The Food and Drug Administration has given Fast Track designation to the development of dapagliflozin (Farxiga) to delay progression of renal failure and to prevent cardiovascular and renal death in patients with chronic kidney disease with and without type 2 diabetes, according to a release from AstraZeneca.

The Fast Track designation is meant to accelerate the development and review process for the treatment of serious conditions that have unmet therapeutic needs.

Dapagliflozin, an oral daily sodium-glucose transporter 2 inhibitor, is approved both as a monotherapy and a component of combination therapy for the improvement of glycemic control in patients with type 2 diabetes, according to the release. It is given as an adjunct to diet and exercise, and has also shown additional benefits of weight loss and reduction in blood pressure.

A phase 3, randomized, placebo-controlled trial, DAPA-CVD (NCT03036150), is currently underway to evaluate the drug’s efficacy specifically in terms of renal outcomes and cardiovascular mortality in patients with chronic kidney disease, with and without type 2 diabetes. Participants receive once-daily dapagliflozin or placebo in addition to standard care.

Taking dapagliflozin carries risks of hypotension, renal impairment, hypoglycemia, and other concerns. The most common adverse reactions (5% or greater incidence) include female genital mycotic infections, nasopharyngitis, and urinary tract infections. Full prescribing information can be found on the agency’s website.
 

cpalmer@mdedge.com

The Food and Drug Administration has given Fast Track designation to the development of dapagliflozin (Farxiga) to delay progression of renal failure and to prevent cardiovascular and renal death in patients with chronic kidney disease with and without type 2 diabetes, according to a release from AstraZeneca.

The Fast Track designation is meant to accelerate the development and review process for the treatment of serious conditions that have unmet therapeutic needs.

Dapagliflozin, an oral daily sodium-glucose transporter 2 inhibitor, is approved both as a monotherapy and a component of combination therapy for the improvement of glycemic control in patients with type 2 diabetes, according to the release. It is given as an adjunct to diet and exercise, and has also shown additional benefits of weight loss and reduction in blood pressure.

A phase 3, randomized, placebo-controlled trial, DAPA-CVD (NCT03036150), is currently underway to evaluate the drug’s efficacy specifically in terms of renal outcomes and cardiovascular mortality in patients with chronic kidney disease, with and without type 2 diabetes. Participants receive once-daily dapagliflozin or placebo in addition to standard care.

Taking dapagliflozin carries risks of hypotension, renal impairment, hypoglycemia, and other concerns. The most common adverse reactions (5% or greater incidence) include female genital mycotic infections, nasopharyngitis, and urinary tract infections. Full prescribing information can be found on the agency’s website.
 

cpalmer@mdedge.com

The Food and Drug Administration has given Fast Track designation to the development of dapagliflozin (Farxiga) to delay progression of renal failure and to prevent cardiovascular and renal death in patients with chronic kidney disease with and without type 2 diabetes, according to a release from AstraZeneca.

The Fast Track designation is meant to accelerate the development and review process for the treatment of serious conditions that have unmet therapeutic needs.

Dapagliflozin, an oral daily sodium-glucose transporter 2 inhibitor, is approved both as a monotherapy and a component of combination therapy for the improvement of glycemic control in patients with type 2 diabetes, according to the release. It is given as an adjunct to diet and exercise, and has also shown additional benefits of weight loss and reduction in blood pressure.

A phase 3, randomized, placebo-controlled trial, DAPA-CVD (NCT03036150), is currently underway to evaluate the drug’s efficacy specifically in terms of renal outcomes and cardiovascular mortality in patients with chronic kidney disease, with and without type 2 diabetes. Participants receive once-daily dapagliflozin or placebo in addition to standard care.

Taking dapagliflozin carries risks of hypotension, renal impairment, hypoglycemia, and other concerns. The most common adverse reactions (5% or greater incidence) include female genital mycotic infections, nasopharyngitis, and urinary tract infections. Full prescribing information can be found on the agency’s website.
 

cpalmer@mdedge.com

When the summons arrived, Nataly Minkina, MD, took one look at the lawsuit and fainted.

Leonid Weinstein

The Boston-area internist had treated the plaintiff just once while covering for the patient’s primary care physician. During a visit for an upper respiratory infection, the patient mentioned a lump in her breast, and Dr. Minkina confirmed a small thickening in the woman’s right breast. She sent the patient for a mammogram and ultrasound, the results of which the radiologist reported were normal, according to court documents.

Five years later, the patient claimed Dr. Minkina was one of several providers responsible for a missed breast cancer diagnosis.

Even worse than the lawsuit, however, was how her former insurer resolved the case, said Dr. Minkina, now an internist at Brigham and Women’s Hospital in Chestnut Hill, Mass. The claim was settled against the defendants for $500,000, and Dr. Minkina was alloted 30% of the liability. No fault was assigned to the other physicians named, while a nurse practitioner was alloted 10%, and the medical practice was alloted 60% liability, according to court documents.

“I was very upset,” Dr. Minkina said. “First of all, I was kept in the dark. Nobody ever talked to me. I did not get a single report or any document from my attorney in 12 months. When I asked why was I assigned the [30%] liability, they said the experts gave me bad evaluations, but they would not show reports to me. I was literally scapegoated.”

When the insurer refused to reconsider the allocation, Dr. Minkina took her complaint to court. The internist now has been embroiled in a legal challenge against Medical Professional Mutual Insurance Company (ProMutual) for 7 years. Dr. Minkina’s lawsuit alleges the insurer engaged in a bad faith allocation to serve its own economic interests by shifting fault for the claim from its insureds to its former client, Dr. Minkina. The insurance company contends the allocation was a careful and rational decision based on case evidence. In late July, the case went to trial in Dedham, Mass.

ProMutual declined comment on the case; the insurer also would not address general questions about its allocation policies.

“I started this fight because I felt violated and betrayed, not to make money,” Dr. Minkina said. “I am not rich by a long shot, and I wanted to clear my name because [a] good name is all I have. Additionally, having [a] record about malpractice payment in my physician profile makes me vulnerable.”

Liability experts say the case highlights the conflicts that can arise between physicians and insurers during malpractice lawsuits. The legal challenge also raises questions about allocations of liability by insurers, how the determinations are made, and what impact they have on doctors going forward.

The proportion of liability assigned after a settlement matters, said Jeffrey Segal, MD, JD, a neurosurgeon and founder of Medical Justice, a medicolegal consulting firm for physicians.

Vidyard Video

“There’s a subtext that your piece of the pie – the part that is allocated to you – is your liability, your culpability, your guilt,” Dr. Segal said in an interview. “This has impact going down the road in terms of reputation, in terms of credibility, and potentially of your premiums going forward. There are some real-world economic consequences.”

 

 

Bad care or bad faith?

In Dr. Minkina’s case, some facts are undisputed. In 2002, Dr. Minkina, then a physician at Blue Hills Medical Associates in Braintree, Mass., referred a 55-year-old patient for a mammogram and an ultrasound after confirming some nodularity in the women’s breast. A radiologist twice reported no abnormalities which Dr. Minkina relayed to the patient, advising her to follow-up with her primary care physician and to schedule yearly mammograms. The patient did neither, according to court records. Dr. Minkina left the practice shortly after the visit.

In early 2006, the patient visited the practice, and a nurse practitioner sent her for another mammogram and an ultrasound. The mammogram report included some signs of malignancy, but the nurse misread, misunderstood, or overlooked the signs and recorded that “the benign breast condition had no changes,” according to court transcripts. Later that year, the patient visited the practice complaining of headaches and a droopy eye at which time her primary care physician diagnosed sinusitis and prescribed antibiotics. In 2007, the patient underwent a brain MRI and a breast MRI, which revealed widespread metastatic carcinoma. She and her family sued Dr. Minkina and several others in June 2007. The patient died in 2008.

The agreement between parties ends there. Dr. Minkina believes she followed the standard of care and was not responsible for the delayed breast cancer diagnosis. Given the radiologist’s negative report and the patient’s lack of visual abnormalities, she contends she adequately referred the patient to her primary care physician for further consultation and evaluation. Dr. Minkina argues the insurer allocated an unjustifiably high percentage of liability to her because she was no longer an insured and because the company had an economic incentive to allocate a disproportionate percentage of responsibility and damages.

ProMutual contends Dr. Minkina bore more responsibility than the other health care professionals named for the delayed diagnosis because of violations of standards of care and because of causation factors. The insurer’s experts asserted that when treating an older woman with a palpable lump, the standard of care is to obtain a biopsy, according to opening arguments by ProMutual defense counsel Tamara Wolfson.

The experts also concluded that, when the nurse practitioner and primary care physician saw the patient in 2006, the patient would have already had metastatic disease, and a cancer diagnosis at that time would not have saved her, according to court transcripts. Had the cancer been diagnosed in 2002 when Dr. Minkina saw the patient, the disease would have been “very treatable,” the experts further concluded.

“So, faced with negative opinions on both the standard of care and causation, [the claim representative] was very concerned that Dr. Minkina not only faced a very substantial risk of an adverse verdict in the ... suit, but a verdict that would exceed Dr. Minkina’s policy limits,” Ms. Wolfson said during opening arguments.

The evidence led to the settlement and the allocation decision, Ms. Wolfson said, adding that the majority – 60% – fell on Blue Hills Medical Associates because it lacked a good system to track and follow up with patients. There was zero benefit to ProMutual as to how the $500,000 settlement was parsed, she said during trial.

A lower court initially dismissed Dr. Minkina’s suit, but the Commonwealth of Massachusetts Appeals Court in 2015 overturned that decision, ruling the case could move forward. In 2018, the superior court agreed Dr. Minkina had a valid bad faith claim, stating that she had provided information about ProMutual’s conduct from which “a reasonable juror could infer the defendant’s bad faith in connection with its settling the underlying malpractice suit, including the allocation of liability.”

Dr. Minkina had been a plaintiff in unrelated litigation in the past. In 2005, she sued her former employer for alleged discrimination and retaliation after claiming she was mistreated and terminated for complaining about fumes. She prevailed and was awarded an arbitration award of about $266,000. In 2009, Dr. Minkina sued the original law firm that represented her in the discrimination suit for malpractice, alleging the firm’s negligence cost her the chance to go to trial. A judge dismissed the claim as frivolous and ordered Dr. Minkina to pay the firm’s legal fees. The doctor twice has been jailed for failing to fully resolve that legal payment. The case remains outstanding, and Dr. Minkina is now in bankruptcy.
 

 

 

What’s in an allocation?

Liability allocations are an integral part of multiparty medical malpractice claims, said Brian Atchinson, president and CEO for the Medical Professional Liability Association, a trade association for medical liability insurers.

“In any case involving more than one party, there is a potential allocation issue,” Mr. Atchinson said in an interview. “[Insurers] generally look to the liability and damages incurred with regard to their respective insureds in a case and work to establish an allocation that reflects actual liability.”

If the case goes to a jury and jurors find for the plaintiff, depending on the nature of the damages awarded, the jury may be called on to allocate liability among multiple defendants, he said.

Because settlements are reported to the National Practitioner Data Bank (NPDB), the proportion of liability assigned to each defendant has significance, said J. Richard Moore, a medical liability defense attorney based in Indianapolis and chair for the Defense Research Institute’s Medical Liability and Health Care Law Committee.

Vidyard Video

“The allocation matters because the amount of settlement matters,” Mr. Moore said. “A lower settlement amount suggests the physician’s insurance company made a cost-benefit business decision to end litigation without more expense, while an extremely high settlement suggests actual malpractice.”

State medical boards have varying reporting requirements. Some state boards require both the amount paid by the individual provider and the global settlement amount – if known – while other state boards require only the amount paid on behalf of the provider.

Conflicts over allocations are not common, Dr. Segal said. More frequent are disputes among physicians and insurers over the potential settling of a claim. Such conflicts underscore the importance of paying close attention to contract language when signing with an insurer, Dr. Segal said.

Whether the contract includes a consent to settle clause, for example, can markedly change the case outcome. The clause means the insurer must have the doctor’s approval to settle the case. Absent the clause, insurers generally have authority to settle all claims arising under the policy.

Other contracts may include a “hammer clause,” Dr. Segal notes. This gives doctors the ultimate vote on settling, but it stipulates that if the physician refuses a settlement offer and opts for trial, the doctor is responsible for any surplus award, should the doctor lose.

In Dr. Minkina’s case, the doctor’s contract allowed ProMutual to settle without her consent, but the contract was silent on allocations.

Dr. Segal and Mr. Moore both said the odds of Dr. Minkina prevailing are fairly low. In another case, a South Carolina doctor similarly sued the South Carolina Medical Malpractice Liability Joint Underwriting Association over an allocation of liability following a settlement. The doctor claimed he should not be assigned any portion of the $500,000 settlement, and he sued after his insurer assigned him one-seventh liability.

A trial court found in his favor, ruling the insurer breached the covenant of good faith and fair dealing by failing to treat each physician equally when determining liability. The Supreme Court of South Carolina in 2001 overturned that decision, finding the evidence did not support a bad faith finding and that the insurer’s allocation decision was reasonable.

If the Massachusetts case ends in Dr. Minkina’s favor, it will be as a result of strong evidence that the insurer placed its interests ahead of the physician’s financial and other interests, Mr. Moore said.

“If that happens, I anticipate that insurers may revise their standard policy provisions to clarify and limit the extent to which physicians have the right to be involved in allocation decisions,” he said.

agallegos@mdedge.com

When the summons arrived, Nataly Minkina, MD, took one look at the lawsuit and fainted.

Leonid Weinstein

The Boston-area internist had treated the plaintiff just once while covering for the patient’s primary care physician. During a visit for an upper respiratory infection, the patient mentioned a lump in her breast, and Dr. Minkina confirmed a small thickening in the woman’s right breast. She sent the patient for a mammogram and ultrasound, the results of which the radiologist reported were normal, according to court documents.

Five years later, the patient claimed Dr. Minkina was one of several providers responsible for a missed breast cancer diagnosis.

Even worse than the lawsuit, however, was how her former insurer resolved the case, said Dr. Minkina, now an internist at Brigham and Women’s Hospital in Chestnut Hill, Mass. The claim was settled against the defendants for $500,000, and Dr. Minkina was alloted 30% of the liability. No fault was assigned to the other physicians named, while a nurse practitioner was alloted 10%, and the medical practice was alloted 60% liability, according to court documents.

“I was very upset,” Dr. Minkina said. “First of all, I was kept in the dark. Nobody ever talked to me. I did not get a single report or any document from my attorney in 12 months. When I asked why was I assigned the [30%] liability, they said the experts gave me bad evaluations, but they would not show reports to me. I was literally scapegoated.”

When the insurer refused to reconsider the allocation, Dr. Minkina took her complaint to court. The internist now has been embroiled in a legal challenge against Medical Professional Mutual Insurance Company (ProMutual) for 7 years. Dr. Minkina’s lawsuit alleges the insurer engaged in a bad faith allocation to serve its own economic interests by shifting fault for the claim from its insureds to its former client, Dr. Minkina. The insurance company contends the allocation was a careful and rational decision based on case evidence. In late July, the case went to trial in Dedham, Mass.

ProMutual declined comment on the case; the insurer also would not address general questions about its allocation policies.

“I started this fight because I felt violated and betrayed, not to make money,” Dr. Minkina said. “I am not rich by a long shot, and I wanted to clear my name because [a] good name is all I have. Additionally, having [a] record about malpractice payment in my physician profile makes me vulnerable.”

Liability experts say the case highlights the conflicts that can arise between physicians and insurers during malpractice lawsuits. The legal challenge also raises questions about allocations of liability by insurers, how the determinations are made, and what impact they have on doctors going forward.

The proportion of liability assigned after a settlement matters, said Jeffrey Segal, MD, JD, a neurosurgeon and founder of Medical Justice, a medicolegal consulting firm for physicians.

Vidyard Video

“There’s a subtext that your piece of the pie – the part that is allocated to you – is your liability, your culpability, your guilt,” Dr. Segal said in an interview. “This has impact going down the road in terms of reputation, in terms of credibility, and potentially of your premiums going forward. There are some real-world economic consequences.”

 

 

Bad care or bad faith?

In Dr. Minkina’s case, some facts are undisputed. In 2002, Dr. Minkina, then a physician at Blue Hills Medical Associates in Braintree, Mass., referred a 55-year-old patient for a mammogram and an ultrasound after confirming some nodularity in the women’s breast. A radiologist twice reported no abnormalities which Dr. Minkina relayed to the patient, advising her to follow-up with her primary care physician and to schedule yearly mammograms. The patient did neither, according to court records. Dr. Minkina left the practice shortly after the visit.

In early 2006, the patient visited the practice, and a nurse practitioner sent her for another mammogram and an ultrasound. The mammogram report included some signs of malignancy, but the nurse misread, misunderstood, or overlooked the signs and recorded that “the benign breast condition had no changes,” according to court transcripts. Later that year, the patient visited the practice complaining of headaches and a droopy eye at which time her primary care physician diagnosed sinusitis and prescribed antibiotics. In 2007, the patient underwent a brain MRI and a breast MRI, which revealed widespread metastatic carcinoma. She and her family sued Dr. Minkina and several others in June 2007. The patient died in 2008.

The agreement between parties ends there. Dr. Minkina believes she followed the standard of care and was not responsible for the delayed breast cancer diagnosis. Given the radiologist’s negative report and the patient’s lack of visual abnormalities, she contends she adequately referred the patient to her primary care physician for further consultation and evaluation. Dr. Minkina argues the insurer allocated an unjustifiably high percentage of liability to her because she was no longer an insured and because the company had an economic incentive to allocate a disproportionate percentage of responsibility and damages.

ProMutual contends Dr. Minkina bore more responsibility than the other health care professionals named for the delayed diagnosis because of violations of standards of care and because of causation factors. The insurer’s experts asserted that when treating an older woman with a palpable lump, the standard of care is to obtain a biopsy, according to opening arguments by ProMutual defense counsel Tamara Wolfson.

The experts also concluded that, when the nurse practitioner and primary care physician saw the patient in 2006, the patient would have already had metastatic disease, and a cancer diagnosis at that time would not have saved her, according to court transcripts. Had the cancer been diagnosed in 2002 when Dr. Minkina saw the patient, the disease would have been “very treatable,” the experts further concluded.

“So, faced with negative opinions on both the standard of care and causation, [the claim representative] was very concerned that Dr. Minkina not only faced a very substantial risk of an adverse verdict in the ... suit, but a verdict that would exceed Dr. Minkina’s policy limits,” Ms. Wolfson said during opening arguments.

The evidence led to the settlement and the allocation decision, Ms. Wolfson said, adding that the majority – 60% – fell on Blue Hills Medical Associates because it lacked a good system to track and follow up with patients. There was zero benefit to ProMutual as to how the $500,000 settlement was parsed, she said during trial.

A lower court initially dismissed Dr. Minkina’s suit, but the Commonwealth of Massachusetts Appeals Court in 2015 overturned that decision, ruling the case could move forward. In 2018, the superior court agreed Dr. Minkina had a valid bad faith claim, stating that she had provided information about ProMutual’s conduct from which “a reasonable juror could infer the defendant’s bad faith in connection with its settling the underlying malpractice suit, including the allocation of liability.”

Dr. Minkina had been a plaintiff in unrelated litigation in the past. In 2005, she sued her former employer for alleged discrimination and retaliation after claiming she was mistreated and terminated for complaining about fumes. She prevailed and was awarded an arbitration award of about $266,000. In 2009, Dr. Minkina sued the original law firm that represented her in the discrimination suit for malpractice, alleging the firm’s negligence cost her the chance to go to trial. A judge dismissed the claim as frivolous and ordered Dr. Minkina to pay the firm’s legal fees. The doctor twice has been jailed for failing to fully resolve that legal payment. The case remains outstanding, and Dr. Minkina is now in bankruptcy.
 

 

 

What’s in an allocation?

Liability allocations are an integral part of multiparty medical malpractice claims, said Brian Atchinson, president and CEO for the Medical Professional Liability Association, a trade association for medical liability insurers.

“In any case involving more than one party, there is a potential allocation issue,” Mr. Atchinson said in an interview. “[Insurers] generally look to the liability and damages incurred with regard to their respective insureds in a case and work to establish an allocation that reflects actual liability.”

If the case goes to a jury and jurors find for the plaintiff, depending on the nature of the damages awarded, the jury may be called on to allocate liability among multiple defendants, he said.

Because settlements are reported to the National Practitioner Data Bank (NPDB), the proportion of liability assigned to each defendant has significance, said J. Richard Moore, a medical liability defense attorney based in Indianapolis and chair for the Defense Research Institute’s Medical Liability and Health Care Law Committee.

Vidyard Video

“The allocation matters because the amount of settlement matters,” Mr. Moore said. “A lower settlement amount suggests the physician’s insurance company made a cost-benefit business decision to end litigation without more expense, while an extremely high settlement suggests actual malpractice.”

State medical boards have varying reporting requirements. Some state boards require both the amount paid by the individual provider and the global settlement amount – if known – while other state boards require only the amount paid on behalf of the provider.

Conflicts over allocations are not common, Dr. Segal said. More frequent are disputes among physicians and insurers over the potential settling of a claim. Such conflicts underscore the importance of paying close attention to contract language when signing with an insurer, Dr. Segal said.

Whether the contract includes a consent to settle clause, for example, can markedly change the case outcome. The clause means the insurer must have the doctor’s approval to settle the case. Absent the clause, insurers generally have authority to settle all claims arising under the policy.

Other contracts may include a “hammer clause,” Dr. Segal notes. This gives doctors the ultimate vote on settling, but it stipulates that if the physician refuses a settlement offer and opts for trial, the doctor is responsible for any surplus award, should the doctor lose.

In Dr. Minkina’s case, the doctor’s contract allowed ProMutual to settle without her consent, but the contract was silent on allocations.

Dr. Segal and Mr. Moore both said the odds of Dr. Minkina prevailing are fairly low. In another case, a South Carolina doctor similarly sued the South Carolina Medical Malpractice Liability Joint Underwriting Association over an allocation of liability following a settlement. The doctor claimed he should not be assigned any portion of the $500,000 settlement, and he sued after his insurer assigned him one-seventh liability.

A trial court found in his favor, ruling the insurer breached the covenant of good faith and fair dealing by failing to treat each physician equally when determining liability. The Supreme Court of South Carolina in 2001 overturned that decision, finding the evidence did not support a bad faith finding and that the insurer’s allocation decision was reasonable.

If the Massachusetts case ends in Dr. Minkina’s favor, it will be as a result of strong evidence that the insurer placed its interests ahead of the physician’s financial and other interests, Mr. Moore said.

“If that happens, I anticipate that insurers may revise their standard policy provisions to clarify and limit the extent to which physicians have the right to be involved in allocation decisions,” he said.

agallegos@mdedge.com

When the summons arrived, Nataly Minkina, MD, took one look at the lawsuit and fainted.

Leonid Weinstein

The Boston-area internist had treated the plaintiff just once while covering for the patient’s primary care physician. During a visit for an upper respiratory infection, the patient mentioned a lump in her breast, and Dr. Minkina confirmed a small thickening in the woman’s right breast. She sent the patient for a mammogram and ultrasound, the results of which the radiologist reported were normal, according to court documents.

Five years later, the patient claimed Dr. Minkina was one of several providers responsible for a missed breast cancer diagnosis.

Even worse than the lawsuit, however, was how her former insurer resolved the case, said Dr. Minkina, now an internist at Brigham and Women’s Hospital in Chestnut Hill, Mass. The claim was settled against the defendants for $500,000, and Dr. Minkina was alloted 30% of the liability. No fault was assigned to the other physicians named, while a nurse practitioner was alloted 10%, and the medical practice was alloted 60% liability, according to court documents.

“I was very upset,” Dr. Minkina said. “First of all, I was kept in the dark. Nobody ever talked to me. I did not get a single report or any document from my attorney in 12 months. When I asked why was I assigned the [30%] liability, they said the experts gave me bad evaluations, but they would not show reports to me. I was literally scapegoated.”

When the insurer refused to reconsider the allocation, Dr. Minkina took her complaint to court. The internist now has been embroiled in a legal challenge against Medical Professional Mutual Insurance Company (ProMutual) for 7 years. Dr. Minkina’s lawsuit alleges the insurer engaged in a bad faith allocation to serve its own economic interests by shifting fault for the claim from its insureds to its former client, Dr. Minkina. The insurance company contends the allocation was a careful and rational decision based on case evidence. In late July, the case went to trial in Dedham, Mass.

ProMutual declined comment on the case; the insurer also would not address general questions about its allocation policies.

“I started this fight because I felt violated and betrayed, not to make money,” Dr. Minkina said. “I am not rich by a long shot, and I wanted to clear my name because [a] good name is all I have. Additionally, having [a] record about malpractice payment in my physician profile makes me vulnerable.”

Liability experts say the case highlights the conflicts that can arise between physicians and insurers during malpractice lawsuits. The legal challenge also raises questions about allocations of liability by insurers, how the determinations are made, and what impact they have on doctors going forward.

The proportion of liability assigned after a settlement matters, said Jeffrey Segal, MD, JD, a neurosurgeon and founder of Medical Justice, a medicolegal consulting firm for physicians.

Vidyard Video

“There’s a subtext that your piece of the pie – the part that is allocated to you – is your liability, your culpability, your guilt,” Dr. Segal said in an interview. “This has impact going down the road in terms of reputation, in terms of credibility, and potentially of your premiums going forward. There are some real-world economic consequences.”

 

 

Bad care or bad faith?

In Dr. Minkina’s case, some facts are undisputed. In 2002, Dr. Minkina, then a physician at Blue Hills Medical Associates in Braintree, Mass., referred a 55-year-old patient for a mammogram and an ultrasound after confirming some nodularity in the women’s breast. A radiologist twice reported no abnormalities which Dr. Minkina relayed to the patient, advising her to follow-up with her primary care physician and to schedule yearly mammograms. The patient did neither, according to court records. Dr. Minkina left the practice shortly after the visit.

In early 2006, the patient visited the practice, and a nurse practitioner sent her for another mammogram and an ultrasound. The mammogram report included some signs of malignancy, but the nurse misread, misunderstood, or overlooked the signs and recorded that “the benign breast condition had no changes,” according to court transcripts. Later that year, the patient visited the practice complaining of headaches and a droopy eye at which time her primary care physician diagnosed sinusitis and prescribed antibiotics. In 2007, the patient underwent a brain MRI and a breast MRI, which revealed widespread metastatic carcinoma. She and her family sued Dr. Minkina and several others in June 2007. The patient died in 2008.

The agreement between parties ends there. Dr. Minkina believes she followed the standard of care and was not responsible for the delayed breast cancer diagnosis. Given the radiologist’s negative report and the patient’s lack of visual abnormalities, she contends she adequately referred the patient to her primary care physician for further consultation and evaluation. Dr. Minkina argues the insurer allocated an unjustifiably high percentage of liability to her because she was no longer an insured and because the company had an economic incentive to allocate a disproportionate percentage of responsibility and damages.

ProMutual contends Dr. Minkina bore more responsibility than the other health care professionals named for the delayed diagnosis because of violations of standards of care and because of causation factors. The insurer’s experts asserted that when treating an older woman with a palpable lump, the standard of care is to obtain a biopsy, according to opening arguments by ProMutual defense counsel Tamara Wolfson.

The experts also concluded that, when the nurse practitioner and primary care physician saw the patient in 2006, the patient would have already had metastatic disease, and a cancer diagnosis at that time would not have saved her, according to court transcripts. Had the cancer been diagnosed in 2002 when Dr. Minkina saw the patient, the disease would have been “very treatable,” the experts further concluded.

“So, faced with negative opinions on both the standard of care and causation, [the claim representative] was very concerned that Dr. Minkina not only faced a very substantial risk of an adverse verdict in the ... suit, but a verdict that would exceed Dr. Minkina’s policy limits,” Ms. Wolfson said during opening arguments.

The evidence led to the settlement and the allocation decision, Ms. Wolfson said, adding that the majority – 60% – fell on Blue Hills Medical Associates because it lacked a good system to track and follow up with patients. There was zero benefit to ProMutual as to how the $500,000 settlement was parsed, she said during trial.

A lower court initially dismissed Dr. Minkina’s suit, but the Commonwealth of Massachusetts Appeals Court in 2015 overturned that decision, ruling the case could move forward. In 2018, the superior court agreed Dr. Minkina had a valid bad faith claim, stating that she had provided information about ProMutual’s conduct from which “a reasonable juror could infer the defendant’s bad faith in connection with its settling the underlying malpractice suit, including the allocation of liability.”

Dr. Minkina had been a plaintiff in unrelated litigation in the past. In 2005, she sued her former employer for alleged discrimination and retaliation after claiming she was mistreated and terminated for complaining about fumes. She prevailed and was awarded an arbitration award of about $266,000. In 2009, Dr. Minkina sued the original law firm that represented her in the discrimination suit for malpractice, alleging the firm’s negligence cost her the chance to go to trial. A judge dismissed the claim as frivolous and ordered Dr. Minkina to pay the firm’s legal fees. The doctor twice has been jailed for failing to fully resolve that legal payment. The case remains outstanding, and Dr. Minkina is now in bankruptcy.
 

 

 

What’s in an allocation?

Liability allocations are an integral part of multiparty medical malpractice claims, said Brian Atchinson, president and CEO for the Medical Professional Liability Association, a trade association for medical liability insurers.

“In any case involving more than one party, there is a potential allocation issue,” Mr. Atchinson said in an interview. “[Insurers] generally look to the liability and damages incurred with regard to their respective insureds in a case and work to establish an allocation that reflects actual liability.”

If the case goes to a jury and jurors find for the plaintiff, depending on the nature of the damages awarded, the jury may be called on to allocate liability among multiple defendants, he said.

Because settlements are reported to the National Practitioner Data Bank (NPDB), the proportion of liability assigned to each defendant has significance, said J. Richard Moore, a medical liability defense attorney based in Indianapolis and chair for the Defense Research Institute’s Medical Liability and Health Care Law Committee.

Vidyard Video

“The allocation matters because the amount of settlement matters,” Mr. Moore said. “A lower settlement amount suggests the physician’s insurance company made a cost-benefit business decision to end litigation without more expense, while an extremely high settlement suggests actual malpractice.”

State medical boards have varying reporting requirements. Some state boards require both the amount paid by the individual provider and the global settlement amount – if known – while other state boards require only the amount paid on behalf of the provider.

Conflicts over allocations are not common, Dr. Segal said. More frequent are disputes among physicians and insurers over the potential settling of a claim. Such conflicts underscore the importance of paying close attention to contract language when signing with an insurer, Dr. Segal said.

Whether the contract includes a consent to settle clause, for example, can markedly change the case outcome. The clause means the insurer must have the doctor’s approval to settle the case. Absent the clause, insurers generally have authority to settle all claims arising under the policy.

Other contracts may include a “hammer clause,” Dr. Segal notes. This gives doctors the ultimate vote on settling, but it stipulates that if the physician refuses a settlement offer and opts for trial, the doctor is responsible for any surplus award, should the doctor lose.

In Dr. Minkina’s case, the doctor’s contract allowed ProMutual to settle without her consent, but the contract was silent on allocations.

Dr. Segal and Mr. Moore both said the odds of Dr. Minkina prevailing are fairly low. In another case, a South Carolina doctor similarly sued the South Carolina Medical Malpractice Liability Joint Underwriting Association over an allocation of liability following a settlement. The doctor claimed he should not be assigned any portion of the $500,000 settlement, and he sued after his insurer assigned him one-seventh liability.

A trial court found in his favor, ruling the insurer breached the covenant of good faith and fair dealing by failing to treat each physician equally when determining liability. The Supreme Court of South Carolina in 2001 overturned that decision, finding the evidence did not support a bad faith finding and that the insurer’s allocation decision was reasonable.

If the Massachusetts case ends in Dr. Minkina’s favor, it will be as a result of strong evidence that the insurer placed its interests ahead of the physician’s financial and other interests, Mr. Moore said.

“If that happens, I anticipate that insurers may revise their standard policy provisions to clarify and limit the extent to which physicians have the right to be involved in allocation decisions,” he said.

agallegos@mdedge.com

Women with postmenopausal osteoporosis who discontinued denosumab treatment after achieving osteopenia maintained bone mineral density at the spine and hip with a single infusion of zoledronate given 6 months after the last infusion of denosumab, according to results from a small, multicenter, randomized trial published in the Journal of Bone and Mineral Research.

ogichobanov/iStock/Getty Images Plus

The cessation of the monoclonal antibody denosumab is typically followed by a “rebound phenomenon” often attributed to an increase in bone turnover above pretreatment values caused by the up-regulation of osteoclastogenesis, according to Athanasios D. Anastasilakis, MD, of 424 General Military Hospital, Thessaloníki, Greece, and colleagues. Guidelines recommend that patients take a bisphosphonate to prevent this effect, but the optimal bisphosphonate regimen is unknown and evidence is inconsistent.

To address this question, the investigators randomized 57 postmenopausal women with osteoporosis who had received six monthly injections of denosumab (for an average of 2.2 years) and had achieved nonosteoporotic bone mineral density (BMD) T scores greater than –2.5 but no greater than –1 at the hip or the spine. A total of 27 received a single IV infusion of zoledronate 5 mg given 6 months after the last denosumab injection with a 3-week window, and 30 continued denosumab and received two additional monthly 60-mg injections. Following either the zoledronate infusion or the last denosumab injection, all women received no treatment and were followed until 2 years from randomization. All women were given vitamin D supplements and were seen in clinic appointments at baseline, 6, 12, 15, 18, and 24 months.

Areal BMD of the lumbar spine and femoral neck of the nondominant hip were measured at baseline, 12, and 24 months by dual-energy x-ray absorptiometry, and least significant changes were 5% or less at the spine and 4% or less at the femoral neck, based on proposals from the International Foundation for Osteoporosis and the National Osteoporosis Foundation USA.

At 24 months, lumbar spine BMD (LS‐BMD) returned to baseline in the zoledronate group, but decreased in the denosumab group by 4.82% from the 12‐month value (P less than .001).

The difference in LS-BMD changes between the two groups from month 12 to 24, the primary endpoint of the study, was statistically significant (–0.018 with zoledronate vs. –0.045 with denosumab; P = .025). Differences in changes of femoral neck BMD were also statistically significant (–0.004 with zoledronate vs. –0.038 with denosumab; P = .005), the researchers reported.

The differences in BMD changes between the two groups 24 and 12 months after discontinuation of denosumab (6 months after the last injection) for the zoledronate and denosumab group respectively were also statistically significant both at the lumbar spine (–0.002 with zoledronate vs. –0.045 with denosumab; P = .03) and at the femoral neck (–0.004 with zoledronate vs. –0.038 with denosumab; P = .007).

The authors observed no relationship between the number of denosumab injections and LS-BMD changes in either group of women; however, they noted that responses of individual patients to zoledronate were variable. For example, three women who took zoledronate experienced decreases of LS-BMD greater than the least significant change observed at 24 months, a finding which could not be explained by the timing of the infusion, baseline rate of bone turnover, or baseline BMD.

“It appears that intrinsic factors that still need to be defined may affect the response of a few individuals,” they wrote.

This was further illustrated by one patient in the zoledronate group who sustained clinical vertebral fractures associated with significant, unexplained decreases of BMD that could not be prevented with the zoledronate infusion.

“In clinical practice, it is, therefore, advisable to measure BMD at 12 months after the zoledronate infusion and decide whether additional treatment may be required,” the authors wrote.

Another significant finding reported by the authors was that neither baseline nor 12‐month bone turnover marker (BTM) values were associated with BMD changes in either group of women during the entire study period.

“Particularly important for clinical practice was the lack of a relationship in zoledronate-treated women; even when women were divided according to baseline median BTM values (below or above) there were no significant difference in BMD changes at 12 or 24 months,” they wrote.

“In a substantial number of women in the denosumab group BTMs were still above the upper limit of normal of the postmenopausal age 18 months after the last Dmab [denosumab] injection but also in 7.4% of patients treated with zoledronate at 2 years,” they added.

“Whether in the latter patients BTMs were also increased before the start of Dmab treatment, as it is known to occur in some patients with osteoporosis, or are due to a prolonged effect of Dmab withdrawal on bone metabolism could not be prevented by zoledronate, is not known because pretreatment data were not available,” the study authors noted.

For adverse events, in addition to the one patient in the zoledronate group with clinical vertebral fractures, three patients in the denosumab group sustained vertebral fractures.

“Prevalent vertebral fractures have been previously reported as the most important risk factor for clinical vertebral fractures following cessation of Dmab therapy [which] strongly suggest that spine x-rays should be performed in all patients in whom discontinuation of Dmab treatment is considered,” the authors wrote.

“In most women with postmenopausal osteoporosis treated with [denosumab] in whom discontinuation of treatment is considered when a nonosteoporotic BMD is achieved, a single intravenous infusion of zoledronate 5 mg given 6 months after the last Dmab injection prevents bone loss for at least 2 years independently of the rate of bone turnover. Follow-up is recommended, as in a few patients treatment might not have the expected effect at 2 years for currently unknown reasons,” they concluded.

The study was funded by institutional funds and the Hellenic Endocrine Society. Several authors reported receiving consulting or lecture fees from Amgen, which markets denosumab, as well as other pharmaceutical companies.

SOURCE: Anastasilakis A et al. J Bone Miner Res. 2019 Aug 21. doi: 10.1002/jbmr.3853.

Women with postmenopausal osteoporosis who discontinued denosumab treatment after achieving osteopenia maintained bone mineral density at the spine and hip with a single infusion of zoledronate given 6 months after the last infusion of denosumab, according to results from a small, multicenter, randomized trial published in the Journal of Bone and Mineral Research.

ogichobanov/iStock/Getty Images Plus

The cessation of the monoclonal antibody denosumab is typically followed by a “rebound phenomenon” often attributed to an increase in bone turnover above pretreatment values caused by the up-regulation of osteoclastogenesis, according to Athanasios D. Anastasilakis, MD, of 424 General Military Hospital, Thessaloníki, Greece, and colleagues. Guidelines recommend that patients take a bisphosphonate to prevent this effect, but the optimal bisphosphonate regimen is unknown and evidence is inconsistent.

To address this question, the investigators randomized 57 postmenopausal women with osteoporosis who had received six monthly injections of denosumab (for an average of 2.2 years) and had achieved nonosteoporotic bone mineral density (BMD) T scores greater than –2.5 but no greater than –1 at the hip or the spine. A total of 27 received a single IV infusion of zoledronate 5 mg given 6 months after the last denosumab injection with a 3-week window, and 30 continued denosumab and received two additional monthly 60-mg injections. Following either the zoledronate infusion or the last denosumab injection, all women received no treatment and were followed until 2 years from randomization. All women were given vitamin D supplements and were seen in clinic appointments at baseline, 6, 12, 15, 18, and 24 months.

Areal BMD of the lumbar spine and femoral neck of the nondominant hip were measured at baseline, 12, and 24 months by dual-energy x-ray absorptiometry, and least significant changes were 5% or less at the spine and 4% or less at the femoral neck, based on proposals from the International Foundation for Osteoporosis and the National Osteoporosis Foundation USA.

At 24 months, lumbar spine BMD (LS‐BMD) returned to baseline in the zoledronate group, but decreased in the denosumab group by 4.82% from the 12‐month value (P less than .001).

The difference in LS-BMD changes between the two groups from month 12 to 24, the primary endpoint of the study, was statistically significant (–0.018 with zoledronate vs. –0.045 with denosumab; P = .025). Differences in changes of femoral neck BMD were also statistically significant (–0.004 with zoledronate vs. –0.038 with denosumab; P = .005), the researchers reported.

The differences in BMD changes between the two groups 24 and 12 months after discontinuation of denosumab (6 months after the last injection) for the zoledronate and denosumab group respectively were also statistically significant both at the lumbar spine (–0.002 with zoledronate vs. –0.045 with denosumab; P = .03) and at the femoral neck (–0.004 with zoledronate vs. –0.038 with denosumab; P = .007).

The authors observed no relationship between the number of denosumab injections and LS-BMD changes in either group of women; however, they noted that responses of individual patients to zoledronate were variable. For example, three women who took zoledronate experienced decreases of LS-BMD greater than the least significant change observed at 24 months, a finding which could not be explained by the timing of the infusion, baseline rate of bone turnover, or baseline BMD.

“It appears that intrinsic factors that still need to be defined may affect the response of a few individuals,” they wrote.

This was further illustrated by one patient in the zoledronate group who sustained clinical vertebral fractures associated with significant, unexplained decreases of BMD that could not be prevented with the zoledronate infusion.

“In clinical practice, it is, therefore, advisable to measure BMD at 12 months after the zoledronate infusion and decide whether additional treatment may be required,” the authors wrote.

Another significant finding reported by the authors was that neither baseline nor 12‐month bone turnover marker (BTM) values were associated with BMD changes in either group of women during the entire study period.

“Particularly important for clinical practice was the lack of a relationship in zoledronate-treated women; even when women were divided according to baseline median BTM values (below or above) there were no significant difference in BMD changes at 12 or 24 months,” they wrote.

“In a substantial number of women in the denosumab group BTMs were still above the upper limit of normal of the postmenopausal age 18 months after the last Dmab [denosumab] injection but also in 7.4% of patients treated with zoledronate at 2 years,” they added.

“Whether in the latter patients BTMs were also increased before the start of Dmab treatment, as it is known to occur in some patients with osteoporosis, or are due to a prolonged effect of Dmab withdrawal on bone metabolism could not be prevented by zoledronate, is not known because pretreatment data were not available,” the study authors noted.

For adverse events, in addition to the one patient in the zoledronate group with clinical vertebral fractures, three patients in the denosumab group sustained vertebral fractures.

“Prevalent vertebral fractures have been previously reported as the most important risk factor for clinical vertebral fractures following cessation of Dmab therapy [which] strongly suggest that spine x-rays should be performed in all patients in whom discontinuation of Dmab treatment is considered,” the authors wrote.

“In most women with postmenopausal osteoporosis treated with [denosumab] in whom discontinuation of treatment is considered when a nonosteoporotic BMD is achieved, a single intravenous infusion of zoledronate 5 mg given 6 months after the last Dmab injection prevents bone loss for at least 2 years independently of the rate of bone turnover. Follow-up is recommended, as in a few patients treatment might not have the expected effect at 2 years for currently unknown reasons,” they concluded.

The study was funded by institutional funds and the Hellenic Endocrine Society. Several authors reported receiving consulting or lecture fees from Amgen, which markets denosumab, as well as other pharmaceutical companies.

SOURCE: Anastasilakis A et al. J Bone Miner Res. 2019 Aug 21. doi: 10.1002/jbmr.3853.

Women with postmenopausal osteoporosis who discontinued denosumab treatment after achieving osteopenia maintained bone mineral density at the spine and hip with a single infusion of zoledronate given 6 months after the last infusion of denosumab, according to results from a small, multicenter, randomized trial published in the Journal of Bone and Mineral Research.

ogichobanov/iStock/Getty Images Plus

The cessation of the monoclonal antibody denosumab is typically followed by a “rebound phenomenon” often attributed to an increase in bone turnover above pretreatment values caused by the up-regulation of osteoclastogenesis, according to Athanasios D. Anastasilakis, MD, of 424 General Military Hospital, Thessaloníki, Greece, and colleagues. Guidelines recommend that patients take a bisphosphonate to prevent this effect, but the optimal bisphosphonate regimen is unknown and evidence is inconsistent.

To address this question, the investigators randomized 57 postmenopausal women with osteoporosis who had received six monthly injections of denosumab (for an average of 2.2 years) and had achieved nonosteoporotic bone mineral density (BMD) T scores greater than –2.5 but no greater than –1 at the hip or the spine. A total of 27 received a single IV infusion of zoledronate 5 mg given 6 months after the last denosumab injection with a 3-week window, and 30 continued denosumab and received two additional monthly 60-mg injections. Following either the zoledronate infusion or the last denosumab injection, all women received no treatment and were followed until 2 years from randomization. All women were given vitamin D supplements and were seen in clinic appointments at baseline, 6, 12, 15, 18, and 24 months.

Areal BMD of the lumbar spine and femoral neck of the nondominant hip were measured at baseline, 12, and 24 months by dual-energy x-ray absorptiometry, and least significant changes were 5% or less at the spine and 4% or less at the femoral neck, based on proposals from the International Foundation for Osteoporosis and the National Osteoporosis Foundation USA.

At 24 months, lumbar spine BMD (LS‐BMD) returned to baseline in the zoledronate group, but decreased in the denosumab group by 4.82% from the 12‐month value (P less than .001).

The difference in LS-BMD changes between the two groups from month 12 to 24, the primary endpoint of the study, was statistically significant (–0.018 with zoledronate vs. –0.045 with denosumab; P = .025). Differences in changes of femoral neck BMD were also statistically significant (–0.004 with zoledronate vs. –0.038 with denosumab; P = .005), the researchers reported.

The differences in BMD changes between the two groups 24 and 12 months after discontinuation of denosumab (6 months after the last injection) for the zoledronate and denosumab group respectively were also statistically significant both at the lumbar spine (–0.002 with zoledronate vs. –0.045 with denosumab; P = .03) and at the femoral neck (–0.004 with zoledronate vs. –0.038 with denosumab; P = .007).

The authors observed no relationship between the number of denosumab injections and LS-BMD changes in either group of women; however, they noted that responses of individual patients to zoledronate were variable. For example, three women who took zoledronate experienced decreases of LS-BMD greater than the least significant change observed at 24 months, a finding which could not be explained by the timing of the infusion, baseline rate of bone turnover, or baseline BMD.

“It appears that intrinsic factors that still need to be defined may affect the response of a few individuals,” they wrote.

This was further illustrated by one patient in the zoledronate group who sustained clinical vertebral fractures associated with significant, unexplained decreases of BMD that could not be prevented with the zoledronate infusion.

“In clinical practice, it is, therefore, advisable to measure BMD at 12 months after the zoledronate infusion and decide whether additional treatment may be required,” the authors wrote.

Another significant finding reported by the authors was that neither baseline nor 12‐month bone turnover marker (BTM) values were associated with BMD changes in either group of women during the entire study period.

“Particularly important for clinical practice was the lack of a relationship in zoledronate-treated women; even when women were divided according to baseline median BTM values (below or above) there were no significant difference in BMD changes at 12 or 24 months,” they wrote.

“In a substantial number of women in the denosumab group BTMs were still above the upper limit of normal of the postmenopausal age 18 months after the last Dmab [denosumab] injection but also in 7.4% of patients treated with zoledronate at 2 years,” they added.

“Whether in the latter patients BTMs were also increased before the start of Dmab treatment, as it is known to occur in some patients with osteoporosis, or are due to a prolonged effect of Dmab withdrawal on bone metabolism could not be prevented by zoledronate, is not known because pretreatment data were not available,” the study authors noted.

For adverse events, in addition to the one patient in the zoledronate group with clinical vertebral fractures, three patients in the denosumab group sustained vertebral fractures.

“Prevalent vertebral fractures have been previously reported as the most important risk factor for clinical vertebral fractures following cessation of Dmab therapy [which] strongly suggest that spine x-rays should be performed in all patients in whom discontinuation of Dmab treatment is considered,” the authors wrote.

“In most women with postmenopausal osteoporosis treated with [denosumab] in whom discontinuation of treatment is considered when a nonosteoporotic BMD is achieved, a single intravenous infusion of zoledronate 5 mg given 6 months after the last Dmab injection prevents bone loss for at least 2 years independently of the rate of bone turnover. Follow-up is recommended, as in a few patients treatment might not have the expected effect at 2 years for currently unknown reasons,” they concluded.

The study was funded by institutional funds and the Hellenic Endocrine Society. Several authors reported receiving consulting or lecture fees from Amgen, which markets denosumab, as well as other pharmaceutical companies.

SOURCE: Anastasilakis A et al. J Bone Miner Res. 2019 Aug 21. doi: 10.1002/jbmr.3853.

A novel transplant protocol (WZ-14-TM) improved survival outcomes and rates of graft-versus-host disease (GVHD) in patients with beta-thalassemia major undergoing hematopoietic stem cell transplant (HSCT) from an unrelated donor, according to findings from a single-center study.

“In August 2014, we began using WZ-14-TM in hopes of lowering the [graft failure] rate and transplant-related mortality,” Lan Sun, MD, of Wenzhou (China) Medical University and colleagues wrote in Biology of Blood and Marrow Transplantation.

The study cohort included 48 patients (aged 2-11 years) with beta-thalassemia major who underwent unrelated-donor HSCT from August 2014 to June 2018. Prior to transplantation, all participants received iron chelation therapy and regular red blood cell transfusions.

The original busulfan/cyclophosphamide–based conditioning regimen was modified to include antithymocyte globulin and fludarabine in order to reduce the risk of graft failure.

Additionally, the team lowered the cumulative dose of cyclophosphamide from 200 mg/kg to 100 mg/kg in an effort to lessen treatment-related toxicity.

After analysis, the researchers reported that the rates of thalassemia-free and overall survival were both 100%, while the incidence rates of acute (grade 2-4) and chronic GVHD were both 8.3%. In prior studies, the incidence rates of acute (grade 2-4) and chronic GVHD were 37%-42% and 14%-27%, respectively.

Neutrophil engraftment was achieved in a median duration of 13 days, while the median hemoglobin and platelet recovery times were 11 days and 12 days, respectively.

The low incidence of GVHD in their study may be related to the combination of antithymocyte globulin, cyclosporine A, mycophenolate mofetil, and methotrexate for GVHD prophylaxis, the researchers wrote.

They acknowledged two key limitations of the study were the small sample size and its single-center design. Accordingly, the findings should be validated in future studies.

The results suggest that the WZ-14-TM protocol is a “feasible and safe” conditioning regimen for patients with beta-thalassemia major undergoing unrelated-donor HSCT, they concluded.

The study was funded by the Public Welfare Science and Technology Project of Wenzhou, the Natural Science Foundation of Zhejiang Province, and the National Natural Science Foundation of China. The authors reported having no conflicts of interest.

SOURCE: Sun L et al. Biol Blood Marrow Transplant. 2019; 25(8):1592-6.

A novel transplant protocol (WZ-14-TM) improved survival outcomes and rates of graft-versus-host disease (GVHD) in patients with beta-thalassemia major undergoing hematopoietic stem cell transplant (HSCT) from an unrelated donor, according to findings from a single-center study.

“In August 2014, we began using WZ-14-TM in hopes of lowering the [graft failure] rate and transplant-related mortality,” Lan Sun, MD, of Wenzhou (China) Medical University and colleagues wrote in Biology of Blood and Marrow Transplantation.

The study cohort included 48 patients (aged 2-11 years) with beta-thalassemia major who underwent unrelated-donor HSCT from August 2014 to June 2018. Prior to transplantation, all participants received iron chelation therapy and regular red blood cell transfusions.

The original busulfan/cyclophosphamide–based conditioning regimen was modified to include antithymocyte globulin and fludarabine in order to reduce the risk of graft failure.

Additionally, the team lowered the cumulative dose of cyclophosphamide from 200 mg/kg to 100 mg/kg in an effort to lessen treatment-related toxicity.

After analysis, the researchers reported that the rates of thalassemia-free and overall survival were both 100%, while the incidence rates of acute (grade 2-4) and chronic GVHD were both 8.3%. In prior studies, the incidence rates of acute (grade 2-4) and chronic GVHD were 37%-42% and 14%-27%, respectively.

Neutrophil engraftment was achieved in a median duration of 13 days, while the median hemoglobin and platelet recovery times were 11 days and 12 days, respectively.

The low incidence of GVHD in their study may be related to the combination of antithymocyte globulin, cyclosporine A, mycophenolate mofetil, and methotrexate for GVHD prophylaxis, the researchers wrote.

They acknowledged two key limitations of the study were the small sample size and its single-center design. Accordingly, the findings should be validated in future studies.

The results suggest that the WZ-14-TM protocol is a “feasible and safe” conditioning regimen for patients with beta-thalassemia major undergoing unrelated-donor HSCT, they concluded.

The study was funded by the Public Welfare Science and Technology Project of Wenzhou, the Natural Science Foundation of Zhejiang Province, and the National Natural Science Foundation of China. The authors reported having no conflicts of interest.

SOURCE: Sun L et al. Biol Blood Marrow Transplant. 2019; 25(8):1592-6.

A novel transplant protocol (WZ-14-TM) improved survival outcomes and rates of graft-versus-host disease (GVHD) in patients with beta-thalassemia major undergoing hematopoietic stem cell transplant (HSCT) from an unrelated donor, according to findings from a single-center study.

“In August 2014, we began using WZ-14-TM in hopes of lowering the [graft failure] rate and transplant-related mortality,” Lan Sun, MD, of Wenzhou (China) Medical University and colleagues wrote in Biology of Blood and Marrow Transplantation.

The study cohort included 48 patients (aged 2-11 years) with beta-thalassemia major who underwent unrelated-donor HSCT from August 2014 to June 2018. Prior to transplantation, all participants received iron chelation therapy and regular red blood cell transfusions.

The original busulfan/cyclophosphamide–based conditioning regimen was modified to include antithymocyte globulin and fludarabine in order to reduce the risk of graft failure.

Additionally, the team lowered the cumulative dose of cyclophosphamide from 200 mg/kg to 100 mg/kg in an effort to lessen treatment-related toxicity.

After analysis, the researchers reported that the rates of thalassemia-free and overall survival were both 100%, while the incidence rates of acute (grade 2-4) and chronic GVHD were both 8.3%. In prior studies, the incidence rates of acute (grade 2-4) and chronic GVHD were 37%-42% and 14%-27%, respectively.

Neutrophil engraftment was achieved in a median duration of 13 days, while the median hemoglobin and platelet recovery times were 11 days and 12 days, respectively.

The low incidence of GVHD in their study may be related to the combination of antithymocyte globulin, cyclosporine A, mycophenolate mofetil, and methotrexate for GVHD prophylaxis, the researchers wrote.

They acknowledged two key limitations of the study were the small sample size and its single-center design. Accordingly, the findings should be validated in future studies.

The results suggest that the WZ-14-TM protocol is a “feasible and safe” conditioning regimen for patients with beta-thalassemia major undergoing unrelated-donor HSCT, they concluded.

The study was funded by the Public Welfare Science and Technology Project of Wenzhou, the Natural Science Foundation of Zhejiang Province, and the National Natural Science Foundation of China. The authors reported having no conflicts of interest.

SOURCE: Sun L et al. Biol Blood Marrow Transplant. 2019; 25(8):1592-6.

From 2006 to 2016, the prices of self-administered disease-modifying therapies for multiple sclerosis increased markedly, according to an analysis published in JAMA Neurology. The increased prices raise concern “because they demonstrate that the approval of new therapies did not ameliorate and could have even contributed to high inflation rates observed for incumbent drugs,” wrote the authors.

Four self-administered disease-modifying therapies (DMTs) for multiple sclerosis (MS) were available before 2009, and seven new branded DMTs were introduced after that year. Previous research indicated that the prices of DMTs for MS increased at higher rates than the prices of drugs for other disorders. How these price increases affected pharmaceutical spending during the past decade is uncertain, however.

A review of Medicare claims data

Alvaro San-Juan-Rodriguez, PharmD, a fellow in pharmacoeconomics, outcomes, and pharmacoanalytics research at the University of Pittsburgh, and colleagues examined claims data from 2006 to 2016 from a 5% random sample of Medicare beneficiaries. Information for a mean of 2.8 million Medicare beneficiaries per year was available. The researchers extracted all prescription claims for self-administered DMTs for MS (that is, glatiramer acetate, interferon beta-1a, interferon beta-1b, fingolimod, teriflunomide, dimethyl fumarate, and peginterferon beta-1a).

Dr. San-Juan-Rodriguez and associates chose three main outcomes. The first was the annual cost of treatment with each medication, which was based on Medicare Part D prescription claims gross costs and Food and Drug Administration–approved recommended dosing. The second was the market share of each medication, which the researchers defined as the proportion of pharmaceutical spending accounted for by each drug. The third was pharmaceutical spending per 1,000 Medicare beneficiaries for all drugs. The investigators also examined the relative contributions of Medicare Part D Plans’ payments, patients’ out-of-pocket costs, and other payments toward pharmaceutical spending.

Prices defied market expectations

The annual costs of treatment with self-administered DMTs for MS increased more than 300%. The mean annual cost was $18,660 in 2006 and $75,847 in 2016, and the mean annual rate of price increase was 12.8%. “Prices of most self-administered DMTs for MS increased in parallel, defying standard market expectations,” the investigators wrote.

Branded formulations of glatiramer acetate maintained the largest market share throughout the study period, ranging between 32.2% and 48.4%. However, the market share of platform therapies – glatiramer acetate, interferon beta-1a, and interferon beta-1b – decreased significantly from 2006 to 2016. Market shares for brand-name glatiramers declined from 36.7% to 32.2%, for intramuscular interferon beta-1a (30 mcg) from 32.3% to 14.2%, for interferon beta-1b from 18.7% to 4.5%, and for interferon beta-1a (8.8, 22, or 44 mcg) from 12.2% to 8.3%. The market shares of newer therapies, however, increased to 7.9% for fingolimod, 9.0% for teriflunomide, and 19.2% for dimethyl fumarate.

Pharmaceutical spending per 1,000 beneficiaries increased by a factor of 10.2 throughout the study period (from $7,794 to $79,411). Patients’ out-of-pocket spending per 1,000 beneficiaries increased by a factor of 7.2 (from $372 to $2,673). Furthermore, the relative contribution of federal payments toward pharmaceutical spending increased from 68.5% to 73.8%.

“Large increases in drug prices have not been specific to MS drugs,” said Dr. San-Juan-Rodriguez in an interview. “We previously described similar trends in other specialty medications used to treat severe disease states, such as tumor necrosis factor inhibitors [TNFi] for the treatment of rheumatoid arthritis. Yet these increases took place at a slower pace. For instance, list prices of TNFi increased at an average annual rate of 9.9% in the same time period, 2006-2016.

“It is important to acknowledge that rising list prices of drugs may partially reflect competition for rebates,” he added. “Yet the specific reasons behind the faster growth of prices of MS drugs, compared with the prices of drugs used in other disease states, remain uncertain.”

Neurologists should bear in mind that, although generic drugs are substantially cheaper than branded drugs, generic specialty medications do not always reduce costs for Medicare Part D beneficiaries. “On the contrary, due to incentive misalignments created by the Medicare Part D benefit design, beneficiaries using generic drugs such as Glatopa ... may pay more than those using the branded drug,” Dr. San-Juan-Rodriguez said.

What are neurologists’ responsibilities?

Although the original annual price of interferon beta-1b ($10,920) was stunning, physicians now recall it with nostalgia, wrote Daniel M. Hartung, PharmD, associate professor of biostatistics and epidemiology, and Dennis Bourdette, MD, professor of neurology, both at Oregon Health and Science University, Portland, in an accompanying editorial. “The prices for DMTs for MS have risen dramatically over the last 15 years, far outpacing inflation, and now have a mean price of more than $86,000 per year.”

Neurologists should be concerned about these rising prices, Dr. Hartung and Dr. Bourdette wrote. They should feel responsibility toward the health care system that pays for these medications, and toward patients who pay out of their own pockets. “Neurologists should be seeking to minimize the financial adverse effects of these therapies as much as they try to minimize physical adverse effects.”

One way for neurologists to address increasing prices is to urge state and federal lawmakers to pass legislation to curb them, they wrote. Neurologists also should reexamine their relationships with pharmaceutical and biotechnology companies. “Remaining silent should not be an option. ... Neurologists should not allow the unfettered increases in price for these drugs to hurt the health care system or patients.”

The Myers Family Foundation and the National Heart, Lung, and Blood Institute funded the research. Several authors are employees of health insurance companies such as the UPMC Health Plan Insurance Services Division and Humana. One author received personal fees from Pfizer that were unrelated to this study.

egreb@mdedge.com

SOURCEs: San-Juan-Rodriguez A et al. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2711; Hartung DM and Bourdette D. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2445.

From 2006 to 2016, the prices of self-administered disease-modifying therapies for multiple sclerosis increased markedly, according to an analysis published in JAMA Neurology. The increased prices raise concern “because they demonstrate that the approval of new therapies did not ameliorate and could have even contributed to high inflation rates observed for incumbent drugs,” wrote the authors.

Four self-administered disease-modifying therapies (DMTs) for multiple sclerosis (MS) were available before 2009, and seven new branded DMTs were introduced after that year. Previous research indicated that the prices of DMTs for MS increased at higher rates than the prices of drugs for other disorders. How these price increases affected pharmaceutical spending during the past decade is uncertain, however.

A review of Medicare claims data

Alvaro San-Juan-Rodriguez, PharmD, a fellow in pharmacoeconomics, outcomes, and pharmacoanalytics research at the University of Pittsburgh, and colleagues examined claims data from 2006 to 2016 from a 5% random sample of Medicare beneficiaries. Information for a mean of 2.8 million Medicare beneficiaries per year was available. The researchers extracted all prescription claims for self-administered DMTs for MS (that is, glatiramer acetate, interferon beta-1a, interferon beta-1b, fingolimod, teriflunomide, dimethyl fumarate, and peginterferon beta-1a).

Dr. San-Juan-Rodriguez and associates chose three main outcomes. The first was the annual cost of treatment with each medication, which was based on Medicare Part D prescription claims gross costs and Food and Drug Administration–approved recommended dosing. The second was the market share of each medication, which the researchers defined as the proportion of pharmaceutical spending accounted for by each drug. The third was pharmaceutical spending per 1,000 Medicare beneficiaries for all drugs. The investigators also examined the relative contributions of Medicare Part D Plans’ payments, patients’ out-of-pocket costs, and other payments toward pharmaceutical spending.

Prices defied market expectations

The annual costs of treatment with self-administered DMTs for MS increased more than 300%. The mean annual cost was $18,660 in 2006 and $75,847 in 2016, and the mean annual rate of price increase was 12.8%. “Prices of most self-administered DMTs for MS increased in parallel, defying standard market expectations,” the investigators wrote.

Branded formulations of glatiramer acetate maintained the largest market share throughout the study period, ranging between 32.2% and 48.4%. However, the market share of platform therapies – glatiramer acetate, interferon beta-1a, and interferon beta-1b – decreased significantly from 2006 to 2016. Market shares for brand-name glatiramers declined from 36.7% to 32.2%, for intramuscular interferon beta-1a (30 mcg) from 32.3% to 14.2%, for interferon beta-1b from 18.7% to 4.5%, and for interferon beta-1a (8.8, 22, or 44 mcg) from 12.2% to 8.3%. The market shares of newer therapies, however, increased to 7.9% for fingolimod, 9.0% for teriflunomide, and 19.2% for dimethyl fumarate.

Pharmaceutical spending per 1,000 beneficiaries increased by a factor of 10.2 throughout the study period (from $7,794 to $79,411). Patients’ out-of-pocket spending per 1,000 beneficiaries increased by a factor of 7.2 (from $372 to $2,673). Furthermore, the relative contribution of federal payments toward pharmaceutical spending increased from 68.5% to 73.8%.

“Large increases in drug prices have not been specific to MS drugs,” said Dr. San-Juan-Rodriguez in an interview. “We previously described similar trends in other specialty medications used to treat severe disease states, such as tumor necrosis factor inhibitors [TNFi] for the treatment of rheumatoid arthritis. Yet these increases took place at a slower pace. For instance, list prices of TNFi increased at an average annual rate of 9.9% in the same time period, 2006-2016.

“It is important to acknowledge that rising list prices of drugs may partially reflect competition for rebates,” he added. “Yet the specific reasons behind the faster growth of prices of MS drugs, compared with the prices of drugs used in other disease states, remain uncertain.”

Neurologists should bear in mind that, although generic drugs are substantially cheaper than branded drugs, generic specialty medications do not always reduce costs for Medicare Part D beneficiaries. “On the contrary, due to incentive misalignments created by the Medicare Part D benefit design, beneficiaries using generic drugs such as Glatopa ... may pay more than those using the branded drug,” Dr. San-Juan-Rodriguez said.

What are neurologists’ responsibilities?

Although the original annual price of interferon beta-1b ($10,920) was stunning, physicians now recall it with nostalgia, wrote Daniel M. Hartung, PharmD, associate professor of biostatistics and epidemiology, and Dennis Bourdette, MD, professor of neurology, both at Oregon Health and Science University, Portland, in an accompanying editorial. “The prices for DMTs for MS have risen dramatically over the last 15 years, far outpacing inflation, and now have a mean price of more than $86,000 per year.”

Neurologists should be concerned about these rising prices, Dr. Hartung and Dr. Bourdette wrote. They should feel responsibility toward the health care system that pays for these medications, and toward patients who pay out of their own pockets. “Neurologists should be seeking to minimize the financial adverse effects of these therapies as much as they try to minimize physical adverse effects.”

One way for neurologists to address increasing prices is to urge state and federal lawmakers to pass legislation to curb them, they wrote. Neurologists also should reexamine their relationships with pharmaceutical and biotechnology companies. “Remaining silent should not be an option. ... Neurologists should not allow the unfettered increases in price for these drugs to hurt the health care system or patients.”

The Myers Family Foundation and the National Heart, Lung, and Blood Institute funded the research. Several authors are employees of health insurance companies such as the UPMC Health Plan Insurance Services Division and Humana. One author received personal fees from Pfizer that were unrelated to this study.

egreb@mdedge.com

SOURCEs: San-Juan-Rodriguez A et al. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2711; Hartung DM and Bourdette D. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2445.

From 2006 to 2016, the prices of self-administered disease-modifying therapies for multiple sclerosis increased markedly, according to an analysis published in JAMA Neurology. The increased prices raise concern “because they demonstrate that the approval of new therapies did not ameliorate and could have even contributed to high inflation rates observed for incumbent drugs,” wrote the authors.

Four self-administered disease-modifying therapies (DMTs) for multiple sclerosis (MS) were available before 2009, and seven new branded DMTs were introduced after that year. Previous research indicated that the prices of DMTs for MS increased at higher rates than the prices of drugs for other disorders. How these price increases affected pharmaceutical spending during the past decade is uncertain, however.

A review of Medicare claims data

Alvaro San-Juan-Rodriguez, PharmD, a fellow in pharmacoeconomics, outcomes, and pharmacoanalytics research at the University of Pittsburgh, and colleagues examined claims data from 2006 to 2016 from a 5% random sample of Medicare beneficiaries. Information for a mean of 2.8 million Medicare beneficiaries per year was available. The researchers extracted all prescription claims for self-administered DMTs for MS (that is, glatiramer acetate, interferon beta-1a, interferon beta-1b, fingolimod, teriflunomide, dimethyl fumarate, and peginterferon beta-1a).

Dr. San-Juan-Rodriguez and associates chose three main outcomes. The first was the annual cost of treatment with each medication, which was based on Medicare Part D prescription claims gross costs and Food and Drug Administration–approved recommended dosing. The second was the market share of each medication, which the researchers defined as the proportion of pharmaceutical spending accounted for by each drug. The third was pharmaceutical spending per 1,000 Medicare beneficiaries for all drugs. The investigators also examined the relative contributions of Medicare Part D Plans’ payments, patients’ out-of-pocket costs, and other payments toward pharmaceutical spending.

Prices defied market expectations

The annual costs of treatment with self-administered DMTs for MS increased more than 300%. The mean annual cost was $18,660 in 2006 and $75,847 in 2016, and the mean annual rate of price increase was 12.8%. “Prices of most self-administered DMTs for MS increased in parallel, defying standard market expectations,” the investigators wrote.

Branded formulations of glatiramer acetate maintained the largest market share throughout the study period, ranging between 32.2% and 48.4%. However, the market share of platform therapies – glatiramer acetate, interferon beta-1a, and interferon beta-1b – decreased significantly from 2006 to 2016. Market shares for brand-name glatiramers declined from 36.7% to 32.2%, for intramuscular interferon beta-1a (30 mcg) from 32.3% to 14.2%, for interferon beta-1b from 18.7% to 4.5%, and for interferon beta-1a (8.8, 22, or 44 mcg) from 12.2% to 8.3%. The market shares of newer therapies, however, increased to 7.9% for fingolimod, 9.0% for teriflunomide, and 19.2% for dimethyl fumarate.

Pharmaceutical spending per 1,000 beneficiaries increased by a factor of 10.2 throughout the study period (from $7,794 to $79,411). Patients’ out-of-pocket spending per 1,000 beneficiaries increased by a factor of 7.2 (from $372 to $2,673). Furthermore, the relative contribution of federal payments toward pharmaceutical spending increased from 68.5% to 73.8%.

“Large increases in drug prices have not been specific to MS drugs,” said Dr. San-Juan-Rodriguez in an interview. “We previously described similar trends in other specialty medications used to treat severe disease states, such as tumor necrosis factor inhibitors [TNFi] for the treatment of rheumatoid arthritis. Yet these increases took place at a slower pace. For instance, list prices of TNFi increased at an average annual rate of 9.9% in the same time period, 2006-2016.

“It is important to acknowledge that rising list prices of drugs may partially reflect competition for rebates,” he added. “Yet the specific reasons behind the faster growth of prices of MS drugs, compared with the prices of drugs used in other disease states, remain uncertain.”

Neurologists should bear in mind that, although generic drugs are substantially cheaper than branded drugs, generic specialty medications do not always reduce costs for Medicare Part D beneficiaries. “On the contrary, due to incentive misalignments created by the Medicare Part D benefit design, beneficiaries using generic drugs such as Glatopa ... may pay more than those using the branded drug,” Dr. San-Juan-Rodriguez said.

What are neurologists’ responsibilities?

Although the original annual price of interferon beta-1b ($10,920) was stunning, physicians now recall it with nostalgia, wrote Daniel M. Hartung, PharmD, associate professor of biostatistics and epidemiology, and Dennis Bourdette, MD, professor of neurology, both at Oregon Health and Science University, Portland, in an accompanying editorial. “The prices for DMTs for MS have risen dramatically over the last 15 years, far outpacing inflation, and now have a mean price of more than $86,000 per year.”

Neurologists should be concerned about these rising prices, Dr. Hartung and Dr. Bourdette wrote. They should feel responsibility toward the health care system that pays for these medications, and toward patients who pay out of their own pockets. “Neurologists should be seeking to minimize the financial adverse effects of these therapies as much as they try to minimize physical adverse effects.”

One way for neurologists to address increasing prices is to urge state and federal lawmakers to pass legislation to curb them, they wrote. Neurologists also should reexamine their relationships with pharmaceutical and biotechnology companies. “Remaining silent should not be an option. ... Neurologists should not allow the unfettered increases in price for these drugs to hurt the health care system or patients.”

The Myers Family Foundation and the National Heart, Lung, and Blood Institute funded the research. Several authors are employees of health insurance companies such as the UPMC Health Plan Insurance Services Division and Humana. One author received personal fees from Pfizer that were unrelated to this study.

egreb@mdedge.com

SOURCEs: San-Juan-Rodriguez A et al. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2711; Hartung DM and Bourdette D. JAMA Neurol. 2019 Aug 26. doi: 10.1001/jamaneurol.2019.2445.

LUGANO, Switzerland – In younger patients with previously untreated mantle cell lymphoma, the chemotherapy-free combination of ibrutinib and rituximab followed by a short course of chemotherapy was associated with an “unprecedented” 3-year progression-free survival rate, investigators in the phase 2 WINDOW-1 trial reported.

Neil Osterweil/MDedge News

Among 50 patients aged 65 years and younger who received ibrutinib and rituximab until they achieved a complete or partial response, followed by four cycles of chemotherapy with rituximab plus hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) and rituximab plus methotrexate, the 3-year progression-free survival (PFS) rate was 88%, said Michael Wang, MD, from the University of Texas MD Anderson Cancer Center in Houston.

Additionally, for patients with the low-risk features, the 3-year PFS rate was 90%.

“Chemo-free ibrutinib-rituximab induced unprecedented – unprecedented – efficacy before chemo consolidation,” he said at the International Conference on Malignant Lymphoma.

Dr. Wang presented data from an interim analysis of the investigator-initiated single-center trial. Fifty patients aged 65 years or younger with untreated mantle cell lymphoma (MCL), good performance status, and good organ function were enrolled.

The patients were treated with ibrutinib and rituximab for two cycles and then evaluated for response with PET-CT scan, bone marrow biopsy, and for some patients, esophagogastroduodenoscopy (EGD) and colonoscopy with random biopsies.

In the induction phase, patients received ibrutinib daily on days 1-28 and rituximab intravenously over 6-8 hours on days 1, 8, 15, and 22 of cycle 1, and then over 4 hours on day 1 of cycles 3-12. The treatment was repeated every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity, or until patients achieved a complete response.

In the consolidation phase, patients received rituximab IV over 6 hours on day 1; oral or IV dexamethasone on days 1-4; cyclophosphamide IV over 3 hours twice daily on days 2-4; doxorubicin IV over 15-30 minutes on day 5; and vincristine IV over 15-30 minutes on day 5 of cycles one, three, five, and seven. Patients also received rituximab IV over 6 hours on day 1; methotrexate IV over 24 hours on day 2; and cytarabine IV over 2 hours twice daily on days 3 and 4 of cycles two, four, six, and eight. Treatments were repeated every 28 days for up to eight cycles in the absence of disease progression or unacceptable toxicity.

Patients who had a complete response (CR) after two cycles of induction and those who had disease progression on induction went on to consolidation. Patients with partial responses (PR) to induction continued on ibrutinib/rituximab until either the loss of a PR or best response for up to 12 cycles, with those who achieved a CR then moving on to consolidation.

Patients who had a CR after induction received four cycles of R-hyperCVAD, no subsequent stem cell transplant, and no maintenance therapy. Patients who had a PR after induction received two cycles of R-hyperCVAD, were reassessed, and then continued on R-hyperCVAD until CR or for up to eight total cycles.

Patients with either stable disease or progression during R-hyperCVAD were taken off the study.

Of the 50 patients enrolled, all 50 were evaluable for part A (induction), and 48 were evaluable after induction and consolidation (two patients withdrew for personal reasons).

After a median follow-up of 36 months, the overall response rate (ORR) following induction was 100%, consisting of 46 CRs (92%) and four PRs (8%).

In an intention-to-treat analysis (including the two patients who withdrew), the ORR was 96%, consisting of CRs in 47 patients (94%) and a PR in 1 patient (2%).

Neither the median PFS nor median overall survival had been reached at the time of data cutoff, and no patients have died.

Of the 50 enrolled patients, four experienced disease progression after 17, 24, 34, and 35 months of treatment. The patients with disease progression included one with Ki-67 of less than 30%, and three with KI-67 of 30% or greater.

Grade 3-4 toxicities during induction including myelosuppression in 4%; fatigue, myalgia, and rashes in 8% each; and oral mucositis in 4%.

Dr. Wang said that future studies on minimal residual disease and clonal evolution are ongoing, and that data on more patients will be presented at the next annual meeting of the American Society of Hematology, scheduled for December 2019.

He also noted that the WINDOW-2 trial, in which ibrutinib and rituximab are followed by veneotclax and hyper-CVAD chemotherapy in patients with newly diagnosed MCL, is open and rapidly enrolling patients.

The study is supported by the National Cancer Institute. Dr. Wang reported financial relationships with Janssen, Pharmacyclics, and other companies.

SOURCE: Wang M et al. ICML-15, Abstract 12.

LUGANO, Switzerland – In younger patients with previously untreated mantle cell lymphoma, the chemotherapy-free combination of ibrutinib and rituximab followed by a short course of chemotherapy was associated with an “unprecedented” 3-year progression-free survival rate, investigators in the phase 2 WINDOW-1 trial reported.

Neil Osterweil/MDedge News

Among 50 patients aged 65 years and younger who received ibrutinib and rituximab until they achieved a complete or partial response, followed by four cycles of chemotherapy with rituximab plus hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) and rituximab plus methotrexate, the 3-year progression-free survival (PFS) rate was 88%, said Michael Wang, MD, from the University of Texas MD Anderson Cancer Center in Houston.

Additionally, for patients with the low-risk features, the 3-year PFS rate was 90%.

“Chemo-free ibrutinib-rituximab induced unprecedented – unprecedented – efficacy before chemo consolidation,” he said at the International Conference on Malignant Lymphoma.

Dr. Wang presented data from an interim analysis of the investigator-initiated single-center trial. Fifty patients aged 65 years or younger with untreated mantle cell lymphoma (MCL), good performance status, and good organ function were enrolled.

The patients were treated with ibrutinib and rituximab for two cycles and then evaluated for response with PET-CT scan, bone marrow biopsy, and for some patients, esophagogastroduodenoscopy (EGD) and colonoscopy with random biopsies.

In the induction phase, patients received ibrutinib daily on days 1-28 and rituximab intravenously over 6-8 hours on days 1, 8, 15, and 22 of cycle 1, and then over 4 hours on day 1 of cycles 3-12. The treatment was repeated every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity, or until patients achieved a complete response.

In the consolidation phase, patients received rituximab IV over 6 hours on day 1; oral or IV dexamethasone on days 1-4; cyclophosphamide IV over 3 hours twice daily on days 2-4; doxorubicin IV over 15-30 minutes on day 5; and vincristine IV over 15-30 minutes on day 5 of cycles one, three, five, and seven. Patients also received rituximab IV over 6 hours on day 1; methotrexate IV over 24 hours on day 2; and cytarabine IV over 2 hours twice daily on days 3 and 4 of cycles two, four, six, and eight. Treatments were repeated every 28 days for up to eight cycles in the absence of disease progression or unacceptable toxicity.

Patients who had a complete response (CR) after two cycles of induction and those who had disease progression on induction went on to consolidation. Patients with partial responses (PR) to induction continued on ibrutinib/rituximab until either the loss of a PR or best response for up to 12 cycles, with those who achieved a CR then moving on to consolidation.

Patients who had a CR after induction received four cycles of R-hyperCVAD, no subsequent stem cell transplant, and no maintenance therapy. Patients who had a PR after induction received two cycles of R-hyperCVAD, were reassessed, and then continued on R-hyperCVAD until CR or for up to eight total cycles.

Patients with either stable disease or progression during R-hyperCVAD were taken off the study.

Of the 50 patients enrolled, all 50 were evaluable for part A (induction), and 48 were evaluable after induction and consolidation (two patients withdrew for personal reasons).

After a median follow-up of 36 months, the overall response rate (ORR) following induction was 100%, consisting of 46 CRs (92%) and four PRs (8%).

In an intention-to-treat analysis (including the two patients who withdrew), the ORR was 96%, consisting of CRs in 47 patients (94%) and a PR in 1 patient (2%).

Neither the median PFS nor median overall survival had been reached at the time of data cutoff, and no patients have died.

Of the 50 enrolled patients, four experienced disease progression after 17, 24, 34, and 35 months of treatment. The patients with disease progression included one with Ki-67 of less than 30%, and three with KI-67 of 30% or greater.

Grade 3-4 toxicities during induction including myelosuppression in 4%; fatigue, myalgia, and rashes in 8% each; and oral mucositis in 4%.

Dr. Wang said that future studies on minimal residual disease and clonal evolution are ongoing, and that data on more patients will be presented at the next annual meeting of the American Society of Hematology, scheduled for December 2019.

He also noted that the WINDOW-2 trial, in which ibrutinib and rituximab are followed by veneotclax and hyper-CVAD chemotherapy in patients with newly diagnosed MCL, is open and rapidly enrolling patients.

The study is supported by the National Cancer Institute. Dr. Wang reported financial relationships with Janssen, Pharmacyclics, and other companies.

SOURCE: Wang M et al. ICML-15, Abstract 12.

LUGANO, Switzerland – In younger patients with previously untreated mantle cell lymphoma, the chemotherapy-free combination of ibrutinib and rituximab followed by a short course of chemotherapy was associated with an “unprecedented” 3-year progression-free survival rate, investigators in the phase 2 WINDOW-1 trial reported.

Neil Osterweil/MDedge News

Among 50 patients aged 65 years and younger who received ibrutinib and rituximab until they achieved a complete or partial response, followed by four cycles of chemotherapy with rituximab plus hyper-CVAD (cyclophosphamide, vincristine, doxorubicin and dexamethasone) and rituximab plus methotrexate, the 3-year progression-free survival (PFS) rate was 88%, said Michael Wang, MD, from the University of Texas MD Anderson Cancer Center in Houston.

Additionally, for patients with the low-risk features, the 3-year PFS rate was 90%.

“Chemo-free ibrutinib-rituximab induced unprecedented – unprecedented – efficacy before chemo consolidation,” he said at the International Conference on Malignant Lymphoma.

Dr. Wang presented data from an interim analysis of the investigator-initiated single-center trial. Fifty patients aged 65 years or younger with untreated mantle cell lymphoma (MCL), good performance status, and good organ function were enrolled.

The patients were treated with ibrutinib and rituximab for two cycles and then evaluated for response with PET-CT scan, bone marrow biopsy, and for some patients, esophagogastroduodenoscopy (EGD) and colonoscopy with random biopsies.

In the induction phase, patients received ibrutinib daily on days 1-28 and rituximab intravenously over 6-8 hours on days 1, 8, 15, and 22 of cycle 1, and then over 4 hours on day 1 of cycles 3-12. The treatment was repeated every 28 days for up to 12 cycles in the absence of disease progression or unacceptable toxicity, or until patients achieved a complete response.

In the consolidation phase, patients received rituximab IV over 6 hours on day 1; oral or IV dexamethasone on days 1-4; cyclophosphamide IV over 3 hours twice daily on days 2-4; doxorubicin IV over 15-30 minutes on day 5; and vincristine IV over 15-30 minutes on day 5 of cycles one, three, five, and seven. Patients also received rituximab IV over 6 hours on day 1; methotrexate IV over 24 hours on day 2; and cytarabine IV over 2 hours twice daily on days 3 and 4 of cycles two, four, six, and eight. Treatments were repeated every 28 days for up to eight cycles in the absence of disease progression or unacceptable toxicity.

Patients who had a complete response (CR) after two cycles of induction and those who had disease progression on induction went on to consolidation. Patients with partial responses (PR) to induction continued on ibrutinib/rituximab until either the loss of a PR or best response for up to 12 cycles, with those who achieved a CR then moving on to consolidation.

Patients who had a CR after induction received four cycles of R-hyperCVAD, no subsequent stem cell transplant, and no maintenance therapy. Patients who had a PR after induction received two cycles of R-hyperCVAD, were reassessed, and then continued on R-hyperCVAD until CR or for up to eight total cycles.

Patients with either stable disease or progression during R-hyperCVAD were taken off the study.

Of the 50 patients enrolled, all 50 were evaluable for part A (induction), and 48 were evaluable after induction and consolidation (two patients withdrew for personal reasons).

After a median follow-up of 36 months, the overall response rate (ORR) following induction was 100%, consisting of 46 CRs (92%) and four PRs (8%).

In an intention-to-treat analysis (including the two patients who withdrew), the ORR was 96%, consisting of CRs in 47 patients (94%) and a PR in 1 patient (2%).

Neither the median PFS nor median overall survival had been reached at the time of data cutoff, and no patients have died.

Of the 50 enrolled patients, four experienced disease progression after 17, 24, 34, and 35 months of treatment. The patients with disease progression included one with Ki-67 of less than 30%, and three with KI-67 of 30% or greater.

Grade 3-4 toxicities during induction including myelosuppression in 4%; fatigue, myalgia, and rashes in 8% each; and oral mucositis in 4%.

Dr. Wang said that future studies on minimal residual disease and clonal evolution are ongoing, and that data on more patients will be presented at the next annual meeting of the American Society of Hematology, scheduled for December 2019.

He also noted that the WINDOW-2 trial, in which ibrutinib and rituximab are followed by veneotclax and hyper-CVAD chemotherapy in patients with newly diagnosed MCL, is open and rapidly enrolling patients.

The study is supported by the National Cancer Institute. Dr. Wang reported financial relationships with Janssen, Pharmacyclics, and other companies.

SOURCE: Wang M et al. ICML-15, Abstract 12.

If you work in health care or manage a medical practice, you are aware of all the radical changes in technology, medicine, social values, and interpersonal relations over the past few years and you probably do not expect the next several years to be less stressful and less uncertain. To ensure your practice and your provider’s success, you may need to adjust how your team interacts with patients – starting with the first area of patient interaction.

Patients who seek care for their health problems are looking for some measure of kindness when they approach the window of your office’s receptionist. Many are already apprehensive about their clinical condition and adding to that problem is their concern about the financial impact of their visit on the family’s budget. The medical group’s unwillingness to rethink how it greets patients as they approach the receptionist sets the stage for the patient to feel mishandled or underappreciated.

This initial patient interaction stage must be evaluated and recognized as an area of improvement. If not handled properly, it will significantly affect how a medical practice or provider is graded as a group in the field of patient experience and managing patient expectations. Every medical office needs to recognize that people hold on to negative experiences and are not likely to change their mind after that negative experience. The best way to avoid negative bias is to prevent it from happening in the first place.

Listed below are the five additional patient experience mistakes that can cost your group, if they are not recognized as being priorities for both your staff and your patients.
 

Mistake #1 - Educated patients are taking control of their health care.

When health care is treated like any other paid service, an unhappy patient will move along to a new facility or doctor if they have a bad interaction – whether it is with the doctor or the support staff. Educating, training, or adjusting staff to make changes needed is required to ensure that your staff understands the value of patient appreciation and providing the patient with a positive experience.

Mistake #2 - Patients are customers, and just like customers, patients have options.

It should be recognized that patients are customers who are concerned about their future and do not want to be in a medical practice requesting help. They feel vulnerable and out of their routine comfort zone. Reminding your staff that a patient is a customer who has multiple health care choices, but chose to come to your practice, will help your staff understand the value of providing your patient with a positive experience.

Mistake #3 – Dr. Google is becoming the patient’s best friend.

Research indicates that many patients arrive at the doctor’s office already with some information on their condition. Various websites already have provided the patient with free access to learn about their health condition. Popular medical sites such as WebMD.com give the patient the preliminary education they are looking for, so they are already armed with medical information even before they see the doctor or their support staff.

Mistake # 4 - Surveys are carrying more weight.

Outside surveys are becoming even more popular and are carrying additional weight when combined with various social media outlets. All types of surveys and reviews are being used to measure not only the care the patient received, but also the interpersonal relationship between the patient and the doctor, and the patient’s experience with the medical practice’s support staff. Some surveys cover all levels in the practice area, down to the cleanliness of the reception area or the patient’s treatment area, and even the adequacy of the parking lot. These surveys are conditioning patients to recall their entire experience. With a patient experience plan in place, excellent service becomes second nature and will be recognized by those surveyed.

Mistake #5 - Patient-centered care is customer service, too.

It’s not just about the obvious. Excellent patient (customer) service extends beyond a pleasant demeanor. The patient experience does not start or end at the doctor’s office. Perception is built by gathering information from multiple channels, whether it is through review sites, office visits, or surveys. It is necessary to consider the importance of those channels when looking to build patient loyalty.

To avoid the mistakes listed above, the more progressive medical practices are training their staff to anticipate the customer service needs of their patients, much like other major service industries. By rolling out a patient/customer experience training program, they can prevent these mistakes from ever happening and affecting their potential revenue. This training should focus on integrating the following strategies into their daily work habits to provide their patients with exceptional customer service while they are guests in their practice.

1) Patients are the lifeline to building the future of their practice.

Patients are comparing their health care services to other companies that routinely provide high-end services to their clients. Whether groups like it or not, their front-line personnel are compared to five-star hotel receptionists, who are expected to greet their customers both pleasantly and professionally after a long day of traveling and required business functions. Every medical group must understand that patients have options when they select a medical practice and they expect to be treated with respect and transparency, and not just another person to be cared for at the end of a long day. The same level of service needs to be delivered in the doctor’s office no matter what time of day it is because for that patient, the personal problems and subsequent disposition of the medical staff is not their problem. All they want is someone to listen and help them take care of their medical problem. Their long-term loyalty to the group will be solely dependent on how well each personal interaction is handled. Remember that the patient is a person first and not just a customer. We must approach each patient with humanity first, and then customer service.

2) Be courteous and respectful.

Remind your staff to be courteous, always polite and to use good manners. By treating a patient how they expect to be treated, you are showing the patient that you respect them and care for not only their health but also their feelings. The health care worker must understand that the patient is viewing their interactions with staff and providers as being symbolic of the overall group’s brand identity. The group’s leadership needs to select and train their workforce to recognize their importance in how patients view their clinical offerings and their interactions with the patient.

3) Never show indifference to patients.

Losing patients before they complete their treatment regimen is a significant liability issue for any medical practice. In an article written by Strive Labs CEO and Co-Founder, Scott Hebert, DPT, wrote: “Patient churn is too big of a problem to ignore, and it can have a profound impact on your clinic’s bottom line.” In addition to the rather obvious missed revenue opportunity, a churning patient represents a practice liability, because an unsatisfied patient is significantly more likely to leave you a negative review online — or turn the experience with your practice into a cautionary tale for friends and family members. Either way, it’s bad for business — and your reputation.

4) Don’t contradict, argue, or match wits.

It’s tough for a health care worker who is continually being bombarded in a high-pressure environment to agree to disagree. When a person feels they are right or that their perception is the only logical one, they can be very stubborn in their understanding, and they will dig in their heels. It takes a strong person to allow others to have their opinion and not be judgmental about it. Any customer or patient relations training program to be deployed in a medical office must include skill training to teach the staff member how to diffuse an argument or disagreement. This situation can be dispersed by training your staff to consider the source of the conflict, respect the patient’s perception, and then teach the staff member to tell the patient that they never thought of it that way and ease away from the discussion. Their absence will help diffuse the situation.

5) Tell patients you appreciate their business.

How you relate to a patient will speak volumes to them about how much you appreciate their loyalty, all because they chose your practice for their health care. All patient and customer training programs should include discussions on making eye contact, shaking with a firm grasp, and always closing a personal encounter on a sincere and positive note. Health care workers need to understand that they are in the service business and that the patients they care for have options and they can easily walk out of the medical practice and share any negative experience on social media. Educating and reminding your staff on how easily a patient can leave your practice or share their experience with others, needs to be recognized and discussed at all the group’s town hall meetings.

6) Use plain terms and simple explanations.

We all want to appear to be super intelligent by trying to use complex terms to describe a situation because it creates leverage with the other parties engaged in the conversation. While some of this may be necessary when educating patients on their condition, any additional complex terms can easily annoy or even confuse the patient who is only there seeking help. Health care workers need to talk in a manner that keeps the patients engaged and helps them understand the topic at hand. The worker needs to use every day vernacular examples, so the patient quickly understands the reason that brought them to the clinic and what they need to do to get some relief from what ails them. The phrase “plain and simple” means precisely that – explain the topic using basic and simple terms, so the listener understands it. Using this method when discussing a patient’s condition isn’t just for the patient’s benefit because many confused patients ultimately call the office later in the day only to ask additional questions, which uses your staff’s time.

7) Good manners will get you everywhere.

Emily Post wrote, “Manners are a sensitive awareness of the feelings of others. If you have that awareness, you have good manners, no matter what fork you use.” Proper manners are behaving in a way that is both aware of and considerate of the people around us. A person with good manners treats everyone with kindness and respect. It is knowing how to get along without causing offense or harm, no matter how much the current interaction is going south – especially when you are engaged in a tough conversation.

8) Keep seeing health care as a calling.

All health care workers need to know that their vocation of caring for sick and injured patients is a calling and not just a job and all training programs designed to teach customer service need to stress this point. Practicing your vocation means that you will work hard to eliminate all barriers that exist between the patient and the health care worker. Too often we underestimate the power of a simple touch, a smile, a kind word, a listening ear, an honest compliment, or the smallest act of caring – all of which have the potential to turn a life or a bad interaction into a magical moment for both the patient and the health care worker. One that has meaning and a bit of affirmation of the dignity of both individuals interacting to find some common ground.

9) Stay in touch with patients.

The group needs to find ways to keep in contact with their patients, whether it is by giving them tips on how to remain healthy or the need for proactive and preventive medicine. The use of technology and social media, as well as handing out freebies at health fairs, giving patients informational brochures upon discharge, or even cards telling them how to contact the practice in case of emergencies, is quite helpful. Calling your patients is a significant signal that your group values the health and welfare of your patients. A phone call from either the doctor or their assistant goes further than any advertisement when building brand and doctor loyalty.

10) Keep your promises.

Do what you say you are going to do, should be a commonly shared mantra for the medical practice. While changing your mind from time to time when circumstances prevent you from keeping a promise, is just part of being flexible in life, regularly breaking promises to other people isn’t healthy. Here’s how to keep your promises: Pay close attention to your words – every word you communicate (through speaking or writing), as a patient may take your words as a promise. Study your patterns of making promises. Figure out when you tend to make careless promises and study the situations in which you do, so you can understand why you’re promising what you don’t intend to do. Take time and careful consideration before making a promise to someone. Don’t rush yourself into a promise that you won’t be able to keep. Even when you’re in a hurry, you usually don’t have an immediate sense of urgency about promising to do something. Stop yourself before you make a vow, delaying your decision long enough to think it through carefully. The more careful you become about making promises, the easier it will be to keep them.

The last step of deploying a patient/customer service program is handling the change in management that is required to train the staff. Accepting “No, we are not changing any part of the group to meet the needs of our patients better.” is unacceptable. Usually, you will be introducing this program to employees that have been in a group for a while and so to get them to buy into the new ideas will require constant reinforcement. It may take some time to align the focus of the group from the neutral zone to the notion that there are new deliverables that would better serve your patients. The following rules will be helpful when beginning your training program:

Rule #1 – Be consistent. Every policy, procedure, and list of priorities sends a message – make sure it’s the right message.

Rule #2 – Ensure quick successes. Look for ways to get the group’s employees to buy into the program – early on after its deployment.

Rule# 3 – Symbolize the new identity. Make sure the group’s logos and branding support the new identity of the group and the culture change.

Rule #4 – Celebrate all the group’s successes. Make sure the group’s employees recognize the work efforts involved as well as the success the group will enjoy. Stress the fact that the work completed will significantly enhance the care and service levels to the patients, which should feed the ego of the group to do more and more in the future.

And lastly, do not forget how vital the buy-in is of the clinicians of the group. They must be introduced early to the new patient/customer service program and embrace it so that their employees will recognize that these efforts are focused on providing a high quality of care throughout the enterprise. As the French philosopher Albert Schweitzer once stated, “Example is not the main thing in influencing others, it’s the only thing.”
 

References

1. Peters, T. “The Excellence Dividend: Meeting the Tech Tide with Work that Wows and Jobs that Last.” (New York, Vintage Books, 2018).

2. 10 Strategies to Provide Patients with Superior Customer Service. Becker’s Hospital Review 2010 Dec 20.

3. Shell MA, Buell RW. Why anxious customers prefer human customer service. Harvard Business Review 2019 April 15.

4. Matt Brannon. 13 Ways to improve customer services at your medical practice. Blog post Sept 7, 2018.

5. 5 Reasons Why Customer Service Matters in Healthcare. https://www.pointsgroup.com/5-reasons-why-customer-service-matters-in-healthcare/Feb. 25, 2014

6. Senge P, Kleiner A, Roberts C, et al. “The Dance of Change: A fifth discipline resource.” (New York, Doubleday, 1999).

7. Bridges W. “Managing Transitions: Making the Most of Change.” (Boston, Da Capo Books, 2017)

8. Michelli J. “The New Gold Standard – 5 Leadership Principles for Creating the Legendary Customer Experience Courtesy of the Ritz-Carlton Hotel Company.” (New York, McGraw Hill, 2008).

Mr. Turner is chief executive officer of Indianapolis Gastroenterology and Hepatology.

If you work in health care or manage a medical practice, you are aware of all the radical changes in technology, medicine, social values, and interpersonal relations over the past few years and you probably do not expect the next several years to be less stressful and less uncertain. To ensure your practice and your provider’s success, you may need to adjust how your team interacts with patients – starting with the first area of patient interaction.

Patients who seek care for their health problems are looking for some measure of kindness when they approach the window of your office’s receptionist. Many are already apprehensive about their clinical condition and adding to that problem is their concern about the financial impact of their visit on the family’s budget. The medical group’s unwillingness to rethink how it greets patients as they approach the receptionist sets the stage for the patient to feel mishandled or underappreciated.

This initial patient interaction stage must be evaluated and recognized as an area of improvement. If not handled properly, it will significantly affect how a medical practice or provider is graded as a group in the field of patient experience and managing patient expectations. Every medical office needs to recognize that people hold on to negative experiences and are not likely to change their mind after that negative experience. The best way to avoid negative bias is to prevent it from happening in the first place.

Listed below are the five additional patient experience mistakes that can cost your group, if they are not recognized as being priorities for both your staff and your patients.
 

Mistake #1 - Educated patients are taking control of their health care.

When health care is treated like any other paid service, an unhappy patient will move along to a new facility or doctor if they have a bad interaction – whether it is with the doctor or the support staff. Educating, training, or adjusting staff to make changes needed is required to ensure that your staff understands the value of patient appreciation and providing the patient with a positive experience.

Mistake #2 - Patients are customers, and just like customers, patients have options.

It should be recognized that patients are customers who are concerned about their future and do not want to be in a medical practice requesting help. They feel vulnerable and out of their routine comfort zone. Reminding your staff that a patient is a customer who has multiple health care choices, but chose to come to your practice, will help your staff understand the value of providing your patient with a positive experience.

Mistake #3 – Dr. Google is becoming the patient’s best friend.

Research indicates that many patients arrive at the doctor’s office already with some information on their condition. Various websites already have provided the patient with free access to learn about their health condition. Popular medical sites such as WebMD.com give the patient the preliminary education they are looking for, so they are already armed with medical information even before they see the doctor or their support staff.

Mistake # 4 - Surveys are carrying more weight.

Outside surveys are becoming even more popular and are carrying additional weight when combined with various social media outlets. All types of surveys and reviews are being used to measure not only the care the patient received, but also the interpersonal relationship between the patient and the doctor, and the patient’s experience with the medical practice’s support staff. Some surveys cover all levels in the practice area, down to the cleanliness of the reception area or the patient’s treatment area, and even the adequacy of the parking lot. These surveys are conditioning patients to recall their entire experience. With a patient experience plan in place, excellent service becomes second nature and will be recognized by those surveyed.

Mistake #5 - Patient-centered care is customer service, too.

It’s not just about the obvious. Excellent patient (customer) service extends beyond a pleasant demeanor. The patient experience does not start or end at the doctor’s office. Perception is built by gathering information from multiple channels, whether it is through review sites, office visits, or surveys. It is necessary to consider the importance of those channels when looking to build patient loyalty.

To avoid the mistakes listed above, the more progressive medical practices are training their staff to anticipate the customer service needs of their patients, much like other major service industries. By rolling out a patient/customer experience training program, they can prevent these mistakes from ever happening and affecting their potential revenue. This training should focus on integrating the following strategies into their daily work habits to provide their patients with exceptional customer service while they are guests in their practice.

1) Patients are the lifeline to building the future of their practice.

Patients are comparing their health care services to other companies that routinely provide high-end services to their clients. Whether groups like it or not, their front-line personnel are compared to five-star hotel receptionists, who are expected to greet their customers both pleasantly and professionally after a long day of traveling and required business functions. Every medical group must understand that patients have options when they select a medical practice and they expect to be treated with respect and transparency, and not just another person to be cared for at the end of a long day. The same level of service needs to be delivered in the doctor’s office no matter what time of day it is because for that patient, the personal problems and subsequent disposition of the medical staff is not their problem. All they want is someone to listen and help them take care of their medical problem. Their long-term loyalty to the group will be solely dependent on how well each personal interaction is handled. Remember that the patient is a person first and not just a customer. We must approach each patient with humanity first, and then customer service.

2) Be courteous and respectful.

Remind your staff to be courteous, always polite and to use good manners. By treating a patient how they expect to be treated, you are showing the patient that you respect them and care for not only their health but also their feelings. The health care worker must understand that the patient is viewing their interactions with staff and providers as being symbolic of the overall group’s brand identity. The group’s leadership needs to select and train their workforce to recognize their importance in how patients view their clinical offerings and their interactions with the patient.

3) Never show indifference to patients.

Losing patients before they complete their treatment regimen is a significant liability issue for any medical practice. In an article written by Strive Labs CEO and Co-Founder, Scott Hebert, DPT, wrote: “Patient churn is too big of a problem to ignore, and it can have a profound impact on your clinic’s bottom line.” In addition to the rather obvious missed revenue opportunity, a churning patient represents a practice liability, because an unsatisfied patient is significantly more likely to leave you a negative review online — or turn the experience with your practice into a cautionary tale for friends and family members. Either way, it’s bad for business — and your reputation.

4) Don’t contradict, argue, or match wits.

It’s tough for a health care worker who is continually being bombarded in a high-pressure environment to agree to disagree. When a person feels they are right or that their perception is the only logical one, they can be very stubborn in their understanding, and they will dig in their heels. It takes a strong person to allow others to have their opinion and not be judgmental about it. Any customer or patient relations training program to be deployed in a medical office must include skill training to teach the staff member how to diffuse an argument or disagreement. This situation can be dispersed by training your staff to consider the source of the conflict, respect the patient’s perception, and then teach the staff member to tell the patient that they never thought of it that way and ease away from the discussion. Their absence will help diffuse the situation.

5) Tell patients you appreciate their business.

How you relate to a patient will speak volumes to them about how much you appreciate their loyalty, all because they chose your practice for their health care. All patient and customer training programs should include discussions on making eye contact, shaking with a firm grasp, and always closing a personal encounter on a sincere and positive note. Health care workers need to understand that they are in the service business and that the patients they care for have options and they can easily walk out of the medical practice and share any negative experience on social media. Educating and reminding your staff on how easily a patient can leave your practice or share their experience with others, needs to be recognized and discussed at all the group’s town hall meetings.

6) Use plain terms and simple explanations.

We all want to appear to be super intelligent by trying to use complex terms to describe a situation because it creates leverage with the other parties engaged in the conversation. While some of this may be necessary when educating patients on their condition, any additional complex terms can easily annoy or even confuse the patient who is only there seeking help. Health care workers need to talk in a manner that keeps the patients engaged and helps them understand the topic at hand. The worker needs to use every day vernacular examples, so the patient quickly understands the reason that brought them to the clinic and what they need to do to get some relief from what ails them. The phrase “plain and simple” means precisely that – explain the topic using basic and simple terms, so the listener understands it. Using this method when discussing a patient’s condition isn’t just for the patient’s benefit because many confused patients ultimately call the office later in the day only to ask additional questions, which uses your staff’s time.

7) Good manners will get you everywhere.

Emily Post wrote, “Manners are a sensitive awareness of the feelings of others. If you have that awareness, you have good manners, no matter what fork you use.” Proper manners are behaving in a way that is both aware of and considerate of the people around us. A person with good manners treats everyone with kindness and respect. It is knowing how to get along without causing offense or harm, no matter how much the current interaction is going south – especially when you are engaged in a tough conversation.

8) Keep seeing health care as a calling.

All health care workers need to know that their vocation of caring for sick and injured patients is a calling and not just a job and all training programs designed to teach customer service need to stress this point. Practicing your vocation means that you will work hard to eliminate all barriers that exist between the patient and the health care worker. Too often we underestimate the power of a simple touch, a smile, a kind word, a listening ear, an honest compliment, or the smallest act of caring – all of which have the potential to turn a life or a bad interaction into a magical moment for both the patient and the health care worker. One that has meaning and a bit of affirmation of the dignity of both individuals interacting to find some common ground.

9) Stay in touch with patients.

The group needs to find ways to keep in contact with their patients, whether it is by giving them tips on how to remain healthy or the need for proactive and preventive medicine. The use of technology and social media, as well as handing out freebies at health fairs, giving patients informational brochures upon discharge, or even cards telling them how to contact the practice in case of emergencies, is quite helpful. Calling your patients is a significant signal that your group values the health and welfare of your patients. A phone call from either the doctor or their assistant goes further than any advertisement when building brand and doctor loyalty.

10) Keep your promises.

Do what you say you are going to do, should be a commonly shared mantra for the medical practice. While changing your mind from time to time when circumstances prevent you from keeping a promise, is just part of being flexible in life, regularly breaking promises to other people isn’t healthy. Here’s how to keep your promises: Pay close attention to your words – every word you communicate (through speaking or writing), as a patient may take your words as a promise. Study your patterns of making promises. Figure out when you tend to make careless promises and study the situations in which you do, so you can understand why you’re promising what you don’t intend to do. Take time and careful consideration before making a promise to someone. Don’t rush yourself into a promise that you won’t be able to keep. Even when you’re in a hurry, you usually don’t have an immediate sense of urgency about promising to do something. Stop yourself before you make a vow, delaying your decision long enough to think it through carefully. The more careful you become about making promises, the easier it will be to keep them.

The last step of deploying a patient/customer service program is handling the change in management that is required to train the staff. Accepting “No, we are not changing any part of the group to meet the needs of our patients better.” is unacceptable. Usually, you will be introducing this program to employees that have been in a group for a while and so to get them to buy into the new ideas will require constant reinforcement. It may take some time to align the focus of the group from the neutral zone to the notion that there are new deliverables that would better serve your patients. The following rules will be helpful when beginning your training program:

Rule #1 – Be consistent. Every policy, procedure, and list of priorities sends a message – make sure it’s the right message.

Rule #2 – Ensure quick successes. Look for ways to get the group’s employees to buy into the program – early on after its deployment.

Rule# 3 – Symbolize the new identity. Make sure the group’s logos and branding support the new identity of the group and the culture change.

Rule #4 – Celebrate all the group’s successes. Make sure the group’s employees recognize the work efforts involved as well as the success the group will enjoy. Stress the fact that the work completed will significantly enhance the care and service levels to the patients, which should feed the ego of the group to do more and more in the future.

And lastly, do not forget how vital the buy-in is of the clinicians of the group. They must be introduced early to the new patient/customer service program and embrace it so that their employees will recognize that these efforts are focused on providing a high quality of care throughout the enterprise. As the French philosopher Albert Schweitzer once stated, “Example is not the main thing in influencing others, it’s the only thing.”
 

References

1. Peters, T. “The Excellence Dividend: Meeting the Tech Tide with Work that Wows and Jobs that Last.” (New York, Vintage Books, 2018).

2. 10 Strategies to Provide Patients with Superior Customer Service. Becker’s Hospital Review 2010 Dec 20.

3. Shell MA, Buell RW. Why anxious customers prefer human customer service. Harvard Business Review 2019 April 15.

4. Matt Brannon. 13 Ways to improve customer services at your medical practice. Blog post Sept 7, 2018.

5. 5 Reasons Why Customer Service Matters in Healthcare. https://www.pointsgroup.com/5-reasons-why-customer-service-matters-in-healthcare/Feb. 25, 2014

6. Senge P, Kleiner A, Roberts C, et al. “The Dance of Change: A fifth discipline resource.” (New York, Doubleday, 1999).

7. Bridges W. “Managing Transitions: Making the Most of Change.” (Boston, Da Capo Books, 2017)

8. Michelli J. “The New Gold Standard – 5 Leadership Principles for Creating the Legendary Customer Experience Courtesy of the Ritz-Carlton Hotel Company.” (New York, McGraw Hill, 2008).

Mr. Turner is chief executive officer of Indianapolis Gastroenterology and Hepatology.

If you work in health care or manage a medical practice, you are aware of all the radical changes in technology, medicine, social values, and interpersonal relations over the past few years and you probably do not expect the next several years to be less stressful and less uncertain. To ensure your practice and your provider’s success, you may need to adjust how your team interacts with patients – starting with the first area of patient interaction.

Patients who seek care for their health problems are looking for some measure of kindness when they approach the window of your office’s receptionist. Many are already apprehensive about their clinical condition and adding to that problem is their concern about the financial impact of their visit on the family’s budget. The medical group’s unwillingness to rethink how it greets patients as they approach the receptionist sets the stage for the patient to feel mishandled or underappreciated.

This initial patient interaction stage must be evaluated and recognized as an area of improvement. If not handled properly, it will significantly affect how a medical practice or provider is graded as a group in the field of patient experience and managing patient expectations. Every medical office needs to recognize that people hold on to negative experiences and are not likely to change their mind after that negative experience. The best way to avoid negative bias is to prevent it from happening in the first place.

Listed below are the five additional patient experience mistakes that can cost your group, if they are not recognized as being priorities for both your staff and your patients.
 

Mistake #1 - Educated patients are taking control of their health care.

When health care is treated like any other paid service, an unhappy patient will move along to a new facility or doctor if they have a bad interaction – whether it is with the doctor or the support staff. Educating, training, or adjusting staff to make changes needed is required to ensure that your staff understands the value of patient appreciation and providing the patient with a positive experience.

Mistake #2 - Patients are customers, and just like customers, patients have options.

It should be recognized that patients are customers who are concerned about their future and do not want to be in a medical practice requesting help. They feel vulnerable and out of their routine comfort zone. Reminding your staff that a patient is a customer who has multiple health care choices, but chose to come to your practice, will help your staff understand the value of providing your patient with a positive experience.

Mistake #3 – Dr. Google is becoming the patient’s best friend.

Research indicates that many patients arrive at the doctor’s office already with some information on their condition. Various websites already have provided the patient with free access to learn about their health condition. Popular medical sites such as WebMD.com give the patient the preliminary education they are looking for, so they are already armed with medical information even before they see the doctor or their support staff.

Mistake # 4 - Surveys are carrying more weight.

Outside surveys are becoming even more popular and are carrying additional weight when combined with various social media outlets. All types of surveys and reviews are being used to measure not only the care the patient received, but also the interpersonal relationship between the patient and the doctor, and the patient’s experience with the medical practice’s support staff. Some surveys cover all levels in the practice area, down to the cleanliness of the reception area or the patient’s treatment area, and even the adequacy of the parking lot. These surveys are conditioning patients to recall their entire experience. With a patient experience plan in place, excellent service becomes second nature and will be recognized by those surveyed.

Mistake #5 - Patient-centered care is customer service, too.

It’s not just about the obvious. Excellent patient (customer) service extends beyond a pleasant demeanor. The patient experience does not start or end at the doctor’s office. Perception is built by gathering information from multiple channels, whether it is through review sites, office visits, or surveys. It is necessary to consider the importance of those channels when looking to build patient loyalty.

To avoid the mistakes listed above, the more progressive medical practices are training their staff to anticipate the customer service needs of their patients, much like other major service industries. By rolling out a patient/customer experience training program, they can prevent these mistakes from ever happening and affecting their potential revenue. This training should focus on integrating the following strategies into their daily work habits to provide their patients with exceptional customer service while they are guests in their practice.

1) Patients are the lifeline to building the future of their practice.

Patients are comparing their health care services to other companies that routinely provide high-end services to their clients. Whether groups like it or not, their front-line personnel are compared to five-star hotel receptionists, who are expected to greet their customers both pleasantly and professionally after a long day of traveling and required business functions. Every medical group must understand that patients have options when they select a medical practice and they expect to be treated with respect and transparency, and not just another person to be cared for at the end of a long day. The same level of service needs to be delivered in the doctor’s office no matter what time of day it is because for that patient, the personal problems and subsequent disposition of the medical staff is not their problem. All they want is someone to listen and help them take care of their medical problem. Their long-term loyalty to the group will be solely dependent on how well each personal interaction is handled. Remember that the patient is a person first and not just a customer. We must approach each patient with humanity first, and then customer service.

2) Be courteous and respectful.

Remind your staff to be courteous, always polite and to use good manners. By treating a patient how they expect to be treated, you are showing the patient that you respect them and care for not only their health but also their feelings. The health care worker must understand that the patient is viewing their interactions with staff and providers as being symbolic of the overall group’s brand identity. The group’s leadership needs to select and train their workforce to recognize their importance in how patients view their clinical offerings and their interactions with the patient.

3) Never show indifference to patients.

Losing patients before they complete their treatment regimen is a significant liability issue for any medical practice. In an article written by Strive Labs CEO and Co-Founder, Scott Hebert, DPT, wrote: “Patient churn is too big of a problem to ignore, and it can have a profound impact on your clinic’s bottom line.” In addition to the rather obvious missed revenue opportunity, a churning patient represents a practice liability, because an unsatisfied patient is significantly more likely to leave you a negative review online — or turn the experience with your practice into a cautionary tale for friends and family members. Either way, it’s bad for business — and your reputation.

4) Don’t contradict, argue, or match wits.

It’s tough for a health care worker who is continually being bombarded in a high-pressure environment to agree to disagree. When a person feels they are right or that their perception is the only logical one, they can be very stubborn in their understanding, and they will dig in their heels. It takes a strong person to allow others to have their opinion and not be judgmental about it. Any customer or patient relations training program to be deployed in a medical office must include skill training to teach the staff member how to diffuse an argument or disagreement. This situation can be dispersed by training your staff to consider the source of the conflict, respect the patient’s perception, and then teach the staff member to tell the patient that they never thought of it that way and ease away from the discussion. Their absence will help diffuse the situation.

5) Tell patients you appreciate their business.

How you relate to a patient will speak volumes to them about how much you appreciate their loyalty, all because they chose your practice for their health care. All patient and customer training programs should include discussions on making eye contact, shaking with a firm grasp, and always closing a personal encounter on a sincere and positive note. Health care workers need to understand that they are in the service business and that the patients they care for have options and they can easily walk out of the medical practice and share any negative experience on social media. Educating and reminding your staff on how easily a patient can leave your practice or share their experience with others, needs to be recognized and discussed at all the group’s town hall meetings.

6) Use plain terms and simple explanations.

We all want to appear to be super intelligent by trying to use complex terms to describe a situation because it creates leverage with the other parties engaged in the conversation. While some of this may be necessary when educating patients on their condition, any additional complex terms can easily annoy or even confuse the patient who is only there seeking help. Health care workers need to talk in a manner that keeps the patients engaged and helps them understand the topic at hand. The worker needs to use every day vernacular examples, so the patient quickly understands the reason that brought them to the clinic and what they need to do to get some relief from what ails them. The phrase “plain and simple” means precisely that – explain the topic using basic and simple terms, so the listener understands it. Using this method when discussing a patient’s condition isn’t just for the patient’s benefit because many confused patients ultimately call the office later in the day only to ask additional questions, which uses your staff’s time.

7) Good manners will get you everywhere.

Emily Post wrote, “Manners are a sensitive awareness of the feelings of others. If you have that awareness, you have good manners, no matter what fork you use.” Proper manners are behaving in a way that is both aware of and considerate of the people around us. A person with good manners treats everyone with kindness and respect. It is knowing how to get along without causing offense or harm, no matter how much the current interaction is going south – especially when you are engaged in a tough conversation.

8) Keep seeing health care as a calling.

All health care workers need to know that their vocation of caring for sick and injured patients is a calling and not just a job and all training programs designed to teach customer service need to stress this point. Practicing your vocation means that you will work hard to eliminate all barriers that exist between the patient and the health care worker. Too often we underestimate the power of a simple touch, a smile, a kind word, a listening ear, an honest compliment, or the smallest act of caring – all of which have the potential to turn a life or a bad interaction into a magical moment for both the patient and the health care worker. One that has meaning and a bit of affirmation of the dignity of both individuals interacting to find some common ground.

9) Stay in touch with patients.

The group needs to find ways to keep in contact with their patients, whether it is by giving them tips on how to remain healthy or the need for proactive and preventive medicine. The use of technology and social media, as well as handing out freebies at health fairs, giving patients informational brochures upon discharge, or even cards telling them how to contact the practice in case of emergencies, is quite helpful. Calling your patients is a significant signal that your group values the health and welfare of your patients. A phone call from either the doctor or their assistant goes further than any advertisement when building brand and doctor loyalty.

10) Keep your promises.

Do what you say you are going to do, should be a commonly shared mantra for the medical practice. While changing your mind from time to time when circumstances prevent you from keeping a promise, is just part of being flexible in life, regularly breaking promises to other people isn’t healthy. Here’s how to keep your promises: Pay close attention to your words – every word you communicate (through speaking or writing), as a patient may take your words as a promise. Study your patterns of making promises. Figure out when you tend to make careless promises and study the situations in which you do, so you can understand why you’re promising what you don’t intend to do. Take time and careful consideration before making a promise to someone. Don’t rush yourself into a promise that you won’t be able to keep. Even when you’re in a hurry, you usually don’t have an immediate sense of urgency about promising to do something. Stop yourself before you make a vow, delaying your decision long enough to think it through carefully. The more careful you become about making promises, the easier it will be to keep them.

The last step of deploying a patient/customer service program is handling the change in management that is required to train the staff. Accepting “No, we are not changing any part of the group to meet the needs of our patients better.” is unacceptable. Usually, you will be introducing this program to employees that have been in a group for a while and so to get them to buy into the new ideas will require constant reinforcement. It may take some time to align the focus of the group from the neutral zone to the notion that there are new deliverables that would better serve your patients. The following rules will be helpful when beginning your training program:

Rule #1 – Be consistent. Every policy, procedure, and list of priorities sends a message – make sure it’s the right message.

Rule #2 – Ensure quick successes. Look for ways to get the group’s employees to buy into the program – early on after its deployment.

Rule# 3 – Symbolize the new identity. Make sure the group’s logos and branding support the new identity of the group and the culture change.

Rule #4 – Celebrate all the group’s successes. Make sure the group’s employees recognize the work efforts involved as well as the success the group will enjoy. Stress the fact that the work completed will significantly enhance the care and service levels to the patients, which should feed the ego of the group to do more and more in the future.

And lastly, do not forget how vital the buy-in is of the clinicians of the group. They must be introduced early to the new patient/customer service program and embrace it so that their employees will recognize that these efforts are focused on providing a high quality of care throughout the enterprise. As the French philosopher Albert Schweitzer once stated, “Example is not the main thing in influencing others, it’s the only thing.”
 

References

1. Peters, T. “The Excellence Dividend: Meeting the Tech Tide with Work that Wows and Jobs that Last.” (New York, Vintage Books, 2018).

2. 10 Strategies to Provide Patients with Superior Customer Service. Becker’s Hospital Review 2010 Dec 20.

3. Shell MA, Buell RW. Why anxious customers prefer human customer service. Harvard Business Review 2019 April 15.

4. Matt Brannon. 13 Ways to improve customer services at your medical practice. Blog post Sept 7, 2018.

5. 5 Reasons Why Customer Service Matters in Healthcare. https://www.pointsgroup.com/5-reasons-why-customer-service-matters-in-healthcare/Feb. 25, 2014

6. Senge P, Kleiner A, Roberts C, et al. “The Dance of Change: A fifth discipline resource.” (New York, Doubleday, 1999).

7. Bridges W. “Managing Transitions: Making the Most of Change.” (Boston, Da Capo Books, 2017)

8. Michelli J. “The New Gold Standard – 5 Leadership Principles for Creating the Legendary Customer Experience Courtesy of the Ritz-Carlton Hotel Company.” (New York, McGraw Hill, 2008).

Mr. Turner is chief executive officer of Indianapolis Gastroenterology and Hepatology.

Deferasirox plus deferoxamine is more effective than deferasirox alone for treating iron overload in patients with thalassemia major, according to a single-center study.

Over the course of 1 year of treatment, deferasirox plus deferoxamine significantly increased myocardial T2* and significantly reduced serum ferritin, whereas deferasirox alone had no significant effect on either endpoint. Neither treatment had a significant effect on hepatic iron.

Deferasirox plus deferoxamine caused a significantly greater increase in alanine aminotransferase, aspartate aminotransferase, and bilirubin. Other adverse events were similar between the treatment groups.

Aziz Eghbali, MD, of Arak (Iran) University of Medical Sciences and colleagues described this study in Transfusion and Apheresis Science.

The team conducted a randomized, double-blind trial of patients with thalassemia major. Of the 62 patients enrolled, 55 were randomized and evaluable. At baseline, the mean patient age was 24.5 years, and 67.3% were female.

The patients were randomized to receive oral deferasirox at 30 mg/kg daily either alone (n = 27) or with subcutaneous deferoxamine at 50 mg/kg for 5 days a week (n = 28). In both groups, patients received treatment for 12 months.

There were no significant differences between the groups in baseline characteristics such as myocardial or hepatic iron, transfusion volume, or white blood cell and platelet counts.

Results

The study’s primary endpoints were changes in myocardial T2* and hepatic T2* from baseline to 12 months. Changes in serum ferritin and adverse events were secondary endpoints.

Myocardial T2* decreased slightly in the monotherapy group, from 23.3 plus or minus 7.4 ms at baseline to 22.1 plus or minus 6.9 ms at 12 months (P = .3) but increased significantly in the combination group, from 23.1 plus or minus 7.5 ms to 27.1 plus or minus 7.0 ms (P less than .05). The difference between the groups was significant (P = .01).

There was no significant change in hepatic iron in either group. Hepatic T2* was 7.0 plus or minus 5.6 ms at baseline and 7.0 plus or minus 5.3 ms at 12 months in the monotherapy group (P = .7). In the combination group, hepatic T2* increased from 9.8 plus or minus 8.8 ms to 10.2 plus or minus 8.2 ms (P = .5). The between-group difference was not significant (P = .094).

Serum ferritin decreased from 1,390 plus or minus 816 mcg/ml to 1,085 plus or minus 919 mcg/mL in the monotherapy group (P = .06) and from 1,446 plus or minus 987 mcg/mL to 737 plus or minus 459 mcg/mL in the combination group (P less than .01). The between-group difference was significant (P = .001).

Increases in alanine aminotransferase, aspartate aminotransferase, and bilirubin were significantly greater in the combination group than in the monotherapy group (P less than .05 for all). Combination therapy also prompted an increase in alkaline phosphatase, but this was not significantly greater than in the monotherapy group (P = .3).

Blood urea nitrogen levels increased in both groups, but levels remained within the normal range. There were no increases in serum creatinine in either group.

Rates of mild gastrointestinal adverse events were similar in the monotherapy and combination groups (40% and 39%, respectively), as were rates of transient skin rashes (18% and 14%, respectively).

There were no deaths, and none of the patients stopped treatment because of severe adverse events.

This study was supported by Arak University of Medical Sciences. The researchers reported having no conflicts of interest.

jensmith@mdedge.com

SOURCE: Eghbali A et al. Transfus Apher Sci. 2019 Aug;58(4):429-33.
 

Deferasirox plus deferoxamine is more effective than deferasirox alone for treating iron overload in patients with thalassemia major, according to a single-center study.

Over the course of 1 year of treatment, deferasirox plus deferoxamine significantly increased myocardial T2* and significantly reduced serum ferritin, whereas deferasirox alone had no significant effect on either endpoint. Neither treatment had a significant effect on hepatic iron.

Deferasirox plus deferoxamine caused a significantly greater increase in alanine aminotransferase, aspartate aminotransferase, and bilirubin. Other adverse events were similar between the treatment groups.

Aziz Eghbali, MD, of Arak (Iran) University of Medical Sciences and colleagues described this study in Transfusion and Apheresis Science.

The team conducted a randomized, double-blind trial of patients with thalassemia major. Of the 62 patients enrolled, 55 were randomized and evaluable. At baseline, the mean patient age was 24.5 years, and 67.3% were female.

The patients were randomized to receive oral deferasirox at 30 mg/kg daily either alone (n = 27) or with subcutaneous deferoxamine at 50 mg/kg for 5 days a week (n = 28). In both groups, patients received treatment for 12 months.

There were no significant differences between the groups in baseline characteristics such as myocardial or hepatic iron, transfusion volume, or white blood cell and platelet counts.

Results

The study’s primary endpoints were changes in myocardial T2* and hepatic T2* from baseline to 12 months. Changes in serum ferritin and adverse events were secondary endpoints.

Myocardial T2* decreased slightly in the monotherapy group, from 23.3 plus or minus 7.4 ms at baseline to 22.1 plus or minus 6.9 ms at 12 months (P = .3) but increased significantly in the combination group, from 23.1 plus or minus 7.5 ms to 27.1 plus or minus 7.0 ms (P less than .05). The difference between the groups was significant (P = .01).

There was no significant change in hepatic iron in either group. Hepatic T2* was 7.0 plus or minus 5.6 ms at baseline and 7.0 plus or minus 5.3 ms at 12 months in the monotherapy group (P = .7). In the combination group, hepatic T2* increased from 9.8 plus or minus 8.8 ms to 10.2 plus or minus 8.2 ms (P = .5). The between-group difference was not significant (P = .094).

Serum ferritin decreased from 1,390 plus or minus 816 mcg/ml to 1,085 plus or minus 919 mcg/mL in the monotherapy group (P = .06) and from 1,446 plus or minus 987 mcg/mL to 737 plus or minus 459 mcg/mL in the combination group (P less than .01). The between-group difference was significant (P = .001).

Increases in alanine aminotransferase, aspartate aminotransferase, and bilirubin were significantly greater in the combination group than in the monotherapy group (P less than .05 for all). Combination therapy also prompted an increase in alkaline phosphatase, but this was not significantly greater than in the monotherapy group (P = .3).

Blood urea nitrogen levels increased in both groups, but levels remained within the normal range. There were no increases in serum creatinine in either group.

Rates of mild gastrointestinal adverse events were similar in the monotherapy and combination groups (40% and 39%, respectively), as were rates of transient skin rashes (18% and 14%, respectively).

There were no deaths, and none of the patients stopped treatment because of severe adverse events.

This study was supported by Arak University of Medical Sciences. The researchers reported having no conflicts of interest.

jensmith@mdedge.com

SOURCE: Eghbali A et al. Transfus Apher Sci. 2019 Aug;58(4):429-33.
 

Deferasirox plus deferoxamine is more effective than deferasirox alone for treating iron overload in patients with thalassemia major, according to a single-center study.

Over the course of 1 year of treatment, deferasirox plus deferoxamine significantly increased myocardial T2* and significantly reduced serum ferritin, whereas deferasirox alone had no significant effect on either endpoint. Neither treatment had a significant effect on hepatic iron.

Deferasirox plus deferoxamine caused a significantly greater increase in alanine aminotransferase, aspartate aminotransferase, and bilirubin. Other adverse events were similar between the treatment groups.

Aziz Eghbali, MD, of Arak (Iran) University of Medical Sciences and colleagues described this study in Transfusion and Apheresis Science.

The team conducted a randomized, double-blind trial of patients with thalassemia major. Of the 62 patients enrolled, 55 were randomized and evaluable. At baseline, the mean patient age was 24.5 years, and 67.3% were female.

The patients were randomized to receive oral deferasirox at 30 mg/kg daily either alone (n = 27) or with subcutaneous deferoxamine at 50 mg/kg for 5 days a week (n = 28). In both groups, patients received treatment for 12 months.

There were no significant differences between the groups in baseline characteristics such as myocardial or hepatic iron, transfusion volume, or white blood cell and platelet counts.

Results

The study’s primary endpoints were changes in myocardial T2* and hepatic T2* from baseline to 12 months. Changes in serum ferritin and adverse events were secondary endpoints.

Myocardial T2* decreased slightly in the monotherapy group, from 23.3 plus or minus 7.4 ms at baseline to 22.1 plus or minus 6.9 ms at 12 months (P = .3) but increased significantly in the combination group, from 23.1 plus or minus 7.5 ms to 27.1 plus or minus 7.0 ms (P less than .05). The difference between the groups was significant (P = .01).

There was no significant change in hepatic iron in either group. Hepatic T2* was 7.0 plus or minus 5.6 ms at baseline and 7.0 plus or minus 5.3 ms at 12 months in the monotherapy group (P = .7). In the combination group, hepatic T2* increased from 9.8 plus or minus 8.8 ms to 10.2 plus or minus 8.2 ms (P = .5). The between-group difference was not significant (P = .094).

Serum ferritin decreased from 1,390 plus or minus 816 mcg/ml to 1,085 plus or minus 919 mcg/mL in the monotherapy group (P = .06) and from 1,446 plus or minus 987 mcg/mL to 737 plus or minus 459 mcg/mL in the combination group (P less than .01). The between-group difference was significant (P = .001).

Increases in alanine aminotransferase, aspartate aminotransferase, and bilirubin were significantly greater in the combination group than in the monotherapy group (P less than .05 for all). Combination therapy also prompted an increase in alkaline phosphatase, but this was not significantly greater than in the monotherapy group (P = .3).

Blood urea nitrogen levels increased in both groups, but levels remained within the normal range. There were no increases in serum creatinine in either group.

Rates of mild gastrointestinal adverse events were similar in the monotherapy and combination groups (40% and 39%, respectively), as were rates of transient skin rashes (18% and 14%, respectively).

There were no deaths, and none of the patients stopped treatment because of severe adverse events.

This study was supported by Arak University of Medical Sciences. The researchers reported having no conflicts of interest.

jensmith@mdedge.com

SOURCE: Eghbali A et al. Transfus Apher Sci. 2019 Aug;58(4):429-33.
 

Individuals who are carriers of hemophilia genes and have reduced clotting factor activity have at least a twofold higher risk of joint-related comorbidities, compared with the general population, according to new research.

decade3d/Thinkstock

In a population-based cohort study using patient registry data, Swedish researchers identified 539 potential carriers of impaired factor VIII or IX gene in the X chromosome – 213 of whom had documented factor activity – and paired them with sex‐ and birthdate‐matched controls from the general population.

They found that carriers with reduced factor activity had a 2.3-fold higher risk of a joint diagnosis, compared with the general population (95% confidence interval, 1.1-4.5). Carriers with normal factor activity did not show a statistically significant increase in joint diagnosis hazard, however carriers with unknown factor activity had a 2.4-fold higher risk of joint diagnosis, compared with controls (95% CI, 1.8-3.2). The findings were published in Haemophilia.

By the age of 60 years, around 37% of carriers with reduced or unknown factor activity had received a joint diagnosis, compared with 23% of carriers with normal factor activity.

The most common joint diagnoses across carriers and controls were knee related, including gonarthrosis and internal derangement, but these were more common among carriers. Five carriers also recorded a diagnosis of hemophilic arthropathy or systemic disorders of connective tissue in diseases classified elsewhere.

Researchers also saw a 10-fold higher risk of joint surgery (95% CI, 1.0-3.7) among carriers with reduced factor activity – although the numbers were small – and even among carriers with normal factor activity, there was a nearly twofold higher rate (95% CI, 0.9-4.6), compared with the control population.

Carriers with reduced or unknown factor activity also had a higher risk of outpatient hospitalization, compared with the general population, although no effect was seen in carriers with normal factor activity.

“Although the frequency of joint comorbidities overall was relatively low, our results clearly indicate and confirm a higher burden of joint afflictions, including an earlier age at joint diagnosis, for carriers with reduced or unknown factor activity compared with the general population, as well as more joint surgeries and related hospitalizations,” wrote Mehdi Osooli, PhD, from the Skåne University Hospital in Malmö, Sweden, and his coauthors.

The authors noted that the findings correlated with their earlier research on the incidence of arthropathy among males with mild hemophilia, who have previously been found to have a ninefold higher incidence of arthropathy‐related hospital admissions and a 16‐fold higher incidence of joint disease.

“The relatively higher incidence in the male population compared with the carriers in the current study may be explained by the lower median factor activity level, for example, levels between 5% and 40% in males with mild haemophilia compared with a median overall of 50% in carriers,” they wrote.

All authors declared that they had no conflict of interest related to the study findings. Four of the authors reported financial ties to companies including Novo Nordisk, Shire, and Bayer.

SOURCE: Osooli M et al. Haemophilia. 2019 Aug 14. doi: 10.1111/hae.13831.

Individuals who are carriers of hemophilia genes and have reduced clotting factor activity have at least a twofold higher risk of joint-related comorbidities, compared with the general population, according to new research.

decade3d/Thinkstock

In a population-based cohort study using patient registry data, Swedish researchers identified 539 potential carriers of impaired factor VIII or IX gene in the X chromosome – 213 of whom had documented factor activity – and paired them with sex‐ and birthdate‐matched controls from the general population.

They found that carriers with reduced factor activity had a 2.3-fold higher risk of a joint diagnosis, compared with the general population (95% confidence interval, 1.1-4.5). Carriers with normal factor activity did not show a statistically significant increase in joint diagnosis hazard, however carriers with unknown factor activity had a 2.4-fold higher risk of joint diagnosis, compared with controls (95% CI, 1.8-3.2). The findings were published in Haemophilia.

By the age of 60 years, around 37% of carriers with reduced or unknown factor activity had received a joint diagnosis, compared with 23% of carriers with normal factor activity.

The most common joint diagnoses across carriers and controls were knee related, including gonarthrosis and internal derangement, but these were more common among carriers. Five carriers also recorded a diagnosis of hemophilic arthropathy or systemic disorders of connective tissue in diseases classified elsewhere.

Researchers also saw a 10-fold higher risk of joint surgery (95% CI, 1.0-3.7) among carriers with reduced factor activity – although the numbers were small – and even among carriers with normal factor activity, there was a nearly twofold higher rate (95% CI, 0.9-4.6), compared with the control population.

Carriers with reduced or unknown factor activity also had a higher risk of outpatient hospitalization, compared with the general population, although no effect was seen in carriers with normal factor activity.

“Although the frequency of joint comorbidities overall was relatively low, our results clearly indicate and confirm a higher burden of joint afflictions, including an earlier age at joint diagnosis, for carriers with reduced or unknown factor activity compared with the general population, as well as more joint surgeries and related hospitalizations,” wrote Mehdi Osooli, PhD, from the Skåne University Hospital in Malmö, Sweden, and his coauthors.

The authors noted that the findings correlated with their earlier research on the incidence of arthropathy among males with mild hemophilia, who have previously been found to have a ninefold higher incidence of arthropathy‐related hospital admissions and a 16‐fold higher incidence of joint disease.

“The relatively higher incidence in the male population compared with the carriers in the current study may be explained by the lower median factor activity level, for example, levels between 5% and 40% in males with mild haemophilia compared with a median overall of 50% in carriers,” they wrote.

All authors declared that they had no conflict of interest related to the study findings. Four of the authors reported financial ties to companies including Novo Nordisk, Shire, and Bayer.

SOURCE: Osooli M et al. Haemophilia. 2019 Aug 14. doi: 10.1111/hae.13831.

Individuals who are carriers of hemophilia genes and have reduced clotting factor activity have at least a twofold higher risk of joint-related comorbidities, compared with the general population, according to new research.

decade3d/Thinkstock

In a population-based cohort study using patient registry data, Swedish researchers identified 539 potential carriers of impaired factor VIII or IX gene in the X chromosome – 213 of whom had documented factor activity – and paired them with sex‐ and birthdate‐matched controls from the general population.

They found that carriers with reduced factor activity had a 2.3-fold higher risk of a joint diagnosis, compared with the general population (95% confidence interval, 1.1-4.5). Carriers with normal factor activity did not show a statistically significant increase in joint diagnosis hazard, however carriers with unknown factor activity had a 2.4-fold higher risk of joint diagnosis, compared with controls (95% CI, 1.8-3.2). The findings were published in Haemophilia.

By the age of 60 years, around 37% of carriers with reduced or unknown factor activity had received a joint diagnosis, compared with 23% of carriers with normal factor activity.

The most common joint diagnoses across carriers and controls were knee related, including gonarthrosis and internal derangement, but these were more common among carriers. Five carriers also recorded a diagnosis of hemophilic arthropathy or systemic disorders of connective tissue in diseases classified elsewhere.

Researchers also saw a 10-fold higher risk of joint surgery (95% CI, 1.0-3.7) among carriers with reduced factor activity – although the numbers were small – and even among carriers with normal factor activity, there was a nearly twofold higher rate (95% CI, 0.9-4.6), compared with the control population.

Carriers with reduced or unknown factor activity also had a higher risk of outpatient hospitalization, compared with the general population, although no effect was seen in carriers with normal factor activity.

“Although the frequency of joint comorbidities overall was relatively low, our results clearly indicate and confirm a higher burden of joint afflictions, including an earlier age at joint diagnosis, for carriers with reduced or unknown factor activity compared with the general population, as well as more joint surgeries and related hospitalizations,” wrote Mehdi Osooli, PhD, from the Skåne University Hospital in Malmö, Sweden, and his coauthors.

The authors noted that the findings correlated with their earlier research on the incidence of arthropathy among males with mild hemophilia, who have previously been found to have a ninefold higher incidence of arthropathy‐related hospital admissions and a 16‐fold higher incidence of joint disease.

“The relatively higher incidence in the male population compared with the carriers in the current study may be explained by the lower median factor activity level, for example, levels between 5% and 40% in males with mild haemophilia compared with a median overall of 50% in carriers,” they wrote.

All authors declared that they had no conflict of interest related to the study findings. Four of the authors reported financial ties to companies including Novo Nordisk, Shire, and Bayer.

SOURCE: Osooli M et al. Haemophilia. 2019 Aug 14. doi: 10.1111/hae.13831.