factors that improve satisfaction rates for female physicians.⁵

Male and female ObGyns tend to agree on their income satisfaction: less than half are satisfied (male, 44%; female, 46%). Many more employed ObGyns (55%) than self-employed ObGyns (31%) believe that they are fairly compensated.¹ 

Which practice settings pay better?
Compensation rates for ObGyns in 2015 are greatest for those in office-based multispecialty group practice ($280,000), followed by those who work in¹:

The lowest paid practice settings are office-based solo practices ($218,000) and hospital-employed ObGyns ($209,000).

In 2013, ObGyns who earned the most worked for health care organizations ($273,000); those who earned the least worked for outpatient clinics ($207,000).¹

Do you take insurance, Medicare, Medicaid?
More employed (82%) than self-employed (53%) ObGyns will continue to take new and current Medicare or Medicaid patients, which is a rise from data published in the 2014 report (employed, 72%; self-employed, 46%).¹

More than half (58%) of all physicians received less than $100 from private insurers for a new-patient office visit in 2014. Among ObGyns, 26% said they would drop insurers that pay poorly; 29% replied that they would not drop an insurer because they need all payers.¹

The rate of participation in Accountable Care Organizations (ACOs) has increased from 25% in 2013 to 35% in 2014, with 8% more expecting to join an ACO in 2015. Concierge practice (2%) and cash-only practice (5%) were reportedly not significant payment models for ObGyns in 2014.¹

Only 26% of ObGyns are planning to participate in health insurance exchanges; 23% said they are not participating, and 51% are not sure whether they will participate. Close to half (41%) of ObGyns believe their income will decrease because of health insurance exchanges, whereas 54% do not anticipate a change in income.¹

Do you offer ancillary services?
When asked, 11% of employed ObGyns and 28% of self-employed ObGyns revealed that they have offered new ancillary services within the past 3 years. These ancillary services can include mammography, bone density testing, ultrasound, in-house laboratory services, bioidentical hormone replacement therapy, and weight management.¹

How much time do you spend with patients?
In 2014, 62% of ObGyns reported spending 9 to 16 minutes with a patient during a visit. This is compared to 56% of family physicians and 44% of internists (TABLE).^1,5

More than one-half (52%) of ObGynsspend 30 to 45 hours per week seeing patients. Fewer (38%) spend more than 45 hours per week, and 9% spend less than 30 hours per week with patients. This decline may be due to the increasing proportion of women and older physicians who tend to work shorter hours and fewer weeks.¹

In the general physician population, 24% of women and 13% of men work part time, whereas 16% of both male and female ObGyns work part time. ObGyns aged 65 years or older constitute 35% of part-timers; 9% of those aged 35 to 49 years, and 11% of those aged 50 to 64 years, work part time. Only 2% of those younger than age 35 work part time.¹

What is most rewarding?
When given several choices to select as the most rewarding aspect of their jobs, more female ObGyns (47%) than males (41%) reported that their physician-patient relationships are the major source of satisfaction. More men (10%) than women (7%) cite that making good money at a job they like is most gratifying. Only 3% of men and 2% of women reported no reward to being an ObGyn.¹

Survey methodology
Medscape reports that the recruitment period for the 2015 Physician Compensation Report was from December 30, 2014, through March 11, 2015. Data were collected via a third-party online survey collection site. The margin of error for the survey was ±0.69%.¹

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

The mean income for ObGyns rose by 2% in 2014 over 2013 to $249,000, according to the 2015 Medscape Compensation Report.¹ This slight rise continues a gradual increase over the past few years ($242,000 in 2012; $220,000 in 2011).^1–4 The 2015 report took into account survey responses from 19,657 physicians across 26 specialties, 5% (982) of whom were ObGyns.

The highest earners among all physician specialties were orthopedists ($421,000), cardiologists, and gastroenterologists. The lowest earners were pediatricians, family physicians, endocrinologists, and internists ($196,000).  The highest ObGyn earners lived in the Northwest ($289,000) and Great Lakes ($268,000) regions; the lowest earners lived in the Mid-Atlantic ($230,000) and Northeast ($235,000) areas.¹

Survey findings
Career satisfaction for ObGyns is dipping
In 2011, 69%, 53%, and 48% of ObGyns indicated they would choose a career in medicine again, select the same specialty, and pick the same practice setting, respectively.⁴ In the 2015 survey, 67% of ObGyns reported that they would still choose medicine; however, only 40% would pick obstetrics and gynecology as their specialty, and only 22% would select the same practice setting.¹

Employment over private practice: Who feels best compensated?
Overall, 63% of all physicians are now employed, with only 23% reporting to be in private practice. Employment appears to be more popular for women: 59% of men and 72% of women responded that they work for a salary. Slightly more than a third (36%) of men and about a quarter (23%) of women are self-employed.⁵

The gender picture. Half of all ObGyns are women, and almost half of medical school graduates are women, yet male ObGyns continue to make more money than their female counterparts.^1,5,6 The 9% difference between compensation rates for self-employed male and female ObGyns ($265,000 vs $242,000, respectively) is less than the 14% difference between their employed colleagues ($266,000 vs $229,000, respectively).¹ Women tend to work shorter hours, fewer weeks, and see fewer patients than men, which could account for the lower compensation rate for female ObGyns. Studies suggest that greater schedule flexibility and fewer hours are key factors that improve satisfaction rates for female physicians.⁵

Male and female ObGyns tend to agree on their income satisfaction: less than half are satisfied (male, 44%; female, 46%). Many more employed ObGyns (55%) than self-employed ObGyns (31%) believe that they are fairly compensated.¹ 

Which practice settings pay better?
Compensation rates for ObGyns in 2015 are greatest for those in office-based multispecialty group practice ($280,000), followed by those who work in¹:

The lowest paid practice settings are office-based solo practices ($218,000) and hospital-employed ObGyns ($209,000).

In 2013, ObGyns who earned the most worked for health care organizations ($273,000); those who earned the least worked for outpatient clinics ($207,000).¹

Do you take insurance, Medicare, Medicaid?
More employed (82%) than self-employed (53%) ObGyns will continue to take new and current Medicare or Medicaid patients, which is a rise from data published in the 2014 report (employed, 72%; self-employed, 46%).¹

More than half (58%) of all physicians received less than $100 from private insurers for a new-patient office visit in 2014. Among ObGyns, 26% said they would drop insurers that pay poorly; 29% replied that they would not drop an insurer because they need all payers.¹

The rate of participation in Accountable Care Organizations (ACOs) has increased from 25% in 2013 to 35% in 2014, with 8% more expecting to join an ACO in 2015. Concierge practice (2%) and cash-only practice (5%) were reportedly not significant payment models for ObGyns in 2014.¹

Only 26% of ObGyns are planning to participate in health insurance exchanges; 23% said they are not participating, and 51% are not sure whether they will participate. Close to half (41%) of ObGyns believe their income will decrease because of health insurance exchanges, whereas 54% do not anticipate a change in income.¹

Do you offer ancillary services?
When asked, 11% of employed ObGyns and 28% of self-employed ObGyns revealed that they have offered new ancillary services within the past 3 years. These ancillary services can include mammography, bone density testing, ultrasound, in-house laboratory services, bioidentical hormone replacement therapy, and weight management.¹

How much time do you spend with patients?
In 2014, 62% of ObGyns reported spending 9 to 16 minutes with a patient during a visit. This is compared to 56% of family physicians and 44% of internists (TABLE).^1,5

More than one-half (52%) of ObGynsspend 30 to 45 hours per week seeing patients. Fewer (38%) spend more than 45 hours per week, and 9% spend less than 30 hours per week with patients. This decline may be due to the increasing proportion of women and older physicians who tend to work shorter hours and fewer weeks.¹

In the general physician population, 24% of women and 13% of men work part time, whereas 16% of both male and female ObGyns work part time. ObGyns aged 65 years or older constitute 35% of part-timers; 9% of those aged 35 to 49 years, and 11% of those aged 50 to 64 years, work part time. Only 2% of those younger than age 35 work part time.¹

What is most rewarding?
When given several choices to select as the most rewarding aspect of their jobs, more female ObGyns (47%) than males (41%) reported that their physician-patient relationships are the major source of satisfaction. More men (10%) than women (7%) cite that making good money at a job they like is most gratifying. Only 3% of men and 2% of women reported no reward to being an ObGyn.¹

Survey methodology
Medscape reports that the recruitment period for the 2015 Physician Compensation Report was from December 30, 2014, through March 11, 2015. Data were collected via a third-party online survey collection site. The margin of error for the survey was ±0.69%.¹

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

The mean income for ObGyns rose by 2% in 2014 over 2013 to $249,000, according to the 2015 Medscape Compensation Report.¹ This slight rise continues a gradual increase over the past few years ($242,000 in 2012; $220,000 in 2011).^1–4 The 2015 report took into account survey responses from 19,657 physicians across 26 specialties, 5% (982) of whom were ObGyns.

The highest earners among all physician specialties were orthopedists ($421,000), cardiologists, and gastroenterologists. The lowest earners were pediatricians, family physicians, endocrinologists, and internists ($196,000).  The highest ObGyn earners lived in the Northwest ($289,000) and Great Lakes ($268,000) regions; the lowest earners lived in the Mid-Atlantic ($230,000) and Northeast ($235,000) areas.¹

Survey findings
Career satisfaction for ObGyns is dipping
In 2011, 69%, 53%, and 48% of ObGyns indicated they would choose a career in medicine again, select the same specialty, and pick the same practice setting, respectively.⁴ In the 2015 survey, 67% of ObGyns reported that they would still choose medicine; however, only 40% would pick obstetrics and gynecology as their specialty, and only 22% would select the same practice setting.¹

Employment over private practice: Who feels best compensated?
Overall, 63% of all physicians are now employed, with only 23% reporting to be in private practice. Employment appears to be more popular for women: 59% of men and 72% of women responded that they work for a salary. Slightly more than a third (36%) of men and about a quarter (23%) of women are self-employed.⁵

The gender picture. Half of all ObGyns are women, and almost half of medical school graduates are women, yet male ObGyns continue to make more money than their female counterparts.^1,5,6 The 9% difference between compensation rates for self-employed male and female ObGyns ($265,000 vs $242,000, respectively) is less than the 14% difference between their employed colleagues ($266,000 vs $229,000, respectively).¹ Women tend to work shorter hours, fewer weeks, and see fewer patients than men, which could account for the lower compensation rate for female ObGyns. Studies suggest that greater schedule flexibility and fewer hours are key factors that improve satisfaction rates for female physicians.⁵

Male and female ObGyns tend to agree on their income satisfaction: less than half are satisfied (male, 44%; female, 46%). Many more employed ObGyns (55%) than self-employed ObGyns (31%) believe that they are fairly compensated.¹ 

Which practice settings pay better?
Compensation rates for ObGyns in 2015 are greatest for those in office-based multispecialty group practice ($280,000), followed by those who work in¹:

The lowest paid practice settings are office-based solo practices ($218,000) and hospital-employed ObGyns ($209,000).

In 2013, ObGyns who earned the most worked for health care organizations ($273,000); those who earned the least worked for outpatient clinics ($207,000).¹

Do you take insurance, Medicare, Medicaid?
More employed (82%) than self-employed (53%) ObGyns will continue to take new and current Medicare or Medicaid patients, which is a rise from data published in the 2014 report (employed, 72%; self-employed, 46%).¹

More than half (58%) of all physicians received less than $100 from private insurers for a new-patient office visit in 2014. Among ObGyns, 26% said they would drop insurers that pay poorly; 29% replied that they would not drop an insurer because they need all payers.¹

The rate of participation in Accountable Care Organizations (ACOs) has increased from 25% in 2013 to 35% in 2014, with 8% more expecting to join an ACO in 2015. Concierge practice (2%) and cash-only practice (5%) were reportedly not significant payment models for ObGyns in 2014.¹

Only 26% of ObGyns are planning to participate in health insurance exchanges; 23% said they are not participating, and 51% are not sure whether they will participate. Close to half (41%) of ObGyns believe their income will decrease because of health insurance exchanges, whereas 54% do not anticipate a change in income.¹

Do you offer ancillary services?
When asked, 11% of employed ObGyns and 28% of self-employed ObGyns revealed that they have offered new ancillary services within the past 3 years. These ancillary services can include mammography, bone density testing, ultrasound, in-house laboratory services, bioidentical hormone replacement therapy, and weight management.¹

How much time do you spend with patients?
In 2014, 62% of ObGyns reported spending 9 to 16 minutes with a patient during a visit. This is compared to 56% of family physicians and 44% of internists (TABLE).^1,5

More than one-half (52%) of ObGynsspend 30 to 45 hours per week seeing patients. Fewer (38%) spend more than 45 hours per week, and 9% spend less than 30 hours per week with patients. This decline may be due to the increasing proportion of women and older physicians who tend to work shorter hours and fewer weeks.¹

In the general physician population, 24% of women and 13% of men work part time, whereas 16% of both male and female ObGyns work part time. ObGyns aged 65 years or older constitute 35% of part-timers; 9% of those aged 35 to 49 years, and 11% of those aged 50 to 64 years, work part time. Only 2% of those younger than age 35 work part time.¹

What is most rewarding?
When given several choices to select as the most rewarding aspect of their jobs, more female ObGyns (47%) than males (41%) reported that their physician-patient relationships are the major source of satisfaction. More men (10%) than women (7%) cite that making good money at a job they like is most gratifying. Only 3% of men and 2% of women reported no reward to being an ObGyn.¹

Survey methodology
Medscape reports that the recruitment period for the 2015 Physician Compensation Report was from December 30, 2014, through March 11, 2015. Data were collected via a third-party online survey collection site. The margin of error for the survey was ±0.69%.¹

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

NEW YORK (Reuters Health) - Following a quality-improvement effort at the Boston Children's Hospital emergency department, the number of head CT scans for children with blunt head trauma has dropped without missing any significant injuries, researchers say.

"A combination of an evidence-based guideline and individual provider feedback was associated with a reduction in cranial CT rates," Dr. Lise Nigrovic from Boston Children's told Reuters Health by email. "Clinicians successfully identified all children with head injuries requiring acute intervention."

The evidence-based guideline was based on the PECARN TBI clinical prediction rules, Dr. Nigrovic and her colleagues explain in a report in Pediatrics, online June 22. Immediate CT is recommended for children with either a single high-risk or at least three of the other PECARN TBI predictors.

A period of observation before deciding on CT is recommended for children with one or two predictors, and no CT is recommended for children without PECARN TBI predictors.

The goal of individual provider feedback was to improve awareness, acceptance, adoption and adherence to head trauma guideline recommendations. Each fall, ED providers receive a confidential report of annual cranial CT rates for ED patients with minor blunt head trauma for the previous year. Providers also get information on median overall division CT rate for the previous year, with the goal of reducing variability between providers while further decreasing overall CT rate.

Dr. Nigrovic's team analyzed more than 6,800 ED visits for minor head injuries, of which 62% occurred after implementation of the initiative.

From a baseline head CT rate of 21%, they observed a significant reduction of 6 percentage points in cranial CT rate after initial guideline implementation, and an additional drop of 6 percentage points after initiation of individual provider feedback, the researchers report.

"No children discharged from the ED required admission within 72 hours of initial evaluation," they note.

"Importantly," they add, the decline in the head CT rate has been sustained for two years so far after implementation, "which supports the sustainability of the QI (quality improvement) interventions."

"We believe that these changes are generalizable," Dr. Nigrovic told Reuters Health. "In fact, we have described our QI intervention in detail to help with adoption by other centers."

The study had no commercial funding and the authors have disclosed no potential conflicts of interest.

—Reuters Health

NEW YORK (Reuters Health) - Following a quality-improvement effort at the Boston Children's Hospital emergency department, the number of head CT scans for children with blunt head trauma has dropped without missing any significant injuries, researchers say.

"A combination of an evidence-based guideline and individual provider feedback was associated with a reduction in cranial CT rates," Dr. Lise Nigrovic from Boston Children's told Reuters Health by email. "Clinicians successfully identified all children with head injuries requiring acute intervention."

The evidence-based guideline was based on the PECARN TBI clinical prediction rules, Dr. Nigrovic and her colleagues explain in a report in Pediatrics, online June 22. Immediate CT is recommended for children with either a single high-risk or at least three of the other PECARN TBI predictors.

A period of observation before deciding on CT is recommended for children with one or two predictors, and no CT is recommended for children without PECARN TBI predictors.

The goal of individual provider feedback was to improve awareness, acceptance, adoption and adherence to head trauma guideline recommendations. Each fall, ED providers receive a confidential report of annual cranial CT rates for ED patients with minor blunt head trauma for the previous year. Providers also get information on median overall division CT rate for the previous year, with the goal of reducing variability between providers while further decreasing overall CT rate.

Dr. Nigrovic's team analyzed more than 6,800 ED visits for minor head injuries, of which 62% occurred after implementation of the initiative.

From a baseline head CT rate of 21%, they observed a significant reduction of 6 percentage points in cranial CT rate after initial guideline implementation, and an additional drop of 6 percentage points after initiation of individual provider feedback, the researchers report.

"No children discharged from the ED required admission within 72 hours of initial evaluation," they note.

"Importantly," they add, the decline in the head CT rate has been sustained for two years so far after implementation, "which supports the sustainability of the QI (quality improvement) interventions."

"We believe that these changes are generalizable," Dr. Nigrovic told Reuters Health. "In fact, we have described our QI intervention in detail to help with adoption by other centers."

The study had no commercial funding and the authors have disclosed no potential conflicts of interest.

—Reuters Health

NEW YORK (Reuters Health) - Following a quality-improvement effort at the Boston Children's Hospital emergency department, the number of head CT scans for children with blunt head trauma has dropped without missing any significant injuries, researchers say.

"A combination of an evidence-based guideline and individual provider feedback was associated with a reduction in cranial CT rates," Dr. Lise Nigrovic from Boston Children's told Reuters Health by email. "Clinicians successfully identified all children with head injuries requiring acute intervention."

The evidence-based guideline was based on the PECARN TBI clinical prediction rules, Dr. Nigrovic and her colleagues explain in a report in Pediatrics, online June 22. Immediate CT is recommended for children with either a single high-risk or at least three of the other PECARN TBI predictors.

A period of observation before deciding on CT is recommended for children with one or two predictors, and no CT is recommended for children without PECARN TBI predictors.

The goal of individual provider feedback was to improve awareness, acceptance, adoption and adherence to head trauma guideline recommendations. Each fall, ED providers receive a confidential report of annual cranial CT rates for ED patients with minor blunt head trauma for the previous year. Providers also get information on median overall division CT rate for the previous year, with the goal of reducing variability between providers while further decreasing overall CT rate.

Dr. Nigrovic's team analyzed more than 6,800 ED visits for minor head injuries, of which 62% occurred after implementation of the initiative.

From a baseline head CT rate of 21%, they observed a significant reduction of 6 percentage points in cranial CT rate after initial guideline implementation, and an additional drop of 6 percentage points after initiation of individual provider feedback, the researchers report.

"No children discharged from the ED required admission within 72 hours of initial evaluation," they note.

"Importantly," they add, the decline in the head CT rate has been sustained for two years so far after implementation, "which supports the sustainability of the QI (quality improvement) interventions."

"We believe that these changes are generalizable," Dr. Nigrovic told Reuters Health. "In fact, we have described our QI intervention in detail to help with adoption by other centers."

The study had no commercial funding and the authors have disclosed no potential conflicts of interest.

—Reuters Health

Patient receives chemotherapy

Photo by Rhoda Baer

LUGANO—Long-awaited results of the Intergroup H10 trial in PET-positive Hodgkin lymphoma (HL) patients have shown that intensifying chemotherapy significantly increases 5-year progression-free survival (PFS) and produces a non-significant increase in overall survival (OS).

Switching patients who are PET-positive after 2 cycles of ABVD to escalated BEACOPP and involved-node radiotherapy increased 5-year PFS to 91% and 5-year OS to 96%.

The trial was a cooperative effort of the European Organisation for Research and Treatment of Cancer (EORTC), Lymphoma Study Association (LYSA), and Fondazione Italiana Linfomi (FIL).

The investigators already knew that early FDG-PET scans have prognostic impact. Patients with a negative PET scan after 2 cycles of chemotherapy have very good outcomes, while those with PET-positive interim scans have poor outcomes.

So the team designed the H10 trial to learn whether they could reduce long-term toxicity in the majority of patients and improve outcomes in the unfavorable subgroups.

Results of the primary endpoint—whether chemotherapy alone is as effective as, but less toxic than, combined-modality treatment in PET-negative patients after 2 cycles of ABVD—were published in the Journal of Clinical Oncology.

The secondary endpoint was an improvement in PFS with an early change from ABVD to escalated BEACOPP in stage I or II HL patients who are PET-positive after 2 cycles of ABVD.

John M. M. Raemaekers, MD, PhD, of Radboud University Medical Center in The Netherlands, presented details on the trial’s secondary endpoint at the 13th International Congress on Malignant Lymphoma (no abstract available).

H10 trial design

The investigators enrolled patients with favorable and unfavorable prognostic characteristics.

Unfavorable characteristics consisted of age 50 or older, more than 3 nodal areas, mediastinal-to-thorax ratio of 0.35 or higher, erythrocyte sedimentation rate of 50 mm or greater without B symptoms, or erythrocyte sedimentation rate of 30 mm or greater with B symptoms.

In the standard treatment arm, patients with favorable or unfavorable characteristics were treated similarly. After 2 cycles of ABVD, a PET scan was performed, and, irrespective of the result, patients received combined-modality treatment of ABVD followed by involved-node radiotherapy.

In the experimental arm, patients who were PET-negative had chemotherapy alone without involved-node radiotherapy. PET-negative patients were not discussed further in this presentation.

For the PET-positive patients in the experimental arm, the treatment for those with favorable and unfavorable characteristics was identical.

Patients who were PET-positive after 2 cycles were switched to 2 escalated BEACOPP cycles plus involved-node radiotherapy. Patients were considered PET-positive if they had a Deauville score of 3, 4, or 5.

Randomization

The first patient was enrolled in November 2006 and the last in June 2011. Investigators randomized 1950 patients, 754 with favorable and 1196 with unfavorable characteristics. All patients had untreated, supradiaphragmatic, clinical stage I or II HL.

Nine hundred fifty-four patients were enrolled in the standard arm, 371 with favorable characteristics and 583 with unfavorable. Nine hundred seventy-one patients entered the experimental arm, 376 with favorable and 595 with unfavorable characteristics.

Twenty-five patients were excluded because they did not complete the first 2 cycles of ABVD or did not have a PET scan.

After 2 cycles of ABVD, 361 patients were PET-positive, 192 in the ABVD arm (54 favorable, 138 unfavorable), and 169 in the escalated BEACOPP arm (43 favorable, 126 unfavorable).

The median age was 30 years in both arms (range, 15 to 70), and the investigators followed patients for a median of 4.5 years.

Results

The only grade 3-4 toxicities were hematologic events and infection.

“As expected, the neutropenia, thrombocytopenia, and anemia, grade 3-4, were more frequent in the experimental BEACOPP arm,” Dr Raemaekers said.

The incidence of grade 3-4 neutropenia was 30.3% (ABVD) and 53.5% (BEACOPP), thrombocytopenia was 0% (ABVD) and 19.7% (BEACOPP), and anemia was 0% (ABVD) and 4.9% (BEACOPP).

The incidence of grade 3-4 febrile neutropenia was 1.1% (ABVD) and 23.9% (BEACOPP), and infection without neutropenia was 1.1% (ABVD) and 11.2% (BEACOPP).

Progression or relapse occurred in 18.8% of patients in the ABVD arm and 7.7% in the BEACOPP arm.

There were 18 deaths in the ABVD arm and 7 deaths in the BEACOPP arm. Eleven deaths in the ABVD arm and 3 in the BEACOPP arm were due to progressive disease or relapse.

The investigators also tallied up the number of patients who progressed, relapsed, or died, whichever occurred first. Forty-one patients in the ABVD arm fulfilled one of these criteria, compared to 16 in the BEACOPP arm.

“Progression and relapse had to be established by conventional restaging, including physical exam, chest X-ray, and CT scan,” Dr Raemaekers pointed out. “And it was based on any new lesion or increase by 50% or more in size of previously involved sites.”

Patients in the BEACOPP arm experienced a significantly better PFS than the ABVD arm, with a hazard ratio of 0.42 (P=0.002). The 5-year PFS was 91% in the BEACOPP arm and 77% in the ABVD arm.

The 5-year OS was 89% in the ABVD arm and 96% in the BEACOPP arm, a difference that was not statistically significant.

“But [the trial] was also not powered for overall survival,” Dr Raemaekers said. “[T]here is a hint, at least, that, even in overall survival, the BEACOPP arm is superior to the ABVD arm.”

Based on these findings, the investigators concluded that, despite increased toxicity, physicians should consider intensifying chemotherapy in early PET-positive patients with stage I/II HL in the combined-modality setting.

Patient receives chemotherapy

Photo by Rhoda Baer

LUGANO—Long-awaited results of the Intergroup H10 trial in PET-positive Hodgkin lymphoma (HL) patients have shown that intensifying chemotherapy significantly increases 5-year progression-free survival (PFS) and produces a non-significant increase in overall survival (OS).

Switching patients who are PET-positive after 2 cycles of ABVD to escalated BEACOPP and involved-node radiotherapy increased 5-year PFS to 91% and 5-year OS to 96%.

The trial was a cooperative effort of the European Organisation for Research and Treatment of Cancer (EORTC), Lymphoma Study Association (LYSA), and Fondazione Italiana Linfomi (FIL).

The investigators already knew that early FDG-PET scans have prognostic impact. Patients with a negative PET scan after 2 cycles of chemotherapy have very good outcomes, while those with PET-positive interim scans have poor outcomes.

So the team designed the H10 trial to learn whether they could reduce long-term toxicity in the majority of patients and improve outcomes in the unfavorable subgroups.

Results of the primary endpoint—whether chemotherapy alone is as effective as, but less toxic than, combined-modality treatment in PET-negative patients after 2 cycles of ABVD—were published in the Journal of Clinical Oncology.

The secondary endpoint was an improvement in PFS with an early change from ABVD to escalated BEACOPP in stage I or II HL patients who are PET-positive after 2 cycles of ABVD.

John M. M. Raemaekers, MD, PhD, of Radboud University Medical Center in The Netherlands, presented details on the trial’s secondary endpoint at the 13th International Congress on Malignant Lymphoma (no abstract available).

H10 trial design

The investigators enrolled patients with favorable and unfavorable prognostic characteristics.

Unfavorable characteristics consisted of age 50 or older, more than 3 nodal areas, mediastinal-to-thorax ratio of 0.35 or higher, erythrocyte sedimentation rate of 50 mm or greater without B symptoms, or erythrocyte sedimentation rate of 30 mm or greater with B symptoms.

In the standard treatment arm, patients with favorable or unfavorable characteristics were treated similarly. After 2 cycles of ABVD, a PET scan was performed, and, irrespective of the result, patients received combined-modality treatment of ABVD followed by involved-node radiotherapy.

In the experimental arm, patients who were PET-negative had chemotherapy alone without involved-node radiotherapy. PET-negative patients were not discussed further in this presentation.

For the PET-positive patients in the experimental arm, the treatment for those with favorable and unfavorable characteristics was identical.

Patients who were PET-positive after 2 cycles were switched to 2 escalated BEACOPP cycles plus involved-node radiotherapy. Patients were considered PET-positive if they had a Deauville score of 3, 4, or 5.

Randomization

The first patient was enrolled in November 2006 and the last in June 2011. Investigators randomized 1950 patients, 754 with favorable and 1196 with unfavorable characteristics. All patients had untreated, supradiaphragmatic, clinical stage I or II HL.

Nine hundred fifty-four patients were enrolled in the standard arm, 371 with favorable characteristics and 583 with unfavorable. Nine hundred seventy-one patients entered the experimental arm, 376 with favorable and 595 with unfavorable characteristics.

Twenty-five patients were excluded because they did not complete the first 2 cycles of ABVD or did not have a PET scan.

After 2 cycles of ABVD, 361 patients were PET-positive, 192 in the ABVD arm (54 favorable, 138 unfavorable), and 169 in the escalated BEACOPP arm (43 favorable, 126 unfavorable).

The median age was 30 years in both arms (range, 15 to 70), and the investigators followed patients for a median of 4.5 years.

Results

The only grade 3-4 toxicities were hematologic events and infection.

“As expected, the neutropenia, thrombocytopenia, and anemia, grade 3-4, were more frequent in the experimental BEACOPP arm,” Dr Raemaekers said.

The incidence of grade 3-4 neutropenia was 30.3% (ABVD) and 53.5% (BEACOPP), thrombocytopenia was 0% (ABVD) and 19.7% (BEACOPP), and anemia was 0% (ABVD) and 4.9% (BEACOPP).

The incidence of grade 3-4 febrile neutropenia was 1.1% (ABVD) and 23.9% (BEACOPP), and infection without neutropenia was 1.1% (ABVD) and 11.2% (BEACOPP).

Progression or relapse occurred in 18.8% of patients in the ABVD arm and 7.7% in the BEACOPP arm.

There were 18 deaths in the ABVD arm and 7 deaths in the BEACOPP arm. Eleven deaths in the ABVD arm and 3 in the BEACOPP arm were due to progressive disease or relapse.

The investigators also tallied up the number of patients who progressed, relapsed, or died, whichever occurred first. Forty-one patients in the ABVD arm fulfilled one of these criteria, compared to 16 in the BEACOPP arm.

“Progression and relapse had to be established by conventional restaging, including physical exam, chest X-ray, and CT scan,” Dr Raemaekers pointed out. “And it was based on any new lesion or increase by 50% or more in size of previously involved sites.”

Patients in the BEACOPP arm experienced a significantly better PFS than the ABVD arm, with a hazard ratio of 0.42 (P=0.002). The 5-year PFS was 91% in the BEACOPP arm and 77% in the ABVD arm.

The 5-year OS was 89% in the ABVD arm and 96% in the BEACOPP arm, a difference that was not statistically significant.

“But [the trial] was also not powered for overall survival,” Dr Raemaekers said. “[T]here is a hint, at least, that, even in overall survival, the BEACOPP arm is superior to the ABVD arm.”

Based on these findings, the investigators concluded that, despite increased toxicity, physicians should consider intensifying chemotherapy in early PET-positive patients with stage I/II HL in the combined-modality setting.

Patient receives chemotherapy

Photo by Rhoda Baer

LUGANO—Long-awaited results of the Intergroup H10 trial in PET-positive Hodgkin lymphoma (HL) patients have shown that intensifying chemotherapy significantly increases 5-year progression-free survival (PFS) and produces a non-significant increase in overall survival (OS).

Switching patients who are PET-positive after 2 cycles of ABVD to escalated BEACOPP and involved-node radiotherapy increased 5-year PFS to 91% and 5-year OS to 96%.

The trial was a cooperative effort of the European Organisation for Research and Treatment of Cancer (EORTC), Lymphoma Study Association (LYSA), and Fondazione Italiana Linfomi (FIL).

The investigators already knew that early FDG-PET scans have prognostic impact. Patients with a negative PET scan after 2 cycles of chemotherapy have very good outcomes, while those with PET-positive interim scans have poor outcomes.

So the team designed the H10 trial to learn whether they could reduce long-term toxicity in the majority of patients and improve outcomes in the unfavorable subgroups.

Results of the primary endpoint—whether chemotherapy alone is as effective as, but less toxic than, combined-modality treatment in PET-negative patients after 2 cycles of ABVD—were published in the Journal of Clinical Oncology.

The secondary endpoint was an improvement in PFS with an early change from ABVD to escalated BEACOPP in stage I or II HL patients who are PET-positive after 2 cycles of ABVD.

John M. M. Raemaekers, MD, PhD, of Radboud University Medical Center in The Netherlands, presented details on the trial’s secondary endpoint at the 13th International Congress on Malignant Lymphoma (no abstract available).

H10 trial design

The investigators enrolled patients with favorable and unfavorable prognostic characteristics.

Unfavorable characteristics consisted of age 50 or older, more than 3 nodal areas, mediastinal-to-thorax ratio of 0.35 or higher, erythrocyte sedimentation rate of 50 mm or greater without B symptoms, or erythrocyte sedimentation rate of 30 mm or greater with B symptoms.

In the standard treatment arm, patients with favorable or unfavorable characteristics were treated similarly. After 2 cycles of ABVD, a PET scan was performed, and, irrespective of the result, patients received combined-modality treatment of ABVD followed by involved-node radiotherapy.

In the experimental arm, patients who were PET-negative had chemotherapy alone without involved-node radiotherapy. PET-negative patients were not discussed further in this presentation.

For the PET-positive patients in the experimental arm, the treatment for those with favorable and unfavorable characteristics was identical.

Patients who were PET-positive after 2 cycles were switched to 2 escalated BEACOPP cycles plus involved-node radiotherapy. Patients were considered PET-positive if they had a Deauville score of 3, 4, or 5.

Randomization

The first patient was enrolled in November 2006 and the last in June 2011. Investigators randomized 1950 patients, 754 with favorable and 1196 with unfavorable characteristics. All patients had untreated, supradiaphragmatic, clinical stage I or II HL.

Nine hundred fifty-four patients were enrolled in the standard arm, 371 with favorable characteristics and 583 with unfavorable. Nine hundred seventy-one patients entered the experimental arm, 376 with favorable and 595 with unfavorable characteristics.

Twenty-five patients were excluded because they did not complete the first 2 cycles of ABVD or did not have a PET scan.

After 2 cycles of ABVD, 361 patients were PET-positive, 192 in the ABVD arm (54 favorable, 138 unfavorable), and 169 in the escalated BEACOPP arm (43 favorable, 126 unfavorable).

The median age was 30 years in both arms (range, 15 to 70), and the investigators followed patients for a median of 4.5 years.

Results

The only grade 3-4 toxicities were hematologic events and infection.

“As expected, the neutropenia, thrombocytopenia, and anemia, grade 3-4, were more frequent in the experimental BEACOPP arm,” Dr Raemaekers said.

The incidence of grade 3-4 neutropenia was 30.3% (ABVD) and 53.5% (BEACOPP), thrombocytopenia was 0% (ABVD) and 19.7% (BEACOPP), and anemia was 0% (ABVD) and 4.9% (BEACOPP).

The incidence of grade 3-4 febrile neutropenia was 1.1% (ABVD) and 23.9% (BEACOPP), and infection without neutropenia was 1.1% (ABVD) and 11.2% (BEACOPP).

Progression or relapse occurred in 18.8% of patients in the ABVD arm and 7.7% in the BEACOPP arm.

There were 18 deaths in the ABVD arm and 7 deaths in the BEACOPP arm. Eleven deaths in the ABVD arm and 3 in the BEACOPP arm were due to progressive disease or relapse.

The investigators also tallied up the number of patients who progressed, relapsed, or died, whichever occurred first. Forty-one patients in the ABVD arm fulfilled one of these criteria, compared to 16 in the BEACOPP arm.

“Progression and relapse had to be established by conventional restaging, including physical exam, chest X-ray, and CT scan,” Dr Raemaekers pointed out. “And it was based on any new lesion or increase by 50% or more in size of previously involved sites.”

Patients in the BEACOPP arm experienced a significantly better PFS than the ABVD arm, with a hazard ratio of 0.42 (P=0.002). The 5-year PFS was 91% in the BEACOPP arm and 77% in the ABVD arm.

The 5-year OS was 89% in the ABVD arm and 96% in the BEACOPP arm, a difference that was not statistically significant.

“But [the trial] was also not powered for overall survival,” Dr Raemaekers said. “[T]here is a hint, at least, that, even in overall survival, the BEACOPP arm is superior to the ABVD arm.”

Based on these findings, the investigators concluded that, despite increased toxicity, physicians should consider intensifying chemotherapy in early PET-positive patients with stage I/II HL in the combined-modality setting.

Who was responsible for excessive oxytocin doses? $18.2M verdict
Early in the morning, a woman at 40 weeks’ gestation presented to the hospital for induction of labor managed by her ObGyn. Labor was lengthy, and the mother was given increasing doses of 22, 24, and 26 mIU/min of oxytocin to stimulate labor. The baby was delivered in the evening. The child suffered a hypoxic birth injury and has cerebral palsy. 

Parents’ claim Excessive oxytocin was administered, causing uterine hyperstimulation and excessive contractions. Nurses failed to inform the ObGyn of an abnormal fetal heart rate during the afternoon.

Defendants’ defense The parties disputed the oxytocin orders. The ObGyn claimed she has a standing order against oxytocin doses over 20 mIU/min. The nurses claimed that the dosage was based on the ObGyn’s verbal orders, which the ObGyn denied. The ObGyn denied negligence and maintained that if she’d known of the oxytocin administration greater than 20 mIU/min and the abnormal fetal heart rate, she immediately would have called for cesarean delivery. The hospital denied negligence and maintained that the oxytocin was administered 10 hours before delivery and played no role in fetal distress.

Verdict At trial, the ObGyn did not call expert witnesses and, in closing arguments, the physician’s attorney asked for exoneration of the ObGyn and a finding of fault solely against the hospital. An $18.2 million Washington verdict was returned against the hospital.

What caused the child’s Erb’s palsy?
A mother presented to the hospital for induction of labor. Oxytocin was administered and the first stage of labor progressed normally. When the mother began pushing, the ObGyn noted a turtle sign at crowning and called for assistance. The ObGyn attempted to deliver the fetus with downward guidance of the fetal head but encountered shoulder dystocia and a nuchal cord. He unwrapped the cord and instructed the nursing staff to place the mother in the McRobert’s position to help dislodge the right shoulder. When  that did not work, the ObGyn performed a first-degree episiotomy and completed delivery. The child was found to have Erb’s palsy of the right arm. She underwent decompression and neurolysis of the brachial plexus using sural nerve grafts but still has reduced use of her right arm. 

Parents’ claim Shoulder dystocia was improperly managed, causing the brachial plexus injury.

Defendants’ defense The ObGyn and hospital system denied negligence. The child’s injury occurred in utero due to natural forces of the mother’s uterine contractions.

Verdict An Ohio defense verdict was returned.

Woman claims lack of proper consent
A 47-year-old woman underwent endometrial ablation performed by her ObGyn. During the procedure, the uterus was perforated and the ObGyn performed a hysterectomy. Six days later, the patient was found to have peritonitis and underwent bowel repair surgery. The patient developed untreatable bowel adhesions that cause chronic pain.

Patient’s claim There were less expensive and invasive alternatives to the ablation that the ObGyn did not offer. The patient claimed lack of informed consent for the ablation and hysterectomy and negligence in perforating the bowel. The ObGyn was also negligent in failing to recognize the perforation and to diagnose peritonitis in a timely manner. 

Texas state law requires consent for hysterectomies without documented evidence of immediate danger to life. Her husband did not have the authority to consent on her behalf. 

Physician’s defense The husband gave informed consent. Failure to recognize the perforation was not negligent; it is a known risk of the surgery. The patient’s care was transferred to another physician after the second postoperative day.

Verdict A $200,000 Texas settlement was reached. 

Bowel obstruction in pregnant woman
A 29-year-old woman at 27 weeks’ gestation had abdominal pain. She went to a community hospital where a hospitalist was assigned to her care. After a day, the patient was found to have a small bowel obstruction and necrosis of the bowel. The baby was delivered preterm. The mother underwent 12 operations; half of her intestines were resected. The mother is being treated for posttraumatic stress syndrome. The child is autistic.

Parents’ claim The hospitalist did not diagnose the mother’s intestinal blockage in a timely manner and did not obtain an obstetric consult or notify the patient’s ObGyn. The hospital staff did not follow protocol to notify the mother’s ObGyn. The child’s autism is a result of preterm delivery.

Defendants’ defense The hospital denied any duty to notify the ObGyn if the patient was admitted to the hospital for nonobstetric reasons. The case was settled during trial.

Verdict A $4.2 million Washington settlement was reached including $3 million from the hospital. 

Fourth-degree perineal tear and continuing pain after delivery
A woman in her 30s went to the hospital for induction of labor. After many hours, the ObGyn used vacuum extraction due to maternal fatigue. The baby emerged in compound presentation, with her hand at the side of her head. She weighed 9 lb 12 oz at birth. A fourth-degree perineal tear occurred at birth. Postpartum, a rectovaginal fistula developed that required several repair operations. The mother is unable to have intercourse due to continuing vaginal pain and discomfort.

Patient’s Claim Knowing that the father’s head was overly large, the ObGyn should have better estimated the fetus’ size, and should have performed cesarean delivery.

Physician’s defense The ObGyn admitted that he knew the baby was large but maintained that a large fetus does not mandate a cesarean delivery. There were no indications that the baby’s head or body was too large to fit through the mother’s pelvis, so a vaginal delivery was appropriate. A perineal tear is a known complication of childbirth and could not be prevented. The patient’s current pain is unrelated to the perineal tear.

Verdict A Pennsylvania defense verdict was returned. 

Breast cancer missed in woman with dense breasts
In 2003, a 44-year-old woman was told she had dense fibrocystic breasts. From 2003 through 2009 she regularly saw a breast surgeon due to concern that breast cancer might be difficult to detect.

In August 2009, her ObGyn identified a questionable mass in her left breast after ultrasonography and mammography. The patient saw the surgeon in late September 2009; no further imaging was ordered and she was told to return in a year.

The patient, concerned about the mass, returned to the surgeon in May 2010. Testing revealed cancer, and she underwent radical mastectomy and other treatment. 

Patient’s claim Because the mass had not been treated in a timely manner, her 5-year survival rate in May 2010 was less than 50%. The surgeon was negligent in failing to order additional testing in September 2009. Magnetic resonance imaging (MRI) would have detected the cancer at a time when her survival rate could have been 80%.

Physician’s defense The cancer was diagnosed in a timely manner. An earlier diagnosis would not have changed the outcome.

Verdict A Tennessee defense verdict was returned.

Child stillborn, mother injured after vacuum extraction
When the mother’s labor slowed at a birthing center, she received several medications including castor oil, blue cohosh, and black cohosh to induce labor. The mother was later transferred by ambulance to a hospital. Ninety minutes after admission, the ObGyn used vacuum extraction to deliver a stillborn child. The mother sustained damage to her rectum, uterus, and vagina, had repair surgery, and has been unable to get pregnant again. 

Parents’ claim While in labor at the birthing center, the castor oil, blue cohosh, and black cohosh caused the patient’s uterus to contract excessively and contributed to fetal death. The patient should have been transferred to the hospital earlier. Cesarean delivery should have been performed immediately upon her arrival at the hospital but the ObGyn did not arrive at the hospital for an hour after the patient’s admission. 

Defendants’ defense The head midwife at the birthing center conceded negligence. The hospital claimed that the fetus was already dead before the mother arrived. The ObGyn denied negligence, arguing that he had no supervisory role or ownership in the birthing center and was not present during the mother’s labor. He also claimed that the fetus was dead in utero 12 or more hours before delivery and that an infectious process had developed in the mother during the 17 hours that she was at the birthing center.

Verdict A $4,095,000 Florida verdict was returned against the ObGyn. A directed verdict was granted for the hospital.

Patient still in pain after labia reduction
A 44-year-old woman underwent surgical reduction of her labia minora performed by a gynecologist. The procedure was intended to relieve discomfort during sexual activity. The patient continues to have pain.

Patient’s claim An excessive amount of the right labia minora was removed because proper presurgical demarcation of the operative area was not performed. Her pain during intercourse has worsened and she cannot properly urinate.

Physician’s defense Presurgical demarcation was correctly completed using clamps. Surgery was properly performed. The asymmetry is due to poor healing of the surgical wound. The patient’s clitoris was not scarred. The patient never reported complications related to urination to her gynecologist. Her ongoing pain is due to an estrogen deficiency.

Verdict A New York defense verdict was returned.

Uterine rupture after version for breech presentation: $7M
A woman went to the hospital for delivery of her baby. The fetus was in breech position, but the mother requested vaginal delivery. When the ObGyn attempted an external cephalic version to turn the baby, the uterus ruptured and the placenta was damaged. The baby sustained hypoxic-ischemic encephalopathy resulting in cerebral palsy (CP). He requires constant nursing care. 

Parents’ claim The ObGyn failed to recognize fetal distress during the breech version. The ObGyn improperly performed the version, causing the uterine rupture. There was lack of informed consent for the version.

Defendants’ defense The case was settled during trial.

Verdict A $7 million New Jersey settlement was reached.

Sepsis following hysterectomy
An ObGyn performed total abdominal hysterectomy to treat uterine fibroids in a 26-year-old woman. Despite reporting abdominal pain, the patient was discharged on postsurgical day 4.

Three days later, she went to a different hospital with moderate diffuse abdominal pain, constipation, nausea, emesis, tachycardia, and low-grade fever. An abdominal radiograph was taken, the patient was given morphine and ketorolac, and she was sent home.

She returned to the first hospital 3 days later reporting fever, nausea, emesis, diarrhea, and severe abdominal pain. After an abdominal computed tomography (CT) scan revealed numerous fluid- and gas-filled collections, indicative of abscess, intravenous antibiotics were ordered and administered.

Six days later, an infectious disease physician was consulted. He made a diagnosis of sepsis secondary to abdominal infection.

The next day, an abdominal CT scan revealed enlargement of multiple abdominal and pelvic fluid collections.

At exploratory laparotomy, purulent fluid was found in the anterior fascial compartment, with gross pus in the abdomen. The entire bowel was dilated, inflamed, and matted. Necrotic rind and infection were noted on multiple surfaces of the colon and small intestine and the transverse colon was gangrenous and sealed to the right lower quadrant. The patient’s intestines were resected and an ileostomy was placed, which was reversed several months later.

Patient’s claim The ObGyn did not offer an alternative to hysterectomy. The ObGyn was negligent in injuring the small intestine during surgery and failing to recognize and treat it intraoperatively. The patient should not have been discharged based on her reported symptoms. Failure to recognize and treat the injury led to sepsis with severe complications and months of recuperation.

Physician’s defense There was no negligence; small bowel injury is a known risk of hysterectomy. Other caregivers at both hospitals were at fault for not properly diagnosing and treating the infection.

Verdict A $901,420 Nevada verdict was returned; the ObGyn was found 85% at fault and other parties 15% at fault. The court granted the physician’s motion to reduce the verdict to $436,954, which included $371,411 from the ObGyn.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements, & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

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

Who was responsible for excessive oxytocin doses? $18.2M verdict
Early in the morning, a woman at 40 weeks’ gestation presented to the hospital for induction of labor managed by her ObGyn. Labor was lengthy, and the mother was given increasing doses of 22, 24, and 26 mIU/min of oxytocin to stimulate labor. The baby was delivered in the evening. The child suffered a hypoxic birth injury and has cerebral palsy. 

Parents’ claim Excessive oxytocin was administered, causing uterine hyperstimulation and excessive contractions. Nurses failed to inform the ObGyn of an abnormal fetal heart rate during the afternoon.

Defendants’ defense The parties disputed the oxytocin orders. The ObGyn claimed she has a standing order against oxytocin doses over 20 mIU/min. The nurses claimed that the dosage was based on the ObGyn’s verbal orders, which the ObGyn denied. The ObGyn denied negligence and maintained that if she’d known of the oxytocin administration greater than 20 mIU/min and the abnormal fetal heart rate, she immediately would have called for cesarean delivery. The hospital denied negligence and maintained that the oxytocin was administered 10 hours before delivery and played no role in fetal distress.

Verdict At trial, the ObGyn did not call expert witnesses and, in closing arguments, the physician’s attorney asked for exoneration of the ObGyn and a finding of fault solely against the hospital. An $18.2 million Washington verdict was returned against the hospital.

What caused the child’s Erb’s palsy?
A mother presented to the hospital for induction of labor. Oxytocin was administered and the first stage of labor progressed normally. When the mother began pushing, the ObGyn noted a turtle sign at crowning and called for assistance. The ObGyn attempted to deliver the fetus with downward guidance of the fetal head but encountered shoulder dystocia and a nuchal cord. He unwrapped the cord and instructed the nursing staff to place the mother in the McRobert’s position to help dislodge the right shoulder. When  that did not work, the ObGyn performed a first-degree episiotomy and completed delivery. The child was found to have Erb’s palsy of the right arm. She underwent decompression and neurolysis of the brachial plexus using sural nerve grafts but still has reduced use of her right arm. 

Parents’ claim Shoulder dystocia was improperly managed, causing the brachial plexus injury.

Defendants’ defense The ObGyn and hospital system denied negligence. The child’s injury occurred in utero due to natural forces of the mother’s uterine contractions.

Verdict An Ohio defense verdict was returned.

Woman claims lack of proper consent
A 47-year-old woman underwent endometrial ablation performed by her ObGyn. During the procedure, the uterus was perforated and the ObGyn performed a hysterectomy. Six days later, the patient was found to have peritonitis and underwent bowel repair surgery. The patient developed untreatable bowel adhesions that cause chronic pain.

Patient’s claim There were less expensive and invasive alternatives to the ablation that the ObGyn did not offer. The patient claimed lack of informed consent for the ablation and hysterectomy and negligence in perforating the bowel. The ObGyn was also negligent in failing to recognize the perforation and to diagnose peritonitis in a timely manner. 

Texas state law requires consent for hysterectomies without documented evidence of immediate danger to life. Her husband did not have the authority to consent on her behalf. 

Physician’s defense The husband gave informed consent. Failure to recognize the perforation was not negligent; it is a known risk of the surgery. The patient’s care was transferred to another physician after the second postoperative day.

Verdict A $200,000 Texas settlement was reached. 

Bowel obstruction in pregnant woman
A 29-year-old woman at 27 weeks’ gestation had abdominal pain. She went to a community hospital where a hospitalist was assigned to her care. After a day, the patient was found to have a small bowel obstruction and necrosis of the bowel. The baby was delivered preterm. The mother underwent 12 operations; half of her intestines were resected. The mother is being treated for posttraumatic stress syndrome. The child is autistic.

Parents’ claim The hospitalist did not diagnose the mother’s intestinal blockage in a timely manner and did not obtain an obstetric consult or notify the patient’s ObGyn. The hospital staff did not follow protocol to notify the mother’s ObGyn. The child’s autism is a result of preterm delivery.

Defendants’ defense The hospital denied any duty to notify the ObGyn if the patient was admitted to the hospital for nonobstetric reasons. The case was settled during trial.

Verdict A $4.2 million Washington settlement was reached including $3 million from the hospital. 

Fourth-degree perineal tear and continuing pain after delivery
A woman in her 30s went to the hospital for induction of labor. After many hours, the ObGyn used vacuum extraction due to maternal fatigue. The baby emerged in compound presentation, with her hand at the side of her head. She weighed 9 lb 12 oz at birth. A fourth-degree perineal tear occurred at birth. Postpartum, a rectovaginal fistula developed that required several repair operations. The mother is unable to have intercourse due to continuing vaginal pain and discomfort.

Patient’s Claim Knowing that the father’s head was overly large, the ObGyn should have better estimated the fetus’ size, and should have performed cesarean delivery.

Physician’s defense The ObGyn admitted that he knew the baby was large but maintained that a large fetus does not mandate a cesarean delivery. There were no indications that the baby’s head or body was too large to fit through the mother’s pelvis, so a vaginal delivery was appropriate. A perineal tear is a known complication of childbirth and could not be prevented. The patient’s current pain is unrelated to the perineal tear.

Verdict A Pennsylvania defense verdict was returned. 

Breast cancer missed in woman with dense breasts
In 2003, a 44-year-old woman was told she had dense fibrocystic breasts. From 2003 through 2009 she regularly saw a breast surgeon due to concern that breast cancer might be difficult to detect.

In August 2009, her ObGyn identified a questionable mass in her left breast after ultrasonography and mammography. The patient saw the surgeon in late September 2009; no further imaging was ordered and she was told to return in a year.

The patient, concerned about the mass, returned to the surgeon in May 2010. Testing revealed cancer, and she underwent radical mastectomy and other treatment. 

Patient’s claim Because the mass had not been treated in a timely manner, her 5-year survival rate in May 2010 was less than 50%. The surgeon was negligent in failing to order additional testing in September 2009. Magnetic resonance imaging (MRI) would have detected the cancer at a time when her survival rate could have been 80%.

Physician’s defense The cancer was diagnosed in a timely manner. An earlier diagnosis would not have changed the outcome.

Verdict A Tennessee defense verdict was returned.

Child stillborn, mother injured after vacuum extraction
When the mother’s labor slowed at a birthing center, she received several medications including castor oil, blue cohosh, and black cohosh to induce labor. The mother was later transferred by ambulance to a hospital. Ninety minutes after admission, the ObGyn used vacuum extraction to deliver a stillborn child. The mother sustained damage to her rectum, uterus, and vagina, had repair surgery, and has been unable to get pregnant again. 

Parents’ claim While in labor at the birthing center, the castor oil, blue cohosh, and black cohosh caused the patient’s uterus to contract excessively and contributed to fetal death. The patient should have been transferred to the hospital earlier. Cesarean delivery should have been performed immediately upon her arrival at the hospital but the ObGyn did not arrive at the hospital for an hour after the patient’s admission. 

Defendants’ defense The head midwife at the birthing center conceded negligence. The hospital claimed that the fetus was already dead before the mother arrived. The ObGyn denied negligence, arguing that he had no supervisory role or ownership in the birthing center and was not present during the mother’s labor. He also claimed that the fetus was dead in utero 12 or more hours before delivery and that an infectious process had developed in the mother during the 17 hours that she was at the birthing center.

Verdict A $4,095,000 Florida verdict was returned against the ObGyn. A directed verdict was granted for the hospital.

Patient still in pain after labia reduction
A 44-year-old woman underwent surgical reduction of her labia minora performed by a gynecologist. The procedure was intended to relieve discomfort during sexual activity. The patient continues to have pain.

Patient’s claim An excessive amount of the right labia minora was removed because proper presurgical demarcation of the operative area was not performed. Her pain during intercourse has worsened and she cannot properly urinate.

Physician’s defense Presurgical demarcation was correctly completed using clamps. Surgery was properly performed. The asymmetry is due to poor healing of the surgical wound. The patient’s clitoris was not scarred. The patient never reported complications related to urination to her gynecologist. Her ongoing pain is due to an estrogen deficiency.

Verdict A New York defense verdict was returned.

Uterine rupture after version for breech presentation: $7M
A woman went to the hospital for delivery of her baby. The fetus was in breech position, but the mother requested vaginal delivery. When the ObGyn attempted an external cephalic version to turn the baby, the uterus ruptured and the placenta was damaged. The baby sustained hypoxic-ischemic encephalopathy resulting in cerebral palsy (CP). He requires constant nursing care. 

Parents’ claim The ObGyn failed to recognize fetal distress during the breech version. The ObGyn improperly performed the version, causing the uterine rupture. There was lack of informed consent for the version.

Defendants’ defense The case was settled during trial.

Verdict A $7 million New Jersey settlement was reached.

Sepsis following hysterectomy
An ObGyn performed total abdominal hysterectomy to treat uterine fibroids in a 26-year-old woman. Despite reporting abdominal pain, the patient was discharged on postsurgical day 4.

Three days later, she went to a different hospital with moderate diffuse abdominal pain, constipation, nausea, emesis, tachycardia, and low-grade fever. An abdominal radiograph was taken, the patient was given morphine and ketorolac, and she was sent home.

She returned to the first hospital 3 days later reporting fever, nausea, emesis, diarrhea, and severe abdominal pain. After an abdominal computed tomography (CT) scan revealed numerous fluid- and gas-filled collections, indicative of abscess, intravenous antibiotics were ordered and administered.

Six days later, an infectious disease physician was consulted. He made a diagnosis of sepsis secondary to abdominal infection.

The next day, an abdominal CT scan revealed enlargement of multiple abdominal and pelvic fluid collections.

At exploratory laparotomy, purulent fluid was found in the anterior fascial compartment, with gross pus in the abdomen. The entire bowel was dilated, inflamed, and matted. Necrotic rind and infection were noted on multiple surfaces of the colon and small intestine and the transverse colon was gangrenous and sealed to the right lower quadrant. The patient’s intestines were resected and an ileostomy was placed, which was reversed several months later.

Patient’s claim The ObGyn did not offer an alternative to hysterectomy. The ObGyn was negligent in injuring the small intestine during surgery and failing to recognize and treat it intraoperatively. The patient should not have been discharged based on her reported symptoms. Failure to recognize and treat the injury led to sepsis with severe complications and months of recuperation.

Physician’s defense There was no negligence; small bowel injury is a known risk of hysterectomy. Other caregivers at both hospitals were at fault for not properly diagnosing and treating the infection.

Verdict A $901,420 Nevada verdict was returned; the ObGyn was found 85% at fault and other parties 15% at fault. The court granted the physician’s motion to reduce the verdict to $436,954, which included $371,411 from the ObGyn.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements, & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

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

Who was responsible for excessive oxytocin doses? $18.2M verdict
Early in the morning, a woman at 40 weeks’ gestation presented to the hospital for induction of labor managed by her ObGyn. Labor was lengthy, and the mother was given increasing doses of 22, 24, and 26 mIU/min of oxytocin to stimulate labor. The baby was delivered in the evening. The child suffered a hypoxic birth injury and has cerebral palsy. 

Parents’ claim Excessive oxytocin was administered, causing uterine hyperstimulation and excessive contractions. Nurses failed to inform the ObGyn of an abnormal fetal heart rate during the afternoon.

Defendants’ defense The parties disputed the oxytocin orders. The ObGyn claimed she has a standing order against oxytocin doses over 20 mIU/min. The nurses claimed that the dosage was based on the ObGyn’s verbal orders, which the ObGyn denied. The ObGyn denied negligence and maintained that if she’d known of the oxytocin administration greater than 20 mIU/min and the abnormal fetal heart rate, she immediately would have called for cesarean delivery. The hospital denied negligence and maintained that the oxytocin was administered 10 hours before delivery and played no role in fetal distress.

Verdict At trial, the ObGyn did not call expert witnesses and, in closing arguments, the physician’s attorney asked for exoneration of the ObGyn and a finding of fault solely against the hospital. An $18.2 million Washington verdict was returned against the hospital.

What caused the child’s Erb’s palsy?
A mother presented to the hospital for induction of labor. Oxytocin was administered and the first stage of labor progressed normally. When the mother began pushing, the ObGyn noted a turtle sign at crowning and called for assistance. The ObGyn attempted to deliver the fetus with downward guidance of the fetal head but encountered shoulder dystocia and a nuchal cord. He unwrapped the cord and instructed the nursing staff to place the mother in the McRobert’s position to help dislodge the right shoulder. When  that did not work, the ObGyn performed a first-degree episiotomy and completed delivery. The child was found to have Erb’s palsy of the right arm. She underwent decompression and neurolysis of the brachial plexus using sural nerve grafts but still has reduced use of her right arm. 

Parents’ claim Shoulder dystocia was improperly managed, causing the brachial plexus injury.

Defendants’ defense The ObGyn and hospital system denied negligence. The child’s injury occurred in utero due to natural forces of the mother’s uterine contractions.

Verdict An Ohio defense verdict was returned.

Woman claims lack of proper consent
A 47-year-old woman underwent endometrial ablation performed by her ObGyn. During the procedure, the uterus was perforated and the ObGyn performed a hysterectomy. Six days later, the patient was found to have peritonitis and underwent bowel repair surgery. The patient developed untreatable bowel adhesions that cause chronic pain.

Patient’s claim There were less expensive and invasive alternatives to the ablation that the ObGyn did not offer. The patient claimed lack of informed consent for the ablation and hysterectomy and negligence in perforating the bowel. The ObGyn was also negligent in failing to recognize the perforation and to diagnose peritonitis in a timely manner. 

Texas state law requires consent for hysterectomies without documented evidence of immediate danger to life. Her husband did not have the authority to consent on her behalf. 

Physician’s defense The husband gave informed consent. Failure to recognize the perforation was not negligent; it is a known risk of the surgery. The patient’s care was transferred to another physician after the second postoperative day.

Verdict A $200,000 Texas settlement was reached. 

Bowel obstruction in pregnant woman
A 29-year-old woman at 27 weeks’ gestation had abdominal pain. She went to a community hospital where a hospitalist was assigned to her care. After a day, the patient was found to have a small bowel obstruction and necrosis of the bowel. The baby was delivered preterm. The mother underwent 12 operations; half of her intestines were resected. The mother is being treated for posttraumatic stress syndrome. The child is autistic.

Parents’ claim The hospitalist did not diagnose the mother’s intestinal blockage in a timely manner and did not obtain an obstetric consult or notify the patient’s ObGyn. The hospital staff did not follow protocol to notify the mother’s ObGyn. The child’s autism is a result of preterm delivery.

Defendants’ defense The hospital denied any duty to notify the ObGyn if the patient was admitted to the hospital for nonobstetric reasons. The case was settled during trial.

Verdict A $4.2 million Washington settlement was reached including $3 million from the hospital. 

Fourth-degree perineal tear and continuing pain after delivery
A woman in her 30s went to the hospital for induction of labor. After many hours, the ObGyn used vacuum extraction due to maternal fatigue. The baby emerged in compound presentation, with her hand at the side of her head. She weighed 9 lb 12 oz at birth. A fourth-degree perineal tear occurred at birth. Postpartum, a rectovaginal fistula developed that required several repair operations. The mother is unable to have intercourse due to continuing vaginal pain and discomfort.

Patient’s Claim Knowing that the father’s head was overly large, the ObGyn should have better estimated the fetus’ size, and should have performed cesarean delivery.

Physician’s defense The ObGyn admitted that he knew the baby was large but maintained that a large fetus does not mandate a cesarean delivery. There were no indications that the baby’s head or body was too large to fit through the mother’s pelvis, so a vaginal delivery was appropriate. A perineal tear is a known complication of childbirth and could not be prevented. The patient’s current pain is unrelated to the perineal tear.

Verdict A Pennsylvania defense verdict was returned. 

Breast cancer missed in woman with dense breasts
In 2003, a 44-year-old woman was told she had dense fibrocystic breasts. From 2003 through 2009 she regularly saw a breast surgeon due to concern that breast cancer might be difficult to detect.

In August 2009, her ObGyn identified a questionable mass in her left breast after ultrasonography and mammography. The patient saw the surgeon in late September 2009; no further imaging was ordered and she was told to return in a year.

The patient, concerned about the mass, returned to the surgeon in May 2010. Testing revealed cancer, and she underwent radical mastectomy and other treatment. 

Patient’s claim Because the mass had not been treated in a timely manner, her 5-year survival rate in May 2010 was less than 50%. The surgeon was negligent in failing to order additional testing in September 2009. Magnetic resonance imaging (MRI) would have detected the cancer at a time when her survival rate could have been 80%.

Physician’s defense The cancer was diagnosed in a timely manner. An earlier diagnosis would not have changed the outcome.

Verdict A Tennessee defense verdict was returned.

Child stillborn, mother injured after vacuum extraction
When the mother’s labor slowed at a birthing center, she received several medications including castor oil, blue cohosh, and black cohosh to induce labor. The mother was later transferred by ambulance to a hospital. Ninety minutes after admission, the ObGyn used vacuum extraction to deliver a stillborn child. The mother sustained damage to her rectum, uterus, and vagina, had repair surgery, and has been unable to get pregnant again. 

Parents’ claim While in labor at the birthing center, the castor oil, blue cohosh, and black cohosh caused the patient’s uterus to contract excessively and contributed to fetal death. The patient should have been transferred to the hospital earlier. Cesarean delivery should have been performed immediately upon her arrival at the hospital but the ObGyn did not arrive at the hospital for an hour after the patient’s admission. 

Defendants’ defense The head midwife at the birthing center conceded negligence. The hospital claimed that the fetus was already dead before the mother arrived. The ObGyn denied negligence, arguing that he had no supervisory role or ownership in the birthing center and was not present during the mother’s labor. He also claimed that the fetus was dead in utero 12 or more hours before delivery and that an infectious process had developed in the mother during the 17 hours that she was at the birthing center.

Verdict A $4,095,000 Florida verdict was returned against the ObGyn. A directed verdict was granted for the hospital.

Patient still in pain after labia reduction
A 44-year-old woman underwent surgical reduction of her labia minora performed by a gynecologist. The procedure was intended to relieve discomfort during sexual activity. The patient continues to have pain.

Patient’s claim An excessive amount of the right labia minora was removed because proper presurgical demarcation of the operative area was not performed. Her pain during intercourse has worsened and she cannot properly urinate.

Physician’s defense Presurgical demarcation was correctly completed using clamps. Surgery was properly performed. The asymmetry is due to poor healing of the surgical wound. The patient’s clitoris was not scarred. The patient never reported complications related to urination to her gynecologist. Her ongoing pain is due to an estrogen deficiency.

Verdict A New York defense verdict was returned.

Uterine rupture after version for breech presentation: $7M
A woman went to the hospital for delivery of her baby. The fetus was in breech position, but the mother requested vaginal delivery. When the ObGyn attempted an external cephalic version to turn the baby, the uterus ruptured and the placenta was damaged. The baby sustained hypoxic-ischemic encephalopathy resulting in cerebral palsy (CP). He requires constant nursing care. 

Parents’ claim The ObGyn failed to recognize fetal distress during the breech version. The ObGyn improperly performed the version, causing the uterine rupture. There was lack of informed consent for the version.

Defendants’ defense The case was settled during trial.

Verdict A $7 million New Jersey settlement was reached.

Sepsis following hysterectomy
An ObGyn performed total abdominal hysterectomy to treat uterine fibroids in a 26-year-old woman. Despite reporting abdominal pain, the patient was discharged on postsurgical day 4.

Three days later, she went to a different hospital with moderate diffuse abdominal pain, constipation, nausea, emesis, tachycardia, and low-grade fever. An abdominal radiograph was taken, the patient was given morphine and ketorolac, and she was sent home.

She returned to the first hospital 3 days later reporting fever, nausea, emesis, diarrhea, and severe abdominal pain. After an abdominal computed tomography (CT) scan revealed numerous fluid- and gas-filled collections, indicative of abscess, intravenous antibiotics were ordered and administered.

Six days later, an infectious disease physician was consulted. He made a diagnosis of sepsis secondary to abdominal infection.

The next day, an abdominal CT scan revealed enlargement of multiple abdominal and pelvic fluid collections.

At exploratory laparotomy, purulent fluid was found in the anterior fascial compartment, with gross pus in the abdomen. The entire bowel was dilated, inflamed, and matted. Necrotic rind and infection were noted on multiple surfaces of the colon and small intestine and the transverse colon was gangrenous and sealed to the right lower quadrant. The patient’s intestines were resected and an ileostomy was placed, which was reversed several months later.

Patient’s claim The ObGyn did not offer an alternative to hysterectomy. The ObGyn was negligent in injuring the small intestine during surgery and failing to recognize and treat it intraoperatively. The patient should not have been discharged based on her reported symptoms. Failure to recognize and treat the injury led to sepsis with severe complications and months of recuperation.

Physician’s defense There was no negligence; small bowel injury is a known risk of hysterectomy. Other caregivers at both hospitals were at fault for not properly diagnosing and treating the infection.

Verdict A $901,420 Nevada verdict was returned; the ObGyn was found 85% at fault and other parties 15% at fault. The court granted the physician’s motion to reduce the verdict to $436,954, which included $371,411 from the ObGyn.

These cases were selected by the editors of OBG Management from Medical Malpractice Verdicts, Settlements, & Experts, with permission of the editor, Lewis Laska (www.verdictslaska.com). The information available to the editors about the cases presented here is sometimes incomplete. Moreover, the cases may or may not have merit. Nevertheless, these cases represent the types of clinical situations that typically result in litigation and are meant to illustrate nationwide variation in jury verdicts and awards.

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

Intravenous infusion

TORONTO—An antidote to factor Xa inhibitors can safely reverse the anticoagulant effect of apixaban in healthy volunteers, results of the ANNEXA-A study suggest.

The first part of this study showed that a bolus of the antidote, andexanet alfa, was effective. And none of the volunteers had serious adverse events, thrombotic events, or antibodies to factor X or Xa.

In the second part of the study, researchers tested a bolus and a 2-hour infusion of andexanet alfa.

The drug normalized coagulation parameters immediately post-bolus, and this effect was sustained during the infusion. The reversal of anti-factor Xa activity lasted 1 to 2 hours post-infusion.

As in part 1, there were no serious adverse events or thrombotic events, and none of the subjects developed antibodies to factor X or Xa.

Mark Crowther, MD, of McMaster University in Hamilton, Ontario, Canada, presented details on part 2 of ANNEXA-A at the ISTH 2015 Congress (abstract LB004). The trial was sponsored by Portola Pharmaceuticals, Inc., the company developing andexanet alfa.

The goal of the randomized, double-blind ANNEXA-A study was to evaluate the safety and efficacy of andexanet alfa in reversing apixaban-induced anticoagulation in healthy volunteers ages 50 to 75.

In part 1, 33 healthy volunteers received apixaban at 5 mg twice daily for 4 days and were then randomized in a 3:1 ratio to andexanet alfa administered as a 400 mg intravenous bolus (n=24) or to placebo (n=9). Results from this part of the study were presented at the American Heart Association 2014 Scientific Sessions.

In the second part of the study, 32 healthy volunteers received apixaban at 5 mg twice daily for 4 days and were then randomized in a 3:1 ratio to andexanet alfa administered as a 400 mg intravenous bolus followed by a continuous infusion of 4 mg/min for 120 minutes (n=24) or to placebo (n=8).

Safety

One subject in the andexanet alfa arm discontinued treatment during the infusion due to mild hives. The subject did not have any other allergic

manifestations or cardiorespiratory effects.

Six subjects had mild infusion-related reactions, 4 (16.7%) in the andexanet alfa arm and 2 (25%) in the placebo arm.

None of the subjects had an increase in D-dimer (more than 2 times the upper limit of normal) on more than 1 day.

The majority of andexanet-alfa-treated subjects had transient elevation of F1 and F2, but, in all cases, levels returned to less than or equal to 2 times the upper limit of normal by the fourth day.

Efficacy

Twenty-three subjects in the andexanet alfa arm and all 8 subjects in the placebo arm were evaluable for efficacy.

All evaluable subjects in the andexanet alfa arm had an 80% or greater reduction in anti-factor Xa activity post-infusion nadir, compared to none of the subjects on placebo (P<0.0001).

The mean percent change in anti-factor Xa activity from baseline to post-infusion nadir was 92% in the andexanet alfa arm (P<0.0001 vs placebo). And the mean percent change from baseline to post-bolus nadir was 93% (P<0.0001 vs placebo).

The mean change in free apixaban concentration from baseline to post-infusion nadir was 1.39 ng/mL in the andexanet alfa arm (P=0.0002 vs placebo).

Thrombin generation was restored to the day 1, pre-apixaban baseline range in all 23 subjects on andexanet alfa (P<0.0001). And there was no long-term effect on thrombin generation.

The researchers said andexanet alfa demonstrated rapid onset and offset of action. Furthermore, it seems that either a bolus dose alone or a bolus plus infusion can reverse apixaban’s anticoagulant activity, which could provide flexibility for bleeding patients.

Andexanet alfa is also under investigation as an antidote to rivaroxaban, edoxaban, enoxaparin, and betrixaban.

Intravenous infusion

TORONTO—An antidote to factor Xa inhibitors can safely reverse the anticoagulant effect of apixaban in healthy volunteers, results of the ANNEXA-A study suggest.

The first part of this study showed that a bolus of the antidote, andexanet alfa, was effective. And none of the volunteers had serious adverse events, thrombotic events, or antibodies to factor X or Xa.

In the second part of the study, researchers tested a bolus and a 2-hour infusion of andexanet alfa.

The drug normalized coagulation parameters immediately post-bolus, and this effect was sustained during the infusion. The reversal of anti-factor Xa activity lasted 1 to 2 hours post-infusion.

As in part 1, there were no serious adverse events or thrombotic events, and none of the subjects developed antibodies to factor X or Xa.

Mark Crowther, MD, of McMaster University in Hamilton, Ontario, Canada, presented details on part 2 of ANNEXA-A at the ISTH 2015 Congress (abstract LB004). The trial was sponsored by Portola Pharmaceuticals, Inc., the company developing andexanet alfa.

The goal of the randomized, double-blind ANNEXA-A study was to evaluate the safety and efficacy of andexanet alfa in reversing apixaban-induced anticoagulation in healthy volunteers ages 50 to 75.

In part 1, 33 healthy volunteers received apixaban at 5 mg twice daily for 4 days and were then randomized in a 3:1 ratio to andexanet alfa administered as a 400 mg intravenous bolus (n=24) or to placebo (n=9). Results from this part of the study were presented at the American Heart Association 2014 Scientific Sessions.

In the second part of the study, 32 healthy volunteers received apixaban at 5 mg twice daily for 4 days and were then randomized in a 3:1 ratio to andexanet alfa administered as a 400 mg intravenous bolus followed by a continuous infusion of 4 mg/min for 120 minutes (n=24) or to placebo (n=8).

Safety

One subject in the andexanet alfa arm discontinued treatment during the infusion due to mild hives. The subject did not have any other allergic

manifestations or cardiorespiratory effects.

Six subjects had mild infusion-related reactions, 4 (16.7%) in the andexanet alfa arm and 2 (25%) in the placebo arm.

None of the subjects had an increase in D-dimer (more than 2 times the upper limit of normal) on more than 1 day.

The majority of andexanet-alfa-treated subjects had transient elevation of F1 and F2, but, in all cases, levels returned to less than or equal to 2 times the upper limit of normal by the fourth day.

Efficacy

Twenty-three subjects in the andexanet alfa arm and all 8 subjects in the placebo arm were evaluable for efficacy.

All evaluable subjects in the andexanet alfa arm had an 80% or greater reduction in anti-factor Xa activity post-infusion nadir, compared to none of the subjects on placebo (P<0.0001).

The mean percent change in anti-factor Xa activity from baseline to post-infusion nadir was 92% in the andexanet alfa arm (P<0.0001 vs placebo). And the mean percent change from baseline to post-bolus nadir was 93% (P<0.0001 vs placebo).

The mean change in free apixaban concentration from baseline to post-infusion nadir was 1.39 ng/mL in the andexanet alfa arm (P=0.0002 vs placebo).

Thrombin generation was restored to the day 1, pre-apixaban baseline range in all 23 subjects on andexanet alfa (P<0.0001). And there was no long-term effect on thrombin generation.

The researchers said andexanet alfa demonstrated rapid onset and offset of action. Furthermore, it seems that either a bolus dose alone or a bolus plus infusion can reverse apixaban’s anticoagulant activity, which could provide flexibility for bleeding patients.

Andexanet alfa is also under investigation as an antidote to rivaroxaban, edoxaban, enoxaparin, and betrixaban.

Intravenous infusion

TORONTO—An antidote to factor Xa inhibitors can safely reverse the anticoagulant effect of apixaban in healthy volunteers, results of the ANNEXA-A study suggest.

The first part of this study showed that a bolus of the antidote, andexanet alfa, was effective. And none of the volunteers had serious adverse events, thrombotic events, or antibodies to factor X or Xa.

In the second part of the study, researchers tested a bolus and a 2-hour infusion of andexanet alfa.

The drug normalized coagulation parameters immediately post-bolus, and this effect was sustained during the infusion. The reversal of anti-factor Xa activity lasted 1 to 2 hours post-infusion.

As in part 1, there were no serious adverse events or thrombotic events, and none of the subjects developed antibodies to factor X or Xa.

Mark Crowther, MD, of McMaster University in Hamilton, Ontario, Canada, presented details on part 2 of ANNEXA-A at the ISTH 2015 Congress (abstract LB004). The trial was sponsored by Portola Pharmaceuticals, Inc., the company developing andexanet alfa.

The goal of the randomized, double-blind ANNEXA-A study was to evaluate the safety and efficacy of andexanet alfa in reversing apixaban-induced anticoagulation in healthy volunteers ages 50 to 75.

In part 1, 33 healthy volunteers received apixaban at 5 mg twice daily for 4 days and were then randomized in a 3:1 ratio to andexanet alfa administered as a 400 mg intravenous bolus (n=24) or to placebo (n=9). Results from this part of the study were presented at the American Heart Association 2014 Scientific Sessions.

In the second part of the study, 32 healthy volunteers received apixaban at 5 mg twice daily for 4 days and were then randomized in a 3:1 ratio to andexanet alfa administered as a 400 mg intravenous bolus followed by a continuous infusion of 4 mg/min for 120 minutes (n=24) or to placebo (n=8).

Safety

One subject in the andexanet alfa arm discontinued treatment during the infusion due to mild hives. The subject did not have any other allergic

manifestations or cardiorespiratory effects.

Six subjects had mild infusion-related reactions, 4 (16.7%) in the andexanet alfa arm and 2 (25%) in the placebo arm.

None of the subjects had an increase in D-dimer (more than 2 times the upper limit of normal) on more than 1 day.

The majority of andexanet-alfa-treated subjects had transient elevation of F1 and F2, but, in all cases, levels returned to less than or equal to 2 times the upper limit of normal by the fourth day.

Efficacy

Twenty-three subjects in the andexanet alfa arm and all 8 subjects in the placebo arm were evaluable for efficacy.

All evaluable subjects in the andexanet alfa arm had an 80% or greater reduction in anti-factor Xa activity post-infusion nadir, compared to none of the subjects on placebo (P<0.0001).

The mean percent change in anti-factor Xa activity from baseline to post-infusion nadir was 92% in the andexanet alfa arm (P<0.0001 vs placebo). And the mean percent change from baseline to post-bolus nadir was 93% (P<0.0001 vs placebo).

The mean change in free apixaban concentration from baseline to post-infusion nadir was 1.39 ng/mL in the andexanet alfa arm (P=0.0002 vs placebo).

Thrombin generation was restored to the day 1, pre-apixaban baseline range in all 23 subjects on andexanet alfa (P<0.0001). And there was no long-term effect on thrombin generation.

The researchers said andexanet alfa demonstrated rapid onset and offset of action. Furthermore, it seems that either a bolus dose alone or a bolus plus infusion can reverse apixaban’s anticoagulant activity, which could provide flexibility for bleeding patients.

Andexanet alfa is also under investigation as an antidote to rivaroxaban, edoxaban, enoxaparin, and betrixaban.

 

 

Owen O’Connor, MD, PhD

Photo by Larry Young

 

LUGANO—Updated phase 1 results with TGR-1202 suggest this next-generation PI3kδ inhibitor lacks the hepatotoxicity associated with other PI3Kδ inhibitors.

Investigators also confirmed that no case of colitis has been reported to date with TGR-1202, and only 2% of evaluable patients on this trial have experienced grade 3-4 diarrhea.

The study is an ongoing, first-in-human trial in patients with relapsed or refractory hematologic malignancies.

Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, New York, shared results from this trial at the 13th International Congress on Malignant Lymphoma (abstract 038*). The trial is sponsored by TG Therapeutics, Inc., the company developing TGR-1202.

“TGR-1202 is a radically different sort of PI3kδ inhibitor,” Dr O’Connor said. “[I]t’s really a unique chemical entity that is different from the previous 2 structures [idelalisib and duvelisib] that you’ve probably heard something about.”

Study design

This ongoing trial of TGR-1202 is open to patients with hematologic malignancies who relapsed after or were refractory to at least 1 prior treatment regimen. Patients are eligible if they have an ECOG performance status of 2 or less with adequate organ system function, including absolute neutrophil count of 750/μL or greater and platelets of 50,000/μL or greater.

TGR-1202 is dosed orally, once a day in continuous, 28-day cycles. The original dose-escalation portion of the study was a classic 3+3 design, starting at 50 mg and increasing to 1800 mg. Patients who received prior therapy with a PI3K and/or mTOR inhibitor were excluded from the dose-escalation cohorts but were allowed in the expansion cohorts.

Dr O’Connor pointed out that, through cohort 5, TGR-1202 was taken in the fasting state. However, pharmacokinetic studies performed in the fed state revealed that the area under the curve (AUC) and Cmax could be doubled by taking the drug with food. So the expansions in the ongoing 800 mg and 1200 mg cohorts are being conducted in the fed state.

Dr O’Connor also noted that a subsequent, micronized version of TGR-1202 was developed. The micronization “essentially increases the surface area of the formulation, allowing for better bioavailability and markedly increases the AUC and Cmax exposure,” he said.

So the investigators conducted a second escalation with the micronized formulation, starting at 200 mg and increasing to 800 mg. At present, they are enrolling patients to the 800 mg and 1200 mg cohorts conducted in the fed state with the micronized formulation.

Demographics

Dr O’Connor presented data on 66 patients who were evaluable for safety and 51 for efficacy. The patients’ median age was 66 (range, 22–85), and 46 were male.

In all, there were 20 patients with chronic lymphocytic leukemia (CLL), 17 with follicular lymphoma, 10 with diffuse large B-cell lymphoma, 9 with Hodgkin lymphoma, 5 with mantle cell lymphoma, 3 with marginal zone lymphoma, 1 with Waldenström’s macroglobulinemia, and 1 with hairy cell leukemia.

Patients had received a median of 3 prior therapies (range, 1–14), and 36 (55%) had 3 or more prior therapies. Thirty-four patients (52%) were refractory to their prior therapy.

Efficacy

Dr O’Connor reported that higher doses of TGR-1202—1200 mg of the initial formulation and 600 mg or more of the micronized version—demonstrated rapid and profound responses in CLL, follicular lymphoma, and marginal zone lymphoma.

Responses have been limited in diffuse large B-cell lymphoma, Hodgkin lymphoma, and mantle cell lymphoma.

Eighty-eight percent of CLL patients achieved a nodal partial remission, and 63% achieved a response according to iwCLL criteria (Hallek 2008).

Safety and tolerability

Adverse events occurring in more than 10% of patients included nausea (41%), diarrhea (32%), fatigue (32%), headache (23%), vomiting (23%), cough (21%), decreased appetite (17%), rash (17%), constipation (14%), hypokalemia (14%), anemia, dizziness, dyspnea, neutropenia, and pyrexia (12% each), and abdominal pain (11%).

The most common grade 3-4 toxicity was neutropenia, occurring in 11% of patients.

“But other than that, the bulk of the toxicities in terms of grade 3-4 events were relatively modest,” Dr O’Connor said. “[I]t’s worth pointing out that diarrhea grade 3-4 only occurred in about 2% of patients in the population.”

Approximately 50% of patients (n=31) have been on study for more than 6 months, and approximately 30% taking a higher dose level have been on study for 6 months or more. Twenty-five of 37 patients exposed to 800 mg or more of the micronized formulation currently remain on study.

“So this gives you a sense that it is a very well-tolerated drug, with patients staying on for extended periods of time,” Dr O’Connor said.

He added that time on study becomes relevant in assessing some of the gastrointestinal toxicities seen with other PI3Kδ inhibitors, where it seems the median time to gastrointestinal toxicity is beyond 6 months.

“So far, and I’m willing to concede it’s early, but with half the patients being treated for over 6 months, [diarrhea/colitis] seems to be much lower than the experience with the other PI3 kinase inhibitors,” Dr O’Connor said.

“I think one of the more important features of [TGR-1202], and one that allows me to think we might be able to integrate this drug a little more readily into various combination regimens, are the discontinuations due to other adverse events.”

“Only 4% treated with [TGR-1202] had discontinuations secondary to adverse events. [A]nd it looks like the efficacy is in line with what we’d expect with some of the other drugs, but this [study] is actively accruing still.”

*Information in the abstract differs from that presented at the meeting.

 

 

Owen O’Connor, MD, PhD

Photo by Larry Young

 

LUGANO—Updated phase 1 results with TGR-1202 suggest this next-generation PI3kδ inhibitor lacks the hepatotoxicity associated with other PI3Kδ inhibitors.

Investigators also confirmed that no case of colitis has been reported to date with TGR-1202, and only 2% of evaluable patients on this trial have experienced grade 3-4 diarrhea.

The study is an ongoing, first-in-human trial in patients with relapsed or refractory hematologic malignancies.

Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, New York, shared results from this trial at the 13th International Congress on Malignant Lymphoma (abstract 038*). The trial is sponsored by TG Therapeutics, Inc., the company developing TGR-1202.

“TGR-1202 is a radically different sort of PI3kδ inhibitor,” Dr O’Connor said. “[I]t’s really a unique chemical entity that is different from the previous 2 structures [idelalisib and duvelisib] that you’ve probably heard something about.”

Study design

This ongoing trial of TGR-1202 is open to patients with hematologic malignancies who relapsed after or were refractory to at least 1 prior treatment regimen. Patients are eligible if they have an ECOG performance status of 2 or less with adequate organ system function, including absolute neutrophil count of 750/μL or greater and platelets of 50,000/μL or greater.

TGR-1202 is dosed orally, once a day in continuous, 28-day cycles. The original dose-escalation portion of the study was a classic 3+3 design, starting at 50 mg and increasing to 1800 mg. Patients who received prior therapy with a PI3K and/or mTOR inhibitor were excluded from the dose-escalation cohorts but were allowed in the expansion cohorts.

Dr O’Connor pointed out that, through cohort 5, TGR-1202 was taken in the fasting state. However, pharmacokinetic studies performed in the fed state revealed that the area under the curve (AUC) and Cmax could be doubled by taking the drug with food. So the expansions in the ongoing 800 mg and 1200 mg cohorts are being conducted in the fed state.

Dr O’Connor also noted that a subsequent, micronized version of TGR-1202 was developed. The micronization “essentially increases the surface area of the formulation, allowing for better bioavailability and markedly increases the AUC and Cmax exposure,” he said.

So the investigators conducted a second escalation with the micronized formulation, starting at 200 mg and increasing to 800 mg. At present, they are enrolling patients to the 800 mg and 1200 mg cohorts conducted in the fed state with the micronized formulation.

Demographics

Dr O’Connor presented data on 66 patients who were evaluable for safety and 51 for efficacy. The patients’ median age was 66 (range, 22–85), and 46 were male.

In all, there were 20 patients with chronic lymphocytic leukemia (CLL), 17 with follicular lymphoma, 10 with diffuse large B-cell lymphoma, 9 with Hodgkin lymphoma, 5 with mantle cell lymphoma, 3 with marginal zone lymphoma, 1 with Waldenström’s macroglobulinemia, and 1 with hairy cell leukemia.

Patients had received a median of 3 prior therapies (range, 1–14), and 36 (55%) had 3 or more prior therapies. Thirty-four patients (52%) were refractory to their prior therapy.

Efficacy

Dr O’Connor reported that higher doses of TGR-1202—1200 mg of the initial formulation and 600 mg or more of the micronized version—demonstrated rapid and profound responses in CLL, follicular lymphoma, and marginal zone lymphoma.

Responses have been limited in diffuse large B-cell lymphoma, Hodgkin lymphoma, and mantle cell lymphoma.

Eighty-eight percent of CLL patients achieved a nodal partial remission, and 63% achieved a response according to iwCLL criteria (Hallek 2008).

Safety and tolerability

Adverse events occurring in more than 10% of patients included nausea (41%), diarrhea (32%), fatigue (32%), headache (23%), vomiting (23%), cough (21%), decreased appetite (17%), rash (17%), constipation (14%), hypokalemia (14%), anemia, dizziness, dyspnea, neutropenia, and pyrexia (12% each), and abdominal pain (11%).

The most common grade 3-4 toxicity was neutropenia, occurring in 11% of patients.

“But other than that, the bulk of the toxicities in terms of grade 3-4 events were relatively modest,” Dr O’Connor said. “[I]t’s worth pointing out that diarrhea grade 3-4 only occurred in about 2% of patients in the population.”

Approximately 50% of patients (n=31) have been on study for more than 6 months, and approximately 30% taking a higher dose level have been on study for 6 months or more. Twenty-five of 37 patients exposed to 800 mg or more of the micronized formulation currently remain on study.

“So this gives you a sense that it is a very well-tolerated drug, with patients staying on for extended periods of time,” Dr O’Connor said.

He added that time on study becomes relevant in assessing some of the gastrointestinal toxicities seen with other PI3Kδ inhibitors, where it seems the median time to gastrointestinal toxicity is beyond 6 months.

“So far, and I’m willing to concede it’s early, but with half the patients being treated for over 6 months, [diarrhea/colitis] seems to be much lower than the experience with the other PI3 kinase inhibitors,” Dr O’Connor said.

“I think one of the more important features of [TGR-1202], and one that allows me to think we might be able to integrate this drug a little more readily into various combination regimens, are the discontinuations due to other adverse events.”

“Only 4% treated with [TGR-1202] had discontinuations secondary to adverse events. [A]nd it looks like the efficacy is in line with what we’d expect with some of the other drugs, but this [study] is actively accruing still.”

*Information in the abstract differs from that presented at the meeting.

 

 

Owen O’Connor, MD, PhD

Photo by Larry Young

 

LUGANO—Updated phase 1 results with TGR-1202 suggest this next-generation PI3kδ inhibitor lacks the hepatotoxicity associated with other PI3Kδ inhibitors.

Investigators also confirmed that no case of colitis has been reported to date with TGR-1202, and only 2% of evaluable patients on this trial have experienced grade 3-4 diarrhea.

The study is an ongoing, first-in-human trial in patients with relapsed or refractory hematologic malignancies.

Owen O’Connor, MD, PhD, of Columbia University Medical Center in New York, New York, shared results from this trial at the 13th International Congress on Malignant Lymphoma (abstract 038*). The trial is sponsored by TG Therapeutics, Inc., the company developing TGR-1202.

“TGR-1202 is a radically different sort of PI3kδ inhibitor,” Dr O’Connor said. “[I]t’s really a unique chemical entity that is different from the previous 2 structures [idelalisib and duvelisib] that you’ve probably heard something about.”

Study design

This ongoing trial of TGR-1202 is open to patients with hematologic malignancies who relapsed after or were refractory to at least 1 prior treatment regimen. Patients are eligible if they have an ECOG performance status of 2 or less with adequate organ system function, including absolute neutrophil count of 750/μL or greater and platelets of 50,000/μL or greater.

TGR-1202 is dosed orally, once a day in continuous, 28-day cycles. The original dose-escalation portion of the study was a classic 3+3 design, starting at 50 mg and increasing to 1800 mg. Patients who received prior therapy with a PI3K and/or mTOR inhibitor were excluded from the dose-escalation cohorts but were allowed in the expansion cohorts.

Dr O’Connor pointed out that, through cohort 5, TGR-1202 was taken in the fasting state. However, pharmacokinetic studies performed in the fed state revealed that the area under the curve (AUC) and Cmax could be doubled by taking the drug with food. So the expansions in the ongoing 800 mg and 1200 mg cohorts are being conducted in the fed state.

Dr O’Connor also noted that a subsequent, micronized version of TGR-1202 was developed. The micronization “essentially increases the surface area of the formulation, allowing for better bioavailability and markedly increases the AUC and Cmax exposure,” he said.

So the investigators conducted a second escalation with the micronized formulation, starting at 200 mg and increasing to 800 mg. At present, they are enrolling patients to the 800 mg and 1200 mg cohorts conducted in the fed state with the micronized formulation.

Demographics

Dr O’Connor presented data on 66 patients who were evaluable for safety and 51 for efficacy. The patients’ median age was 66 (range, 22–85), and 46 were male.

In all, there were 20 patients with chronic lymphocytic leukemia (CLL), 17 with follicular lymphoma, 10 with diffuse large B-cell lymphoma, 9 with Hodgkin lymphoma, 5 with mantle cell lymphoma, 3 with marginal zone lymphoma, 1 with Waldenström’s macroglobulinemia, and 1 with hairy cell leukemia.

Patients had received a median of 3 prior therapies (range, 1–14), and 36 (55%) had 3 or more prior therapies. Thirty-four patients (52%) were refractory to their prior therapy.

Efficacy

Dr O’Connor reported that higher doses of TGR-1202—1200 mg of the initial formulation and 600 mg or more of the micronized version—demonstrated rapid and profound responses in CLL, follicular lymphoma, and marginal zone lymphoma.

Responses have been limited in diffuse large B-cell lymphoma, Hodgkin lymphoma, and mantle cell lymphoma.

Eighty-eight percent of CLL patients achieved a nodal partial remission, and 63% achieved a response according to iwCLL criteria (Hallek 2008).

Safety and tolerability

Adverse events occurring in more than 10% of patients included nausea (41%), diarrhea (32%), fatigue (32%), headache (23%), vomiting (23%), cough (21%), decreased appetite (17%), rash (17%), constipation (14%), hypokalemia (14%), anemia, dizziness, dyspnea, neutropenia, and pyrexia (12% each), and abdominal pain (11%).

The most common grade 3-4 toxicity was neutropenia, occurring in 11% of patients.

“But other than that, the bulk of the toxicities in terms of grade 3-4 events were relatively modest,” Dr O’Connor said. “[I]t’s worth pointing out that diarrhea grade 3-4 only occurred in about 2% of patients in the population.”

Approximately 50% of patients (n=31) have been on study for more than 6 months, and approximately 30% taking a higher dose level have been on study for 6 months or more. Twenty-five of 37 patients exposed to 800 mg or more of the micronized formulation currently remain on study.

“So this gives you a sense that it is a very well-tolerated drug, with patients staying on for extended periods of time,” Dr O’Connor said.

He added that time on study becomes relevant in assessing some of the gastrointestinal toxicities seen with other PI3Kδ inhibitors, where it seems the median time to gastrointestinal toxicity is beyond 6 months.

“So far, and I’m willing to concede it’s early, but with half the patients being treated for over 6 months, [diarrhea/colitis] seems to be much lower than the experience with the other PI3 kinase inhibitors,” Dr O’Connor said.

“I think one of the more important features of [TGR-1202], and one that allows me to think we might be able to integrate this drug a little more readily into various combination regimens, are the discontinuations due to other adverse events.”

“Only 4% treated with [TGR-1202] had discontinuations secondary to adverse events. [A]nd it looks like the efficacy is in line with what we’d expect with some of the other drugs, but this [study] is actively accruing still.”

*Information in the abstract differs from that presented at the meeting.

Umbilical cord clamping

Photo courtesy of Meutia

Chaerani & Indradi Soemardjan

Umbilical cord milking may be more beneficial than delayed cord clamping for preterm infants delivered by Cesarean section, according to new research.

The study showed that cord milking produced greater blood circulation, higher hemoglobin levels, and higher blood pressure, but only in preterm infants delivered by Cesarean.

For preterm infants delivered vaginally, there was no significant difference between the milking and delayed clamping groups.

Anup C. Katheria, MD, of the Neonatal Research Institute at the Sharp Mary Birch Hospital in San Diego, California, and his colleagues reported these findings in Pediatrics.

The researchers noted that, in 2012, the American College of Obstetricians and Gynecologists recommended a 30- to 60-second delay before clamping the umbilical cord in all preterm deliveries.

This is thought to allow sufficient time for blood from the umbilical cord to fill the blood vessels in the infant’s lungs and to protect infants from intraventricular hemorrhage. However, some previous studies failed to find a reduction in intraventricular hemorrhage from delayed cord clamping among preterm infants delivered by Cesarean.

Dr Katheria and his colleagues theorized that the use of an anesthetic in Cesarean delivery reduces uterine contractions and therefore hinders the exodus of blood from the umbilical cord.

They reasoned that cord milking—encircling the cord with thumb and forefingers, gently squeezing, and slowly pushing the blood through the cord to the infant’s abdomen—might compensate for diminished blood flow through the umbilical cord and increase the amount of blood available to the infant.

To test this theory, the researchers enrolled 197 infants in a prospective study. Mothers went into labor at or before the 32nd week of pregnancy.

Of the 154 infants delivered by Cesarean, 75 were randomized to the umbilical cord milking (UCM) group and 79 to the delayed cord clamping (DCC) group.

Infants in the UCM group had significantly higher blood flow in the superior vena cava than those in the DCC group—93 ± 24 mL/kg per min vs 81 ± 29 mL/kg per min (P<0.05)—and a significantly higher output of blood from the right ventricle—261 ± 80 mL/kg per min vs 216 ±73 mL/kg per min (P<0.001).

These measures, taken together, are an indication of blood circulation in the brain and body.

Infants in the UCM group had significantly higher hemoglobin levels at birth than infants in the DCC group—16.3 ± 2.4 g/dL vs 15.6 ± 2.2 g/dL (P<0.05). And mean arterial pressure in the first 15 hours of life was significantly higher in the UCM group than the DCC group (P=0.02).

Among the 43 infants who were delivered vaginally, the researchers found no significant differences in outcomes between infants randomized to UCM or DCC.

Umbilical cord clamping

Photo courtesy of Meutia

Chaerani & Indradi Soemardjan

Umbilical cord milking may be more beneficial than delayed cord clamping for preterm infants delivered by Cesarean section, according to new research.

The study showed that cord milking produced greater blood circulation, higher hemoglobin levels, and higher blood pressure, but only in preterm infants delivered by Cesarean.

For preterm infants delivered vaginally, there was no significant difference between the milking and delayed clamping groups.

Anup C. Katheria, MD, of the Neonatal Research Institute at the Sharp Mary Birch Hospital in San Diego, California, and his colleagues reported these findings in Pediatrics.

The researchers noted that, in 2012, the American College of Obstetricians and Gynecologists recommended a 30- to 60-second delay before clamping the umbilical cord in all preterm deliveries.

This is thought to allow sufficient time for blood from the umbilical cord to fill the blood vessels in the infant’s lungs and to protect infants from intraventricular hemorrhage. However, some previous studies failed to find a reduction in intraventricular hemorrhage from delayed cord clamping among preterm infants delivered by Cesarean.

Dr Katheria and his colleagues theorized that the use of an anesthetic in Cesarean delivery reduces uterine contractions and therefore hinders the exodus of blood from the umbilical cord.

They reasoned that cord milking—encircling the cord with thumb and forefingers, gently squeezing, and slowly pushing the blood through the cord to the infant’s abdomen—might compensate for diminished blood flow through the umbilical cord and increase the amount of blood available to the infant.

To test this theory, the researchers enrolled 197 infants in a prospective study. Mothers went into labor at or before the 32nd week of pregnancy.

Of the 154 infants delivered by Cesarean, 75 were randomized to the umbilical cord milking (UCM) group and 79 to the delayed cord clamping (DCC) group.

Infants in the UCM group had significantly higher blood flow in the superior vena cava than those in the DCC group—93 ± 24 mL/kg per min vs 81 ± 29 mL/kg per min (P<0.05)—and a significantly higher output of blood from the right ventricle—261 ± 80 mL/kg per min vs 216 ±73 mL/kg per min (P<0.001).

These measures, taken together, are an indication of blood circulation in the brain and body.

Infants in the UCM group had significantly higher hemoglobin levels at birth than infants in the DCC group—16.3 ± 2.4 g/dL vs 15.6 ± 2.2 g/dL (P<0.05). And mean arterial pressure in the first 15 hours of life was significantly higher in the UCM group than the DCC group (P=0.02).

Among the 43 infants who were delivered vaginally, the researchers found no significant differences in outcomes between infants randomized to UCM or DCC.

Umbilical cord clamping

Photo courtesy of Meutia

Chaerani & Indradi Soemardjan

Umbilical cord milking may be more beneficial than delayed cord clamping for preterm infants delivered by Cesarean section, according to new research.

The study showed that cord milking produced greater blood circulation, higher hemoglobin levels, and higher blood pressure, but only in preterm infants delivered by Cesarean.

For preterm infants delivered vaginally, there was no significant difference between the milking and delayed clamping groups.

Anup C. Katheria, MD, of the Neonatal Research Institute at the Sharp Mary Birch Hospital in San Diego, California, and his colleagues reported these findings in Pediatrics.

The researchers noted that, in 2012, the American College of Obstetricians and Gynecologists recommended a 30- to 60-second delay before clamping the umbilical cord in all preterm deliveries.

This is thought to allow sufficient time for blood from the umbilical cord to fill the blood vessels in the infant’s lungs and to protect infants from intraventricular hemorrhage. However, some previous studies failed to find a reduction in intraventricular hemorrhage from delayed cord clamping among preterm infants delivered by Cesarean.

Dr Katheria and his colleagues theorized that the use of an anesthetic in Cesarean delivery reduces uterine contractions and therefore hinders the exodus of blood from the umbilical cord.

They reasoned that cord milking—encircling the cord with thumb and forefingers, gently squeezing, and slowly pushing the blood through the cord to the infant’s abdomen—might compensate for diminished blood flow through the umbilical cord and increase the amount of blood available to the infant.

To test this theory, the researchers enrolled 197 infants in a prospective study. Mothers went into labor at or before the 32nd week of pregnancy.

Of the 154 infants delivered by Cesarean, 75 were randomized to the umbilical cord milking (UCM) group and 79 to the delayed cord clamping (DCC) group.

Infants in the UCM group had significantly higher blood flow in the superior vena cava than those in the DCC group—93 ± 24 mL/kg per min vs 81 ± 29 mL/kg per min (P<0.05)—and a significantly higher output of blood from the right ventricle—261 ± 80 mL/kg per min vs 216 ±73 mL/kg per min (P<0.001).

These measures, taken together, are an indication of blood circulation in the brain and body.

Infants in the UCM group had significantly higher hemoglobin levels at birth than infants in the DCC group—16.3 ± 2.4 g/dL vs 15.6 ± 2.2 g/dL (P<0.05). And mean arterial pressure in the first 15 hours of life was significantly higher in the UCM group than the DCC group (P=0.02).

Among the 43 infants who were delivered vaginally, the researchers found no significant differences in outcomes between infants randomized to UCM or DCC.