Hyperhidrosis (HH) is sweating beyond that which is required for thermoregulation.¹ Secondary HH, which is usually caused by an underlying medical condition or drug, may be seen in patients with spinal cord injury (SCI) and can negatively impact psychosocial well-being and quality of life (QOL) if not treated.¹

Information on the current prevalence of HH is lacking. In 2004, one study projected the prevalence of HH in the U.S. to be 2.8%.² A previous study found that about 27% of the 154 patients with SCI reported experiencing HH that was annoying, with 28 (14.6%) of those reporting no contributing somatic causes.³ Somatic causes of HH include autonomic dysreflexia, posttraumatic syringomyelia, or orthostatic hypotension.⁴

Autonomic dysreflexia is a syndrome that describes a dramatic increase in blood pressure (BP) in patients with spinal cord lesion at or above T6 and is characterized by exaggerated autonomic responses to stimuli that are innocuous to individuals without SCI.^5,6 Noxious stimuli that may trigger autonomic dysreflexia include bowel or bladder distension or obstruction, urinary infection, catheter insertion, suprapubic palpation, or skin irritation.⁶ Syringomyelia, another somatic cause of HH, is a cystic lesion on the spinal cord that may develop secondary to congenital anomalies or SCI.^6-8

The following case reports describe 2 patients with SCI with different diagnoses and presentations of HH. Both were treated with oxybutynin for HH.

Case 1 Presentation

Mr. J is a 49-year-old with C6-C7 SCI attributed to a motor vehicle accident 26 years before. He presented to the primary care clinic for a routine visit in a self-propelled wheelchair. His diagnosis included tetraplegia, muscle spasms, osteoporosis, chronic pain syndrome, benign prosthetic hypertrophy, neurogenic bladder, and neurogenic bowel. He was noted to have a bath towel around his neck to wipe sweat from his face and neck. He did not recall when this condition started; however, he reported a prior trial of diazepam 5 mg as needed in 2006 in the mornings and before transfers when sweating was usually worst. He continued to use diazepam because it helped with his muscle spasms but not with sweating. His other medications included oral baclofen, alendronate, ibuprofen, docusate sodium, tamsulosin, calcium/vitamin C supplement, and bisacodyl suppository.

The patient’s surgical history was significant for anterior discectomy with C6-C7 fusion, sphincterotomy, transurethral resection of the prostate, and right urethral stent placement for hydronephrosis in 2004. His cystoscopy and renal sonogram were within normal limits. On physical examination, his vital signs were within normal limits. However, his long-sleeved shirt was wet on the front, and his neck, chest, and arms also were moist from excessive sweating. During his transfer to and from his wheelchair, he was noted to have chattering of his teeth. The remainder of the physical examination was negative for any other acute findings.

Mr. J was prescribed a 30-day trial of oxybutynin 5 mg 1 tablet by mouth per day for HH. During a 3-week follow-up telephone call, Mr. J reported that the oxybutynin was working well; the sweating on his chest had improved and had resolved on his face. Except for mild dryness of mouth, he was tolerating the medication well. There were no changes in his neurogenic bladder, which was managed with an external urinary device.

Six months later, Mr. J reported that oxybutynin continued to work well, and he no longer had to travel with a towel. He was able to go to a football game, social activities were more enjoyable, and he was not embarrassed because of excessive sweating.

Case 2 Presentation

Mr. B is a 48-year-old with T12 paraplegia secondary to a motor vehicle accident in 1994. He called the primary clinic for a visit because he was concerned about cold clammy hands for the past 6 to 7 months when he woke up in the morning and sometimes throughout the day. He was preparing to start his first semester in college. His diagnosis included neurogenic bowel and bladder and muscle spasms. There was no history of posttraumatic syringomyelia, and his medications included baclofen, dantrolene, diazepam, and multivitamins.

Mr. B took tolterodine 4 mg/d for several years, and for unknown reasons, about 6 years previously the prescription was changed to oxybutynin 15-mg extended release for his neurogenic bladder. He continued to have urinary leakage between the every 4-hour intermittent catherization, and oxybutynin was increased to 10-mg tablet twice per day.

About 7 months prior to this appointment, Mr. B independently stopped the oxybutynin as he felt that it was not making a difference in the management of his neurogenic bladder. It was noted that his cold clammy hands started about the same time that he discontinued the oxybutynin. He could not recall whether he had this symptom prior to initiation of any medication. It was mutually decided to restart the oxybutynin at a lower dose, this time not for his bladder but for the HH. He was ordered a 30-day trial of a 5-mg tablet once per day. About 3 weeks later, he sent a secure message to report oxybutynin’s effectiveness and to request a refill.

Discussion

Sweating is a physiological process that involves the active secretion of water by specialized sweat glands in the skin.^9-11 There are 2 types of sweat glands in the skin; apocrine and eccrine.⁹ Collectively the 3 million eccrine sweat glands of the average person approximately equal the mass of a kidney and exceed the secretory rate of exocrine glands.⁹ They function in evaporative cooling in response to thermal or physiologic stimuli and are widely distributed over the body, especially on the forehead, back, palms, and soles.¹⁰

Sympathetic cholinergic nerves are mainly responsible for sweat secretion by the release of acetylcholine to activate muscarinic receptors on the gland.¹¹ Postganglionic fibers from sympathetic nerve cells innervate sweat glands that release cholinergics.⁶ Postganglionic cholinergic receptors that are activated by muscarinic drugs are termed muscarinic receptors and are readily accessible to antimuscarinic drugs.^6,12 Anticholinergic/antimuscarinic agents antagonize muscarinic receptors and suppress premature detrusor contractions to enhance bladder storage.¹³ They include oxybutynin, tolterodine, trospium, solifenacin, darifenacin, and fesoterodine.¹³ Oxybutynin was used in both cases because it is on VA formulary. It was effective in treating HH, although the etiology is unclear and the presentations were different.

One retrospective study that analyzed 20 patients who received oxybutynin for primary HH at uncommon sites, such as the back and groin, found that QOL improved in 85% of the subjects after 6 weeks.¹⁴ Randomized placebo-controlled trials also have found oxybutynin effective for treatment of palmar and axillary HH and generalized HH.^15,16

Syringomyelia was ruled out in both cases based on history and radiologic studies, specifically magnetic resonance imaging. Autonomic dysreflexia was ruled out as the HH was not an acute finding and BP was within normal limits. Orthostatic hypotension is a common finding in SCI, mainly in tetraplegic patients, and could be suspected in both cases. Sweating was usually worse in the mornings in both cases and during transfers, as noted in the first case.¹⁷ However, chronic autoregulation allows for chronic adaption to tissue hypoperfusion over time.¹⁶

Hyperhidrosis or other disorders of eccrine sweating can occur for various reasons, including changes in the spinal sympathetic preganglionic, ganglionic, or postganglionic neurons; dysfunction of the thermoregulatory centers in the brain’s central autonomic network; or changes in the muscarinic cholinergic synapse on sweat glands.¹⁸

Conclusion

Patients with SCI may have an acute or chronic presentation of HH. Removal of the inciting cause in the case of autonomic dysreflexia and/or the administration of a pharmaceutical agent is the usual treatment.

Regardless of the etiology of HH that persists, effective treatment should be a goal, especially in those patients whose QOL is affected by this condition. The outcome of treatment with oxybutynin in these case reports is consistent with the findings of the limited retrospective study and randomized placebo-controlled studies that show oxybutynin is effective for treating bothersome HH.^14-16

The results of these case reports are not generalizable to patients with SCI and HH, nor are the results of the limited retrospective study and randomized placebo-controlled studies, as their sample sizes were small.^14,16,17 However, information on the use of oxybutynin for the effective treatment of HH in the SCI population is promising. Research studies on the prevalence of HH and randomized placebo-controlled trials with a larger SCI population are considerations for future studies.

Hyperhidrosis (HH) is sweating beyond that which is required for thermoregulation.¹ Secondary HH, which is usually caused by an underlying medical condition or drug, may be seen in patients with spinal cord injury (SCI) and can negatively impact psychosocial well-being and quality of life (QOL) if not treated.¹

Information on the current prevalence of HH is lacking. In 2004, one study projected the prevalence of HH in the U.S. to be 2.8%.² A previous study found that about 27% of the 154 patients with SCI reported experiencing HH that was annoying, with 28 (14.6%) of those reporting no contributing somatic causes.³ Somatic causes of HH include autonomic dysreflexia, posttraumatic syringomyelia, or orthostatic hypotension.⁴

Autonomic dysreflexia is a syndrome that describes a dramatic increase in blood pressure (BP) in patients with spinal cord lesion at or above T6 and is characterized by exaggerated autonomic responses to stimuli that are innocuous to individuals without SCI.^5,6 Noxious stimuli that may trigger autonomic dysreflexia include bowel or bladder distension or obstruction, urinary infection, catheter insertion, suprapubic palpation, or skin irritation.⁶ Syringomyelia, another somatic cause of HH, is a cystic lesion on the spinal cord that may develop secondary to congenital anomalies or SCI.^6-8

The following case reports describe 2 patients with SCI with different diagnoses and presentations of HH. Both were treated with oxybutynin for HH.

Case 1 Presentation

Mr. J is a 49-year-old with C6-C7 SCI attributed to a motor vehicle accident 26 years before. He presented to the primary care clinic for a routine visit in a self-propelled wheelchair. His diagnosis included tetraplegia, muscle spasms, osteoporosis, chronic pain syndrome, benign prosthetic hypertrophy, neurogenic bladder, and neurogenic bowel. He was noted to have a bath towel around his neck to wipe sweat from his face and neck. He did not recall when this condition started; however, he reported a prior trial of diazepam 5 mg as needed in 2006 in the mornings and before transfers when sweating was usually worst. He continued to use diazepam because it helped with his muscle spasms but not with sweating. His other medications included oral baclofen, alendronate, ibuprofen, docusate sodium, tamsulosin, calcium/vitamin C supplement, and bisacodyl suppository.

The patient’s surgical history was significant for anterior discectomy with C6-C7 fusion, sphincterotomy, transurethral resection of the prostate, and right urethral stent placement for hydronephrosis in 2004. His cystoscopy and renal sonogram were within normal limits. On physical examination, his vital signs were within normal limits. However, his long-sleeved shirt was wet on the front, and his neck, chest, and arms also were moist from excessive sweating. During his transfer to and from his wheelchair, he was noted to have chattering of his teeth. The remainder of the physical examination was negative for any other acute findings.

Mr. J was prescribed a 30-day trial of oxybutynin 5 mg 1 tablet by mouth per day for HH. During a 3-week follow-up telephone call, Mr. J reported that the oxybutynin was working well; the sweating on his chest had improved and had resolved on his face. Except for mild dryness of mouth, he was tolerating the medication well. There were no changes in his neurogenic bladder, which was managed with an external urinary device.

Six months later, Mr. J reported that oxybutynin continued to work well, and he no longer had to travel with a towel. He was able to go to a football game, social activities were more enjoyable, and he was not embarrassed because of excessive sweating.

Case 2 Presentation

Mr. B is a 48-year-old with T12 paraplegia secondary to a motor vehicle accident in 1994. He called the primary clinic for a visit because he was concerned about cold clammy hands for the past 6 to 7 months when he woke up in the morning and sometimes throughout the day. He was preparing to start his first semester in college. His diagnosis included neurogenic bowel and bladder and muscle spasms. There was no history of posttraumatic syringomyelia, and his medications included baclofen, dantrolene, diazepam, and multivitamins.

Mr. B took tolterodine 4 mg/d for several years, and for unknown reasons, about 6 years previously the prescription was changed to oxybutynin 15-mg extended release for his neurogenic bladder. He continued to have urinary leakage between the every 4-hour intermittent catherization, and oxybutynin was increased to 10-mg tablet twice per day.

About 7 months prior to this appointment, Mr. B independently stopped the oxybutynin as he felt that it was not making a difference in the management of his neurogenic bladder. It was noted that his cold clammy hands started about the same time that he discontinued the oxybutynin. He could not recall whether he had this symptom prior to initiation of any medication. It was mutually decided to restart the oxybutynin at a lower dose, this time not for his bladder but for the HH. He was ordered a 30-day trial of a 5-mg tablet once per day. About 3 weeks later, he sent a secure message to report oxybutynin’s effectiveness and to request a refill.

Discussion

Sweating is a physiological process that involves the active secretion of water by specialized sweat glands in the skin.^9-11 There are 2 types of sweat glands in the skin; apocrine and eccrine.⁹ Collectively the 3 million eccrine sweat glands of the average person approximately equal the mass of a kidney and exceed the secretory rate of exocrine glands.⁹ They function in evaporative cooling in response to thermal or physiologic stimuli and are widely distributed over the body, especially on the forehead, back, palms, and soles.¹⁰

Sympathetic cholinergic nerves are mainly responsible for sweat secretion by the release of acetylcholine to activate muscarinic receptors on the gland.¹¹ Postganglionic fibers from sympathetic nerve cells innervate sweat glands that release cholinergics.⁶ Postganglionic cholinergic receptors that are activated by muscarinic drugs are termed muscarinic receptors and are readily accessible to antimuscarinic drugs.^6,12 Anticholinergic/antimuscarinic agents antagonize muscarinic receptors and suppress premature detrusor contractions to enhance bladder storage.¹³ They include oxybutynin, tolterodine, trospium, solifenacin, darifenacin, and fesoterodine.¹³ Oxybutynin was used in both cases because it is on VA formulary. It was effective in treating HH, although the etiology is unclear and the presentations were different.

One retrospective study that analyzed 20 patients who received oxybutynin for primary HH at uncommon sites, such as the back and groin, found that QOL improved in 85% of the subjects after 6 weeks.¹⁴ Randomized placebo-controlled trials also have found oxybutynin effective for treatment of palmar and axillary HH and generalized HH.^15,16

Syringomyelia was ruled out in both cases based on history and radiologic studies, specifically magnetic resonance imaging. Autonomic dysreflexia was ruled out as the HH was not an acute finding and BP was within normal limits. Orthostatic hypotension is a common finding in SCI, mainly in tetraplegic patients, and could be suspected in both cases. Sweating was usually worse in the mornings in both cases and during transfers, as noted in the first case.¹⁷ However, chronic autoregulation allows for chronic adaption to tissue hypoperfusion over time.¹⁶

Hyperhidrosis or other disorders of eccrine sweating can occur for various reasons, including changes in the spinal sympathetic preganglionic, ganglionic, or postganglionic neurons; dysfunction of the thermoregulatory centers in the brain’s central autonomic network; or changes in the muscarinic cholinergic synapse on sweat glands.¹⁸

Conclusion

Patients with SCI may have an acute or chronic presentation of HH. Removal of the inciting cause in the case of autonomic dysreflexia and/or the administration of a pharmaceutical agent is the usual treatment.

Regardless of the etiology of HH that persists, effective treatment should be a goal, especially in those patients whose QOL is affected by this condition. The outcome of treatment with oxybutynin in these case reports is consistent with the findings of the limited retrospective study and randomized placebo-controlled studies that show oxybutynin is effective for treating bothersome HH.^14-16

The results of these case reports are not generalizable to patients with SCI and HH, nor are the results of the limited retrospective study and randomized placebo-controlled studies, as their sample sizes were small.^14,16,17 However, information on the use of oxybutynin for the effective treatment of HH in the SCI population is promising. Research studies on the prevalence of HH and randomized placebo-controlled trials with a larger SCI population are considerations for future studies.

Hyperhidrosis (HH) is sweating beyond that which is required for thermoregulation.¹ Secondary HH, which is usually caused by an underlying medical condition or drug, may be seen in patients with spinal cord injury (SCI) and can negatively impact psychosocial well-being and quality of life (QOL) if not treated.¹

Information on the current prevalence of HH is lacking. In 2004, one study projected the prevalence of HH in the U.S. to be 2.8%.² A previous study found that about 27% of the 154 patients with SCI reported experiencing HH that was annoying, with 28 (14.6%) of those reporting no contributing somatic causes.³ Somatic causes of HH include autonomic dysreflexia, posttraumatic syringomyelia, or orthostatic hypotension.⁴

Autonomic dysreflexia is a syndrome that describes a dramatic increase in blood pressure (BP) in patients with spinal cord lesion at or above T6 and is characterized by exaggerated autonomic responses to stimuli that are innocuous to individuals without SCI.^5,6 Noxious stimuli that may trigger autonomic dysreflexia include bowel or bladder distension or obstruction, urinary infection, catheter insertion, suprapubic palpation, or skin irritation.⁶ Syringomyelia, another somatic cause of HH, is a cystic lesion on the spinal cord that may develop secondary to congenital anomalies or SCI.^6-8

The following case reports describe 2 patients with SCI with different diagnoses and presentations of HH. Both were treated with oxybutynin for HH.

Case 1 Presentation

Mr. J is a 49-year-old with C6-C7 SCI attributed to a motor vehicle accident 26 years before. He presented to the primary care clinic for a routine visit in a self-propelled wheelchair. His diagnosis included tetraplegia, muscle spasms, osteoporosis, chronic pain syndrome, benign prosthetic hypertrophy, neurogenic bladder, and neurogenic bowel. He was noted to have a bath towel around his neck to wipe sweat from his face and neck. He did not recall when this condition started; however, he reported a prior trial of diazepam 5 mg as needed in 2006 in the mornings and before transfers when sweating was usually worst. He continued to use diazepam because it helped with his muscle spasms but not with sweating. His other medications included oral baclofen, alendronate, ibuprofen, docusate sodium, tamsulosin, calcium/vitamin C supplement, and bisacodyl suppository.

The patient’s surgical history was significant for anterior discectomy with C6-C7 fusion, sphincterotomy, transurethral resection of the prostate, and right urethral stent placement for hydronephrosis in 2004. His cystoscopy and renal sonogram were within normal limits. On physical examination, his vital signs were within normal limits. However, his long-sleeved shirt was wet on the front, and his neck, chest, and arms also were moist from excessive sweating. During his transfer to and from his wheelchair, he was noted to have chattering of his teeth. The remainder of the physical examination was negative for any other acute findings.

Mr. J was prescribed a 30-day trial of oxybutynin 5 mg 1 tablet by mouth per day for HH. During a 3-week follow-up telephone call, Mr. J reported that the oxybutynin was working well; the sweating on his chest had improved and had resolved on his face. Except for mild dryness of mouth, he was tolerating the medication well. There were no changes in his neurogenic bladder, which was managed with an external urinary device.

Six months later, Mr. J reported that oxybutynin continued to work well, and he no longer had to travel with a towel. He was able to go to a football game, social activities were more enjoyable, and he was not embarrassed because of excessive sweating.

Case 2 Presentation

Mr. B is a 48-year-old with T12 paraplegia secondary to a motor vehicle accident in 1994. He called the primary clinic for a visit because he was concerned about cold clammy hands for the past 6 to 7 months when he woke up in the morning and sometimes throughout the day. He was preparing to start his first semester in college. His diagnosis included neurogenic bowel and bladder and muscle spasms. There was no history of posttraumatic syringomyelia, and his medications included baclofen, dantrolene, diazepam, and multivitamins.

Mr. B took tolterodine 4 mg/d for several years, and for unknown reasons, about 6 years previously the prescription was changed to oxybutynin 15-mg extended release for his neurogenic bladder. He continued to have urinary leakage between the every 4-hour intermittent catherization, and oxybutynin was increased to 10-mg tablet twice per day.

About 7 months prior to this appointment, Mr. B independently stopped the oxybutynin as he felt that it was not making a difference in the management of his neurogenic bladder. It was noted that his cold clammy hands started about the same time that he discontinued the oxybutynin. He could not recall whether he had this symptom prior to initiation of any medication. It was mutually decided to restart the oxybutynin at a lower dose, this time not for his bladder but for the HH. He was ordered a 30-day trial of a 5-mg tablet once per day. About 3 weeks later, he sent a secure message to report oxybutynin’s effectiveness and to request a refill.

Discussion

Sweating is a physiological process that involves the active secretion of water by specialized sweat glands in the skin.^9-11 There are 2 types of sweat glands in the skin; apocrine and eccrine.⁹ Collectively the 3 million eccrine sweat glands of the average person approximately equal the mass of a kidney and exceed the secretory rate of exocrine glands.⁹ They function in evaporative cooling in response to thermal or physiologic stimuli and are widely distributed over the body, especially on the forehead, back, palms, and soles.¹⁰

Sympathetic cholinergic nerves are mainly responsible for sweat secretion by the release of acetylcholine to activate muscarinic receptors on the gland.¹¹ Postganglionic fibers from sympathetic nerve cells innervate sweat glands that release cholinergics.⁶ Postganglionic cholinergic receptors that are activated by muscarinic drugs are termed muscarinic receptors and are readily accessible to antimuscarinic drugs.^6,12 Anticholinergic/antimuscarinic agents antagonize muscarinic receptors and suppress premature detrusor contractions to enhance bladder storage.¹³ They include oxybutynin, tolterodine, trospium, solifenacin, darifenacin, and fesoterodine.¹³ Oxybutynin was used in both cases because it is on VA formulary. It was effective in treating HH, although the etiology is unclear and the presentations were different.

One retrospective study that analyzed 20 patients who received oxybutynin for primary HH at uncommon sites, such as the back and groin, found that QOL improved in 85% of the subjects after 6 weeks.¹⁴ Randomized placebo-controlled trials also have found oxybutynin effective for treatment of palmar and axillary HH and generalized HH.^15,16

Syringomyelia was ruled out in both cases based on history and radiologic studies, specifically magnetic resonance imaging. Autonomic dysreflexia was ruled out as the HH was not an acute finding and BP was within normal limits. Orthostatic hypotension is a common finding in SCI, mainly in tetraplegic patients, and could be suspected in both cases. Sweating was usually worse in the mornings in both cases and during transfers, as noted in the first case.¹⁷ However, chronic autoregulation allows for chronic adaption to tissue hypoperfusion over time.¹⁶

Hyperhidrosis or other disorders of eccrine sweating can occur for various reasons, including changes in the spinal sympathetic preganglionic, ganglionic, or postganglionic neurons; dysfunction of the thermoregulatory centers in the brain’s central autonomic network; or changes in the muscarinic cholinergic synapse on sweat glands.¹⁸

Conclusion

Patients with SCI may have an acute or chronic presentation of HH. Removal of the inciting cause in the case of autonomic dysreflexia and/or the administration of a pharmaceutical agent is the usual treatment.

Regardless of the etiology of HH that persists, effective treatment should be a goal, especially in those patients whose QOL is affected by this condition. The outcome of treatment with oxybutynin in these case reports is consistent with the findings of the limited retrospective study and randomized placebo-controlled studies that show oxybutynin is effective for treating bothersome HH.^14-16

The results of these case reports are not generalizable to patients with SCI and HH, nor are the results of the limited retrospective study and randomized placebo-controlled studies, as their sample sizes were small.^14,16,17 However, information on the use of oxybutynin for the effective treatment of HH in the SCI population is promising. Research studies on the prevalence of HH and randomized placebo-controlled trials with a larger SCI population are considerations for future studies.

Photo by Patrick Pelletier

Long-term follow-up of patients treated with imatinib suggests the drug can remain effective beyond 10 years and does not confer “unacceptable” cumulative toxicity, according to researchers.

The group evaluated data on patients who had newly diagnosed, chronic-phase chronic myeloid leukemia (CML) when they began treatment with imatinib.

The median treatment duration was 8.9 years, and the estimated 10-year survival rate ranged from 64.4% to 84.4%.

The researchers said serious adverse events (AEs) thought to be related to imatinib were uncommon and typically occurred early, within the first year of treatment.

These results were reported in NEJM. The research was funded by Novartis Pharmaceuticals, which markets imatinib as Gleevec.

“The long-term success of this treatment confirms the remarkable success we’ve seen since the very first Gleevec trials,” said study author Brian Druker, MD, a physician-scientist at Oregon Health & Science University in Portland, Oregon, who led the original clinical development of Gleevec.

“This study reinforces the notion that we can create effective and non-toxic therapies.”

The study enrolled 1106 newly diagnosed, chronic-phase CML patients at 177 cancer centers in more than 16 countries. Half were assigned to treatment with imatinib (n=533) and the other half to interferon alfa plus cytarabine.

This study allowed for cross-over between the treatment arms, and 65.6% of patients in the cytarabine/interferon alfa arm ultimately crossed over to the imatinib arm.

However, when assessing the effects of imatinib, the researchers focused only on the patients who were first randomized to receive imatinib.

The median follow-up was 10.9 years (range, 0 to 11.7, which included follow-up after patients discontinued study treatment).

Of the patients randomized to imatinib, 48.3% (n=267) completed treatment with the drug. The median duration of first-line imatinib was 8.9 years (range, <0.1 to 11.7).

For patients who did not complete imatinib treatment, reasons for discontinuation included a lack of efficacy (15.9%), withdrawn consent (10.3%), AEs (6.9%), because they proceeded to transplant (3.8%), death (3.4%), protocol violation (3.1%), loss to follow-up (2.7%), cross over to the interferon arm (2.5%), administrative problems (2.2%), abnormal laboratory values (0.5%), or abnormal procedure (0.4%).

Safety

The incidence of serious AEs considered related to imatinib was 9.3% (51/551).

Drug-related serious AEs occurring in at least 2 patients included abdominal pain (n=4), anemia (n=3), congestive cardiac failure (n=3), gastrointestinal hemorrhage (n=3), vomiting (n=3), alanine aminotransferase increase (n=2), cardiac arrest (n=2), conjunctival hemorrhage (n=2), and melana (n=2).

Six patients had a second neoplasm (benign, malignant, or unspecified).

Response

The cumulative rate of complete cytogenetic response (CCR) at the end of the trial was 82.8%.

In the intent-to-treat population, the rate of CCR went from 52.8% in the first year to 22.2% at year 10.

Among evaluable patients, the rate of CCR went from 70.9% (292/412) in the first year to 91.8% (123/134) in year 10.

In the intent-to-treat population, the rate of major molecular response went from 27.7% in the first year to 34.4% at year 10.

Among evaluable patients, the rate of major molecular response went from 50.2% (153/305) in the first year to 93.1% (190/204) in year 10.

Progression and survival

The rate of progression was 6.9% (38/553) in the intent-to-treat population. Most of these patients (n=34) progressed during the first 4 years.

There were 260 patients who were still alive and receiving imatinib at 10 years and 96 patients who were alive but not receiving imatinib.

The researchers did not know the survival status of 111 patients, and there were 86 known deaths at 10 years (89 by the end of the study).

The estimated 10-year survival rate ranged from 64.4% (assuming all 111 patients with unknown status had died) to 84.4% (assuming all 111 were alive).

The cause of death was CML in 50 patients, a secondary malignant condition in 11, a cardiac disorder/cardiovascular disease in 7, infectious disease in 5, and “other” causes in 16 patients.

Photo by Patrick Pelletier

Long-term follow-up of patients treated with imatinib suggests the drug can remain effective beyond 10 years and does not confer “unacceptable” cumulative toxicity, according to researchers.

The group evaluated data on patients who had newly diagnosed, chronic-phase chronic myeloid leukemia (CML) when they began treatment with imatinib.

The median treatment duration was 8.9 years, and the estimated 10-year survival rate ranged from 64.4% to 84.4%.

The researchers said serious adverse events (AEs) thought to be related to imatinib were uncommon and typically occurred early, within the first year of treatment.

These results were reported in NEJM. The research was funded by Novartis Pharmaceuticals, which markets imatinib as Gleevec.

“The long-term success of this treatment confirms the remarkable success we’ve seen since the very first Gleevec trials,” said study author Brian Druker, MD, a physician-scientist at Oregon Health & Science University in Portland, Oregon, who led the original clinical development of Gleevec.

“This study reinforces the notion that we can create effective and non-toxic therapies.”

The study enrolled 1106 newly diagnosed, chronic-phase CML patients at 177 cancer centers in more than 16 countries. Half were assigned to treatment with imatinib (n=533) and the other half to interferon alfa plus cytarabine.

This study allowed for cross-over between the treatment arms, and 65.6% of patients in the cytarabine/interferon alfa arm ultimately crossed over to the imatinib arm.

However, when assessing the effects of imatinib, the researchers focused only on the patients who were first randomized to receive imatinib.

The median follow-up was 10.9 years (range, 0 to 11.7, which included follow-up after patients discontinued study treatment).

Of the patients randomized to imatinib, 48.3% (n=267) completed treatment with the drug. The median duration of first-line imatinib was 8.9 years (range, <0.1 to 11.7).

For patients who did not complete imatinib treatment, reasons for discontinuation included a lack of efficacy (15.9%), withdrawn consent (10.3%), AEs (6.9%), because they proceeded to transplant (3.8%), death (3.4%), protocol violation (3.1%), loss to follow-up (2.7%), cross over to the interferon arm (2.5%), administrative problems (2.2%), abnormal laboratory values (0.5%), or abnormal procedure (0.4%).

Safety

The incidence of serious AEs considered related to imatinib was 9.3% (51/551).

Drug-related serious AEs occurring in at least 2 patients included abdominal pain (n=4), anemia (n=3), congestive cardiac failure (n=3), gastrointestinal hemorrhage (n=3), vomiting (n=3), alanine aminotransferase increase (n=2), cardiac arrest (n=2), conjunctival hemorrhage (n=2), and melana (n=2).

Six patients had a second neoplasm (benign, malignant, or unspecified).

Response

The cumulative rate of complete cytogenetic response (CCR) at the end of the trial was 82.8%.

In the intent-to-treat population, the rate of CCR went from 52.8% in the first year to 22.2% at year 10.

Among evaluable patients, the rate of CCR went from 70.9% (292/412) in the first year to 91.8% (123/134) in year 10.

In the intent-to-treat population, the rate of major molecular response went from 27.7% in the first year to 34.4% at year 10.

Among evaluable patients, the rate of major molecular response went from 50.2% (153/305) in the first year to 93.1% (190/204) in year 10.

Progression and survival

The rate of progression was 6.9% (38/553) in the intent-to-treat population. Most of these patients (n=34) progressed during the first 4 years.

There were 260 patients who were still alive and receiving imatinib at 10 years and 96 patients who were alive but not receiving imatinib.

The researchers did not know the survival status of 111 patients, and there were 86 known deaths at 10 years (89 by the end of the study).

The estimated 10-year survival rate ranged from 64.4% (assuming all 111 patients with unknown status had died) to 84.4% (assuming all 111 were alive).

The cause of death was CML in 50 patients, a secondary malignant condition in 11, a cardiac disorder/cardiovascular disease in 7, infectious disease in 5, and “other” causes in 16 patients.

Photo by Patrick Pelletier

Long-term follow-up of patients treated with imatinib suggests the drug can remain effective beyond 10 years and does not confer “unacceptable” cumulative toxicity, according to researchers.

The group evaluated data on patients who had newly diagnosed, chronic-phase chronic myeloid leukemia (CML) when they began treatment with imatinib.

The median treatment duration was 8.9 years, and the estimated 10-year survival rate ranged from 64.4% to 84.4%.

The researchers said serious adverse events (AEs) thought to be related to imatinib were uncommon and typically occurred early, within the first year of treatment.

These results were reported in NEJM. The research was funded by Novartis Pharmaceuticals, which markets imatinib as Gleevec.

“The long-term success of this treatment confirms the remarkable success we’ve seen since the very first Gleevec trials,” said study author Brian Druker, MD, a physician-scientist at Oregon Health & Science University in Portland, Oregon, who led the original clinical development of Gleevec.

“This study reinforces the notion that we can create effective and non-toxic therapies.”

The study enrolled 1106 newly diagnosed, chronic-phase CML patients at 177 cancer centers in more than 16 countries. Half were assigned to treatment with imatinib (n=533) and the other half to interferon alfa plus cytarabine.

This study allowed for cross-over between the treatment arms, and 65.6% of patients in the cytarabine/interferon alfa arm ultimately crossed over to the imatinib arm.

However, when assessing the effects of imatinib, the researchers focused only on the patients who were first randomized to receive imatinib.

The median follow-up was 10.9 years (range, 0 to 11.7, which included follow-up after patients discontinued study treatment).

Of the patients randomized to imatinib, 48.3% (n=267) completed treatment with the drug. The median duration of first-line imatinib was 8.9 years (range, <0.1 to 11.7).

For patients who did not complete imatinib treatment, reasons for discontinuation included a lack of efficacy (15.9%), withdrawn consent (10.3%), AEs (6.9%), because they proceeded to transplant (3.8%), death (3.4%), protocol violation (3.1%), loss to follow-up (2.7%), cross over to the interferon arm (2.5%), administrative problems (2.2%), abnormal laboratory values (0.5%), or abnormal procedure (0.4%).

Safety

The incidence of serious AEs considered related to imatinib was 9.3% (51/551).

Drug-related serious AEs occurring in at least 2 patients included abdominal pain (n=4), anemia (n=3), congestive cardiac failure (n=3), gastrointestinal hemorrhage (n=3), vomiting (n=3), alanine aminotransferase increase (n=2), cardiac arrest (n=2), conjunctival hemorrhage (n=2), and melana (n=2).

Six patients had a second neoplasm (benign, malignant, or unspecified).

Response

The cumulative rate of complete cytogenetic response (CCR) at the end of the trial was 82.8%.

In the intent-to-treat population, the rate of CCR went from 52.8% in the first year to 22.2% at year 10.

Among evaluable patients, the rate of CCR went from 70.9% (292/412) in the first year to 91.8% (123/134) in year 10.

In the intent-to-treat population, the rate of major molecular response went from 27.7% in the first year to 34.4% at year 10.

Among evaluable patients, the rate of major molecular response went from 50.2% (153/305) in the first year to 93.1% (190/204) in year 10.

Progression and survival

The rate of progression was 6.9% (38/553) in the intent-to-treat population. Most of these patients (n=34) progressed during the first 4 years.

There were 260 patients who were still alive and receiving imatinib at 10 years and 96 patients who were alive but not receiving imatinib.

The researchers did not know the survival status of 111 patients, and there were 86 known deaths at 10 years (89 by the end of the study).

The estimated 10-year survival rate ranged from 64.4% (assuming all 111 patients with unknown status had died) to 84.4% (assuming all 111 were alive).

The cause of death was CML in 50 patients, a secondary malignant condition in 11, a cardiac disorder/cardiovascular disease in 7, infectious disease in 5, and “other” causes in 16 patients.

Lab mouse

An experimental drug called LCL161 stimulates the immune system to fight multiple myeloma (MM), according to research published in Nature Medicine.

Investigators said LCL161 exhibited “robust” activity in a transgenic myeloma mouse model and in patients with relapsed/refractory MM.

Single-agent LCL161 did not produce responses in MM patients, but patients did respond to treatment with LCL161 and cyclophosphamide.

The investigators also found that single-agent LCL161 provided “long-term anti-tumor protection” in mice, and combining LCL161 with an antibody against PD-1 could cure mice of MM.

“The drug, LCL161, was initially developed to promote tumor death,” said study author Marta Chesi, PhD, of Mayo Clinic Arizona in Scottsdale.

“However, we found that the drug does not kill tumor cells directly. Rather, it makes them more visible to the immune system that recognizes them as foreign invaders and eliminates them.”

Dr Chesi and her colleagues explained that the cellular inhibitors of apoptosis (cIAP) 1 and 2 have been identified as potential therapeutic targets in some cancers.

And LCL161 is a small-molecule IAP antagonist that induces tumor necrosis factor-mediated apoptosis in cancer cells. However, the investigators found that LCL161 was not directly cytotoxic to MM cells.

Instead, the drug upregulated tumor-cell-autonomous type I interferon signaling and induced an acute inflammatory response. This led to the activation of macrophages and dendritic cells, which prompted phagocytosis in MM cells.

Results in mice

The investigators first tested LCL161 alone (at a dose previously shown to be well-tolerated) in Vk*MYC transgenic mice with established MM.

The team said they observed a reduction in tumor burden that was comparable to that observed in response to drugs currently used to treat MM—carfilzomib, bortezomib, melphalan, cyclophosphamide, panobinostat, dexamethasone, and pomalidomide.

The investigators then tested the combination of LCL161 and a PD1 antibody in Vk12598-tumor-bearing mice.

The team said the combination was curative in all mice that completed 2 weeks of treatment. In fact, it was more effective than combination treatment with LCL161 and cyclophosphamide.

Results in patients

Dr Chesi and her colleagues conducted a phase 2 trial of LCL161 in 25 patients with relapsed/refractory MM. Patients could receive cyclophosphamide if they failed to respond or progressed after 8 weeks of treatment with LCL161 alone.

The patients’ median age was 68 (range, 47-90), and they had a median of 3 prior therapies (range, 1-6). Forty-four percent of patients had high-risk features, 28% had relapsed disease, and 72% had relapsed and refractory disease.

Four patients experienced grade 2 cytokine release syndrome when they received LCL161 at a dose of 1800 mg weekly, so the dose was lowered to 1200 mg.

None of the patients responded to single-agent LCL161. So 23 of the patients received 500 mg of weekly cyclophosphamide as well.

There was 1 complete response to the combination therapy, 1 very good partial response, 2 partial responses, and 1 minimal response. The median progression-free survival in these patients was 10 months.

Grade 3 adverse events included decrease in neutrophil count (28%), decrease in lymphocyte count (28%), anemia (24%), fatigue (16%), hyperglycemia (12%), syncope (12%), decrease in white blood cell count (12%), decrease in platelet count (8%), increase in lymphocyte count (8%), nausea (4%), vomiting (4%), diarrhea (4%), maculo-papular rash (4%), hypotension (4%), lung infection (4%), pain in extremity (4%), and urticaria (4%).

Grade 4 events included decrease in lymphocyte count (24%), decrease in neutrophil count (8%), decrease in white blood cell count (8%), hyperuricemia (4%), decrease in platelet count (4%), and sepsis (4%).

Based on these results, the investigators said the combination of LCL161 and cyclophosphamide is “an attractive platform for future trials,” and the same is true for LCL161 in combination with anti-PD1 therapy.

The phase 2 trial was sponsored by Mayo Clinic and the National Cancer Institute. Novartis provided LCL161 for this research and supported the trial. 

Lab mouse

An experimental drug called LCL161 stimulates the immune system to fight multiple myeloma (MM), according to research published in Nature Medicine.

Investigators said LCL161 exhibited “robust” activity in a transgenic myeloma mouse model and in patients with relapsed/refractory MM.

Single-agent LCL161 did not produce responses in MM patients, but patients did respond to treatment with LCL161 and cyclophosphamide.

The investigators also found that single-agent LCL161 provided “long-term anti-tumor protection” in mice, and combining LCL161 with an antibody against PD-1 could cure mice of MM.

“The drug, LCL161, was initially developed to promote tumor death,” said study author Marta Chesi, PhD, of Mayo Clinic Arizona in Scottsdale.

“However, we found that the drug does not kill tumor cells directly. Rather, it makes them more visible to the immune system that recognizes them as foreign invaders and eliminates them.”

Dr Chesi and her colleagues explained that the cellular inhibitors of apoptosis (cIAP) 1 and 2 have been identified as potential therapeutic targets in some cancers.

And LCL161 is a small-molecule IAP antagonist that induces tumor necrosis factor-mediated apoptosis in cancer cells. However, the investigators found that LCL161 was not directly cytotoxic to MM cells.

Instead, the drug upregulated tumor-cell-autonomous type I interferon signaling and induced an acute inflammatory response. This led to the activation of macrophages and dendritic cells, which prompted phagocytosis in MM cells.

Results in mice

The investigators first tested LCL161 alone (at a dose previously shown to be well-tolerated) in Vk*MYC transgenic mice with established MM.

The team said they observed a reduction in tumor burden that was comparable to that observed in response to drugs currently used to treat MM—carfilzomib, bortezomib, melphalan, cyclophosphamide, panobinostat, dexamethasone, and pomalidomide.

The investigators then tested the combination of LCL161 and a PD1 antibody in Vk12598-tumor-bearing mice.

The team said the combination was curative in all mice that completed 2 weeks of treatment. In fact, it was more effective than combination treatment with LCL161 and cyclophosphamide.

Results in patients

Dr Chesi and her colleagues conducted a phase 2 trial of LCL161 in 25 patients with relapsed/refractory MM. Patients could receive cyclophosphamide if they failed to respond or progressed after 8 weeks of treatment with LCL161 alone.

The patients’ median age was 68 (range, 47-90), and they had a median of 3 prior therapies (range, 1-6). Forty-four percent of patients had high-risk features, 28% had relapsed disease, and 72% had relapsed and refractory disease.

Four patients experienced grade 2 cytokine release syndrome when they received LCL161 at a dose of 1800 mg weekly, so the dose was lowered to 1200 mg.

None of the patients responded to single-agent LCL161. So 23 of the patients received 500 mg of weekly cyclophosphamide as well.

There was 1 complete response to the combination therapy, 1 very good partial response, 2 partial responses, and 1 minimal response. The median progression-free survival in these patients was 10 months.

Grade 3 adverse events included decrease in neutrophil count (28%), decrease in lymphocyte count (28%), anemia (24%), fatigue (16%), hyperglycemia (12%), syncope (12%), decrease in white blood cell count (12%), decrease in platelet count (8%), increase in lymphocyte count (8%), nausea (4%), vomiting (4%), diarrhea (4%), maculo-papular rash (4%), hypotension (4%), lung infection (4%), pain in extremity (4%), and urticaria (4%).

Grade 4 events included decrease in lymphocyte count (24%), decrease in neutrophil count (8%), decrease in white blood cell count (8%), hyperuricemia (4%), decrease in platelet count (4%), and sepsis (4%).

Based on these results, the investigators said the combination of LCL161 and cyclophosphamide is “an attractive platform for future trials,” and the same is true for LCL161 in combination with anti-PD1 therapy.

The phase 2 trial was sponsored by Mayo Clinic and the National Cancer Institute. Novartis provided LCL161 for this research and supported the trial. 

Lab mouse

An experimental drug called LCL161 stimulates the immune system to fight multiple myeloma (MM), according to research published in Nature Medicine.

Investigators said LCL161 exhibited “robust” activity in a transgenic myeloma mouse model and in patients with relapsed/refractory MM.

Single-agent LCL161 did not produce responses in MM patients, but patients did respond to treatment with LCL161 and cyclophosphamide.

The investigators also found that single-agent LCL161 provided “long-term anti-tumor protection” in mice, and combining LCL161 with an antibody against PD-1 could cure mice of MM.

“The drug, LCL161, was initially developed to promote tumor death,” said study author Marta Chesi, PhD, of Mayo Clinic Arizona in Scottsdale.

“However, we found that the drug does not kill tumor cells directly. Rather, it makes them more visible to the immune system that recognizes them as foreign invaders and eliminates them.”

Dr Chesi and her colleagues explained that the cellular inhibitors of apoptosis (cIAP) 1 and 2 have been identified as potential therapeutic targets in some cancers.

And LCL161 is a small-molecule IAP antagonist that induces tumor necrosis factor-mediated apoptosis in cancer cells. However, the investigators found that LCL161 was not directly cytotoxic to MM cells.

Instead, the drug upregulated tumor-cell-autonomous type I interferon signaling and induced an acute inflammatory response. This led to the activation of macrophages and dendritic cells, which prompted phagocytosis in MM cells.

Results in mice

The investigators first tested LCL161 alone (at a dose previously shown to be well-tolerated) in Vk*MYC transgenic mice with established MM.

The team said they observed a reduction in tumor burden that was comparable to that observed in response to drugs currently used to treat MM—carfilzomib, bortezomib, melphalan, cyclophosphamide, panobinostat, dexamethasone, and pomalidomide.

The investigators then tested the combination of LCL161 and a PD1 antibody in Vk12598-tumor-bearing mice.

The team said the combination was curative in all mice that completed 2 weeks of treatment. In fact, it was more effective than combination treatment with LCL161 and cyclophosphamide.

Results in patients

Dr Chesi and her colleagues conducted a phase 2 trial of LCL161 in 25 patients with relapsed/refractory MM. Patients could receive cyclophosphamide if they failed to respond or progressed after 8 weeks of treatment with LCL161 alone.

The patients’ median age was 68 (range, 47-90), and they had a median of 3 prior therapies (range, 1-6). Forty-four percent of patients had high-risk features, 28% had relapsed disease, and 72% had relapsed and refractory disease.

Four patients experienced grade 2 cytokine release syndrome when they received LCL161 at a dose of 1800 mg weekly, so the dose was lowered to 1200 mg.

None of the patients responded to single-agent LCL161. So 23 of the patients received 500 mg of weekly cyclophosphamide as well.

There was 1 complete response to the combination therapy, 1 very good partial response, 2 partial responses, and 1 minimal response. The median progression-free survival in these patients was 10 months.

Grade 3 adverse events included decrease in neutrophil count (28%), decrease in lymphocyte count (28%), anemia (24%), fatigue (16%), hyperglycemia (12%), syncope (12%), decrease in white blood cell count (12%), decrease in platelet count (8%), increase in lymphocyte count (8%), nausea (4%), vomiting (4%), diarrhea (4%), maculo-papular rash (4%), hypotension (4%), lung infection (4%), pain in extremity (4%), and urticaria (4%).

Grade 4 events included decrease in lymphocyte count (24%), decrease in neutrophil count (8%), decrease in white blood cell count (8%), hyperuricemia (4%), decrease in platelet count (4%), and sepsis (4%).

Based on these results, the investigators said the combination of LCL161 and cyclophosphamide is “an attractive platform for future trials,” and the same is true for LCL161 in combination with anti-PD1 therapy.

The phase 2 trial was sponsored by Mayo Clinic and the National Cancer Institute. Novartis provided LCL161 for this research and supported the trial. 

Photo from UAB Hospital

A retrospective study indicates that a high transfusion ratio of fresh frozen plasma (FFP) to red blood cells (RBCs) may not be beneficial for surgical patients who do not have traumatic injuries.

In fact, the data suggest a high FFP:RBC ratio may be harmful for some of these patients.

“The strategy of giving patients requiring massive transfusion greater amounts of fresh frozen plasma, relative to the amount of red blood cells, has spilled over from trauma patients into unstudied patient populations,” said Daniel Dante Yeh, MD, of Massachusetts General Hospital in Boston.

“This may have important consequences, since our results suggest that certain populations may be harmed by this practice.”

Dr Yeh and his colleagues reported these results in JAMA Surgery.

The researchers reviewed all massive transfusions performed at Massachusetts General Hospital from January 1, 2009, through December 31, 2012.

A transfusion qualified as “massive” if at least 10 units of RBCs were given in the first 24 hours after a patient’s admission to the operating room, emergency department, or intensive care unit.

The researchers included all patients who received massive transfusions during the study period and survived more than 30 minutes after hospital arrival.

According to these criteria, there were 865 massive transfusion events. The total number of units transfused was 16,569 for RBCs, 13,933 for FFP, 5228 for cryoprecipitate, and 22,635 for platelets.

A majority of the massive transfusion recipients were not trauma patients (88.7%). Most of the transfusions were performed for intraoperative bleeding (62.9%).

The researchers compared patients who survived at least 30 days from hospital arrival to those who did not. Patients who died were older and received more RBCs (P<0.001), FFP (P<0.001), and cryoprecipitate (P=0.008).

However, the FFP:RBC ratios of survivors and non-survivors were similar. The median was 1:1.5 for survivors and 1:1.4 for non-survivors (P=0.43).

Patients without trauma

Among all non-trauma patients (n=767), there was no significant difference in the adjusted odds ratio (aOR) for 30-day mortality between patients who received a transfusion with a high FFP:RBC ratio and those who received one with a low FFP:RBC ratio (aOR=1.10, P=0.65). (The analysis was adjusted for patient age and total units of RBCs transfused.)

Among patients undergoing vascular surgery, those who received transfusions with a high FFP:RBC ratio were less likely to die within 30 days than those who received transfusions with a low FFP:RBC ratio (aOR=0.16, P=0.02).

However, among general surgery and medical service patients, those receiving transfusions with a high FFP:RBC ratio were more likely to die within 30 days than those receiving low-ratio transfusions. The aOR was 4.27 (P=0.02) for general surgery and 8.48 (P=0.02) for medicine.

“Finding evidence of increased mortality in some patients was surprising because that is directly contradictory to what is expected and intended,” Dr Yeh said. “Avoiding unnecessary FFP transfusion is important because there have been reports that associated the use of excess FFP with worse outcomes among patients that required less-than-massive transfusions.”

“Because our study is retrospective, it can only point to the need for further research. Ratio-based transfusion has been studied in trauma patients, most recently in a landmark, multicenter, randomized study called the PROPRR trial. Similar studies now need to be performed in non-trauma patients before the approach can be accepted as standard practice here at MGH [Massachusetts General Hospital] and elsewhere.”

Photo from UAB Hospital

A retrospective study indicates that a high transfusion ratio of fresh frozen plasma (FFP) to red blood cells (RBCs) may not be beneficial for surgical patients who do not have traumatic injuries.

In fact, the data suggest a high FFP:RBC ratio may be harmful for some of these patients.

“The strategy of giving patients requiring massive transfusion greater amounts of fresh frozen plasma, relative to the amount of red blood cells, has spilled over from trauma patients into unstudied patient populations,” said Daniel Dante Yeh, MD, of Massachusetts General Hospital in Boston.

“This may have important consequences, since our results suggest that certain populations may be harmed by this practice.”

Dr Yeh and his colleagues reported these results in JAMA Surgery.

The researchers reviewed all massive transfusions performed at Massachusetts General Hospital from January 1, 2009, through December 31, 2012.

A transfusion qualified as “massive” if at least 10 units of RBCs were given in the first 24 hours after a patient’s admission to the operating room, emergency department, or intensive care unit.

The researchers included all patients who received massive transfusions during the study period and survived more than 30 minutes after hospital arrival.

According to these criteria, there were 865 massive transfusion events. The total number of units transfused was 16,569 for RBCs, 13,933 for FFP, 5228 for cryoprecipitate, and 22,635 for platelets.

A majority of the massive transfusion recipients were not trauma patients (88.7%). Most of the transfusions were performed for intraoperative bleeding (62.9%).

The researchers compared patients who survived at least 30 days from hospital arrival to those who did not. Patients who died were older and received more RBCs (P<0.001), FFP (P<0.001), and cryoprecipitate (P=0.008).

However, the FFP:RBC ratios of survivors and non-survivors were similar. The median was 1:1.5 for survivors and 1:1.4 for non-survivors (P=0.43).

Patients without trauma

Among all non-trauma patients (n=767), there was no significant difference in the adjusted odds ratio (aOR) for 30-day mortality between patients who received a transfusion with a high FFP:RBC ratio and those who received one with a low FFP:RBC ratio (aOR=1.10, P=0.65). (The analysis was adjusted for patient age and total units of RBCs transfused.)

Among patients undergoing vascular surgery, those who received transfusions with a high FFP:RBC ratio were less likely to die within 30 days than those who received transfusions with a low FFP:RBC ratio (aOR=0.16, P=0.02).

However, among general surgery and medical service patients, those receiving transfusions with a high FFP:RBC ratio were more likely to die within 30 days than those receiving low-ratio transfusions. The aOR was 4.27 (P=0.02) for general surgery and 8.48 (P=0.02) for medicine.

“Finding evidence of increased mortality in some patients was surprising because that is directly contradictory to what is expected and intended,” Dr Yeh said. “Avoiding unnecessary FFP transfusion is important because there have been reports that associated the use of excess FFP with worse outcomes among patients that required less-than-massive transfusions.”

“Because our study is retrospective, it can only point to the need for further research. Ratio-based transfusion has been studied in trauma patients, most recently in a landmark, multicenter, randomized study called the PROPRR trial. Similar studies now need to be performed in non-trauma patients before the approach can be accepted as standard practice here at MGH [Massachusetts General Hospital] and elsewhere.”

Photo from UAB Hospital

A retrospective study indicates that a high transfusion ratio of fresh frozen plasma (FFP) to red blood cells (RBCs) may not be beneficial for surgical patients who do not have traumatic injuries.

In fact, the data suggest a high FFP:RBC ratio may be harmful for some of these patients.

“The strategy of giving patients requiring massive transfusion greater amounts of fresh frozen plasma, relative to the amount of red blood cells, has spilled over from trauma patients into unstudied patient populations,” said Daniel Dante Yeh, MD, of Massachusetts General Hospital in Boston.

“This may have important consequences, since our results suggest that certain populations may be harmed by this practice.”

Dr Yeh and his colleagues reported these results in JAMA Surgery.

The researchers reviewed all massive transfusions performed at Massachusetts General Hospital from January 1, 2009, through December 31, 2012.

A transfusion qualified as “massive” if at least 10 units of RBCs were given in the first 24 hours after a patient’s admission to the operating room, emergency department, or intensive care unit.

The researchers included all patients who received massive transfusions during the study period and survived more than 30 minutes after hospital arrival.

According to these criteria, there were 865 massive transfusion events. The total number of units transfused was 16,569 for RBCs, 13,933 for FFP, 5228 for cryoprecipitate, and 22,635 for platelets.

A majority of the massive transfusion recipients were not trauma patients (88.7%). Most of the transfusions were performed for intraoperative bleeding (62.9%).

The researchers compared patients who survived at least 30 days from hospital arrival to those who did not. Patients who died were older and received more RBCs (P<0.001), FFP (P<0.001), and cryoprecipitate (P=0.008).

However, the FFP:RBC ratios of survivors and non-survivors were similar. The median was 1:1.5 for survivors and 1:1.4 for non-survivors (P=0.43).

Patients without trauma

Among all non-trauma patients (n=767), there was no significant difference in the adjusted odds ratio (aOR) for 30-day mortality between patients who received a transfusion with a high FFP:RBC ratio and those who received one with a low FFP:RBC ratio (aOR=1.10, P=0.65). (The analysis was adjusted for patient age and total units of RBCs transfused.)

Among patients undergoing vascular surgery, those who received transfusions with a high FFP:RBC ratio were less likely to die within 30 days than those who received transfusions with a low FFP:RBC ratio (aOR=0.16, P=0.02).

However, among general surgery and medical service patients, those receiving transfusions with a high FFP:RBC ratio were more likely to die within 30 days than those receiving low-ratio transfusions. The aOR was 4.27 (P=0.02) for general surgery and 8.48 (P=0.02) for medicine.

“Finding evidence of increased mortality in some patients was surprising because that is directly contradictory to what is expected and intended,” Dr Yeh said. “Avoiding unnecessary FFP transfusion is important because there have been reports that associated the use of excess FFP with worse outcomes among patients that required less-than-massive transfusions.”

“Because our study is retrospective, it can only point to the need for further research. Ratio-based transfusion has been studied in trauma patients, most recently in a landmark, multicenter, randomized study called the PROPRR trial. Similar studies now need to be performed in non-trauma patients before the approach can be accepted as standard practice here at MGH [Massachusetts General Hospital] and elsewhere.”

Image by Lance Liotta

The US Food and Drug Administration (FDA) has lifted the clinical hold placed on 3 trials of vadastuximab talirine (SGN-CD33A), an antibody-drug conjugate targeting CD33, in acute myeloid leukemia (AML).

Last December, 1 trial was placed on full clinical hold (enrollment was halted and no further dosing of subjects was allowed), and 2 were placed on partial hold (enrollment was halted, but existing patients could continue treatment with re-consent).

All 3 of the holds were due to the potential risk of hepatotoxicity in patients who underwent allogeneic hematopoietic stem cell transplant (HSCT) before or after treatment with vadastuximab talirine.

In particular, the holds were in response to 6 cases of hepatotoxicity, including several cases of veno-occlusive disease (VOD), with 4 fatal events.

At the time the holds were announced, Seattle Genetics, Inc., the company developing vadastuximab talirine, said it was working with the FDA to determine whether there is an association between hepatotoxicity and treatment with the drug.

The company analyzed data from more than 350 patients treated with vadastuximab talirine and found no such association.

The rate of VOD they observed was “within the background rate of VOD in AML patients receiving allo-transplant,” according to Clay B. Siegall, PhD, president, chief executive officer, and chairman of the board at Seattle Genetics.

Dr Siegall said the company would not disclose the exact rate of VOD in these trials.

Resuming trials

As Seattle Genetics found no evidence to suggest that vadastuximab talirine increased the risk of hepatotoxicity, the FDA lifted the clinical holds on all 3 trials. The 2 trials placed on partial hold will continue, but the trial placed on full hold will not.

One of the trials that will continue is a phase 1 study of vadastuximab talirine alone and in combination with hypomethylating agents in both newly diagnosed and relapsed AML patients.

The other trial is a phase 1 study of vadastuximab talirine in combination with 7+3 chemotherapy in newly diagnosed, younger AML patients. (Results from this trial were presented at the 2016 ASH Annual Meeting.)

Cancelled trial

The trial that will not resume is a phase 1/2 study of vadastuximab talirine monotherapy pre- and post-allogeneic HSCT in patients with relapsed, chemo-resistant AML.

Seattle Genetics said it will not continue with this trial because of the challenges of developing therapies in this specific setting.

“It’s a very small group of patients, and we’re going to focus on the 3 biggest groups of patients [older and younger patients newly diagnosed with AML and patients with myelodysplastic syndromes] so we can really impact AML in the biggest way,” Dr Siegall said.

He noted that this decision does not prevent patients from undergoing HSCT after receiving vadastuximab talirine.

In the phase 1/2 trial, patients received vadastuximab talirine directly before HSCT, a practice that will not continue. However, patients can undergo HSCT as long as the transplant doesn’t occur immediately after treatment with vadastuximab talirine.

Moving forward

Two other trials of vadastuximab talirine were not affected by the clinical holds and have continued to enroll patients.

One is CASCADE, a randomized, phase 3 trial of vadastuximab talirine as front-line therapy in older AML patients. The other is a phase 1/2 trial of vadastuximab talirine as front-line therapy in patients with myelodysplastic syndromes.

Seattle Genetics is also planning to begin a randomized, phase 2 trial comparing 7+3 chemotherapy alone to 7+3 in combination with vadastuximab talirine in younger patients with previously untreated AML. The company plans to start the trial later this year.

Going forward, additional risk mitigation measures will be implemented in all vadastuximab talirine studies, including revised eligibility criteria and stopping rules for VOD.

Specifically, trials will not be stopped if the incidence of VOD is considered within the normal range, and an adjudication committee consisting of 2 experts will be tasked with verifying reports of VOD.

In addition, patients with liver cirrhosis due to alcohol abuse are no longer eligible for trials of vadastuximab talirine.

Image by Lance Liotta

The US Food and Drug Administration (FDA) has lifted the clinical hold placed on 3 trials of vadastuximab talirine (SGN-CD33A), an antibody-drug conjugate targeting CD33, in acute myeloid leukemia (AML).

Last December, 1 trial was placed on full clinical hold (enrollment was halted and no further dosing of subjects was allowed), and 2 were placed on partial hold (enrollment was halted, but existing patients could continue treatment with re-consent).

All 3 of the holds were due to the potential risk of hepatotoxicity in patients who underwent allogeneic hematopoietic stem cell transplant (HSCT) before or after treatment with vadastuximab talirine.

In particular, the holds were in response to 6 cases of hepatotoxicity, including several cases of veno-occlusive disease (VOD), with 4 fatal events.

At the time the holds were announced, Seattle Genetics, Inc., the company developing vadastuximab talirine, said it was working with the FDA to determine whether there is an association between hepatotoxicity and treatment with the drug.

The company analyzed data from more than 350 patients treated with vadastuximab talirine and found no such association.

The rate of VOD they observed was “within the background rate of VOD in AML patients receiving allo-transplant,” according to Clay B. Siegall, PhD, president, chief executive officer, and chairman of the board at Seattle Genetics.

Dr Siegall said the company would not disclose the exact rate of VOD in these trials.

Resuming trials

As Seattle Genetics found no evidence to suggest that vadastuximab talirine increased the risk of hepatotoxicity, the FDA lifted the clinical holds on all 3 trials. The 2 trials placed on partial hold will continue, but the trial placed on full hold will not.

One of the trials that will continue is a phase 1 study of vadastuximab talirine alone and in combination with hypomethylating agents in both newly diagnosed and relapsed AML patients.

The other trial is a phase 1 study of vadastuximab talirine in combination with 7+3 chemotherapy in newly diagnosed, younger AML patients. (Results from this trial were presented at the 2016 ASH Annual Meeting.)

Cancelled trial

The trial that will not resume is a phase 1/2 study of vadastuximab talirine monotherapy pre- and post-allogeneic HSCT in patients with relapsed, chemo-resistant AML.

Seattle Genetics said it will not continue with this trial because of the challenges of developing therapies in this specific setting.

“It’s a very small group of patients, and we’re going to focus on the 3 biggest groups of patients [older and younger patients newly diagnosed with AML and patients with myelodysplastic syndromes] so we can really impact AML in the biggest way,” Dr Siegall said.

He noted that this decision does not prevent patients from undergoing HSCT after receiving vadastuximab talirine.

In the phase 1/2 trial, patients received vadastuximab talirine directly before HSCT, a practice that will not continue. However, patients can undergo HSCT as long as the transplant doesn’t occur immediately after treatment with vadastuximab talirine.

Moving forward

Two other trials of vadastuximab talirine were not affected by the clinical holds and have continued to enroll patients.

One is CASCADE, a randomized, phase 3 trial of vadastuximab talirine as front-line therapy in older AML patients. The other is a phase 1/2 trial of vadastuximab talirine as front-line therapy in patients with myelodysplastic syndromes.

Seattle Genetics is also planning to begin a randomized, phase 2 trial comparing 7+3 chemotherapy alone to 7+3 in combination with vadastuximab talirine in younger patients with previously untreated AML. The company plans to start the trial later this year.

Going forward, additional risk mitigation measures will be implemented in all vadastuximab talirine studies, including revised eligibility criteria and stopping rules for VOD.

Specifically, trials will not be stopped if the incidence of VOD is considered within the normal range, and an adjudication committee consisting of 2 experts will be tasked with verifying reports of VOD.

In addition, patients with liver cirrhosis due to alcohol abuse are no longer eligible for trials of vadastuximab talirine.

Image by Lance Liotta

The US Food and Drug Administration (FDA) has lifted the clinical hold placed on 3 trials of vadastuximab talirine (SGN-CD33A), an antibody-drug conjugate targeting CD33, in acute myeloid leukemia (AML).

Last December, 1 trial was placed on full clinical hold (enrollment was halted and no further dosing of subjects was allowed), and 2 were placed on partial hold (enrollment was halted, but existing patients could continue treatment with re-consent).

All 3 of the holds were due to the potential risk of hepatotoxicity in patients who underwent allogeneic hematopoietic stem cell transplant (HSCT) before or after treatment with vadastuximab talirine.

In particular, the holds were in response to 6 cases of hepatotoxicity, including several cases of veno-occlusive disease (VOD), with 4 fatal events.

At the time the holds were announced, Seattle Genetics, Inc., the company developing vadastuximab talirine, said it was working with the FDA to determine whether there is an association between hepatotoxicity and treatment with the drug.

The company analyzed data from more than 350 patients treated with vadastuximab talirine and found no such association.

The rate of VOD they observed was “within the background rate of VOD in AML patients receiving allo-transplant,” according to Clay B. Siegall, PhD, president, chief executive officer, and chairman of the board at Seattle Genetics.

Dr Siegall said the company would not disclose the exact rate of VOD in these trials.

Resuming trials

As Seattle Genetics found no evidence to suggest that vadastuximab talirine increased the risk of hepatotoxicity, the FDA lifted the clinical holds on all 3 trials. The 2 trials placed on partial hold will continue, but the trial placed on full hold will not.

One of the trials that will continue is a phase 1 study of vadastuximab talirine alone and in combination with hypomethylating agents in both newly diagnosed and relapsed AML patients.

The other trial is a phase 1 study of vadastuximab talirine in combination with 7+3 chemotherapy in newly diagnosed, younger AML patients. (Results from this trial were presented at the 2016 ASH Annual Meeting.)

Cancelled trial

The trial that will not resume is a phase 1/2 study of vadastuximab talirine monotherapy pre- and post-allogeneic HSCT in patients with relapsed, chemo-resistant AML.

Seattle Genetics said it will not continue with this trial because of the challenges of developing therapies in this specific setting.

“It’s a very small group of patients, and we’re going to focus on the 3 biggest groups of patients [older and younger patients newly diagnosed with AML and patients with myelodysplastic syndromes] so we can really impact AML in the biggest way,” Dr Siegall said.

He noted that this decision does not prevent patients from undergoing HSCT after receiving vadastuximab talirine.

In the phase 1/2 trial, patients received vadastuximab talirine directly before HSCT, a practice that will not continue. However, patients can undergo HSCT as long as the transplant doesn’t occur immediately after treatment with vadastuximab talirine.

Moving forward

Two other trials of vadastuximab talirine were not affected by the clinical holds and have continued to enroll patients.

One is CASCADE, a randomized, phase 3 trial of vadastuximab talirine as front-line therapy in older AML patients. The other is a phase 1/2 trial of vadastuximab talirine as front-line therapy in patients with myelodysplastic syndromes.

Seattle Genetics is also planning to begin a randomized, phase 2 trial comparing 7+3 chemotherapy alone to 7+3 in combination with vadastuximab talirine in younger patients with previously untreated AML. The company plans to start the trial later this year.

Going forward, additional risk mitigation measures will be implemented in all vadastuximab talirine studies, including revised eligibility criteria and stopping rules for VOD.

Specifically, trials will not be stopped if the incidence of VOD is considered within the normal range, and an adjudication committee consisting of 2 experts will be tasked with verifying reports of VOD.

In addition, patients with liver cirrhosis due to alcohol abuse are no longer eligible for trials of vadastuximab talirine.

President Trump’s revised executive order blocking travelers from six Muslim-majority countries from entering the United States could land a damaging blow to global cooperation in scientific research and could impede assemblies of the world’s top medical experts.

The March 6 executive order bars citizens of Iran, Libya, Somalia, Sudan, Syria, and Yemen from obtaining visas for 90 days and blocks refugees from those countries from entering the United States for 120 days. The measure, which takes effect March 16, supersedes President Trump’s original Jan. 27 travel ban. The new order exempts citizens of the six countries who are legal permanent U.S. residents or who have current visas.

The policy could have detrimental effects on future collaboration between U.S. and international scientists and may ultimately endanger the health and well-being of patients, said International Antiviral Society–U.S.A. executive director and president Donna M. Jacobsen, regarding the original travel ban.

There is “serious reason for concern” that the policy will dissuade scientists and researchers “from traveling to the [United States] in the future overall and sharing their work with colleagues here,” she said.

Thousands of academics from around the world, including physicians, researchers, and professors, have vowed to boycott U.S.-based conferences in light of the Trump administration policy. A Google Docs petition started shortly after the original ban was announced garnered more than 5,000 signatures by professionals acting in solidarity with those affected by the travel restrictions. The academicians who signed the petition said they would not attend international conferences in the United States until those restricted from participating could rejoin their colleagues and freely share their ideas.

The new executive order comes nearly 2 months after President Trump’s original travel ban caused nationwide protests and led to a series of legal challenges. The states of Washington and Minnesota, which sued President Trump over his original ban, argued that such a ban harms the teaching and research missions of their universities and prevents students and faculty from traveling for research and academic collaboration. In addition, the executive order restricts universities from hiring attractive candidates from countries affected by the ban, state officials said. A federal court temporarily blocked the original travel ban on Feb. 3, a decision upheld by the 9^th U.S. Circuit Court of Appeals on Feb. 9. The circuit judges said the plaintiffs were likely to succeed in their arguments and that the president had demonstrated no evidence that his executive order advances national security.

The new executive order excludes Iraq and also removes language that had indefinitely banned Syrian refugees. In a March 6 memorandum, the White House said the purpose of the ban is to prevent “foreign nationals who may aid, support, or commit violent, criminal, or terrorist acts,” while the administration enhances the screening and vetting protocols and procedures for granting visas and admission to the United States.

“This nation cannot delay the immediate implementation of additional heightened screening and vetting protocols and procedures for issuing visas to ensure that we strengthen the safety and security of our country,” the memo states.

agallegos@frontlinemedcom.com

On Twitter @legal_med

President Trump’s revised executive order blocking travelers from six Muslim-majority countries from entering the United States could land a damaging blow to global cooperation in scientific research and could impede assemblies of the world’s top medical experts.

The March 6 executive order bars citizens of Iran, Libya, Somalia, Sudan, Syria, and Yemen from obtaining visas for 90 days and blocks refugees from those countries from entering the United States for 120 days. The measure, which takes effect March 16, supersedes President Trump’s original Jan. 27 travel ban. The new order exempts citizens of the six countries who are legal permanent U.S. residents or who have current visas.

The policy could have detrimental effects on future collaboration between U.S. and international scientists and may ultimately endanger the health and well-being of patients, said International Antiviral Society–U.S.A. executive director and president Donna M. Jacobsen, regarding the original travel ban.

There is “serious reason for concern” that the policy will dissuade scientists and researchers “from traveling to the [United States] in the future overall and sharing their work with colleagues here,” she said.

Thousands of academics from around the world, including physicians, researchers, and professors, have vowed to boycott U.S.-based conferences in light of the Trump administration policy. A Google Docs petition started shortly after the original ban was announced garnered more than 5,000 signatures by professionals acting in solidarity with those affected by the travel restrictions. The academicians who signed the petition said they would not attend international conferences in the United States until those restricted from participating could rejoin their colleagues and freely share their ideas.

The new executive order comes nearly 2 months after President Trump’s original travel ban caused nationwide protests and led to a series of legal challenges. The states of Washington and Minnesota, which sued President Trump over his original ban, argued that such a ban harms the teaching and research missions of their universities and prevents students and faculty from traveling for research and academic collaboration. In addition, the executive order restricts universities from hiring attractive candidates from countries affected by the ban, state officials said. A federal court temporarily blocked the original travel ban on Feb. 3, a decision upheld by the 9^th U.S. Circuit Court of Appeals on Feb. 9. The circuit judges said the plaintiffs were likely to succeed in their arguments and that the president had demonstrated no evidence that his executive order advances national security.

The new executive order excludes Iraq and also removes language that had indefinitely banned Syrian refugees. In a March 6 memorandum, the White House said the purpose of the ban is to prevent “foreign nationals who may aid, support, or commit violent, criminal, or terrorist acts,” while the administration enhances the screening and vetting protocols and procedures for granting visas and admission to the United States.

“This nation cannot delay the immediate implementation of additional heightened screening and vetting protocols and procedures for issuing visas to ensure that we strengthen the safety and security of our country,” the memo states.

agallegos@frontlinemedcom.com

On Twitter @legal_med

President Trump’s revised executive order blocking travelers from six Muslim-majority countries from entering the United States could land a damaging blow to global cooperation in scientific research and could impede assemblies of the world’s top medical experts.

The March 6 executive order bars citizens of Iran, Libya, Somalia, Sudan, Syria, and Yemen from obtaining visas for 90 days and blocks refugees from those countries from entering the United States for 120 days. The measure, which takes effect March 16, supersedes President Trump’s original Jan. 27 travel ban. The new order exempts citizens of the six countries who are legal permanent U.S. residents or who have current visas.

The policy could have detrimental effects on future collaboration between U.S. and international scientists and may ultimately endanger the health and well-being of patients, said International Antiviral Society–U.S.A. executive director and president Donna M. Jacobsen, regarding the original travel ban.

There is “serious reason for concern” that the policy will dissuade scientists and researchers “from traveling to the [United States] in the future overall and sharing their work with colleagues here,” she said.

Thousands of academics from around the world, including physicians, researchers, and professors, have vowed to boycott U.S.-based conferences in light of the Trump administration policy. A Google Docs petition started shortly after the original ban was announced garnered more than 5,000 signatures by professionals acting in solidarity with those affected by the travel restrictions. The academicians who signed the petition said they would not attend international conferences in the United States until those restricted from participating could rejoin their colleagues and freely share their ideas.

The new executive order comes nearly 2 months after President Trump’s original travel ban caused nationwide protests and led to a series of legal challenges. The states of Washington and Minnesota, which sued President Trump over his original ban, argued that such a ban harms the teaching and research missions of their universities and prevents students and faculty from traveling for research and academic collaboration. In addition, the executive order restricts universities from hiring attractive candidates from countries affected by the ban, state officials said. A federal court temporarily blocked the original travel ban on Feb. 3, a decision upheld by the 9^th U.S. Circuit Court of Appeals on Feb. 9. The circuit judges said the plaintiffs were likely to succeed in their arguments and that the president had demonstrated no evidence that his executive order advances national security.

The new executive order excludes Iraq and also removes language that had indefinitely banned Syrian refugees. In a March 6 memorandum, the White House said the purpose of the ban is to prevent “foreign nationals who may aid, support, or commit violent, criminal, or terrorist acts,” while the administration enhances the screening and vetting protocols and procedures for granting visas and admission to the United States.

“This nation cannot delay the immediate implementation of additional heightened screening and vetting protocols and procedures for issuing visas to ensure that we strengthen the safety and security of our country,” the memo states.

agallegos@frontlinemedcom.com

On Twitter @legal_med

Efforts to delay or prevent rheumatoid arthritis (RA) in individuals at high risk for the disease received a boost from the findings of a subgroup analysis of an older Dutch prevention trial involving methotrexate that were published recently in Arthritis & Rheumatology.

However, while the 22-patient subgroup analysis of the 2007 trial, called PROMPT (Probable RA: Methotrexate Versus Placebo Treatment), showed that 1 year of methotrexate prevented the development of rheumatoid arthritis in significantly more individuals at high risk for the disease than did placebo, hindsight has shown that most of these high-risk individuals actually had RA at baseline as defined by the 2010 American College or Rheumatology/European League Against Rheumatism classification criteria.

Efforts to delay or prevent rheumatoid arthritis (RA) in individuals at high risk for the disease received a boost from the findings of a subgroup analysis of an older Dutch prevention trial involving methotrexate that were published recently in Arthritis & Rheumatology.

However, while the 22-patient subgroup analysis of the 2007 trial, called PROMPT (Probable RA: Methotrexate Versus Placebo Treatment), showed that 1 year of methotrexate prevented the development of rheumatoid arthritis in significantly more individuals at high risk for the disease than did placebo, hindsight has shown that most of these high-risk individuals actually had RA at baseline as defined by the 2010 American College or Rheumatology/European League Against Rheumatism classification criteria.

Efforts to delay or prevent rheumatoid arthritis (RA) in individuals at high risk for the disease received a boost from the findings of a subgroup analysis of an older Dutch prevention trial involving methotrexate that were published recently in Arthritis & Rheumatology.

However, while the 22-patient subgroup analysis of the 2007 trial, called PROMPT (Probable RA: Methotrexate Versus Placebo Treatment), showed that 1 year of methotrexate prevented the development of rheumatoid arthritis in significantly more individuals at high risk for the disease than did placebo, hindsight has shown that most of these high-risk individuals actually had RA at baseline as defined by the 2010 American College or Rheumatology/European League Against Rheumatism classification criteria.

The Republican plan to replace the Affordable Care Act cleared the first legislative hurdle when two house committees passed language that would repeal revenue provisions of the Affordable Care Act and lay the foundation for replacing the health care reform law.

The House Ways and Means Committee–approved legislation would eliminate the individual mandate in favor of allowing insurance companies to penalize individuals by up to 30% of premiums for lapses in coverage and would repeal taxes on high-cost health plans (Cadillac tax), over-the-counter and prescription medications, health savings accounts, tanning, investment, and on health insurers.

franckreporter/Thinkstock

gtwachtman@frontlinemedcom.com
 

The Republican plan to replace the Affordable Care Act cleared the first legislative hurdle when two house committees passed language that would repeal revenue provisions of the Affordable Care Act and lay the foundation for replacing the health care reform law.

The House Ways and Means Committee–approved legislation would eliminate the individual mandate in favor of allowing insurance companies to penalize individuals by up to 30% of premiums for lapses in coverage and would repeal taxes on high-cost health plans (Cadillac tax), over-the-counter and prescription medications, health savings accounts, tanning, investment, and on health insurers.

franckreporter/Thinkstock

gtwachtman@frontlinemedcom.com
 

The Republican plan to replace the Affordable Care Act cleared the first legislative hurdle when two house committees passed language that would repeal revenue provisions of the Affordable Care Act and lay the foundation for replacing the health care reform law.

The House Ways and Means Committee–approved legislation would eliminate the individual mandate in favor of allowing insurance companies to penalize individuals by up to 30% of premiums for lapses in coverage and would repeal taxes on high-cost health plans (Cadillac tax), over-the-counter and prescription medications, health savings accounts, tanning, investment, and on health insurers.

franckreporter/Thinkstock

gtwachtman@frontlinemedcom.com
 

Editor’s note: “Everything We Say and Do” is an informational series developed by the Society of Hospital Medicine’s Patient Experience Committee to provide readers with thoughtful and actionable tactics that have great potential to positively impact patients’ experience of care.

Patient and Family Advisory Councils (PFACs) provide a tool for understanding the patient perspective and are utilized nationwide. These councils, typically consisting of former and current patients and/or their family members, meet on a regular basis to advise provider communities on a wide range of care-related matters. At my institution, Beth Israel Deaconess Medical Center, our PFAC has weighed in on a wide range of issues, such as how to conduct effective nursing rounds and the best methods for supporting patients with disabilities.

Most recently, we have utilized an innovative approach to both understanding the patient experience and capitalizing on the expertise of our PFAC members. Modeled after a program developed at the Dartmouth-Hitchcock Medical Center, we have trained members of our PFAC to interview inpatients at the bedside about their experience. Time-sensitive information is immediately reported back to the nurse manager, who responds with real-time solutions. Oftentimes, problems can be easily resolved using the right communication, or just providing the “listening ear” of someone to whom the patient relates.

Amber Moore, MD, MPH, is a hospitalist at Beth Israel Deaconess Medical Center, and instructor of medicine, Harvard Medical School.

Editor’s note: “Everything We Say and Do” is an informational series developed by the Society of Hospital Medicine’s Patient Experience Committee to provide readers with thoughtful and actionable tactics that have great potential to positively impact patients’ experience of care.

Patient and Family Advisory Councils (PFACs) provide a tool for understanding the patient perspective and are utilized nationwide. These councils, typically consisting of former and current patients and/or their family members, meet on a regular basis to advise provider communities on a wide range of care-related matters. At my institution, Beth Israel Deaconess Medical Center, our PFAC has weighed in on a wide range of issues, such as how to conduct effective nursing rounds and the best methods for supporting patients with disabilities.

Most recently, we have utilized an innovative approach to both understanding the patient experience and capitalizing on the expertise of our PFAC members. Modeled after a program developed at the Dartmouth-Hitchcock Medical Center, we have trained members of our PFAC to interview inpatients at the bedside about their experience. Time-sensitive information is immediately reported back to the nurse manager, who responds with real-time solutions. Oftentimes, problems can be easily resolved using the right communication, or just providing the “listening ear” of someone to whom the patient relates.

Amber Moore, MD, MPH, is a hospitalist at Beth Israel Deaconess Medical Center, and instructor of medicine, Harvard Medical School.

Editor’s note: “Everything We Say and Do” is an informational series developed by the Society of Hospital Medicine’s Patient Experience Committee to provide readers with thoughtful and actionable tactics that have great potential to positively impact patients’ experience of care.

Patient and Family Advisory Councils (PFACs) provide a tool for understanding the patient perspective and are utilized nationwide. These councils, typically consisting of former and current patients and/or their family members, meet on a regular basis to advise provider communities on a wide range of care-related matters. At my institution, Beth Israel Deaconess Medical Center, our PFAC has weighed in on a wide range of issues, such as how to conduct effective nursing rounds and the best methods for supporting patients with disabilities.

Most recently, we have utilized an innovative approach to both understanding the patient experience and capitalizing on the expertise of our PFAC members. Modeled after a program developed at the Dartmouth-Hitchcock Medical Center, we have trained members of our PFAC to interview inpatients at the bedside about their experience. Time-sensitive information is immediately reported back to the nurse manager, who responds with real-time solutions. Oftentimes, problems can be easily resolved using the right communication, or just providing the “listening ear” of someone to whom the patient relates.

Amber Moore, MD, MPH, is a hospitalist at Beth Israel Deaconess Medical Center, and instructor of medicine, Harvard Medical School.