CORONADO, CALIF. – Some patients with treatment-refractory obstructive sleep apnea may be candidates for upper airway stimulation, though those with complete concentric palatal collapse may not respond, according to Dr. Marion Boyd Gillespie.

“There’s been sound research showing that patients with obstructive sleep apnea have reduced neural tone, so it may not be due to fat in the tongue; some of it may have to do with reduced neural tone,” Dr. Gillespie, who directs the snoring clinics at the Medical University of South Carolina, Charleston, said at the Triological Society’s Combined Sections Meeting. “During these apneic events, there’s a reduction in the neural tone of the genioglossus muscle, which is the main dilator of the upper airway. With upper airway stimulation, we’re trying to account for that loss of neural tone by providing more neural impulse to these muscle groups that perform the dilator functions.”

In 2014 the Food and Drug Administration cleared an upper airway stimulation system manufactured by Inspire Medical Systems, a pacemakerlike device that’s implanted in the subclavicular space. The system features a stimulator lead that attaches to the right hypoglossal nerve and a sensing lead that goes between the external and internal intercostal muscles to detect breathing. “That allows the device to know when in the phase of respiration to fire,” said Dr. Gillespie, professor of otolaryngology–head and neck surgery at the university. “The sensing lead detects the respiratory wave, and the stimulatory lead starts stimulation at the end of expiration, because that’s when the airway is in its most collapsible state. It continues about two-thirds of the way through the inspiratory cycle to keep the airway open.”

Titration of the device is very similar to continuous positive airway pressure, he continued. Once implanted, the patient “will go back to the sleep lab where a tech who’s trained in the device will ramp up stimulation until observed apneas and hypopneas are adequately reduced. You would think that isolated stimulation of the hypoglossal nerve would only open up the airway at the level of the tongue. However, our initial investigation showed that there is dilation at the velopharynx as well,” Dr. Gillespie said. By moving the tongue out of the posterior airway, “you’re moving the dorsum of the tongue away from the velopharynx. You’re also getting active traction on the palatoglossal fold,” he added.

Results of the initial trial of the system in 126 patients with a mean body mass index of 28.4 kg/m² were published last year (N. Engl. J. Med. 2014;370:139-49). At 12 months of follow-up, patients experienced a 68% overall reduction in their apnea-hypopnea index (AHI) score, from a preoperative mean of 29 to a postoperative mean of 9. In addition, patients had a 70% overall reduction in their oxygen desaturation index (ODI). The researchers also observed normalization of patient-based outcomes, with improvement in the Functional Outcomes of Sleep Questionnaire score and reduction of the Epworth Sleepiness Scale score to a level of 10 on average. “We also saw a reduction of snoring,” said Dr. Gillespie, who was a member of the research team. “Snoring went from 72% of patients having severe, annoying snoring to the point where a bed partner leaves the room, to 15% postoperatively.” Even so, 96% of patients who had a previous history of uvulopalatopharyngoplasty (UPPP) or laser-assisted uvulopalatoplasty (LAUP) still had tongue-based collapse after 12 months of follow-up. “But we found that their response to this therapy was just as good as people who had never had a UPPP or LAUP,” Dr. Gillespie said at the meeting, jointly sponsored by the Triological Society and the American College of Surgeons. “So it seems like patients who have failed UPPP are still good candidates for upper airway stimulation therapy.”

Dr. Gillespie noted that selection criteria for the trial were limited to patients with a BMI of less than 32 kg/m² and to those who did not have complete circumferential collapse at the level of the soft palate on preoperative drug-induced endoscopy. These criteria were based on an earlier pilot study that showed that patients with complete circumferential collapse at the level of the soft palate did not respond to upper airway stimulation (J. Clin. Sleep Med. 2013;9:433-8).

Dr. Gillespie disclosed that he has received research support from Inspire Medical Systems, Olympus, and Surgical Specialties. He is also a consultant for those companies as well as for Medtronic.

[email protected]

On Twitter @dougbrunk

CORONADO, CALIF. – Some patients with treatment-refractory obstructive sleep apnea may be candidates for upper airway stimulation, though those with complete concentric palatal collapse may not respond, according to Dr. Marion Boyd Gillespie.

“There’s been sound research showing that patients with obstructive sleep apnea have reduced neural tone, so it may not be due to fat in the tongue; some of it may have to do with reduced neural tone,” Dr. Gillespie, who directs the snoring clinics at the Medical University of South Carolina, Charleston, said at the Triological Society’s Combined Sections Meeting. “During these apneic events, there’s a reduction in the neural tone of the genioglossus muscle, which is the main dilator of the upper airway. With upper airway stimulation, we’re trying to account for that loss of neural tone by providing more neural impulse to these muscle groups that perform the dilator functions.”

In 2014 the Food and Drug Administration cleared an upper airway stimulation system manufactured by Inspire Medical Systems, a pacemakerlike device that’s implanted in the subclavicular space. The system features a stimulator lead that attaches to the right hypoglossal nerve and a sensing lead that goes between the external and internal intercostal muscles to detect breathing. “That allows the device to know when in the phase of respiration to fire,” said Dr. Gillespie, professor of otolaryngology–head and neck surgery at the university. “The sensing lead detects the respiratory wave, and the stimulatory lead starts stimulation at the end of expiration, because that’s when the airway is in its most collapsible state. It continues about two-thirds of the way through the inspiratory cycle to keep the airway open.”

Titration of the device is very similar to continuous positive airway pressure, he continued. Once implanted, the patient “will go back to the sleep lab where a tech who’s trained in the device will ramp up stimulation until observed apneas and hypopneas are adequately reduced. You would think that isolated stimulation of the hypoglossal nerve would only open up the airway at the level of the tongue. However, our initial investigation showed that there is dilation at the velopharynx as well,” Dr. Gillespie said. By moving the tongue out of the posterior airway, “you’re moving the dorsum of the tongue away from the velopharynx. You’re also getting active traction on the palatoglossal fold,” he added.

Results of the initial trial of the system in 126 patients with a mean body mass index of 28.4 kg/m² were published last year (N. Engl. J. Med. 2014;370:139-49). At 12 months of follow-up, patients experienced a 68% overall reduction in their apnea-hypopnea index (AHI) score, from a preoperative mean of 29 to a postoperative mean of 9. In addition, patients had a 70% overall reduction in their oxygen desaturation index (ODI). The researchers also observed normalization of patient-based outcomes, with improvement in the Functional Outcomes of Sleep Questionnaire score and reduction of the Epworth Sleepiness Scale score to a level of 10 on average. “We also saw a reduction of snoring,” said Dr. Gillespie, who was a member of the research team. “Snoring went from 72% of patients having severe, annoying snoring to the point where a bed partner leaves the room, to 15% postoperatively.” Even so, 96% of patients who had a previous history of uvulopalatopharyngoplasty (UPPP) or laser-assisted uvulopalatoplasty (LAUP) still had tongue-based collapse after 12 months of follow-up. “But we found that their response to this therapy was just as good as people who had never had a UPPP or LAUP,” Dr. Gillespie said at the meeting, jointly sponsored by the Triological Society and the American College of Surgeons. “So it seems like patients who have failed UPPP are still good candidates for upper airway stimulation therapy.”

Dr. Gillespie noted that selection criteria for the trial were limited to patients with a BMI of less than 32 kg/m² and to those who did not have complete circumferential collapse at the level of the soft palate on preoperative drug-induced endoscopy. These criteria were based on an earlier pilot study that showed that patients with complete circumferential collapse at the level of the soft palate did not respond to upper airway stimulation (J. Clin. Sleep Med. 2013;9:433-8).

Dr. Gillespie disclosed that he has received research support from Inspire Medical Systems, Olympus, and Surgical Specialties. He is also a consultant for those companies as well as for Medtronic.

[email protected]

On Twitter @dougbrunk

CORONADO, CALIF. – Some patients with treatment-refractory obstructive sleep apnea may be candidates for upper airway stimulation, though those with complete concentric palatal collapse may not respond, according to Dr. Marion Boyd Gillespie.

“There’s been sound research showing that patients with obstructive sleep apnea have reduced neural tone, so it may not be due to fat in the tongue; some of it may have to do with reduced neural tone,” Dr. Gillespie, who directs the snoring clinics at the Medical University of South Carolina, Charleston, said at the Triological Society’s Combined Sections Meeting. “During these apneic events, there’s a reduction in the neural tone of the genioglossus muscle, which is the main dilator of the upper airway. With upper airway stimulation, we’re trying to account for that loss of neural tone by providing more neural impulse to these muscle groups that perform the dilator functions.”

In 2014 the Food and Drug Administration cleared an upper airway stimulation system manufactured by Inspire Medical Systems, a pacemakerlike device that’s implanted in the subclavicular space. The system features a stimulator lead that attaches to the right hypoglossal nerve and a sensing lead that goes between the external and internal intercostal muscles to detect breathing. “That allows the device to know when in the phase of respiration to fire,” said Dr. Gillespie, professor of otolaryngology–head and neck surgery at the university. “The sensing lead detects the respiratory wave, and the stimulatory lead starts stimulation at the end of expiration, because that’s when the airway is in its most collapsible state. It continues about two-thirds of the way through the inspiratory cycle to keep the airway open.”

Titration of the device is very similar to continuous positive airway pressure, he continued. Once implanted, the patient “will go back to the sleep lab where a tech who’s trained in the device will ramp up stimulation until observed apneas and hypopneas are adequately reduced. You would think that isolated stimulation of the hypoglossal nerve would only open up the airway at the level of the tongue. However, our initial investigation showed that there is dilation at the velopharynx as well,” Dr. Gillespie said. By moving the tongue out of the posterior airway, “you’re moving the dorsum of the tongue away from the velopharynx. You’re also getting active traction on the palatoglossal fold,” he added.

Results of the initial trial of the system in 126 patients with a mean body mass index of 28.4 kg/m² were published last year (N. Engl. J. Med. 2014;370:139-49). At 12 months of follow-up, patients experienced a 68% overall reduction in their apnea-hypopnea index (AHI) score, from a preoperative mean of 29 to a postoperative mean of 9. In addition, patients had a 70% overall reduction in their oxygen desaturation index (ODI). The researchers also observed normalization of patient-based outcomes, with improvement in the Functional Outcomes of Sleep Questionnaire score and reduction of the Epworth Sleepiness Scale score to a level of 10 on average. “We also saw a reduction of snoring,” said Dr. Gillespie, who was a member of the research team. “Snoring went from 72% of patients having severe, annoying snoring to the point where a bed partner leaves the room, to 15% postoperatively.” Even so, 96% of patients who had a previous history of uvulopalatopharyngoplasty (UPPP) or laser-assisted uvulopalatoplasty (LAUP) still had tongue-based collapse after 12 months of follow-up. “But we found that their response to this therapy was just as good as people who had never had a UPPP or LAUP,” Dr. Gillespie said at the meeting, jointly sponsored by the Triological Society and the American College of Surgeons. “So it seems like patients who have failed UPPP are still good candidates for upper airway stimulation therapy.”

Dr. Gillespie noted that selection criteria for the trial were limited to patients with a BMI of less than 32 kg/m² and to those who did not have complete circumferential collapse at the level of the soft palate on preoperative drug-induced endoscopy. These criteria were based on an earlier pilot study that showed that patients with complete circumferential collapse at the level of the soft palate did not respond to upper airway stimulation (J. Clin. Sleep Med. 2013;9:433-8).

Dr. Gillespie disclosed that he has received research support from Inspire Medical Systems, Olympus, and Surgical Specialties. He is also a consultant for those companies as well as for Medtronic.

[email protected]

On Twitter @dougbrunk

HSCT preparation

Photo by Chad McNeeley

Leukocyte telomere length is associated with survival in patients who undergo hematopoietic stem cell transplant (HSCT) to treat severe aplastic anemia, according to research published in JAMA.

But it’s the donor’s telomere length—not the recipient’s—that makes the difference, the study showed.

Patients who received an HSCT from an unrelated donor had better overall survival at 5 years if that donor’s leukocytes had longer telomeres.

Shahinaz M. Gadalla, MD, PhD, of the National Cancer Institute in Rockville, Maryland, and colleagues conducted this research.

The group compared recipient and donor leukocyte telomere length prior to transplant with outcomes after unrelated HSCT for 330 patients with severe aplastic anemia.

The patients and their donors had pre-HSCT blood samples and other clinical results available at the Center for International Blood and Marrow Transplant Research. Patients underwent HSCT between 1989 and 2007 in 84 centers and were followed until March 2013.

The researchers categorized leukocyte telomere length for both recipients and donors based on the leukocyte telomere length tertiles in the donors: long (third tertile) and short (first and second tertiles combined).

The team found that longer donor leukocyte telomere length was associated with a higher overall survival. The 5-year overall survival was 56% in the longer telomere group and 40% in the shorter telomere group (P=0.009).

After adjusting for donor age and clinical factors associated with survival following HSCT in severe aplastic anemia, the risk of post-HSCT all-cause mortality remained approximately 40% lower in patients receiving HSCT from donors with long vs short leukocyte telomeres (hazard ratio [HR]=0.61).

There was no association between donor leukocyte telomere length and engraftment at 28 days (HR=0.94). Likewise, there was no association between telomere length and acute (HR=0.77) or chronic graft-vs-host disease (HR=0.81).

And recipient telomere length was not associated with overall survival (HR=0.91).

The researchers said these results suggest that donor leukocyte telomere length may have a role in long-term post-transplant survival. Authors of a related editorial explored what this discovery could mean for transplant centers.

HSCT preparation

Photo by Chad McNeeley

Leukocyte telomere length is associated with survival in patients who undergo hematopoietic stem cell transplant (HSCT) to treat severe aplastic anemia, according to research published in JAMA.

But it’s the donor’s telomere length—not the recipient’s—that makes the difference, the study showed.

Patients who received an HSCT from an unrelated donor had better overall survival at 5 years if that donor’s leukocytes had longer telomeres.

Shahinaz M. Gadalla, MD, PhD, of the National Cancer Institute in Rockville, Maryland, and colleagues conducted this research.

The group compared recipient and donor leukocyte telomere length prior to transplant with outcomes after unrelated HSCT for 330 patients with severe aplastic anemia.

The patients and their donors had pre-HSCT blood samples and other clinical results available at the Center for International Blood and Marrow Transplant Research. Patients underwent HSCT between 1989 and 2007 in 84 centers and were followed until March 2013.

The researchers categorized leukocyte telomere length for both recipients and donors based on the leukocyte telomere length tertiles in the donors: long (third tertile) and short (first and second tertiles combined).

The team found that longer donor leukocyte telomere length was associated with a higher overall survival. The 5-year overall survival was 56% in the longer telomere group and 40% in the shorter telomere group (P=0.009).

After adjusting for donor age and clinical factors associated with survival following HSCT in severe aplastic anemia, the risk of post-HSCT all-cause mortality remained approximately 40% lower in patients receiving HSCT from donors with long vs short leukocyte telomeres (hazard ratio [HR]=0.61).

There was no association between donor leukocyte telomere length and engraftment at 28 days (HR=0.94). Likewise, there was no association between telomere length and acute (HR=0.77) or chronic graft-vs-host disease (HR=0.81).

And recipient telomere length was not associated with overall survival (HR=0.91).

The researchers said these results suggest that donor leukocyte telomere length may have a role in long-term post-transplant survival. Authors of a related editorial explored what this discovery could mean for transplant centers.

HSCT preparation

Photo by Chad McNeeley

Leukocyte telomere length is associated with survival in patients who undergo hematopoietic stem cell transplant (HSCT) to treat severe aplastic anemia, according to research published in JAMA.

But it’s the donor’s telomere length—not the recipient’s—that makes the difference, the study showed.

Patients who received an HSCT from an unrelated donor had better overall survival at 5 years if that donor’s leukocytes had longer telomeres.

Shahinaz M. Gadalla, MD, PhD, of the National Cancer Institute in Rockville, Maryland, and colleagues conducted this research.

The group compared recipient and donor leukocyte telomere length prior to transplant with outcomes after unrelated HSCT for 330 patients with severe aplastic anemia.

The patients and their donors had pre-HSCT blood samples and other clinical results available at the Center for International Blood and Marrow Transplant Research. Patients underwent HSCT between 1989 and 2007 in 84 centers and were followed until March 2013.

The researchers categorized leukocyte telomere length for both recipients and donors based on the leukocyte telomere length tertiles in the donors: long (third tertile) and short (first and second tertiles combined).

The team found that longer donor leukocyte telomere length was associated with a higher overall survival. The 5-year overall survival was 56% in the longer telomere group and 40% in the shorter telomere group (P=0.009).

After adjusting for donor age and clinical factors associated with survival following HSCT in severe aplastic anemia, the risk of post-HSCT all-cause mortality remained approximately 40% lower in patients receiving HSCT from donors with long vs short leukocyte telomeres (hazard ratio [HR]=0.61).

There was no association between donor leukocyte telomere length and engraftment at 28 days (HR=0.94). Likewise, there was no association between telomere length and acute (HR=0.77) or chronic graft-vs-host disease (HR=0.81).

And recipient telomere length was not associated with overall survival (HR=0.91).

The researchers said these results suggest that donor leukocyte telomere length may have a role in long-term post-transplant survival. Authors of a related editorial explored what this discovery could mean for transplant centers.

Prescription medications

Photo courtesy of CDC

New research indicates that a tyrosine kinase inhibitor (TKI) approved to treat advanced renal cell carcinoma could prove useful in treating patients with drug-resistant chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL).

The study showed that the TKI, axitinib, can inhibit BCR-ABL1 (T315I), a mutation known to confer drug resistance in CML and ALL.

“Since axitinib is already used to treat cancer, its safety is known,” said Kimmo Porkka, MD, PhD, of the University of Helsinki in Finland.

“[A] formal exploration of its clinical utility in drug-resistant leukemia can now be done in a fast-track mode. Thus, the normally very long path from lab bench to bedside is now significantly shortened.”

Dr Porkka and his colleagues described the newfound activity of axitinib in Nature.

The researchers used a drug sensitivity and resistance testing method developed at the University of Helsinki’s Institute for Molecular Medicine Finland (FIMM) to examine how patient-derived leukemia cells responded to a large panel of drugs.

In this way, the group identified axitinib as a promising drug candidate for CML and ALL. Axitinib effectively eliminated drug-resistant leukemia cells.

The TKI inhibited BCR-ABL1 (T315I) at biochemical and cellular levels by binding to the active form of ABL1 (T315I) in a mutation-selective binding mode.

The researchers said this suggests the T315I mutation shifts the conformational equilibrium of the kinase in favor of an active (DFG-in) A-loop conformation, which has more optimal binding interactions with axitinib.

“If you think of the targeted protein as a lock into which the cancer drug fits in as a key, the resistant protein changes in such a way that we need a different key,” said study author Brion Murray, PhD, of Pfizer Worldwide Research & Development in San Diego, California.

“In the case of axitinib, it acts as two distinct keys—one for renal cell carcinoma and one for leukemia.”

The researchers also treated a CML patient with axitinib and observed a “rapid reduction” of T315I-positive cells in the patient’s bone marrow.

“Further research will determine whether these findings have the potential to significantly improve the standard of care for this select group of CML patients and patients with other related leukemias,” Dr Murray concluded.

Prescription medications

Photo courtesy of CDC

New research indicates that a tyrosine kinase inhibitor (TKI) approved to treat advanced renal cell carcinoma could prove useful in treating patients with drug-resistant chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL).

The study showed that the TKI, axitinib, can inhibit BCR-ABL1 (T315I), a mutation known to confer drug resistance in CML and ALL.

“Since axitinib is already used to treat cancer, its safety is known,” said Kimmo Porkka, MD, PhD, of the University of Helsinki in Finland.

“[A] formal exploration of its clinical utility in drug-resistant leukemia can now be done in a fast-track mode. Thus, the normally very long path from lab bench to bedside is now significantly shortened.”

Dr Porkka and his colleagues described the newfound activity of axitinib in Nature.

The researchers used a drug sensitivity and resistance testing method developed at the University of Helsinki’s Institute for Molecular Medicine Finland (FIMM) to examine how patient-derived leukemia cells responded to a large panel of drugs.

In this way, the group identified axitinib as a promising drug candidate for CML and ALL. Axitinib effectively eliminated drug-resistant leukemia cells.

The TKI inhibited BCR-ABL1 (T315I) at biochemical and cellular levels by binding to the active form of ABL1 (T315I) in a mutation-selective binding mode.

The researchers said this suggests the T315I mutation shifts the conformational equilibrium of the kinase in favor of an active (DFG-in) A-loop conformation, which has more optimal binding interactions with axitinib.

“If you think of the targeted protein as a lock into which the cancer drug fits in as a key, the resistant protein changes in such a way that we need a different key,” said study author Brion Murray, PhD, of Pfizer Worldwide Research & Development in San Diego, California.

“In the case of axitinib, it acts as two distinct keys—one for renal cell carcinoma and one for leukemia.”

The researchers also treated a CML patient with axitinib and observed a “rapid reduction” of T315I-positive cells in the patient’s bone marrow.

“Further research will determine whether these findings have the potential to significantly improve the standard of care for this select group of CML patients and patients with other related leukemias,” Dr Murray concluded.

Prescription medications

Photo courtesy of CDC

New research indicates that a tyrosine kinase inhibitor (TKI) approved to treat advanced renal cell carcinoma could prove useful in treating patients with drug-resistant chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL).

The study showed that the TKI, axitinib, can inhibit BCR-ABL1 (T315I), a mutation known to confer drug resistance in CML and ALL.

“Since axitinib is already used to treat cancer, its safety is known,” said Kimmo Porkka, MD, PhD, of the University of Helsinki in Finland.

“[A] formal exploration of its clinical utility in drug-resistant leukemia can now be done in a fast-track mode. Thus, the normally very long path from lab bench to bedside is now significantly shortened.”

Dr Porkka and his colleagues described the newfound activity of axitinib in Nature.

The researchers used a drug sensitivity and resistance testing method developed at the University of Helsinki’s Institute for Molecular Medicine Finland (FIMM) to examine how patient-derived leukemia cells responded to a large panel of drugs.

In this way, the group identified axitinib as a promising drug candidate for CML and ALL. Axitinib effectively eliminated drug-resistant leukemia cells.

The TKI inhibited BCR-ABL1 (T315I) at biochemical and cellular levels by binding to the active form of ABL1 (T315I) in a mutation-selective binding mode.

The researchers said this suggests the T315I mutation shifts the conformational equilibrium of the kinase in favor of an active (DFG-in) A-loop conformation, which has more optimal binding interactions with axitinib.

“If you think of the targeted protein as a lock into which the cancer drug fits in as a key, the resistant protein changes in such a way that we need a different key,” said study author Brion Murray, PhD, of Pfizer Worldwide Research & Development in San Diego, California.

“In the case of axitinib, it acts as two distinct keys—one for renal cell carcinoma and one for leukemia.”

The researchers also treated a CML patient with axitinib and observed a “rapid reduction” of T315I-positive cells in the patient’s bone marrow.

“Further research will determine whether these findings have the potential to significantly improve the standard of care for this select group of CML patients and patients with other related leukemias,” Dr Murray concluded.

Preparing capsules for a trial

Photo by Esther Dyson

A new study suggests that, when the US Food and Drug Administration (FDA) identifies problems at clinical trial sites, those findings are seldom reported in peer-reviewed articles later written about the research.

Only 4% of the articles analyzed in this study disclosed that an FDA inspection revealed significant problems at a trial site.

Charles Seife, of the Carter Institute of Journalism at New York University in New York, New York, reported this finding in JAMA Internal Medicine.

Seife noted that the FDA classifies its inspections based on the severity of the violations, and the most severe is “official action indicated (OAI),” which means objectionable conditions or practices that warrant regulatory action.

During the 2013 fiscal year, about 2% of the 644 inspections the FDA conducted at trial sites were classified as OAI.

With this in mind, Seife and his students set out to identify published trials in which an FDA inspection revealed significant problems and determine whether there was mention of it in the medical literature.

The group identified 57 trials in which an FDA inspection uncovered the following problems:

• Falsification or submission of false information (22 trials, 39%)
• Problems with adverse events reporting (14 trials, 25%)
• Protocol violations (42 trials, 74%)
• Inadequate or inaccurate recordkeeping (35 trials, 61%)
• Failure to protect the safety of patients and/or issues with oversight or informed consent (30 trials, 53%)
• Violations that were not otherwise characterized (20 trials, 35%).

Only 3 of the 78 publications (4%) that resulted from these trials mentioned the objectionable conditions or practices.

“The FDA does not typically notify journals when a site participating in a published clinical trial receives an OAI inspection, nor does it generally make any announcement intended to alert the public about the research misconduct that it finds,” Seife wrote.

“The documents the agency discloses tend to be heavily redacted. As a result, it is usually very difficult, or even impossible, to determine which published clinical trials are implicated by the FDA’s allegations of research misconduct.”

In a related editorial, Robert Steinbrook, MD, of the Yale School of Medicine in New Haven, Connecticut, and Rita F. Redberg, MD, of the University of California, San Francisco, wrote that Seife’s study highlights an important area for improved reporting of clinical trials and enhanced transparency at the FDA.

“A central responsibility of medical journals is maintaining and improving trust in the medical literature,” they wrote. “Journals should expect that investigators and sponsors of clinical trials would promptly notify them of substantial findings from FDA and other regulatory agency inspections and modify their reports of clinical trials as needed, either before or after publication.”

Preparing capsules for a trial

Photo by Esther Dyson

A new study suggests that, when the US Food and Drug Administration (FDA) identifies problems at clinical trial sites, those findings are seldom reported in peer-reviewed articles later written about the research.

Only 4% of the articles analyzed in this study disclosed that an FDA inspection revealed significant problems at a trial site.

Charles Seife, of the Carter Institute of Journalism at New York University in New York, New York, reported this finding in JAMA Internal Medicine.

Seife noted that the FDA classifies its inspections based on the severity of the violations, and the most severe is “official action indicated (OAI),” which means objectionable conditions or practices that warrant regulatory action.

During the 2013 fiscal year, about 2% of the 644 inspections the FDA conducted at trial sites were classified as OAI.

With this in mind, Seife and his students set out to identify published trials in which an FDA inspection revealed significant problems and determine whether there was mention of it in the medical literature.

The group identified 57 trials in which an FDA inspection uncovered the following problems:

• Falsification or submission of false information (22 trials, 39%)
• Problems with adverse events reporting (14 trials, 25%)
• Protocol violations (42 trials, 74%)
• Inadequate or inaccurate recordkeeping (35 trials, 61%)
• Failure to protect the safety of patients and/or issues with oversight or informed consent (30 trials, 53%)
• Violations that were not otherwise characterized (20 trials, 35%).

Only 3 of the 78 publications (4%) that resulted from these trials mentioned the objectionable conditions or practices.

“The FDA does not typically notify journals when a site participating in a published clinical trial receives an OAI inspection, nor does it generally make any announcement intended to alert the public about the research misconduct that it finds,” Seife wrote.

“The documents the agency discloses tend to be heavily redacted. As a result, it is usually very difficult, or even impossible, to determine which published clinical trials are implicated by the FDA’s allegations of research misconduct.”

In a related editorial, Robert Steinbrook, MD, of the Yale School of Medicine in New Haven, Connecticut, and Rita F. Redberg, MD, of the University of California, San Francisco, wrote that Seife’s study highlights an important area for improved reporting of clinical trials and enhanced transparency at the FDA.

“A central responsibility of medical journals is maintaining and improving trust in the medical literature,” they wrote. “Journals should expect that investigators and sponsors of clinical trials would promptly notify them of substantial findings from FDA and other regulatory agency inspections and modify their reports of clinical trials as needed, either before or after publication.”

Preparing capsules for a trial

Photo by Esther Dyson

A new study suggests that, when the US Food and Drug Administration (FDA) identifies problems at clinical trial sites, those findings are seldom reported in peer-reviewed articles later written about the research.

Only 4% of the articles analyzed in this study disclosed that an FDA inspection revealed significant problems at a trial site.

Charles Seife, of the Carter Institute of Journalism at New York University in New York, New York, reported this finding in JAMA Internal Medicine.

Seife noted that the FDA classifies its inspections based on the severity of the violations, and the most severe is “official action indicated (OAI),” which means objectionable conditions or practices that warrant regulatory action.

During the 2013 fiscal year, about 2% of the 644 inspections the FDA conducted at trial sites were classified as OAI.

With this in mind, Seife and his students set out to identify published trials in which an FDA inspection revealed significant problems and determine whether there was mention of it in the medical literature.

The group identified 57 trials in which an FDA inspection uncovered the following problems:

• Falsification or submission of false information (22 trials, 39%)
• Problems with adverse events reporting (14 trials, 25%)
• Protocol violations (42 trials, 74%)
• Inadequate or inaccurate recordkeeping (35 trials, 61%)
• Failure to protect the safety of patients and/or issues with oversight or informed consent (30 trials, 53%)
• Violations that were not otherwise characterized (20 trials, 35%).

Only 3 of the 78 publications (4%) that resulted from these trials mentioned the objectionable conditions or practices.

“The FDA does not typically notify journals when a site participating in a published clinical trial receives an OAI inspection, nor does it generally make any announcement intended to alert the public about the research misconduct that it finds,” Seife wrote.

“The documents the agency discloses tend to be heavily redacted. As a result, it is usually very difficult, or even impossible, to determine which published clinical trials are implicated by the FDA’s allegations of research misconduct.”

In a related editorial, Robert Steinbrook, MD, of the Yale School of Medicine in New Haven, Connecticut, and Rita F. Redberg, MD, of the University of California, San Francisco, wrote that Seife’s study highlights an important area for improved reporting of clinical trials and enhanced transparency at the FDA.

“A central responsibility of medical journals is maintaining and improving trust in the medical literature,” they wrote. “Journals should expect that investigators and sponsors of clinical trials would promptly notify them of substantial findings from FDA and other regulatory agency inspections and modify their reports of clinical trials as needed, either before or after publication.”

Blood donation

Photo by Charles Haymond

Low-dose oral iron supplementation can reduce the time to hemoglobin recovery after blood donation, according to a study published in JAMA.

Researchers found that a daily dose of ferrous gluconate (37.5 mg of elemental iron) reduced blood donors’ time to 80% hemoglobin recovery, whether the donors were iron-depleted (with ferritin levels of 26 ng/mL or lower) or iron-replete (with ferritin levels higher than 26 ng/mL).

Joseph E. Kiss, MD, of the Institute for Transfusion Medicine in Pittsburgh, Pennsylvania, and his colleagues conducted this study at 4 regional blood centers in the US.

The researchers randomized 215 subjects (who had not donated whole blood or red blood cells within 4 months) to receive one tablet of ferrous gluconate daily or no iron for 24 weeks after donating a unit of whole blood (500 mL).

The study’s primary outcomes were time to recovery of 80% of the post-donation decrease in hemoglobin and recovery of baseline ferritin levels.

The researchers found that subjects who received iron supplementation achieved 80% hemoglobin recovery more quickly than subjects who did not receive iron, regardless of ferritin levels.

In the low-ferritin group, the mean time to 80% hemoglobin recovery was 32 days in subjects who received iron and 158 days in those who did not (P<0.001). In the higher-ferritin group, the mean time to 80% hemoglobin recovery was 31 days in subjects who received iron and 78 days in those who did not (P=0.02).

In the low-ferritin group, the median time to recovery of baseline ferritin levels was 21 days in subjects who received iron and more than 168 days in subjects who did not. In the higher-ferritin group, the median time to recovery of baseline ferritin levels was 107 days in subjects who received iron and more than 168 days in those who did not.

The median time to recovery of iron stores was 76 days in all subjects who received iron supplements and more than 168 days in those who did not (P<0.001). Sixty-seven percent of subjects who did not receive iron had failed to recover their iron stores by 168 days.

The researchers said these findings raise important considerations regarding the 8-week minimum waiting period between blood donations that is required in the US and Canada. This is a shorter period than those allowed in many other countries.

The study suggests that hemoglobin recovery differs according to a donor’s pre-donation ferritin level, but, even in iron-replete donors, the mean recovery was only 70% at 8 weeks.

Prolonging the minimum wait time between blood donations would allow for more thorough recovery, the researchers noted, but it could also compromise the blood supply. Furthermore, increasing the waiting period might not be adequate for donors who do not take iron supplements.

Blood donation

Photo by Charles Haymond

Low-dose oral iron supplementation can reduce the time to hemoglobin recovery after blood donation, according to a study published in JAMA.

Researchers found that a daily dose of ferrous gluconate (37.5 mg of elemental iron) reduced blood donors’ time to 80% hemoglobin recovery, whether the donors were iron-depleted (with ferritin levels of 26 ng/mL or lower) or iron-replete (with ferritin levels higher than 26 ng/mL).

Joseph E. Kiss, MD, of the Institute for Transfusion Medicine in Pittsburgh, Pennsylvania, and his colleagues conducted this study at 4 regional blood centers in the US.

The researchers randomized 215 subjects (who had not donated whole blood or red blood cells within 4 months) to receive one tablet of ferrous gluconate daily or no iron for 24 weeks after donating a unit of whole blood (500 mL).

The study’s primary outcomes were time to recovery of 80% of the post-donation decrease in hemoglobin and recovery of baseline ferritin levels.

The researchers found that subjects who received iron supplementation achieved 80% hemoglobin recovery more quickly than subjects who did not receive iron, regardless of ferritin levels.

In the low-ferritin group, the mean time to 80% hemoglobin recovery was 32 days in subjects who received iron and 158 days in those who did not (P<0.001). In the higher-ferritin group, the mean time to 80% hemoglobin recovery was 31 days in subjects who received iron and 78 days in those who did not (P=0.02).

In the low-ferritin group, the median time to recovery of baseline ferritin levels was 21 days in subjects who received iron and more than 168 days in subjects who did not. In the higher-ferritin group, the median time to recovery of baseline ferritin levels was 107 days in subjects who received iron and more than 168 days in those who did not.

The median time to recovery of iron stores was 76 days in all subjects who received iron supplements and more than 168 days in those who did not (P<0.001). Sixty-seven percent of subjects who did not receive iron had failed to recover their iron stores by 168 days.

The researchers said these findings raise important considerations regarding the 8-week minimum waiting period between blood donations that is required in the US and Canada. This is a shorter period than those allowed in many other countries.

The study suggests that hemoglobin recovery differs according to a donor’s pre-donation ferritin level, but, even in iron-replete donors, the mean recovery was only 70% at 8 weeks.

Prolonging the minimum wait time between blood donations would allow for more thorough recovery, the researchers noted, but it could also compromise the blood supply. Furthermore, increasing the waiting period might not be adequate for donors who do not take iron supplements.

Blood donation

Photo by Charles Haymond

Low-dose oral iron supplementation can reduce the time to hemoglobin recovery after blood donation, according to a study published in JAMA.

Researchers found that a daily dose of ferrous gluconate (37.5 mg of elemental iron) reduced blood donors’ time to 80% hemoglobin recovery, whether the donors were iron-depleted (with ferritin levels of 26 ng/mL or lower) or iron-replete (with ferritin levels higher than 26 ng/mL).

Joseph E. Kiss, MD, of the Institute for Transfusion Medicine in Pittsburgh, Pennsylvania, and his colleagues conducted this study at 4 regional blood centers in the US.

The researchers randomized 215 subjects (who had not donated whole blood or red blood cells within 4 months) to receive one tablet of ferrous gluconate daily or no iron for 24 weeks after donating a unit of whole blood (500 mL).

The study’s primary outcomes were time to recovery of 80% of the post-donation decrease in hemoglobin and recovery of baseline ferritin levels.

The researchers found that subjects who received iron supplementation achieved 80% hemoglobin recovery more quickly than subjects who did not receive iron, regardless of ferritin levels.

In the low-ferritin group, the mean time to 80% hemoglobin recovery was 32 days in subjects who received iron and 158 days in those who did not (P<0.001). In the higher-ferritin group, the mean time to 80% hemoglobin recovery was 31 days in subjects who received iron and 78 days in those who did not (P=0.02).

In the low-ferritin group, the median time to recovery of baseline ferritin levels was 21 days in subjects who received iron and more than 168 days in subjects who did not. In the higher-ferritin group, the median time to recovery of baseline ferritin levels was 107 days in subjects who received iron and more than 168 days in those who did not.

The median time to recovery of iron stores was 76 days in all subjects who received iron supplements and more than 168 days in those who did not (P<0.001). Sixty-seven percent of subjects who did not receive iron had failed to recover their iron stores by 168 days.

The researchers said these findings raise important considerations regarding the 8-week minimum waiting period between blood donations that is required in the US and Canada. This is a shorter period than those allowed in many other countries.

The study suggests that hemoglobin recovery differs according to a donor’s pre-donation ferritin level, but, even in iron-replete donors, the mean recovery was only 70% at 8 weeks.

Prolonging the minimum wait time between blood donations would allow for more thorough recovery, the researchers noted, but it could also compromise the blood supply. Furthermore, increasing the waiting period might not be adequate for donors who do not take iron supplements.

Follow a case and the associated discussion, to learn the latest evidence on fetal heart rate monitoring and the appropriate approaches to monitoring in labor and delivery units via an exercise sponsored by the Agency for Healthcare Research and Quality.

Click here to learn more at the AHRQ Web M&M site.

Follow a case and the associated discussion, to learn the latest evidence on fetal heart rate monitoring and the appropriate approaches to monitoring in labor and delivery units via an exercise sponsored by the Agency for Healthcare Research and Quality.

Click here to learn more at the AHRQ Web M&M site.

Follow a case and the associated discussion, to learn the latest evidence on fetal heart rate monitoring and the appropriate approaches to monitoring in labor and delivery units via an exercise sponsored by the Agency for Healthcare Research and Quality.

Click here to learn more at the AHRQ Web M&M site.

During transitions in care, unintentional medication discrepancies commonly occur and can threaten patient safety. To improve medication reconciliation, and in response to Joint Commission requirements, most hospitals have developed medication reconciliation processes.

The successes of such programs have been varied, but there is now collective experience about effective approaches to medication reconciliation.

MARQUIS identifies best practices and offers a framework for assembling a team and adaptable implementation strategy.

To download a copy of the implementation strategy developed by the Society of Hospital Medicine, click here.

During transitions in care, unintentional medication discrepancies commonly occur and can threaten patient safety. To improve medication reconciliation, and in response to Joint Commission requirements, most hospitals have developed medication reconciliation processes.

The successes of such programs have been varied, but there is now collective experience about effective approaches to medication reconciliation.

MARQUIS identifies best practices and offers a framework for assembling a team and adaptable implementation strategy.

To download a copy of the implementation strategy developed by the Society of Hospital Medicine, click here.

During transitions in care, unintentional medication discrepancies commonly occur and can threaten patient safety. To improve medication reconciliation, and in response to Joint Commission requirements, most hospitals have developed medication reconciliation processes.

The successes of such programs have been varied, but there is now collective experience about effective approaches to medication reconciliation.

MARQUIS identifies best practices and offers a framework for assembling a team and adaptable implementation strategy.

To download a copy of the implementation strategy developed by the Society of Hospital Medicine, click here.

Hospitalists should not only lead efforts to control potential Ebola outbreaks in the U.S. but should also play a role in improving global healthcare, say the authors of a recent article in the Journal of Hospital Medicine.

Author Phuoc Le, MD, MPH, assistant professor of medicine and pediatrics at the University of California San Francisco where he co-directs the Global Health-Hospital Medicine Fellowship, is also cofounder of the HEAL Initiative, a global healthcare campaign designed to improve the health of vulnerable populations worldwide. HEAL, short for Health, Equity, Action, and Leadership, recently won the 2015 SHM Award for Excellence in Humanitarian Service.

Dr. Le recently spoke with TH about why hospitalists are well-equipped to handle global health problems.

Question: In your paper, you call on hospitalists to join the ranks of global health hospitalists. Can you explain?

Answer: Whether it’s Navajo Nation in Arizona or rural Haiti, the healthcare needs of the poor are very similar. Global health hospitalists play an important role in building capacity, running a health system, improving quality while reducing costs, working in teams to provide holistic care for the inpatient, and improving transitions to the outpatient setting.

Q: How do the skills learned in resource-poor settings apply back home?

A: Let's say you have a patient with tuberculosis, which is very common in places like Liberia, and you suspect fluid in the lungs. [In Liberia], you would insert a needle and remove the fluid. In the U.S., a lot of providers would not be able to remove the fluid without getting an ultrasound and multiple other studies. Those costs add up. Global health hospitalists are very well-versed in the skills of ultrasonography because there are no ultrasonographers in the field working with us.

Q: You've spent time in Haiti and said that is where you began to notice volunteers arriving with good intentions but without needed skills. What exactly did you learn?

A: I spent a lot of time there, responding to the earthquake and also the cholera epidemic in 2010. I came across dozens of healthcare volunteers who had passion and commitment but really came ill-prepared, not through any fault of their own but because they never had an opportunity to learn the skills needed to be effective in the field. For example, take a nurse from an ivory-tower hospital and suddenly put her where she doesn’t have IVs to work with or the right type of fluids or tubing. Well, suddenly she feels like her efficacy has gone way down. That could easily lead to a lot of frustration and potential burnout. That’s why we started the HEAL Initiative, which is a two-year program for healthcare workers who want to learn the skills needed to work in poor settings.

Q: How can hospitalists get involved in global health?

A: Come to the Society of Hospital Medicine annual meeting in March where we’ll be hosting a special-interest session called Global Health and Human Rights.

Visit our website for more information about global health hospitalists.

Hospitalists should not only lead efforts to control potential Ebola outbreaks in the U.S. but should also play a role in improving global healthcare, say the authors of a recent article in the Journal of Hospital Medicine.

Author Phuoc Le, MD, MPH, assistant professor of medicine and pediatrics at the University of California San Francisco where he co-directs the Global Health-Hospital Medicine Fellowship, is also cofounder of the HEAL Initiative, a global healthcare campaign designed to improve the health of vulnerable populations worldwide. HEAL, short for Health, Equity, Action, and Leadership, recently won the 2015 SHM Award for Excellence in Humanitarian Service.

Dr. Le recently spoke with TH about why hospitalists are well-equipped to handle global health problems.

Question: In your paper, you call on hospitalists to join the ranks of global health hospitalists. Can you explain?

Answer: Whether it’s Navajo Nation in Arizona or rural Haiti, the healthcare needs of the poor are very similar. Global health hospitalists play an important role in building capacity, running a health system, improving quality while reducing costs, working in teams to provide holistic care for the inpatient, and improving transitions to the outpatient setting.

Q: How do the skills learned in resource-poor settings apply back home?

A: Let's say you have a patient with tuberculosis, which is very common in places like Liberia, and you suspect fluid in the lungs. [In Liberia], you would insert a needle and remove the fluid. In the U.S., a lot of providers would not be able to remove the fluid without getting an ultrasound and multiple other studies. Those costs add up. Global health hospitalists are very well-versed in the skills of ultrasonography because there are no ultrasonographers in the field working with us.

Q: You've spent time in Haiti and said that is where you began to notice volunteers arriving with good intentions but without needed skills. What exactly did you learn?

A: I spent a lot of time there, responding to the earthquake and also the cholera epidemic in 2010. I came across dozens of healthcare volunteers who had passion and commitment but really came ill-prepared, not through any fault of their own but because they never had an opportunity to learn the skills needed to be effective in the field. For example, take a nurse from an ivory-tower hospital and suddenly put her where she doesn’t have IVs to work with or the right type of fluids or tubing. Well, suddenly she feels like her efficacy has gone way down. That could easily lead to a lot of frustration and potential burnout. That’s why we started the HEAL Initiative, which is a two-year program for healthcare workers who want to learn the skills needed to work in poor settings.

Q: How can hospitalists get involved in global health?

A: Come to the Society of Hospital Medicine annual meeting in March where we’ll be hosting a special-interest session called Global Health and Human Rights.

Visit our website for more information about global health hospitalists.

Hospitalists should not only lead efforts to control potential Ebola outbreaks in the U.S. but should also play a role in improving global healthcare, say the authors of a recent article in the Journal of Hospital Medicine.

Author Phuoc Le, MD, MPH, assistant professor of medicine and pediatrics at the University of California San Francisco where he co-directs the Global Health-Hospital Medicine Fellowship, is also cofounder of the HEAL Initiative, a global healthcare campaign designed to improve the health of vulnerable populations worldwide. HEAL, short for Health, Equity, Action, and Leadership, recently won the 2015 SHM Award for Excellence in Humanitarian Service.

Dr. Le recently spoke with TH about why hospitalists are well-equipped to handle global health problems.

Question: In your paper, you call on hospitalists to join the ranks of global health hospitalists. Can you explain?

Answer: Whether it’s Navajo Nation in Arizona or rural Haiti, the healthcare needs of the poor are very similar. Global health hospitalists play an important role in building capacity, running a health system, improving quality while reducing costs, working in teams to provide holistic care for the inpatient, and improving transitions to the outpatient setting.

Q: How do the skills learned in resource-poor settings apply back home?

A: Let's say you have a patient with tuberculosis, which is very common in places like Liberia, and you suspect fluid in the lungs. [In Liberia], you would insert a needle and remove the fluid. In the U.S., a lot of providers would not be able to remove the fluid without getting an ultrasound and multiple other studies. Those costs add up. Global health hospitalists are very well-versed in the skills of ultrasonography because there are no ultrasonographers in the field working with us.

Q: You've spent time in Haiti and said that is where you began to notice volunteers arriving with good intentions but without needed skills. What exactly did you learn?

A: I spent a lot of time there, responding to the earthquake and also the cholera epidemic in 2010. I came across dozens of healthcare volunteers who had passion and commitment but really came ill-prepared, not through any fault of their own but because they never had an opportunity to learn the skills needed to be effective in the field. For example, take a nurse from an ivory-tower hospital and suddenly put her where she doesn’t have IVs to work with or the right type of fluids or tubing. Well, suddenly she feels like her efficacy has gone way down. That could easily lead to a lot of frustration and potential burnout. That’s why we started the HEAL Initiative, which is a two-year program for healthcare workers who want to learn the skills needed to work in poor settings.

Q: How can hospitalists get involved in global health?

A: Come to the Society of Hospital Medicine annual meeting in March where we’ll be hosting a special-interest session called Global Health and Human Rights.

Visit our website for more information about global health hospitalists.

News that the American Board of Internal Medicine (ABIM) will reboot its controversial Maintenance of Certification (MOC) program is an opportunity for hospitalists to help shape their own professional development, according to former ABIM chair and hospital medicine pioneer Robert Wachter, MD, MHM.

A year ago, ABIM moved from an MOC every 10 years to a more continuous certification process. The goal was to keep physicians more current, but the change sparked backlash over education costs, the applicability and usefulness of exam questions, and bureaucratic burdens of the new process.

In a public statement last week, ABIM president and CEO Richard Baron, MD, acknowledged that "ABIM clearly got it wrong. We launched programs that weren't ready and we didn't deliver an MOC program that physicians found meaningful."

Dr. Wachter, who was ABIM's chair when Dr. Baron was hired, says that ABIM's new plan to reach out to specialty societies means SHM can lobby for an MOC process that is more current, more applicable, and more meaningful to practitioners. Given that HM as a specialty was launched as a novel idea on what would make a good care model for hospitalized patients, Dr. Wachter is confident that SHM can be helpful in guiding the creation of a better MOC process.

Hospital medicine "was built on out-of-the-box thinking, on accepting certain parts of the old model of what a good doctor was but throwing other parts out and saying, 'We want to rethink this,'" Dr. Wachter says. "I can't think of a specialty that’s better positioned to help."

Meanwhile, hospitalist and ABIM Council member Jeff Wiese, MD, MHM, sees an opportunity to make sure the overall process for "knowledge improvement" is enhanced so that disconnects between practitioners and ABIM do not continue.

"We have to ensure that what happened over the past 20 years doesn't happen again," Dr. Wiese says. "Namely, that the world of medicine doesn't move so fast that the ABIM MOC requirements don't keep up. If we engage as physicians and specialty organizations in meaningful dialogues…then we have a much better chance of making MOC sufficiently dynamic to meet the changing times."

SHM President Burke Kealey, MD, SFHM, says that hospitalists were less impacted than some other specialists by the MOC change because they could use the Focused Practice in Hospital Medicine (FPHM) exam. The FPHM test was crafted by "real practicing hospitalists [writing] the questions for hospitalists from the point of view of what a hospitalist needs to know to do their job," he says.

Dr. Kealey adds that SHM plans to help hospitalists prepare for exams through courses featured at next month’s annual meeting and with the publication of a study guide due out this fall focused on the test's nonclinical aspects. Since it was posted last week, Dr. Kealey's blog on "The Hospital Leader" has attracted the interest of thousands of hospitalists and has been shared more than 70 times.

Visit our website for more information on Maintenance of Certification issues.

News that the American Board of Internal Medicine (ABIM) will reboot its controversial Maintenance of Certification (MOC) program is an opportunity for hospitalists to help shape their own professional development, according to former ABIM chair and hospital medicine pioneer Robert Wachter, MD, MHM.

A year ago, ABIM moved from an MOC every 10 years to a more continuous certification process. The goal was to keep physicians more current, but the change sparked backlash over education costs, the applicability and usefulness of exam questions, and bureaucratic burdens of the new process.

In a public statement last week, ABIM president and CEO Richard Baron, MD, acknowledged that "ABIM clearly got it wrong. We launched programs that weren't ready and we didn't deliver an MOC program that physicians found meaningful."

Dr. Wachter, who was ABIM's chair when Dr. Baron was hired, says that ABIM's new plan to reach out to specialty societies means SHM can lobby for an MOC process that is more current, more applicable, and more meaningful to practitioners. Given that HM as a specialty was launched as a novel idea on what would make a good care model for hospitalized patients, Dr. Wachter is confident that SHM can be helpful in guiding the creation of a better MOC process.

Hospital medicine "was built on out-of-the-box thinking, on accepting certain parts of the old model of what a good doctor was but throwing other parts out and saying, 'We want to rethink this,'" Dr. Wachter says. "I can't think of a specialty that’s better positioned to help."

Meanwhile, hospitalist and ABIM Council member Jeff Wiese, MD, MHM, sees an opportunity to make sure the overall process for "knowledge improvement" is enhanced so that disconnects between practitioners and ABIM do not continue.

"We have to ensure that what happened over the past 20 years doesn't happen again," Dr. Wiese says. "Namely, that the world of medicine doesn't move so fast that the ABIM MOC requirements don't keep up. If we engage as physicians and specialty organizations in meaningful dialogues…then we have a much better chance of making MOC sufficiently dynamic to meet the changing times."

SHM President Burke Kealey, MD, SFHM, says that hospitalists were less impacted than some other specialists by the MOC change because they could use the Focused Practice in Hospital Medicine (FPHM) exam. The FPHM test was crafted by "real practicing hospitalists [writing] the questions for hospitalists from the point of view of what a hospitalist needs to know to do their job," he says.

Dr. Kealey adds that SHM plans to help hospitalists prepare for exams through courses featured at next month’s annual meeting and with the publication of a study guide due out this fall focused on the test's nonclinical aspects. Since it was posted last week, Dr. Kealey's blog on "The Hospital Leader" has attracted the interest of thousands of hospitalists and has been shared more than 70 times.

Visit our website for more information on Maintenance of Certification issues.

News that the American Board of Internal Medicine (ABIM) will reboot its controversial Maintenance of Certification (MOC) program is an opportunity for hospitalists to help shape their own professional development, according to former ABIM chair and hospital medicine pioneer Robert Wachter, MD, MHM.

A year ago, ABIM moved from an MOC every 10 years to a more continuous certification process. The goal was to keep physicians more current, but the change sparked backlash over education costs, the applicability and usefulness of exam questions, and bureaucratic burdens of the new process.

In a public statement last week, ABIM president and CEO Richard Baron, MD, acknowledged that "ABIM clearly got it wrong. We launched programs that weren't ready and we didn't deliver an MOC program that physicians found meaningful."

Dr. Wachter, who was ABIM's chair when Dr. Baron was hired, says that ABIM's new plan to reach out to specialty societies means SHM can lobby for an MOC process that is more current, more applicable, and more meaningful to practitioners. Given that HM as a specialty was launched as a novel idea on what would make a good care model for hospitalized patients, Dr. Wachter is confident that SHM can be helpful in guiding the creation of a better MOC process.

Hospital medicine "was built on out-of-the-box thinking, on accepting certain parts of the old model of what a good doctor was but throwing other parts out and saying, 'We want to rethink this,'" Dr. Wachter says. "I can't think of a specialty that’s better positioned to help."

Meanwhile, hospitalist and ABIM Council member Jeff Wiese, MD, MHM, sees an opportunity to make sure the overall process for "knowledge improvement" is enhanced so that disconnects between practitioners and ABIM do not continue.

"We have to ensure that what happened over the past 20 years doesn't happen again," Dr. Wiese says. "Namely, that the world of medicine doesn't move so fast that the ABIM MOC requirements don't keep up. If we engage as physicians and specialty organizations in meaningful dialogues…then we have a much better chance of making MOC sufficiently dynamic to meet the changing times."

SHM President Burke Kealey, MD, SFHM, says that hospitalists were less impacted than some other specialists by the MOC change because they could use the Focused Practice in Hospital Medicine (FPHM) exam. The FPHM test was crafted by "real practicing hospitalists [writing] the questions for hospitalists from the point of view of what a hospitalist needs to know to do their job," he says.

Dr. Kealey adds that SHM plans to help hospitalists prepare for exams through courses featured at next month’s annual meeting and with the publication of a study guide due out this fall focused on the test's nonclinical aspects. Since it was posted last week, Dr. Kealey's blog on "The Hospital Leader" has attracted the interest of thousands of hospitalists and has been shared more than 70 times.

Visit our website for more information on Maintenance of Certification issues.

No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.

To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.

The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.

The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])

Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).

In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.

The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.

Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.

Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.

The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.

[email protected]

No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.

To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.

The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.

The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])

Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).

In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.

The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.

Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.

Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.

The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.

[email protected]

No association between an increased risk of acute pancreatitis and treatment with incretin therapy for type 2 diabetes was found in a large case control-study.

To evaluate whether the risk of acute pancreatitis was increased among patients treated with incretin-based drugs – glucagonlike peptide–1 (GLP-1) receptor agonists and dipeptidyl peptidase–4 (DPP-4) inhibitors – the investigators compared the risks of acute pancreatitis associated with different antihyperglycemic drugs in 12,868 people hospitalized for the first time for acute pancreatitis, and in 12,680 controls matched for birth year, sex, and region of residence in Denmark.

The study addressed evidence indicating that incretins may cause pancreatitis and pancreatic cancer in humans, which includes adverse event reports suggesting a signal of pancreatitis, but the association between incretins and acute pancreatitis is controversial and is an issue that “remains under debate,” they noted.

The data used were from three Danish databases, including one of reimbursed prescriptions. After adjustment for comorbidities and drugs associated with pancreatitis, including alcoholism and obesity, the risk of acute pancreatitis was not increased among those who had ever used an incretin, with an odds ratio of 0.95, according to Dr. Reimar Thomsen of the department of clinical epidemiology, Institute of Clinical Medicine, Aarhus (Denmark) University Hospital, and his associates (Diabetes Care 2015 [doi:10.2337/dc13-2983])

Risk was also not increased among those who had been ever treated with a DPP-4 inhibitor (OR, 1.04), which included an OR of 1.06 for sitagliptin, or among those who had been treated with a GLP-1 receptor agonist (OR, 0.82), which included an OR of 0.75 for liraglutide. Nor was risk elevated among those treated with nonincretin antihyperglycemic drugs (OR, 1.05).

In addition, the adjusted odds ratio comparing the risk of acute pancreatitis associated with incretin treatments and other antihyperglycemics was not increased, approaching 1.

The crude odds ratios, before adjustment for confounding factors, was 1.36 in patients who had been treated with incretins and 1.44 among those who had been treated with other antihyperglycemic drugs. “The fact that crude ORs were increased to very similar levels for all antihyperglycemic drugs – given their different modes of action – points to a general underlying diabetes effect on pancreatitis risk, rather than a specific drug effect,” they commented. In the crude analyses, they determined that obesity, gallstones, and other diabetes-related risk factors “may explain much of the apparent risk increase,” the investigators added.

Other findings included an increased risk of acute pancreatitis among those who had recently started treatment with a DPP-4 inhibitor and in those who had recently started treatment with several other antihyperglycemic drugs, including sulfonylureas and insulin. “This lack of specificity suggests that either the increased pancreatitis risk is related to newly diagnosed and drug-treated type 2 diabetes per se, with a possibility of reverse causality due to pancreatogenic diabetes,” or that starting therapy with sulfonylureas and insulin “also causes acute pancreatitis, which should be further investigated,” they said.

Incretin-based drugs include injectable incretin mimetic agents (GLP-1 receptor agonists) such as liraglutide; and incretin enhancers (DPP-4) inhibitors, such as sitagliptin.

The study was supported by the Clinical Epidemiological Research Foundation in Denmark. One of the authors, from the Danish Center for Strategic Research in Type 2 Diabetes, at Odense University Hospital, disclosed having received research grants form Novo-Nordisk. Of the six authors, four are from the Aarhus University Hospital clinical epidemiology department, a member of the center, which receives funding that includes an unrestricted donation from Novo-Nordisk.

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