Over the past five years, I have worked as a locum tenens hospitalist with more than 12 different locum tenens companies. I have learned a lot through this process. At one point, I even considered starting my own locum tenens company because of the frustrations I was feeling about the inefficiencies of many of these companies. I would like to help those of you either already practicing as a locum tenens physician or considering practicing through this process to make it as painless as possible.

Here are my tips to be aware of when choosing a locum tenens company to work with.

1. Bigger isn’t necessarily better. There are a few companies that advertise a lot. I’m sure you are all very well aware of them. They send out many emails, call numerous times, and somehow have a banner on every website you visit. These companies tend to have large overhead costs. These costs mean that your hourly rate may be lower. Smaller companies are sometimes less efficient, but as long as you make sure your expectations are heard, they will often give you a rate that the bigger companies cannot afford.
2. State your terms. As physicians, we are often not the most business savvy. Remember that locum tenens companies exist because there is a shortage of hospitalists in some areas. We need to be able to state certain terms; if you don’t like something, then make sure you add that into your contract. For example, patient safety should always come first; make sure you establish a cap for the number of patients you are willing to see per day.
3. Be protective of your CV. Remember that locum tenens companies profit when you work, so they will want to hand out your CV to as many hospitals as possible. While they make it sound like it is in your best interest, it may not be. If a company presents you to a hospital, most of the time the contract you sign with them states that they “own” your presentation for two years. This means that if you do not like the locum tenens company or if another company is offering you more for the same hospital, you have to work with the company that presented you first. Make sure you have a written agreement between you and your locum tenens company with regard to presentations stating which hospitals the locum tenens company can present you to, with a follow-up response from the locum tenens company stating when they presented you.
4. Your recruiter is your best advocate. Make sure you get along. Make sure you have very good communication with your recruiter, who is the one who will be doing all of your scheduling and negotiating. If you do not have a good relationship, move on to a new recruiter or to a new company.
5. Have fun! Working as a locum tenens physician, in my opinion, is the best of everything combined. There are very few jobs where you can decide when you want to work, dictate your terms, and get paid well doing something you love. Locum tenens takes a little bit of getting used to; when you have it figured out, it is empowering and enjoyable. TH

Geeta Arora, MD, is board certified in internal medicine and integrative holistic medicine.

Over the past five years, I have worked as a locum tenens hospitalist with more than 12 different locum tenens companies. I have learned a lot through this process. At one point, I even considered starting my own locum tenens company because of the frustrations I was feeling about the inefficiencies of many of these companies. I would like to help those of you either already practicing as a locum tenens physician or considering practicing through this process to make it as painless as possible.

Here are my tips to be aware of when choosing a locum tenens company to work with.

1. Bigger isn’t necessarily better. There are a few companies that advertise a lot. I’m sure you are all very well aware of them. They send out many emails, call numerous times, and somehow have a banner on every website you visit. These companies tend to have large overhead costs. These costs mean that your hourly rate may be lower. Smaller companies are sometimes less efficient, but as long as you make sure your expectations are heard, they will often give you a rate that the bigger companies cannot afford.
2. State your terms. As physicians, we are often not the most business savvy. Remember that locum tenens companies exist because there is a shortage of hospitalists in some areas. We need to be able to state certain terms; if you don’t like something, then make sure you add that into your contract. For example, patient safety should always come first; make sure you establish a cap for the number of patients you are willing to see per day.
3. Be protective of your CV. Remember that locum tenens companies profit when you work, so they will want to hand out your CV to as many hospitals as possible. While they make it sound like it is in your best interest, it may not be. If a company presents you to a hospital, most of the time the contract you sign with them states that they “own” your presentation for two years. This means that if you do not like the locum tenens company or if another company is offering you more for the same hospital, you have to work with the company that presented you first. Make sure you have a written agreement between you and your locum tenens company with regard to presentations stating which hospitals the locum tenens company can present you to, with a follow-up response from the locum tenens company stating when they presented you.
4. Your recruiter is your best advocate. Make sure you get along. Make sure you have very good communication with your recruiter, who is the one who will be doing all of your scheduling and negotiating. If you do not have a good relationship, move on to a new recruiter or to a new company.
5. Have fun! Working as a locum tenens physician, in my opinion, is the best of everything combined. There are very few jobs where you can decide when you want to work, dictate your terms, and get paid well doing something you love. Locum tenens takes a little bit of getting used to; when you have it figured out, it is empowering and enjoyable. TH

Geeta Arora, MD, is board certified in internal medicine and integrative holistic medicine.

Over the past five years, I have worked as a locum tenens hospitalist with more than 12 different locum tenens companies. I have learned a lot through this process. At one point, I even considered starting my own locum tenens company because of the frustrations I was feeling about the inefficiencies of many of these companies. I would like to help those of you either already practicing as a locum tenens physician or considering practicing through this process to make it as painless as possible.

Here are my tips to be aware of when choosing a locum tenens company to work with.

1. Bigger isn’t necessarily better. There are a few companies that advertise a lot. I’m sure you are all very well aware of them. They send out many emails, call numerous times, and somehow have a banner on every website you visit. These companies tend to have large overhead costs. These costs mean that your hourly rate may be lower. Smaller companies are sometimes less efficient, but as long as you make sure your expectations are heard, they will often give you a rate that the bigger companies cannot afford.
2. State your terms. As physicians, we are often not the most business savvy. Remember that locum tenens companies exist because there is a shortage of hospitalists in some areas. We need to be able to state certain terms; if you don’t like something, then make sure you add that into your contract. For example, patient safety should always come first; make sure you establish a cap for the number of patients you are willing to see per day.
3. Be protective of your CV. Remember that locum tenens companies profit when you work, so they will want to hand out your CV to as many hospitals as possible. While they make it sound like it is in your best interest, it may not be. If a company presents you to a hospital, most of the time the contract you sign with them states that they “own” your presentation for two years. This means that if you do not like the locum tenens company or if another company is offering you more for the same hospital, you have to work with the company that presented you first. Make sure you have a written agreement between you and your locum tenens company with regard to presentations stating which hospitals the locum tenens company can present you to, with a follow-up response from the locum tenens company stating when they presented you.
4. Your recruiter is your best advocate. Make sure you get along. Make sure you have very good communication with your recruiter, who is the one who will be doing all of your scheduling and negotiating. If you do not have a good relationship, move on to a new recruiter or to a new company.
5. Have fun! Working as a locum tenens physician, in my opinion, is the best of everything combined. There are very few jobs where you can decide when you want to work, dictate your terms, and get paid well doing something you love. Locum tenens takes a little bit of getting used to; when you have it figured out, it is empowering and enjoyable. TH

Geeta Arora, MD, is board certified in internal medicine and integrative holistic medicine.

NEW YORK (Reuters Health) - Outcomes of inpatient laparoscopic cholecystectomy in Medicare patients vary widely among hospitals, and most adverse outcomes occur well after patients have been discharged, new findings show.

While the overall adverse outcome rate was 20.7%, risk-adjusted adverse outcomes ranged from 10% in the best-performing decile of hospitals to 32.1% for the worst-performing decile, Dr. Donald E. Fry of MPA Healthcare Solutions in Chicago and colleagues found.

"These differences indicate that a significant number of readmissions and overall adverse outcomes of care after laparoscopic cholecystectomy are potentially preventable," Dr. Fry and his team state in their report, online February 1 in the Annals of Surgery.

Risk-adjusted measurement of care has typically been limited to inpatient events and 30-day mortality rates, they note, but declines in mortality rates, shorter patient stays and a shift toward ambulatory procedures have made this measurement more difficult.

"Surgery for gallbladder disease has experienced one of the most dramatic transitions from extended inpatient care to outpatient or limited inpatient care," they write.

To compare outcomes among hospitals, Dr. Fry and his team looked at Medicare data for 2010-2012 including both inpatient and 90-day post-discharge adverse outcomes for inpatient laparoscopic cholecystectomy.

They created a developmental database including more than 73,000 patients to construct predictive models for adverse outcomes, and a database of more than 83,000 patients treated at 1,570 hospitals, each with 20 or more qualifying cases and 4.5 or more predicted total adverse outcomes, to compare performance.

A total of 509 patients (0.6%) died in the hospital, 5,761 (6.9%) had prolonged length of stay, 1,154 (1.4%) died within 90 days of discharge without being readmitted, and 12,038 (14.5%) were readmitted at least once in the 90 days after discharge.

Gastrointestinal, infectious and cardiovascular events were the most common readmission causes.

"Strategies for improvement begin with hospitals and surgeons knowing what the results of their care happen to be," Dr. Fry told Reuters Health by email. "Since many readmissions and Emergency Department visits of post-discharge surgical cases occur at hospitals other than the facility of the index

hospitalization, the actual results of care may not be appreciated by the providers."

He added: "Improvement strategies need to focus on the reasons patients were readmitted. Better pain management will reduce readmissions for constipation, abdominal distention, nausea and vomiting. Increased contact by clinicians with their patients after discharge can identify early evidence of

pulmonary problems or potential urinary tract infection. Earlier recognition of evolving issues can provide interventions that avoid readmissions. Better overall strategies to avoid cardiac events and hypovolemia that may play in central nervous system events and renal failure should be of benefit."

Dr. Fry and his colleagues are now investigating whether similar differences in outcomes occur with other types of surgical procedures, as well as the frequency of and reasons for post-discharge emergency room visits.

"A final message for surgeons in this research is that Medicare has begun an initiative into bundled payments," Dr. Fry said. "Surgeons and hospitals need to establish better trackingmethods for post-discharge patients so that they know the results of care and so that they can develop focused strategies for better outcomes. There will be a substantial financial penalty for those who cannot adapt to the new payment model that CMS is implementing."

NEW YORK (Reuters Health) - Outcomes of inpatient laparoscopic cholecystectomy in Medicare patients vary widely among hospitals, and most adverse outcomes occur well after patients have been discharged, new findings show.

While the overall adverse outcome rate was 20.7%, risk-adjusted adverse outcomes ranged from 10% in the best-performing decile of hospitals to 32.1% for the worst-performing decile, Dr. Donald E. Fry of MPA Healthcare Solutions in Chicago and colleagues found.

"These differences indicate that a significant number of readmissions and overall adverse outcomes of care after laparoscopic cholecystectomy are potentially preventable," Dr. Fry and his team state in their report, online February 1 in the Annals of Surgery.

Risk-adjusted measurement of care has typically been limited to inpatient events and 30-day mortality rates, they note, but declines in mortality rates, shorter patient stays and a shift toward ambulatory procedures have made this measurement more difficult.

"Surgery for gallbladder disease has experienced one of the most dramatic transitions from extended inpatient care to outpatient or limited inpatient care," they write.

To compare outcomes among hospitals, Dr. Fry and his team looked at Medicare data for 2010-2012 including both inpatient and 90-day post-discharge adverse outcomes for inpatient laparoscopic cholecystectomy.

They created a developmental database including more than 73,000 patients to construct predictive models for adverse outcomes, and a database of more than 83,000 patients treated at 1,570 hospitals, each with 20 or more qualifying cases and 4.5 or more predicted total adverse outcomes, to compare performance.

A total of 509 patients (0.6%) died in the hospital, 5,761 (6.9%) had prolonged length of stay, 1,154 (1.4%) died within 90 days of discharge without being readmitted, and 12,038 (14.5%) were readmitted at least once in the 90 days after discharge.

Gastrointestinal, infectious and cardiovascular events were the most common readmission causes.

"Strategies for improvement begin with hospitals and surgeons knowing what the results of their care happen to be," Dr. Fry told Reuters Health by email. "Since many readmissions and Emergency Department visits of post-discharge surgical cases occur at hospitals other than the facility of the index

hospitalization, the actual results of care may not be appreciated by the providers."

He added: "Improvement strategies need to focus on the reasons patients were readmitted. Better pain management will reduce readmissions for constipation, abdominal distention, nausea and vomiting. Increased contact by clinicians with their patients after discharge can identify early evidence of

pulmonary problems or potential urinary tract infection. Earlier recognition of evolving issues can provide interventions that avoid readmissions. Better overall strategies to avoid cardiac events and hypovolemia that may play in central nervous system events and renal failure should be of benefit."

Dr. Fry and his colleagues are now investigating whether similar differences in outcomes occur with other types of surgical procedures, as well as the frequency of and reasons for post-discharge emergency room visits.

"A final message for surgeons in this research is that Medicare has begun an initiative into bundled payments," Dr. Fry said. "Surgeons and hospitals need to establish better trackingmethods for post-discharge patients so that they know the results of care and so that they can develop focused strategies for better outcomes. There will be a substantial financial penalty for those who cannot adapt to the new payment model that CMS is implementing."

NEW YORK (Reuters Health) - Outcomes of inpatient laparoscopic cholecystectomy in Medicare patients vary widely among hospitals, and most adverse outcomes occur well after patients have been discharged, new findings show.

While the overall adverse outcome rate was 20.7%, risk-adjusted adverse outcomes ranged from 10% in the best-performing decile of hospitals to 32.1% for the worst-performing decile, Dr. Donald E. Fry of MPA Healthcare Solutions in Chicago and colleagues found.

"These differences indicate that a significant number of readmissions and overall adverse outcomes of care after laparoscopic cholecystectomy are potentially preventable," Dr. Fry and his team state in their report, online February 1 in the Annals of Surgery.

Risk-adjusted measurement of care has typically been limited to inpatient events and 30-day mortality rates, they note, but declines in mortality rates, shorter patient stays and a shift toward ambulatory procedures have made this measurement more difficult.

"Surgery for gallbladder disease has experienced one of the most dramatic transitions from extended inpatient care to outpatient or limited inpatient care," they write.

To compare outcomes among hospitals, Dr. Fry and his team looked at Medicare data for 2010-2012 including both inpatient and 90-day post-discharge adverse outcomes for inpatient laparoscopic cholecystectomy.

They created a developmental database including more than 73,000 patients to construct predictive models for adverse outcomes, and a database of more than 83,000 patients treated at 1,570 hospitals, each with 20 or more qualifying cases and 4.5 or more predicted total adverse outcomes, to compare performance.

A total of 509 patients (0.6%) died in the hospital, 5,761 (6.9%) had prolonged length of stay, 1,154 (1.4%) died within 90 days of discharge without being readmitted, and 12,038 (14.5%) were readmitted at least once in the 90 days after discharge.

Gastrointestinal, infectious and cardiovascular events were the most common readmission causes.

"Strategies for improvement begin with hospitals and surgeons knowing what the results of their care happen to be," Dr. Fry told Reuters Health by email. "Since many readmissions and Emergency Department visits of post-discharge surgical cases occur at hospitals other than the facility of the index

hospitalization, the actual results of care may not be appreciated by the providers."

He added: "Improvement strategies need to focus on the reasons patients were readmitted. Better pain management will reduce readmissions for constipation, abdominal distention, nausea and vomiting. Increased contact by clinicians with their patients after discharge can identify early evidence of

pulmonary problems or potential urinary tract infection. Earlier recognition of evolving issues can provide interventions that avoid readmissions. Better overall strategies to avoid cardiac events and hypovolemia that may play in central nervous system events and renal failure should be of benefit."

Dr. Fry and his colleagues are now investigating whether similar differences in outcomes occur with other types of surgical procedures, as well as the frequency of and reasons for post-discharge emergency room visits.

"A final message for surgeons in this research is that Medicare has begun an initiative into bundled payments," Dr. Fry said. "Surgeons and hospitals need to establish better trackingmethods for post-discharge patients so that they know the results of care and so that they can develop focused strategies for better outcomes. There will be a substantial financial penalty for those who cannot adapt to the new payment model that CMS is implementing."

DNA coiled around histones

Image by Eric Smith

Measuring circulating histones may help physicians predict the onset of thrombocytopenia or allow them to monitor the condition in patients who are critically ill, according to researchers.

They noted that histones induce profound thrombocytopenia in mice and are associated with organ injury when released after extensive cell damage in patients who are critically ill.

So the team decided to examine the association between circulating histones and thrombocytopenia in patients in the intensive care unit (ICU).

Cheng-Hock Toh, MD, of the University of Liverpool in the UK, and his colleagues conducted this research and reported the results in a letter to JAMA.

The researchers analyzed 56 patients with thrombocytopenia and 56 controls with normal platelet counts who were admitted to the ICU at Royal Liverpool University Hospital between June 2013 and January 2014.

Thrombocytopenia was defined as a platelet count less than 150 × 10³/µL, a 25% or greater decrease in platelet count, or both within the first 96 hours of ICU admission.

The researchers noted that, at approximately 30 µg/mL, histones bind platelets and cause platelet aggregation, which results in profound thrombocytopenia in mice.

So the team used this as a cutoff to stratify thrombocytopenic patients. A “high” level of histones was 30 µg/mL or greater, and a “low” level was below 30 µg/mL.

The researchers detected circulating histones in 51 of the thrombocytopenic patients and 31 controls—91% and 55%, respectively (P<0.001). Histone levels were 2.5- to 5.5-fold higher in thrombocytopenic patients than in controls.

Thrombocytopenic patients with high histone levels at ICU admission had significantly lower platelet counts and a significantly higher percentage of decrease in platelet counts at 24 hours (P=0.02 and P=0.04, respectively) and 48 hours (P=0.003 and P=0.005, respectively) after admission.

High admission histone levels were associated with moderate to severe thrombocytopenia and the development of clinically important thrombocytopenia (P<0.001).

A 30 µg/mL histone concentration was able to predict thrombocytopenia with 76% sensitivity and 91% specificity. The positive predictive value was 79.4%, and the negative predictive value was 89.2%.

DNA coiled around histones

Image by Eric Smith

Measuring circulating histones may help physicians predict the onset of thrombocytopenia or allow them to monitor the condition in patients who are critically ill, according to researchers.

They noted that histones induce profound thrombocytopenia in mice and are associated with organ injury when released after extensive cell damage in patients who are critically ill.

So the team decided to examine the association between circulating histones and thrombocytopenia in patients in the intensive care unit (ICU).

Cheng-Hock Toh, MD, of the University of Liverpool in the UK, and his colleagues conducted this research and reported the results in a letter to JAMA.

The researchers analyzed 56 patients with thrombocytopenia and 56 controls with normal platelet counts who were admitted to the ICU at Royal Liverpool University Hospital between June 2013 and January 2014.

Thrombocytopenia was defined as a platelet count less than 150 × 10³/µL, a 25% or greater decrease in platelet count, or both within the first 96 hours of ICU admission.

The researchers noted that, at approximately 30 µg/mL, histones bind platelets and cause platelet aggregation, which results in profound thrombocytopenia in mice.

So the team used this as a cutoff to stratify thrombocytopenic patients. A “high” level of histones was 30 µg/mL or greater, and a “low” level was below 30 µg/mL.

The researchers detected circulating histones in 51 of the thrombocytopenic patients and 31 controls—91% and 55%, respectively (P<0.001). Histone levels were 2.5- to 5.5-fold higher in thrombocytopenic patients than in controls.

Thrombocytopenic patients with high histone levels at ICU admission had significantly lower platelet counts and a significantly higher percentage of decrease in platelet counts at 24 hours (P=0.02 and P=0.04, respectively) and 48 hours (P=0.003 and P=0.005, respectively) after admission.

High admission histone levels were associated with moderate to severe thrombocytopenia and the development of clinically important thrombocytopenia (P<0.001).

A 30 µg/mL histone concentration was able to predict thrombocytopenia with 76% sensitivity and 91% specificity. The positive predictive value was 79.4%, and the negative predictive value was 89.2%.

DNA coiled around histones

Image by Eric Smith

Measuring circulating histones may help physicians predict the onset of thrombocytopenia or allow them to monitor the condition in patients who are critically ill, according to researchers.

They noted that histones induce profound thrombocytopenia in mice and are associated with organ injury when released after extensive cell damage in patients who are critically ill.

So the team decided to examine the association between circulating histones and thrombocytopenia in patients in the intensive care unit (ICU).

Cheng-Hock Toh, MD, of the University of Liverpool in the UK, and his colleagues conducted this research and reported the results in a letter to JAMA.

The researchers analyzed 56 patients with thrombocytopenia and 56 controls with normal platelet counts who were admitted to the ICU at Royal Liverpool University Hospital between June 2013 and January 2014.

Thrombocytopenia was defined as a platelet count less than 150 × 10³/µL, a 25% or greater decrease in platelet count, or both within the first 96 hours of ICU admission.

The researchers noted that, at approximately 30 µg/mL, histones bind platelets and cause platelet aggregation, which results in profound thrombocytopenia in mice.

So the team used this as a cutoff to stratify thrombocytopenic patients. A “high” level of histones was 30 µg/mL or greater, and a “low” level was below 30 µg/mL.

The researchers detected circulating histones in 51 of the thrombocytopenic patients and 31 controls—91% and 55%, respectively (P<0.001). Histone levels were 2.5- to 5.5-fold higher in thrombocytopenic patients than in controls.

Thrombocytopenic patients with high histone levels at ICU admission had significantly lower platelet counts and a significantly higher percentage of decrease in platelet counts at 24 hours (P=0.02 and P=0.04, respectively) and 48 hours (P=0.003 and P=0.005, respectively) after admission.

High admission histone levels were associated with moderate to severe thrombocytopenia and the development of clinically important thrombocytopenia (P<0.001).

A 30 µg/mL histone concentration was able to predict thrombocytopenia with 76% sensitivity and 91% specificity. The positive predictive value was 79.4%, and the negative predictive value was 89.2%.

The US Food and Drug Administration (FDA) has granted orphan drug designation for BPX-501, an adjunct T-cell therapy.

The designation is for the combination of BPX-501 genetically modified T cells and the activator agent rimiducid as replacement T-cell therapy for the treatment of immunodeficiency and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplant (HSCT).

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.

The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. Infusion of rimiducid is designed to trigger activation of this domain of caspase-9 (iCasp9), which leads to selective apoptosis of the CaspaCIDe-containing cells.

This technology is intended to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs, ostensibly enabling physicians to more safely perform haploidentical HSCTs by adding back the BPX-501 genetically engineered T cells to speed immune reconstitution and provide control over viral infections.

Following an allogeneic HSCT, a lack of sufficient mature T cells constitutes immune deficiency that can contribute to infections, viral reactivation, and relapse.

The ability to correct this immune deficiency by adding back mature donor T cells, without raising the risk of uncontrollable GVHD, has the potential to change the risk profile of allogeneic transplant, according to Bellicum Pharmaceuticals, the company developing BPX-501.

BPX-501 is being evaluated in multiple phase 1/2 trials in adults and pediatric patients with leukemias, lymphomas, and genetic blood diseases in the US and Europe.

About orphan designation

The FDA’s Office of Orphan Products Development grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases and disorders that affect fewer than 200,000 people in the US.

Orphan designation qualifies a company for various development incentives, including tax credits for qualified clinical testing and marketing exclusivity for a period of 7 years.

The US Food and Drug Administration (FDA) has granted orphan drug designation for BPX-501, an adjunct T-cell therapy.

The designation is for the combination of BPX-501 genetically modified T cells and the activator agent rimiducid as replacement T-cell therapy for the treatment of immunodeficiency and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplant (HSCT).

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.

The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. Infusion of rimiducid is designed to trigger activation of this domain of caspase-9 (iCasp9), which leads to selective apoptosis of the CaspaCIDe-containing cells.

This technology is intended to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs, ostensibly enabling physicians to more safely perform haploidentical HSCTs by adding back the BPX-501 genetically engineered T cells to speed immune reconstitution and provide control over viral infections.

Following an allogeneic HSCT, a lack of sufficient mature T cells constitutes immune deficiency that can contribute to infections, viral reactivation, and relapse.

The ability to correct this immune deficiency by adding back mature donor T cells, without raising the risk of uncontrollable GVHD, has the potential to change the risk profile of allogeneic transplant, according to Bellicum Pharmaceuticals, the company developing BPX-501.

BPX-501 is being evaluated in multiple phase 1/2 trials in adults and pediatric patients with leukemias, lymphomas, and genetic blood diseases in the US and Europe.

About orphan designation

The FDA’s Office of Orphan Products Development grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases and disorders that affect fewer than 200,000 people in the US.

Orphan designation qualifies a company for various development incentives, including tax credits for qualified clinical testing and marketing exclusivity for a period of 7 years.

The US Food and Drug Administration (FDA) has granted orphan drug designation for BPX-501, an adjunct T-cell therapy.

The designation is for the combination of BPX-501 genetically modified T cells and the activator agent rimiducid as replacement T-cell therapy for the treatment of immunodeficiency and graft-versus-host disease (GVHD) after allogeneic hematopoietic stem cell transplant (HSCT).

BPX-501 consists of genetically modified donor T cells incorporating the CaspaCIDe safety switch, which is designed to eliminate cells in the event of toxicity.

The CaspaCIDe switch consists of the CID-binding domain coupled to the signaling domain of caspase-9, an enzyme that is part of the apoptotic pathway. Infusion of rimiducid is designed to trigger activation of this domain of caspase-9 (iCasp9), which leads to selective apoptosis of the CaspaCIDe-containing cells.

This technology is intended to provide a safety net to eliminate BPX-501 alloreactive T cells if severe GVHD occurs, ostensibly enabling physicians to more safely perform haploidentical HSCTs by adding back the BPX-501 genetically engineered T cells to speed immune reconstitution and provide control over viral infections.

Following an allogeneic HSCT, a lack of sufficient mature T cells constitutes immune deficiency that can contribute to infections, viral reactivation, and relapse.

The ability to correct this immune deficiency by adding back mature donor T cells, without raising the risk of uncontrollable GVHD, has the potential to change the risk profile of allogeneic transplant, according to Bellicum Pharmaceuticals, the company developing BPX-501.

BPX-501 is being evaluated in multiple phase 1/2 trials in adults and pediatric patients with leukemias, lymphomas, and genetic blood diseases in the US and Europe.

About orphan designation

The FDA’s Office of Orphan Products Development grants orphan designation to drugs and biologics intended to treat, diagnose, or prevent rare diseases and disorders that affect fewer than 200,000 people in the US.

Orphan designation qualifies a company for various development incentives, including tax credits for qualified clinical testing and marketing exclusivity for a period of 7 years.

Mesenchymal stem cells

HONOLULU—A mesenchymal stem cell (MSC) product has shown promise for treating children with steroid-refractory acute graft-versus-host disease (aGVHD), according to researchers.

The product, remestemcel-L (MSC-100-IV, formerly Prochymal), produced an overall response rate of 65% by 28 days after treatment.

And patients who responded to remestemcel-L had significantly better survival at day 100 than patients who did not respond.

Joanne Kurtzberg, MD, of Duke University Medical Center in Durham, North Carolina, presented these data at the 2016 BMT Tandem Meetings (abstract 54). The study was sponsored by Mesoblast, the company developing remestemcel-L.

“There is a critical and urgent need for an effective and well-tolerated treatment for the very ill children who develop [GVHD] after a bone marrow transplant,” Dr Kurtzberg said. “While, historically, there is a high mortality rate associated with this complication, we are now seeing the majority of children who receive Mesoblast’s cell therapy respond and survive.”

For this study, Dr Kurtzberg and her colleagues assessed 241 children treated in Mesoblast’s Expanded Access Program, which was conducted at 50 sites in North American and Europe from 2007 to 2014.

Forty-five percent of the children received a bone marrow transplant, 31% received cord blood, and 45% had a mismatched transplant. Their median age was 9.6 (range, 2 months-18 years), 61% were male, and 60% were Caucasian.

All of the patients had steroid-refractory aGVHD. Thirty percent had grade C GVHD, 50% had grade D, 50% had multi-organ disease, and 79% were classified as “high-risk” disease.

Treatment

All 241 children received remestemcel-L, which consists of bone-marrow derived and culture-expanded human MSCs. The initial treatment was 2 million MSCs/kg twice a week for 4 weeks, at least 3 days apart.

Continued treatment consisted of 2 million MSCs/kg once a week for 4 weeks if patients achieved a partial or mixed response (improvement in one organ with deterioration in another organ) at the day-28 assessment.

The patients received a total of 2434 infusions. The median number of infusions was 11 (range, 1-24), and the median duration of treatment was 46 days (range, 1-186). Eighty-one percent (123/152) of eligible patients with a partial or mixed response at day 28 received continued therapy of 1 infusion a week for 4 weeks.

Results

Fifty-seven percent of patients (n=138) had at least 1 serious adverse event. About 5% (n=11) were considered treatment-related, and 1.7% (n=4) led to study discontinuation. There was 1 infusion reaction.

Thirty-four percent of patients (n=81) died through day 100, and 2.5% (n=6) experienced a relapse of their underlying disease.

At day 28 after treatment, the overall response rate was 65%, with a complete response rate of 14% and  partial response rate of 51%. Responses were observed for all aGVHD grades and did not differ by baseline organ involvement.

When remestemcel-L was used as front-line therapy following steroid failure, the response rate was 81%. In patients with gastrointestinal and liver disease, the overall response rates were 65% and 62%, respectively.

Children who achieved a response at day 28 had significantly improved survival, compared to those who did not—82% and 39%, respectively (P<0.0001).

Extending therapy beyond day 28 in children who had a mixed response at day 28 resulted in significantly improved survival as well. Survival was 72% for these patients, compared to 18% for patients with a mixed response who did not receive additional therapy (P=0.003).

Mesoblast is now conducting a 60-patient, open label, phase 3 trial using remestemcel-L as front-line therapy in children with steroid-refractory aGVHD.

Mesenchymal stem cells

HONOLULU—A mesenchymal stem cell (MSC) product has shown promise for treating children with steroid-refractory acute graft-versus-host disease (aGVHD), according to researchers.

The product, remestemcel-L (MSC-100-IV, formerly Prochymal), produced an overall response rate of 65% by 28 days after treatment.

And patients who responded to remestemcel-L had significantly better survival at day 100 than patients who did not respond.

Joanne Kurtzberg, MD, of Duke University Medical Center in Durham, North Carolina, presented these data at the 2016 BMT Tandem Meetings (abstract 54). The study was sponsored by Mesoblast, the company developing remestemcel-L.

“There is a critical and urgent need for an effective and well-tolerated treatment for the very ill children who develop [GVHD] after a bone marrow transplant,” Dr Kurtzberg said. “While, historically, there is a high mortality rate associated with this complication, we are now seeing the majority of children who receive Mesoblast’s cell therapy respond and survive.”

For this study, Dr Kurtzberg and her colleagues assessed 241 children treated in Mesoblast’s Expanded Access Program, which was conducted at 50 sites in North American and Europe from 2007 to 2014.

Forty-five percent of the children received a bone marrow transplant, 31% received cord blood, and 45% had a mismatched transplant. Their median age was 9.6 (range, 2 months-18 years), 61% were male, and 60% were Caucasian.

All of the patients had steroid-refractory aGVHD. Thirty percent had grade C GVHD, 50% had grade D, 50% had multi-organ disease, and 79% were classified as “high-risk” disease.

Treatment

All 241 children received remestemcel-L, which consists of bone-marrow derived and culture-expanded human MSCs. The initial treatment was 2 million MSCs/kg twice a week for 4 weeks, at least 3 days apart.

Continued treatment consisted of 2 million MSCs/kg once a week for 4 weeks if patients achieved a partial or mixed response (improvement in one organ with deterioration in another organ) at the day-28 assessment.

The patients received a total of 2434 infusions. The median number of infusions was 11 (range, 1-24), and the median duration of treatment was 46 days (range, 1-186). Eighty-one percent (123/152) of eligible patients with a partial or mixed response at day 28 received continued therapy of 1 infusion a week for 4 weeks.

Results

Fifty-seven percent of patients (n=138) had at least 1 serious adverse event. About 5% (n=11) were considered treatment-related, and 1.7% (n=4) led to study discontinuation. There was 1 infusion reaction.

Thirty-four percent of patients (n=81) died through day 100, and 2.5% (n=6) experienced a relapse of their underlying disease.

At day 28 after treatment, the overall response rate was 65%, with a complete response rate of 14% and  partial response rate of 51%. Responses were observed for all aGVHD grades and did not differ by baseline organ involvement.

When remestemcel-L was used as front-line therapy following steroid failure, the response rate was 81%. In patients with gastrointestinal and liver disease, the overall response rates were 65% and 62%, respectively.

Children who achieved a response at day 28 had significantly improved survival, compared to those who did not—82% and 39%, respectively (P<0.0001).

Extending therapy beyond day 28 in children who had a mixed response at day 28 resulted in significantly improved survival as well. Survival was 72% for these patients, compared to 18% for patients with a mixed response who did not receive additional therapy (P=0.003).

Mesoblast is now conducting a 60-patient, open label, phase 3 trial using remestemcel-L as front-line therapy in children with steroid-refractory aGVHD.

Mesenchymal stem cells

HONOLULU—A mesenchymal stem cell (MSC) product has shown promise for treating children with steroid-refractory acute graft-versus-host disease (aGVHD), according to researchers.

The product, remestemcel-L (MSC-100-IV, formerly Prochymal), produced an overall response rate of 65% by 28 days after treatment.

And patients who responded to remestemcel-L had significantly better survival at day 100 than patients who did not respond.

Joanne Kurtzberg, MD, of Duke University Medical Center in Durham, North Carolina, presented these data at the 2016 BMT Tandem Meetings (abstract 54). The study was sponsored by Mesoblast, the company developing remestemcel-L.

“There is a critical and urgent need for an effective and well-tolerated treatment for the very ill children who develop [GVHD] after a bone marrow transplant,” Dr Kurtzberg said. “While, historically, there is a high mortality rate associated with this complication, we are now seeing the majority of children who receive Mesoblast’s cell therapy respond and survive.”

For this study, Dr Kurtzberg and her colleagues assessed 241 children treated in Mesoblast’s Expanded Access Program, which was conducted at 50 sites in North American and Europe from 2007 to 2014.

Forty-five percent of the children received a bone marrow transplant, 31% received cord blood, and 45% had a mismatched transplant. Their median age was 9.6 (range, 2 months-18 years), 61% were male, and 60% were Caucasian.

All of the patients had steroid-refractory aGVHD. Thirty percent had grade C GVHD, 50% had grade D, 50% had multi-organ disease, and 79% were classified as “high-risk” disease.

Treatment

All 241 children received remestemcel-L, which consists of bone-marrow derived and culture-expanded human MSCs. The initial treatment was 2 million MSCs/kg twice a week for 4 weeks, at least 3 days apart.

Continued treatment consisted of 2 million MSCs/kg once a week for 4 weeks if patients achieved a partial or mixed response (improvement in one organ with deterioration in another organ) at the day-28 assessment.

The patients received a total of 2434 infusions. The median number of infusions was 11 (range, 1-24), and the median duration of treatment was 46 days (range, 1-186). Eighty-one percent (123/152) of eligible patients with a partial or mixed response at day 28 received continued therapy of 1 infusion a week for 4 weeks.

Results

Fifty-seven percent of patients (n=138) had at least 1 serious adverse event. About 5% (n=11) were considered treatment-related, and 1.7% (n=4) led to study discontinuation. There was 1 infusion reaction.

Thirty-four percent of patients (n=81) died through day 100, and 2.5% (n=6) experienced a relapse of their underlying disease.

At day 28 after treatment, the overall response rate was 65%, with a complete response rate of 14% and  partial response rate of 51%. Responses were observed for all aGVHD grades and did not differ by baseline organ involvement.

When remestemcel-L was used as front-line therapy following steroid failure, the response rate was 81%. In patients with gastrointestinal and liver disease, the overall response rates were 65% and 62%, respectively.

Children who achieved a response at day 28 had significantly improved survival, compared to those who did not—82% and 39%, respectively (P<0.0001).

Extending therapy beyond day 28 in children who had a mixed response at day 28 resulted in significantly improved survival as well. Survival was 72% for these patients, compared to 18% for patients with a mixed response who did not receive additional therapy (P=0.003).

Mesoblast is now conducting a 60-patient, open label, phase 3 trial using remestemcel-L as front-line therapy in children with steroid-refractory aGVHD.

Doctor and patient

Photo by Logan Tuttle

A new study suggests children with acute lymphoblastic leukemia (ALL) are more likely to suffer early relapse if they live in high-poverty areas.

All of the children studied received the same treatment, and the rates of relapse were similar regardless of poverty level.

But early relapse was more common among children from poorer areas. These children also had a lower rate of 5-year overall survival, but the difference was not significant.

Kira Bona, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues reported these results in Pediatric Blood & Cancer.

The team examined outcomes for 575 children, ages 1 to 18, with newly diagnosed ALL who were treated on Dana-Farber Cancer Institute ALL Consortium Protocols at 7 major academic medical centers in the US between 2000 and 2010.

Using US Census Bureau criteria, the investigators defined high-poverty areas as zip codes where 20% or more of residents have incomes below the federal poverty level. For a family of 4, this translates to an annual income of $24,250 or less.

Dr Bona and her colleagues found the overall rates of relapse were similar between children from low-poverty areas and those from high-poverty areas.

However, the timing of relapse differed significantly. Ninety-two percent of children from high-poverty areas who relapsed suffered early relapse (less than 36 months after first achieving complete remission), while 48% of the other children who relapsed did so early (P=0.008).

The 5-year overall survival was 85% for children from high-poverty areas and 92% for children from low-poverty areas. This difference is statistically significant when considered on its own (P=0.02) but not when the analysis is adjusted for other factors (P=0.07).

Still, the investigators said this suggests a possible disparity in survival.

“These children are getting the same best possible care at well-resourced institutions from highly trained clinicians, and we’re still seeing disparities,” Dr Bona said. “In trying to improve cure rates, we, as a field, have focused almost exclusively on biology. If we want to move forward, we also have to look at social determinants.”

Next steps

Dr Bona and her colleagues are undertaking further research designed to delve deeper into the relationship between socioeconomic status and outcomes and to allow for the development of poverty-targeted interventions.

As part of a prospective trial for children with ALL, the researchers will investigate associations between disease outcomes and the socioeconomic status of patients’ families, using a targetable measure of socioeconomic status called material hardship (food, housing, and/or energy insecurity).

The researchers will also investigate possible mechanisms underlying the relationship between socioeconomic status and early relapse, including adherence to oral chemotherapy and delays or dose reductions in chemotherapy due to a child’s underlying health.

In another study, investigators will conduct in-depth interviews with patients’ families, probing their knowledge and experience to pinpoint factors that might explain the disparity in outcomes and identify factors that can be targeted with interventions.

“Doing these next 2 studies is incredibly important,” Dr Bona said. “This study told us that simply providing the current best treatment regimen is not good enough if our goal is to cure every child with cancer.”

“At the same time that we develop new drugs and new treatment protocols, we need to address social determinants of health. Findings from these next studies will help us develop specific interventions to address disparities in outcomes. That’s an amazing opportunity.”

Doctor and patient

Photo by Logan Tuttle

A new study suggests children with acute lymphoblastic leukemia (ALL) are more likely to suffer early relapse if they live in high-poverty areas.

All of the children studied received the same treatment, and the rates of relapse were similar regardless of poverty level.

But early relapse was more common among children from poorer areas. These children also had a lower rate of 5-year overall survival, but the difference was not significant.

Kira Bona, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues reported these results in Pediatric Blood & Cancer.

The team examined outcomes for 575 children, ages 1 to 18, with newly diagnosed ALL who were treated on Dana-Farber Cancer Institute ALL Consortium Protocols at 7 major academic medical centers in the US between 2000 and 2010.

Using US Census Bureau criteria, the investigators defined high-poverty areas as zip codes where 20% or more of residents have incomes below the federal poverty level. For a family of 4, this translates to an annual income of $24,250 or less.

Dr Bona and her colleagues found the overall rates of relapse were similar between children from low-poverty areas and those from high-poverty areas.

However, the timing of relapse differed significantly. Ninety-two percent of children from high-poverty areas who relapsed suffered early relapse (less than 36 months after first achieving complete remission), while 48% of the other children who relapsed did so early (P=0.008).

The 5-year overall survival was 85% for children from high-poverty areas and 92% for children from low-poverty areas. This difference is statistically significant when considered on its own (P=0.02) but not when the analysis is adjusted for other factors (P=0.07).

Still, the investigators said this suggests a possible disparity in survival.

“These children are getting the same best possible care at well-resourced institutions from highly trained clinicians, and we’re still seeing disparities,” Dr Bona said. “In trying to improve cure rates, we, as a field, have focused almost exclusively on biology. If we want to move forward, we also have to look at social determinants.”

Next steps

Dr Bona and her colleagues are undertaking further research designed to delve deeper into the relationship between socioeconomic status and outcomes and to allow for the development of poverty-targeted interventions.

As part of a prospective trial for children with ALL, the researchers will investigate associations between disease outcomes and the socioeconomic status of patients’ families, using a targetable measure of socioeconomic status called material hardship (food, housing, and/or energy insecurity).

The researchers will also investigate possible mechanisms underlying the relationship between socioeconomic status and early relapse, including adherence to oral chemotherapy and delays or dose reductions in chemotherapy due to a child’s underlying health.

In another study, investigators will conduct in-depth interviews with patients’ families, probing their knowledge and experience to pinpoint factors that might explain the disparity in outcomes and identify factors that can be targeted with interventions.

“Doing these next 2 studies is incredibly important,” Dr Bona said. “This study told us that simply providing the current best treatment regimen is not good enough if our goal is to cure every child with cancer.”

“At the same time that we develop new drugs and new treatment protocols, we need to address social determinants of health. Findings from these next studies will help us develop specific interventions to address disparities in outcomes. That’s an amazing opportunity.”

Doctor and patient

Photo by Logan Tuttle

A new study suggests children with acute lymphoblastic leukemia (ALL) are more likely to suffer early relapse if they live in high-poverty areas.

All of the children studied received the same treatment, and the rates of relapse were similar regardless of poverty level.

But early relapse was more common among children from poorer areas. These children also had a lower rate of 5-year overall survival, but the difference was not significant.

Kira Bona, MD, of Dana-Farber Cancer Institute in Boston, Massachusetts, and her colleagues reported these results in Pediatric Blood & Cancer.

The team examined outcomes for 575 children, ages 1 to 18, with newly diagnosed ALL who were treated on Dana-Farber Cancer Institute ALL Consortium Protocols at 7 major academic medical centers in the US between 2000 and 2010.

Using US Census Bureau criteria, the investigators defined high-poverty areas as zip codes where 20% or more of residents have incomes below the federal poverty level. For a family of 4, this translates to an annual income of $24,250 or less.

Dr Bona and her colleagues found the overall rates of relapse were similar between children from low-poverty areas and those from high-poverty areas.

However, the timing of relapse differed significantly. Ninety-two percent of children from high-poverty areas who relapsed suffered early relapse (less than 36 months after first achieving complete remission), while 48% of the other children who relapsed did so early (P=0.008).

The 5-year overall survival was 85% for children from high-poverty areas and 92% for children from low-poverty areas. This difference is statistically significant when considered on its own (P=0.02) but not when the analysis is adjusted for other factors (P=0.07).

Still, the investigators said this suggests a possible disparity in survival.

“These children are getting the same best possible care at well-resourced institutions from highly trained clinicians, and we’re still seeing disparities,” Dr Bona said. “In trying to improve cure rates, we, as a field, have focused almost exclusively on biology. If we want to move forward, we also have to look at social determinants.”

Next steps

Dr Bona and her colleagues are undertaking further research designed to delve deeper into the relationship between socioeconomic status and outcomes and to allow for the development of poverty-targeted interventions.

As part of a prospective trial for children with ALL, the researchers will investigate associations between disease outcomes and the socioeconomic status of patients’ families, using a targetable measure of socioeconomic status called material hardship (food, housing, and/or energy insecurity).

The researchers will also investigate possible mechanisms underlying the relationship between socioeconomic status and early relapse, including adherence to oral chemotherapy and delays or dose reductions in chemotherapy due to a child’s underlying health.

In another study, investigators will conduct in-depth interviews with patients’ families, probing their knowledge and experience to pinpoint factors that might explain the disparity in outcomes and identify factors that can be targeted with interventions.

“Doing these next 2 studies is incredibly important,” Dr Bona said. “This study told us that simply providing the current best treatment regimen is not good enough if our goal is to cure every child with cancer.”

“At the same time that we develop new drugs and new treatment protocols, we need to address social determinants of health. Findings from these next studies will help us develop specific interventions to address disparities in outcomes. That’s an amazing opportunity.”

JACKSONVILLE, FLA. – General surgeons are among the most sued physicians, and hernia repair is one of the most common operations they perform, so a study was conducted to drill down into the legal data on hernia repair to determine what about the operation is most likely to get surgeons in trouble.

They found that a failure to diagnose a complication caused by damage to a nearby structure during the operation was the most common cause for a malpractice suit for hernia repair, Dr. Nadeem Haddad of the Mayo Clinic in Rochester, Minn., reported at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

“Hernia repair with more than 1 million cases annually is one of the most common surgical procedures,” Dr. Haddad said. “The most common type of operation for malpractice was inguinal hernia repair. The majority of cases were elective cases where the informed consent was not breached.”

The researchers sampled data on 250 malpractice cases arising from hernia surgery filed with the Westlaw Next legal database between 1985 and 2015, Dr. Haddad said. He added that the sample is not inclusive of all malpractice cases related to hernia repair in that time. “Our objective was to analyze reasons for litigation related to hernia repairs,” he said.

Among the hernia cases from the database, physicians (defendants) won 59%, patients (plaintiffs) won around 27%, and the remainder went to settlement before a verdict. Award payments ranged from $10,000 for a case where a Penrose drain was left in the patient to $16 million in the case of death of an infant due to perioperative hyperkalemia.

Eighty-four percent of the cases in the study involved inguinal or ventral hernia repair, Dr. Haddad said, but the Westlaw Next database did not differentiate between the two types of procedures. Nor did it separate out pediatric or adult repairs. Westlaw Next provides the alleged reason for litigation and gives details about lawsuits. The researchers classified the alleged reasons for the lawsuits based on the time period in which they happened: preoperatively, intraoperatively, and postoperatively.

“The single most common reason for malpractice in hernia repair was failure to diagnose a complication following damage to a surrounding structure,” Dr. Haddad said.

The state of New York had the highest number of medical malpractice cases (46), followed closely by California (42). In 15% of cases (38) the patients claimed a breach of informed consent by the surgeon

“While understanding the reasons why surgeons go to trial, the risk of future lawsuits may lessen if measures are enacted to prevent such outcomes,” Dr. Haddad said. “Following protocols in diagnosis and management, attention to good surgical technique, and keeping a checklist of possible complications are some of the ways to improve patients safety and decrease chances of litigation.”

Dr. Haddad and coauthors had no financial relationships to disclose.

JACKSONVILLE, FLA. – General surgeons are among the most sued physicians, and hernia repair is one of the most common operations they perform, so a study was conducted to drill down into the legal data on hernia repair to determine what about the operation is most likely to get surgeons in trouble.

They found that a failure to diagnose a complication caused by damage to a nearby structure during the operation was the most common cause for a malpractice suit for hernia repair, Dr. Nadeem Haddad of the Mayo Clinic in Rochester, Minn., reported at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

“Hernia repair with more than 1 million cases annually is one of the most common surgical procedures,” Dr. Haddad said. “The most common type of operation for malpractice was inguinal hernia repair. The majority of cases were elective cases where the informed consent was not breached.”

The researchers sampled data on 250 malpractice cases arising from hernia surgery filed with the Westlaw Next legal database between 1985 and 2015, Dr. Haddad said. He added that the sample is not inclusive of all malpractice cases related to hernia repair in that time. “Our objective was to analyze reasons for litigation related to hernia repairs,” he said.

Among the hernia cases from the database, physicians (defendants) won 59%, patients (plaintiffs) won around 27%, and the remainder went to settlement before a verdict. Award payments ranged from $10,000 for a case where a Penrose drain was left in the patient to $16 million in the case of death of an infant due to perioperative hyperkalemia.

Eighty-four percent of the cases in the study involved inguinal or ventral hernia repair, Dr. Haddad said, but the Westlaw Next database did not differentiate between the two types of procedures. Nor did it separate out pediatric or adult repairs. Westlaw Next provides the alleged reason for litigation and gives details about lawsuits. The researchers classified the alleged reasons for the lawsuits based on the time period in which they happened: preoperatively, intraoperatively, and postoperatively.

“The single most common reason for malpractice in hernia repair was failure to diagnose a complication following damage to a surrounding structure,” Dr. Haddad said.

The state of New York had the highest number of medical malpractice cases (46), followed closely by California (42). In 15% of cases (38) the patients claimed a breach of informed consent by the surgeon

“While understanding the reasons why surgeons go to trial, the risk of future lawsuits may lessen if measures are enacted to prevent such outcomes,” Dr. Haddad said. “Following protocols in diagnosis and management, attention to good surgical technique, and keeping a checklist of possible complications are some of the ways to improve patients safety and decrease chances of litigation.”

Dr. Haddad and coauthors had no financial relationships to disclose.

JACKSONVILLE, FLA. – General surgeons are among the most sued physicians, and hernia repair is one of the most common operations they perform, so a study was conducted to drill down into the legal data on hernia repair to determine what about the operation is most likely to get surgeons in trouble.

They found that a failure to diagnose a complication caused by damage to a nearby structure during the operation was the most common cause for a malpractice suit for hernia repair, Dr. Nadeem Haddad of the Mayo Clinic in Rochester, Minn., reported at the Association for Academic Surgery/Society of University Surgeons Academic Surgical Congress.

“Hernia repair with more than 1 million cases annually is one of the most common surgical procedures,” Dr. Haddad said. “The most common type of operation for malpractice was inguinal hernia repair. The majority of cases were elective cases where the informed consent was not breached.”

The researchers sampled data on 250 malpractice cases arising from hernia surgery filed with the Westlaw Next legal database between 1985 and 2015, Dr. Haddad said. He added that the sample is not inclusive of all malpractice cases related to hernia repair in that time. “Our objective was to analyze reasons for litigation related to hernia repairs,” he said.

Among the hernia cases from the database, physicians (defendants) won 59%, patients (plaintiffs) won around 27%, and the remainder went to settlement before a verdict. Award payments ranged from $10,000 for a case where a Penrose drain was left in the patient to $16 million in the case of death of an infant due to perioperative hyperkalemia.

Eighty-four percent of the cases in the study involved inguinal or ventral hernia repair, Dr. Haddad said, but the Westlaw Next database did not differentiate between the two types of procedures. Nor did it separate out pediatric or adult repairs. Westlaw Next provides the alleged reason for litigation and gives details about lawsuits. The researchers classified the alleged reasons for the lawsuits based on the time period in which they happened: preoperatively, intraoperatively, and postoperatively.

“The single most common reason for malpractice in hernia repair was failure to diagnose a complication following damage to a surrounding structure,” Dr. Haddad said.

The state of New York had the highest number of medical malpractice cases (46), followed closely by California (42). In 15% of cases (38) the patients claimed a breach of informed consent by the surgeon

“While understanding the reasons why surgeons go to trial, the risk of future lawsuits may lessen if measures are enacted to prevent such outcomes,” Dr. Haddad said. “Following protocols in diagnosis and management, attention to good surgical technique, and keeping a checklist of possible complications are some of the ways to improve patients safety and decrease chances of litigation.”

Dr. Haddad and coauthors had no financial relationships to disclose.

NEW ORLEANS – Protein profiling of cerebrospinal fluid and MRI has revealed the involvement of exacerbated gray matter demyelination and brain atrophy in the progression of multiple sclerosis.

The pattern of the cerebrospinal fluid (CSF) biomarkers, which correspond to the extent of gray matter damage, have potential value in stratifying patients in terms of disease severity from the onset of multiple sclerosis (MS), Roberta Magliozzi, Ph.D., of the University of Verona (Italy) said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Brian Hoyle/Frontline Medical News

Gray matter atrophy and the accumulation of cortical lesions are central to the progressive clinical deterioration that occurs in MS. The damage involves a “compartmentalized immune response” featuring meningeal infiltration of certain immune cells, which is associated with increased cortical demyelination and meningeal inflammation. The gray matter damage and inflammation are harbingers of earlier onset and rapid progression of neurological damage in MS, and a more severe disease outcome.

“We sought to find a combination of CSF biomarkers [and] neuropathological and early neuroimaging correlates of disease progression in order to predict onset and rate of MS progression,” Dr. Magliozzi explained.

The investigators assessed gray matter damage with MRI and analyzed CSF proteins in 36 MS patients and 12 healthy controls and also acquired and analyzed meningeal and CSF samples after death from 20 individuals with secondary progressive MS (SPMS) and 10 healthy individuals to detect inflammatory mediators associated with meningeal infiltration that were released to the CSF.

MS patients with meningeal infiltration displayed more extensive gray matter demyelination and more rapid disease progression. They also demonstrated a “pronounced proinflammatory CSF profile” featuring overexpression of an array of molecules associated with chronic inflammation. Patients with less gray matter damage displayed a pattern of increased regulatory molecules. Consistent with the patient data, similar expression patterns were evident in the meninges and CSF samples of postmortem SPMS cases with a higher level of meningeal inflammation and gray matter demyelination.

“Meningeal infiltrates may represent the main source of intrathecal inflammatory activity mediating the gradient of cortical tissue injury since early disease stages and in progressive MS,” Dr. Magliozzi said.

The markedly different CSF profiles in patients with more and less extensive gray matter damage may be an exploitable characteristic to stratify patients early in the course of MS, with benefits in disease prognosis and monitoring, and treatment that is more rationally geared to the patient’s condition.

“The results indicate that we may be able to get an image-based functional profile of patients in relapse, which would be a phenomenal finding,” Dr. Jerry Wolinsky of the University of Texas Health Science Center at Houston, commented in a press conference following the presentation.

The study was funded by Progressive MS Alliance. Dr. Magliozzi had no disclosures.

NEW ORLEANS – Protein profiling of cerebrospinal fluid and MRI has revealed the involvement of exacerbated gray matter demyelination and brain atrophy in the progression of multiple sclerosis.

The pattern of the cerebrospinal fluid (CSF) biomarkers, which correspond to the extent of gray matter damage, have potential value in stratifying patients in terms of disease severity from the onset of multiple sclerosis (MS), Roberta Magliozzi, Ph.D., of the University of Verona (Italy) said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Brian Hoyle/Frontline Medical News

Gray matter atrophy and the accumulation of cortical lesions are central to the progressive clinical deterioration that occurs in MS. The damage involves a “compartmentalized immune response” featuring meningeal infiltration of certain immune cells, which is associated with increased cortical demyelination and meningeal inflammation. The gray matter damage and inflammation are harbingers of earlier onset and rapid progression of neurological damage in MS, and a more severe disease outcome.

“We sought to find a combination of CSF biomarkers [and] neuropathological and early neuroimaging correlates of disease progression in order to predict onset and rate of MS progression,” Dr. Magliozzi explained.

The investigators assessed gray matter damage with MRI and analyzed CSF proteins in 36 MS patients and 12 healthy controls and also acquired and analyzed meningeal and CSF samples after death from 20 individuals with secondary progressive MS (SPMS) and 10 healthy individuals to detect inflammatory mediators associated with meningeal infiltration that were released to the CSF.

MS patients with meningeal infiltration displayed more extensive gray matter demyelination and more rapid disease progression. They also demonstrated a “pronounced proinflammatory CSF profile” featuring overexpression of an array of molecules associated with chronic inflammation. Patients with less gray matter damage displayed a pattern of increased regulatory molecules. Consistent with the patient data, similar expression patterns were evident in the meninges and CSF samples of postmortem SPMS cases with a higher level of meningeal inflammation and gray matter demyelination.

“Meningeal infiltrates may represent the main source of intrathecal inflammatory activity mediating the gradient of cortical tissue injury since early disease stages and in progressive MS,” Dr. Magliozzi said.

The markedly different CSF profiles in patients with more and less extensive gray matter damage may be an exploitable characteristic to stratify patients early in the course of MS, with benefits in disease prognosis and monitoring, and treatment that is more rationally geared to the patient’s condition.

“The results indicate that we may be able to get an image-based functional profile of patients in relapse, which would be a phenomenal finding,” Dr. Jerry Wolinsky of the University of Texas Health Science Center at Houston, commented in a press conference following the presentation.

The study was funded by Progressive MS Alliance. Dr. Magliozzi had no disclosures.

NEW ORLEANS – Protein profiling of cerebrospinal fluid and MRI has revealed the involvement of exacerbated gray matter demyelination and brain atrophy in the progression of multiple sclerosis.

The pattern of the cerebrospinal fluid (CSF) biomarkers, which correspond to the extent of gray matter damage, have potential value in stratifying patients in terms of disease severity from the onset of multiple sclerosis (MS), Roberta Magliozzi, Ph.D., of the University of Verona (Italy) said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis.

Brian Hoyle/Frontline Medical News

Gray matter atrophy and the accumulation of cortical lesions are central to the progressive clinical deterioration that occurs in MS. The damage involves a “compartmentalized immune response” featuring meningeal infiltration of certain immune cells, which is associated with increased cortical demyelination and meningeal inflammation. The gray matter damage and inflammation are harbingers of earlier onset and rapid progression of neurological damage in MS, and a more severe disease outcome.

“We sought to find a combination of CSF biomarkers [and] neuropathological and early neuroimaging correlates of disease progression in order to predict onset and rate of MS progression,” Dr. Magliozzi explained.

The investigators assessed gray matter damage with MRI and analyzed CSF proteins in 36 MS patients and 12 healthy controls and also acquired and analyzed meningeal and CSF samples after death from 20 individuals with secondary progressive MS (SPMS) and 10 healthy individuals to detect inflammatory mediators associated with meningeal infiltration that were released to the CSF.

MS patients with meningeal infiltration displayed more extensive gray matter demyelination and more rapid disease progression. They also demonstrated a “pronounced proinflammatory CSF profile” featuring overexpression of an array of molecules associated with chronic inflammation. Patients with less gray matter damage displayed a pattern of increased regulatory molecules. Consistent with the patient data, similar expression patterns were evident in the meninges and CSF samples of postmortem SPMS cases with a higher level of meningeal inflammation and gray matter demyelination.

“Meningeal infiltrates may represent the main source of intrathecal inflammatory activity mediating the gradient of cortical tissue injury since early disease stages and in progressive MS,” Dr. Magliozzi said.

The markedly different CSF profiles in patients with more and less extensive gray matter damage may be an exploitable characteristic to stratify patients early in the course of MS, with benefits in disease prognosis and monitoring, and treatment that is more rationally geared to the patient’s condition.

“The results indicate that we may be able to get an image-based functional profile of patients in relapse, which would be a phenomenal finding,” Dr. Jerry Wolinsky of the University of Texas Health Science Center at Houston, commented in a press conference following the presentation.

The study was funded by Progressive MS Alliance. Dr. Magliozzi had no disclosures.