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Add-on mycophenolate boosts efficacy of steroids for Graves’ orbitopathy
VICTORIA, B.C. – Adding a nonsteroidal immunosuppressant to steroid therapy improves control of active, moderate-to-severe Graves’ orbitopathy, according to findings from a randomized controlled trial reported at the annual meeting of the American Thyroid Association.
Relative to counterparts given pulsed intravenous methylprednisolone alone, patients also given oral mycophenolate were twice as likely to achieve reduction of their ophthalmic signs and symptoms, first author George J. Kahaly, MD, PhD, reported in a session on behalf of the European Group on Graves’ Orbitopathy (EUGOGO). And the combination was generally safe and well tolerated.
“Since there is a clear advantage of combination treatment in response rate, in the absence of contraindication to mycophenolate, patients with active and severe orbitopathy may be considered for combination treatment,” he proposed.
A session attendee noted that a similar recent study from China suggests that mycophenolate monotherapy achieves a very high remission rate in this patient population (Clin Endocrinol (Oxf). 2017;86[2]:247-55). “Why don’t we just go for [mycophenolate] alone? Why keep pushing steroids?” he asked.
Methodology of that study was less rigorous, maintained Dr. Kahaly, who is professor of medicine and endocrinology/metabolism, chief physician of the endocrine outpatient clinic, and director of the thyroid research lab at Gutenberg University Medical Center in Mainz, Germany.
“I would say mycophenolate alone is not a powerful enough treatment to observe a response rate of 70%, 80%, 90%,” he stated. “You need more time. This is a lymphocyte-inhibiting agent, so you need the acute effect of the intravenous steroids at the beginning.”
Session cochair Angela M. Leung, MD, assistant professor of medicine at the University of California, Los Angeles, and an endocrinologist at both UCLA and the VA Greater Los Angeles Healthcare System, commented, “This is an intriguing study with very promising data from an active group of investigators.”
At the same time, benefit of add-on mycophenolate remains uncertain, in her opinion. “Clearly, more studies, perhaps longer-duration ones, are needed to assess the true effect and clinical efficacy,” she said.
Introducing the EUGOGO trial, Dr. Kahaly noted that European guidelines recommend intravenous methylprednisolone as first-line therapy for Graves’ orbitopathy that is moderate to severe or sight threatening (Eur Thyroid J. 2016;5:9-26). Some patients, however, do not achieve response on this therapy, and others who do achieve response then go on to experience relapse, underscoring the need for better therapies.
The combination the investigators selected pairs the anti-inflammatory activity of methylprednisolone with the antiproliferative activity of mycophenolate (CellCept), which is mainly used in the transplantation field.
The trial, funded in part by Novartis, was open to patients with Graves’ disease who had been euthyroid for at least 2 months but had untreated, active, moderate-to-severe orbitopathy with involvement of soft tissues and eye muscles. Those with optic neuropathy were excluded.
Patients were randomized to 12 weeks of once-weekly intravenous methylprednisolone either alone or with the addition of 24 weeks of twice-daily oral mycophenolate initiated at the same time.
Blinded observers assessed patients for orbitopathy response, defined as improvement in two or more of six outcome measures (eyelid swelling, clinical activity score, proptosis, lid width, diplopia, and motility) in at least one eye, without deterioration in any of the same measures in either eye.
Results showed that the 24-week rate of response was 71% with methylprednisolone plus mycophenolate and 53% with methylprednisolone alone (odds ratio, 2.16; P = .026).
Dr. Kahaly acknowledged that the rate in the monotherapy group was lower than that in some in past studies and proposed this was due to both a tightening of response criteria and more conservative steroid dosing in recent years.
Benefit was similar across patient subgroups stratified by sex, smoking history, clinical activity score, duration of orbitopathy, and level of antibodies to the thyroid-stimulating hormone receptor.
The group given combination therapy also had a lower 36-week relapse rate, although this difference was not significant (4% vs. 8%; odds ratio, 0.65; P = .613). Quality-of-life scores improved in both the monotherapy group (P = .009) and the combination therapy group (P = .002).
The difference between groups in extent of proptosis was just 1 mm. “This is not enough,” he asserted, noting that teprotumumab, an investigational antibody that inhibits insulin-like growth factor I receptor, was recently found to decrease proptosis in this population by 2.7 mm (N Engl J Med. 2017;376:1748-61). “This is the only drug that has led to a significant decrease of proptosis,” he noted.
“The drugs were well tolerated, and the treatment went smoothly. We didn’t have one single dropout because of drug side effects,” Dr. Kahaly reported.
The incidence of drug-related side effects was 20% with methylprednisolone and 25% with methylprednisolone plus mycophenolate, a nonsignificant difference. In both groups, most side effects were rated as mild or moderate.
Trial limitations included the lack of a placebo control, short duration of follow-up, and missing information about subsequent surgical procedures, such as orbital decompression and squint and lid surgery, acknowledged Dr. Kahaly, who disclosed that he had no relevant conflicts of interest.
VICTORIA, B.C. – Adding a nonsteroidal immunosuppressant to steroid therapy improves control of active, moderate-to-severe Graves’ orbitopathy, according to findings from a randomized controlled trial reported at the annual meeting of the American Thyroid Association.
Relative to counterparts given pulsed intravenous methylprednisolone alone, patients also given oral mycophenolate were twice as likely to achieve reduction of their ophthalmic signs and symptoms, first author George J. Kahaly, MD, PhD, reported in a session on behalf of the European Group on Graves’ Orbitopathy (EUGOGO). And the combination was generally safe and well tolerated.
“Since there is a clear advantage of combination treatment in response rate, in the absence of contraindication to mycophenolate, patients with active and severe orbitopathy may be considered for combination treatment,” he proposed.
A session attendee noted that a similar recent study from China suggests that mycophenolate monotherapy achieves a very high remission rate in this patient population (Clin Endocrinol (Oxf). 2017;86[2]:247-55). “Why don’t we just go for [mycophenolate] alone? Why keep pushing steroids?” he asked.
Methodology of that study was less rigorous, maintained Dr. Kahaly, who is professor of medicine and endocrinology/metabolism, chief physician of the endocrine outpatient clinic, and director of the thyroid research lab at Gutenberg University Medical Center in Mainz, Germany.
“I would say mycophenolate alone is not a powerful enough treatment to observe a response rate of 70%, 80%, 90%,” he stated. “You need more time. This is a lymphocyte-inhibiting agent, so you need the acute effect of the intravenous steroids at the beginning.”
Session cochair Angela M. Leung, MD, assistant professor of medicine at the University of California, Los Angeles, and an endocrinologist at both UCLA and the VA Greater Los Angeles Healthcare System, commented, “This is an intriguing study with very promising data from an active group of investigators.”
At the same time, benefit of add-on mycophenolate remains uncertain, in her opinion. “Clearly, more studies, perhaps longer-duration ones, are needed to assess the true effect and clinical efficacy,” she said.
Introducing the EUGOGO trial, Dr. Kahaly noted that European guidelines recommend intravenous methylprednisolone as first-line therapy for Graves’ orbitopathy that is moderate to severe or sight threatening (Eur Thyroid J. 2016;5:9-26). Some patients, however, do not achieve response on this therapy, and others who do achieve response then go on to experience relapse, underscoring the need for better therapies.
The combination the investigators selected pairs the anti-inflammatory activity of methylprednisolone with the antiproliferative activity of mycophenolate (CellCept), which is mainly used in the transplantation field.
The trial, funded in part by Novartis, was open to patients with Graves’ disease who had been euthyroid for at least 2 months but had untreated, active, moderate-to-severe orbitopathy with involvement of soft tissues and eye muscles. Those with optic neuropathy were excluded.
Patients were randomized to 12 weeks of once-weekly intravenous methylprednisolone either alone or with the addition of 24 weeks of twice-daily oral mycophenolate initiated at the same time.
Blinded observers assessed patients for orbitopathy response, defined as improvement in two or more of six outcome measures (eyelid swelling, clinical activity score, proptosis, lid width, diplopia, and motility) in at least one eye, without deterioration in any of the same measures in either eye.
Results showed that the 24-week rate of response was 71% with methylprednisolone plus mycophenolate and 53% with methylprednisolone alone (odds ratio, 2.16; P = .026).
Dr. Kahaly acknowledged that the rate in the monotherapy group was lower than that in some in past studies and proposed this was due to both a tightening of response criteria and more conservative steroid dosing in recent years.
Benefit was similar across patient subgroups stratified by sex, smoking history, clinical activity score, duration of orbitopathy, and level of antibodies to the thyroid-stimulating hormone receptor.
The group given combination therapy also had a lower 36-week relapse rate, although this difference was not significant (4% vs. 8%; odds ratio, 0.65; P = .613). Quality-of-life scores improved in both the monotherapy group (P = .009) and the combination therapy group (P = .002).
The difference between groups in extent of proptosis was just 1 mm. “This is not enough,” he asserted, noting that teprotumumab, an investigational antibody that inhibits insulin-like growth factor I receptor, was recently found to decrease proptosis in this population by 2.7 mm (N Engl J Med. 2017;376:1748-61). “This is the only drug that has led to a significant decrease of proptosis,” he noted.
“The drugs were well tolerated, and the treatment went smoothly. We didn’t have one single dropout because of drug side effects,” Dr. Kahaly reported.
The incidence of drug-related side effects was 20% with methylprednisolone and 25% with methylprednisolone plus mycophenolate, a nonsignificant difference. In both groups, most side effects were rated as mild or moderate.
Trial limitations included the lack of a placebo control, short duration of follow-up, and missing information about subsequent surgical procedures, such as orbital decompression and squint and lid surgery, acknowledged Dr. Kahaly, who disclosed that he had no relevant conflicts of interest.
VICTORIA, B.C. – Adding a nonsteroidal immunosuppressant to steroid therapy improves control of active, moderate-to-severe Graves’ orbitopathy, according to findings from a randomized controlled trial reported at the annual meeting of the American Thyroid Association.
Relative to counterparts given pulsed intravenous methylprednisolone alone, patients also given oral mycophenolate were twice as likely to achieve reduction of their ophthalmic signs and symptoms, first author George J. Kahaly, MD, PhD, reported in a session on behalf of the European Group on Graves’ Orbitopathy (EUGOGO). And the combination was generally safe and well tolerated.
“Since there is a clear advantage of combination treatment in response rate, in the absence of contraindication to mycophenolate, patients with active and severe orbitopathy may be considered for combination treatment,” he proposed.
A session attendee noted that a similar recent study from China suggests that mycophenolate monotherapy achieves a very high remission rate in this patient population (Clin Endocrinol (Oxf). 2017;86[2]:247-55). “Why don’t we just go for [mycophenolate] alone? Why keep pushing steroids?” he asked.
Methodology of that study was less rigorous, maintained Dr. Kahaly, who is professor of medicine and endocrinology/metabolism, chief physician of the endocrine outpatient clinic, and director of the thyroid research lab at Gutenberg University Medical Center in Mainz, Germany.
“I would say mycophenolate alone is not a powerful enough treatment to observe a response rate of 70%, 80%, 90%,” he stated. “You need more time. This is a lymphocyte-inhibiting agent, so you need the acute effect of the intravenous steroids at the beginning.”
Session cochair Angela M. Leung, MD, assistant professor of medicine at the University of California, Los Angeles, and an endocrinologist at both UCLA and the VA Greater Los Angeles Healthcare System, commented, “This is an intriguing study with very promising data from an active group of investigators.”
At the same time, benefit of add-on mycophenolate remains uncertain, in her opinion. “Clearly, more studies, perhaps longer-duration ones, are needed to assess the true effect and clinical efficacy,” she said.
Introducing the EUGOGO trial, Dr. Kahaly noted that European guidelines recommend intravenous methylprednisolone as first-line therapy for Graves’ orbitopathy that is moderate to severe or sight threatening (Eur Thyroid J. 2016;5:9-26). Some patients, however, do not achieve response on this therapy, and others who do achieve response then go on to experience relapse, underscoring the need for better therapies.
The combination the investigators selected pairs the anti-inflammatory activity of methylprednisolone with the antiproliferative activity of mycophenolate (CellCept), which is mainly used in the transplantation field.
The trial, funded in part by Novartis, was open to patients with Graves’ disease who had been euthyroid for at least 2 months but had untreated, active, moderate-to-severe orbitopathy with involvement of soft tissues and eye muscles. Those with optic neuropathy were excluded.
Patients were randomized to 12 weeks of once-weekly intravenous methylprednisolone either alone or with the addition of 24 weeks of twice-daily oral mycophenolate initiated at the same time.
Blinded observers assessed patients for orbitopathy response, defined as improvement in two or more of six outcome measures (eyelid swelling, clinical activity score, proptosis, lid width, diplopia, and motility) in at least one eye, without deterioration in any of the same measures in either eye.
Results showed that the 24-week rate of response was 71% with methylprednisolone plus mycophenolate and 53% with methylprednisolone alone (odds ratio, 2.16; P = .026).
Dr. Kahaly acknowledged that the rate in the monotherapy group was lower than that in some in past studies and proposed this was due to both a tightening of response criteria and more conservative steroid dosing in recent years.
Benefit was similar across patient subgroups stratified by sex, smoking history, clinical activity score, duration of orbitopathy, and level of antibodies to the thyroid-stimulating hormone receptor.
The group given combination therapy also had a lower 36-week relapse rate, although this difference was not significant (4% vs. 8%; odds ratio, 0.65; P = .613). Quality-of-life scores improved in both the monotherapy group (P = .009) and the combination therapy group (P = .002).
The difference between groups in extent of proptosis was just 1 mm. “This is not enough,” he asserted, noting that teprotumumab, an investigational antibody that inhibits insulin-like growth factor I receptor, was recently found to decrease proptosis in this population by 2.7 mm (N Engl J Med. 2017;376:1748-61). “This is the only drug that has led to a significant decrease of proptosis,” he noted.
“The drugs were well tolerated, and the treatment went smoothly. We didn’t have one single dropout because of drug side effects,” Dr. Kahaly reported.
The incidence of drug-related side effects was 20% with methylprednisolone and 25% with methylprednisolone plus mycophenolate, a nonsignificant difference. In both groups, most side effects were rated as mild or moderate.
Trial limitations included the lack of a placebo control, short duration of follow-up, and missing information about subsequent surgical procedures, such as orbital decompression and squint and lid surgery, acknowledged Dr. Kahaly, who disclosed that he had no relevant conflicts of interest.
AT ATA 2017
Key clinical point:
Major finding: Relative to peers given methylprednisolone alone, patients given methylprednisolone plus mycophenolate were twice as likely to achieve response (odds ratio, 2.16).
Data source: A multicenter randomized controlled trial in 164 patients with Graves’ disease who had active, moderate-to-severe orbitopathy.
Disclosures: Dr. Kahaly disclosed that he had no relevant conflicts of interest. The trial was partly funded by Novartis.
Intubation for upper GI bleeding may increase cardiopulmonary risk
Prophylactic endotracheal intubation (PEI) prior to endoscopy for upper GI bleeding in critically ill adults may actually increase, rather than decrease, the risk of unplanned cardiopulmonary events, according to results of a retrospective cohort study.
In particular, the study showed a significant increase in risk of patients developing pneumonia, according to study author Umar Hayat, MD, Medicine Institute, Cleveland Clinic, and colleagues.
“The practice of PEI could carry significant risks and might be a factor that leads to this dreaded outcome [pneumonia] in patients presenting with upper GI bleeding, instead of preventing it,” Dr. Hayat and colleagues wrote (Gastrointest Endosc. 2017;86:500-9. doi:10.1016/j.gie.2016.12.008).
The role of PEI in mitigating risk of cardiopulmonary adverse events remains controversial for patients presenting with upper GI bleeding, who can have mortality rates as high as 10% for nonvariceal bleeds and 20% for variceal causes, the investigators said.
Dr. Hayat and colleagues reviewed data for a total of 365 patients who had brisk upper GI bleeding, of whom 144 (39.5%) underwent PEI prior to esophagogastroduodenoscopy (EGD). The average patient age was 59 years, and 64% were male.
The composite primary endpoint of the study, cardiopulmonary unplanned events, was defined as occurrence of pneumonia, pulmonary edema, acute respiratory distress syndrome, shock/hypotension, arrhythmia, myocardial infarction, or cardiac arrest within 48 hours of EGD.
The final analysis included 200 intubated and nonintubated patients matched on a 1:1 basis using propensity score matching.
The researchers found that post-EGD adverse outcomes were more common in patients who had undergone PEI prior to EGD (odds ratio, 3.8; 95% confidence interval, 1.4-10.2), published data show. The rate of unplanned cardiopulmonary events was 20% for intubated patients, compared with 6% for nonintubated patients (P = .008).
Even after adjusting for the presence of esophageal varices, the difference remained significant, Dr. Hayat and colleagues wrote.
Pneumonia in particular was significantly more common in the PEI group: published data show 14% of patients who underwent PEI had pneumonia within 48 hours of EGD, compared with 2% of nonintubated patients (P = .01).
Rates of shock within 48 hours of EGD were also higher in the PEI group (14% vs. 6%), though the finding did not reach statistical significance, the authors added.
Currently, PEI is “variably used” in clinical practice, the authors wrote, and factors that may play into the decision to utilize this strategy include bleeding severity and ongoing hematemesis, among other factors. In survey data cited by Dr. Hayat and associates, 58% of experts said they would consider intubation for patients with ongoing hematemesis, and about one-quarter said they would intubate if they suspected hemodynamic compromise.
Although future prospective, controlled studies are needed to confirm these findings, the authors did advise caution in selecting patients for PEI in critically ill patients presenting with upper GI bleeding.
“The benefits and risks of intubation should be carefully weighed when considering airway protection before an EGD in this group of patients,” they wrote.
The invesigators disclosed no financial relationships relevant to the current study.
Prophylactic endotracheal intubation (PEI) prior to endoscopy for upper GI bleeding in critically ill adults may actually increase, rather than decrease, the risk of unplanned cardiopulmonary events, according to results of a retrospective cohort study.
In particular, the study showed a significant increase in risk of patients developing pneumonia, according to study author Umar Hayat, MD, Medicine Institute, Cleveland Clinic, and colleagues.
“The practice of PEI could carry significant risks and might be a factor that leads to this dreaded outcome [pneumonia] in patients presenting with upper GI bleeding, instead of preventing it,” Dr. Hayat and colleagues wrote (Gastrointest Endosc. 2017;86:500-9. doi:10.1016/j.gie.2016.12.008).
The role of PEI in mitigating risk of cardiopulmonary adverse events remains controversial for patients presenting with upper GI bleeding, who can have mortality rates as high as 10% for nonvariceal bleeds and 20% for variceal causes, the investigators said.
Dr. Hayat and colleagues reviewed data for a total of 365 patients who had brisk upper GI bleeding, of whom 144 (39.5%) underwent PEI prior to esophagogastroduodenoscopy (EGD). The average patient age was 59 years, and 64% were male.
The composite primary endpoint of the study, cardiopulmonary unplanned events, was defined as occurrence of pneumonia, pulmonary edema, acute respiratory distress syndrome, shock/hypotension, arrhythmia, myocardial infarction, or cardiac arrest within 48 hours of EGD.
The final analysis included 200 intubated and nonintubated patients matched on a 1:1 basis using propensity score matching.
The researchers found that post-EGD adverse outcomes were more common in patients who had undergone PEI prior to EGD (odds ratio, 3.8; 95% confidence interval, 1.4-10.2), published data show. The rate of unplanned cardiopulmonary events was 20% for intubated patients, compared with 6% for nonintubated patients (P = .008).
Even after adjusting for the presence of esophageal varices, the difference remained significant, Dr. Hayat and colleagues wrote.
Pneumonia in particular was significantly more common in the PEI group: published data show 14% of patients who underwent PEI had pneumonia within 48 hours of EGD, compared with 2% of nonintubated patients (P = .01).
Rates of shock within 48 hours of EGD were also higher in the PEI group (14% vs. 6%), though the finding did not reach statistical significance, the authors added.
Currently, PEI is “variably used” in clinical practice, the authors wrote, and factors that may play into the decision to utilize this strategy include bleeding severity and ongoing hematemesis, among other factors. In survey data cited by Dr. Hayat and associates, 58% of experts said they would consider intubation for patients with ongoing hematemesis, and about one-quarter said they would intubate if they suspected hemodynamic compromise.
Although future prospective, controlled studies are needed to confirm these findings, the authors did advise caution in selecting patients for PEI in critically ill patients presenting with upper GI bleeding.
“The benefits and risks of intubation should be carefully weighed when considering airway protection before an EGD in this group of patients,” they wrote.
The invesigators disclosed no financial relationships relevant to the current study.
Prophylactic endotracheal intubation (PEI) prior to endoscopy for upper GI bleeding in critically ill adults may actually increase, rather than decrease, the risk of unplanned cardiopulmonary events, according to results of a retrospective cohort study.
In particular, the study showed a significant increase in risk of patients developing pneumonia, according to study author Umar Hayat, MD, Medicine Institute, Cleveland Clinic, and colleagues.
“The practice of PEI could carry significant risks and might be a factor that leads to this dreaded outcome [pneumonia] in patients presenting with upper GI bleeding, instead of preventing it,” Dr. Hayat and colleagues wrote (Gastrointest Endosc. 2017;86:500-9. doi:10.1016/j.gie.2016.12.008).
The role of PEI in mitigating risk of cardiopulmonary adverse events remains controversial for patients presenting with upper GI bleeding, who can have mortality rates as high as 10% for nonvariceal bleeds and 20% for variceal causes, the investigators said.
Dr. Hayat and colleagues reviewed data for a total of 365 patients who had brisk upper GI bleeding, of whom 144 (39.5%) underwent PEI prior to esophagogastroduodenoscopy (EGD). The average patient age was 59 years, and 64% were male.
The composite primary endpoint of the study, cardiopulmonary unplanned events, was defined as occurrence of pneumonia, pulmonary edema, acute respiratory distress syndrome, shock/hypotension, arrhythmia, myocardial infarction, or cardiac arrest within 48 hours of EGD.
The final analysis included 200 intubated and nonintubated patients matched on a 1:1 basis using propensity score matching.
The researchers found that post-EGD adverse outcomes were more common in patients who had undergone PEI prior to EGD (odds ratio, 3.8; 95% confidence interval, 1.4-10.2), published data show. The rate of unplanned cardiopulmonary events was 20% for intubated patients, compared with 6% for nonintubated patients (P = .008).
Even after adjusting for the presence of esophageal varices, the difference remained significant, Dr. Hayat and colleagues wrote.
Pneumonia in particular was significantly more common in the PEI group: published data show 14% of patients who underwent PEI had pneumonia within 48 hours of EGD, compared with 2% of nonintubated patients (P = .01).
Rates of shock within 48 hours of EGD were also higher in the PEI group (14% vs. 6%), though the finding did not reach statistical significance, the authors added.
Currently, PEI is “variably used” in clinical practice, the authors wrote, and factors that may play into the decision to utilize this strategy include bleeding severity and ongoing hematemesis, among other factors. In survey data cited by Dr. Hayat and associates, 58% of experts said they would consider intubation for patients with ongoing hematemesis, and about one-quarter said they would intubate if they suspected hemodynamic compromise.
Although future prospective, controlled studies are needed to confirm these findings, the authors did advise caution in selecting patients for PEI in critically ill patients presenting with upper GI bleeding.
“The benefits and risks of intubation should be carefully weighed when considering airway protection before an EGD in this group of patients,” they wrote.
The invesigators disclosed no financial relationships relevant to the current study.
FROM GASTROINTESTINAL ENDOSCOPY
Key clinical point: Although many advocate prophylactic endotracheal intubation in critically ill patients presenting with brisk upper GI bleeding, doing so may actually increase, rather than decrease, risk of cardiopulmonary events.
Major finding: The rate of unplanned cardiopulmonary events was 20% for intubated patients, compared with 6% for nonintubated patients (P = .008), with the difference remaining significant even after adjusting for the presence of esophageal varices.
Data source: Retrospective cohort study including data on 365 adult patients who presented with brisk upper GI bleeding at a tertiary care center.
Disclosures: The authors disclosed no financial relationships relevant to the current study.
RBCs from previously pregnant women linked to increased mortality in men
By contrast, all-cause mortality was not higher in female transplant recipients who received transfusions from previously pregnant females and was not higher in male or female recipients of transfusions from never-pregnant female donors.
The results need to be replicated in prospective trials. “Further research is needed to replicate these findings, determine their clinical significance, and identify the underlying mechanism,” wrote Camila Caram-Deelder, MSc, of the Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands, and her coauthors (JAMA. 2017;318[15]:1471-78).
The association “may be related to either immunologic phenomena or other mechanisms,” the investigators said. The cause of increased mortality also could be some difference in iron status between the previously pregnant female donors and male donors.
Ms. Caram-Deelder and her associates studied first-time transfusion recipients treated between 2005 and 2015 at six hospitals in the Netherlands. A total of 42,132 patients received 106,641 units of red blood cells. Among this full cohort, 31,118 patients (52% female) received 59,320 units of red blood cells exclusively from one of the three types of donor (88% male, 6% ever-pregnant female, and 6% never-pregnant female) and were followed up for a median of 245 days. During that time, 13% of the cohort died.
For the 14,995 male recipients in the no-donor-mixture cohort, 13% died during follow-up. The hazard ratio for death after 1 additional unit of red blood cells from a never-pregnant female donor, compared with a unit from a male donor, was 0.93 (95% CI, 0.81 to 1.06) for male recipients and 1.01 (95% CI, 0.88 to 1.15) for female recipients. This difference was not significant. Alternatively, for male recipients the HR for death after 1 additional unit of red blood cells from an ever-pregnant female donor, compared with a unit from a male donor, was 1.13 (95% CI, 1.01 to 1.26). The difference was statistically significant (P = .03).
Of the 16,123 female recipients in the no-donor-mixture cohort, 12% died during follow-up. Mortality rates for an ever-pregnant female donor vs. a male donor were 74 and 62 per 1,000 person-years (HR, 0.99; 95% CI, 0.87 to 1.13); for a never-pregnant female donor vs. a male donor, mortality rates were 74 and 62 per 1,000 person-years (HR, 1.01; 95% CI, 0.88-1.15). The difference was not significant.
The highest HRs for death after transfusion of red blood cells from ever-pregnant female donors were observed in male recipients 50 years and younger.
Study funding came from the Dutch Ministry of Health, Welfare and Sports. One investigator in the study reported receiving a speaking fee from Vifor Pharma and serving on the advisory councils of Novartis and Amgen Science.
The provocative finding that men have an increased mortality risk if they receive red blood cell transplants from women with a history of pregnancy could have significant practical implications if proven true in subsequent studies.
Because of the complex methodology of the study, alternative explanations for the association should be considered.
The differences in mortality seem to increase 1 year or more following the transfusion, suggesting that the trigger may be an immunologic mechanism based on maternal immunization to paternal antigens, but until prospective studies confirm that a donor’s sex and pregnancy status are associated with mortality after transplant, “appropriate and conservative use of blood products continues to be the gold standard for safe transfusion.”
Ritchard G. Cable, MD, is with American Red Cross Blood Services, Connecticut Region, Farmington. Gustaf Edgren, MD, PhD, is with the department of hematology at Karolinska University Hospital, Stockholm. These comments are based on their accompanying editorial (JAMA. 2017 Oct 17;318[15]:1445-7). They reported no financial conflicts of interest.
The provocative finding that men have an increased mortality risk if they receive red blood cell transplants from women with a history of pregnancy could have significant practical implications if proven true in subsequent studies.
Because of the complex methodology of the study, alternative explanations for the association should be considered.
The differences in mortality seem to increase 1 year or more following the transfusion, suggesting that the trigger may be an immunologic mechanism based on maternal immunization to paternal antigens, but until prospective studies confirm that a donor’s sex and pregnancy status are associated with mortality after transplant, “appropriate and conservative use of blood products continues to be the gold standard for safe transfusion.”
Ritchard G. Cable, MD, is with American Red Cross Blood Services, Connecticut Region, Farmington. Gustaf Edgren, MD, PhD, is with the department of hematology at Karolinska University Hospital, Stockholm. These comments are based on their accompanying editorial (JAMA. 2017 Oct 17;318[15]:1445-7). They reported no financial conflicts of interest.
The provocative finding that men have an increased mortality risk if they receive red blood cell transplants from women with a history of pregnancy could have significant practical implications if proven true in subsequent studies.
Because of the complex methodology of the study, alternative explanations for the association should be considered.
The differences in mortality seem to increase 1 year or more following the transfusion, suggesting that the trigger may be an immunologic mechanism based on maternal immunization to paternal antigens, but until prospective studies confirm that a donor’s sex and pregnancy status are associated with mortality after transplant, “appropriate and conservative use of blood products continues to be the gold standard for safe transfusion.”
Ritchard G. Cable, MD, is with American Red Cross Blood Services, Connecticut Region, Farmington. Gustaf Edgren, MD, PhD, is with the department of hematology at Karolinska University Hospital, Stockholm. These comments are based on their accompanying editorial (JAMA. 2017 Oct 17;318[15]:1445-7). They reported no financial conflicts of interest.
By contrast, all-cause mortality was not higher in female transplant recipients who received transfusions from previously pregnant females and was not higher in male or female recipients of transfusions from never-pregnant female donors.
The results need to be replicated in prospective trials. “Further research is needed to replicate these findings, determine their clinical significance, and identify the underlying mechanism,” wrote Camila Caram-Deelder, MSc, of the Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands, and her coauthors (JAMA. 2017;318[15]:1471-78).
The association “may be related to either immunologic phenomena or other mechanisms,” the investigators said. The cause of increased mortality also could be some difference in iron status between the previously pregnant female donors and male donors.
Ms. Caram-Deelder and her associates studied first-time transfusion recipients treated between 2005 and 2015 at six hospitals in the Netherlands. A total of 42,132 patients received 106,641 units of red blood cells. Among this full cohort, 31,118 patients (52% female) received 59,320 units of red blood cells exclusively from one of the three types of donor (88% male, 6% ever-pregnant female, and 6% never-pregnant female) and were followed up for a median of 245 days. During that time, 13% of the cohort died.
For the 14,995 male recipients in the no-donor-mixture cohort, 13% died during follow-up. The hazard ratio for death after 1 additional unit of red blood cells from a never-pregnant female donor, compared with a unit from a male donor, was 0.93 (95% CI, 0.81 to 1.06) for male recipients and 1.01 (95% CI, 0.88 to 1.15) for female recipients. This difference was not significant. Alternatively, for male recipients the HR for death after 1 additional unit of red blood cells from an ever-pregnant female donor, compared with a unit from a male donor, was 1.13 (95% CI, 1.01 to 1.26). The difference was statistically significant (P = .03).
Of the 16,123 female recipients in the no-donor-mixture cohort, 12% died during follow-up. Mortality rates for an ever-pregnant female donor vs. a male donor were 74 and 62 per 1,000 person-years (HR, 0.99; 95% CI, 0.87 to 1.13); for a never-pregnant female donor vs. a male donor, mortality rates were 74 and 62 per 1,000 person-years (HR, 1.01; 95% CI, 0.88-1.15). The difference was not significant.
The highest HRs for death after transfusion of red blood cells from ever-pregnant female donors were observed in male recipients 50 years and younger.
Study funding came from the Dutch Ministry of Health, Welfare and Sports. One investigator in the study reported receiving a speaking fee from Vifor Pharma and serving on the advisory councils of Novartis and Amgen Science.
By contrast, all-cause mortality was not higher in female transplant recipients who received transfusions from previously pregnant females and was not higher in male or female recipients of transfusions from never-pregnant female donors.
The results need to be replicated in prospective trials. “Further research is needed to replicate these findings, determine their clinical significance, and identify the underlying mechanism,” wrote Camila Caram-Deelder, MSc, of the Center for Clinical Transfusion Research, Sanquin Research, Leiden, the Netherlands, and her coauthors (JAMA. 2017;318[15]:1471-78).
The association “may be related to either immunologic phenomena or other mechanisms,” the investigators said. The cause of increased mortality also could be some difference in iron status between the previously pregnant female donors and male donors.
Ms. Caram-Deelder and her associates studied first-time transfusion recipients treated between 2005 and 2015 at six hospitals in the Netherlands. A total of 42,132 patients received 106,641 units of red blood cells. Among this full cohort, 31,118 patients (52% female) received 59,320 units of red blood cells exclusively from one of the three types of donor (88% male, 6% ever-pregnant female, and 6% never-pregnant female) and were followed up for a median of 245 days. During that time, 13% of the cohort died.
For the 14,995 male recipients in the no-donor-mixture cohort, 13% died during follow-up. The hazard ratio for death after 1 additional unit of red blood cells from a never-pregnant female donor, compared with a unit from a male donor, was 0.93 (95% CI, 0.81 to 1.06) for male recipients and 1.01 (95% CI, 0.88 to 1.15) for female recipients. This difference was not significant. Alternatively, for male recipients the HR for death after 1 additional unit of red blood cells from an ever-pregnant female donor, compared with a unit from a male donor, was 1.13 (95% CI, 1.01 to 1.26). The difference was statistically significant (P = .03).
Of the 16,123 female recipients in the no-donor-mixture cohort, 12% died during follow-up. Mortality rates for an ever-pregnant female donor vs. a male donor were 74 and 62 per 1,000 person-years (HR, 0.99; 95% CI, 0.87 to 1.13); for a never-pregnant female donor vs. a male donor, mortality rates were 74 and 62 per 1,000 person-years (HR, 1.01; 95% CI, 0.88-1.15). The difference was not significant.
The highest HRs for death after transfusion of red blood cells from ever-pregnant female donors were observed in male recipients 50 years and younger.
Study funding came from the Dutch Ministry of Health, Welfare and Sports. One investigator in the study reported receiving a speaking fee from Vifor Pharma and serving on the advisory councils of Novartis and Amgen Science.
FROM JAMA
Key clinical point: Receiving a red blood cell transfusion from a female donor with any history of pregnancy was associated with increased mortality in men, but not in women.
Major finding: Among men, all-cause mortality after transfusion from an ever-pregnant female donor vs. a male donor was 101 vs. 80 deaths per 1000 person-years (hazard ratio, 1.13; 95% confidence interval, 1.01-1.26).
Data source: Retrospective cohort study of 31,118 patients who received red blood cell transfusions exclusively from one of the three types of donor – 88% male, 6% ever-pregnant female, and 6% never-pregnant female – at one of six Dutch hospitals.
Disclosures: Study funding came from the Dutch Ministry of Health, Welfare and Sports. One investigator in the study reported receiving a speaking fee from Vifor Pharma and serving on the advisory councils of Novartis and Amgen Science.
AHRQ Practice Toolbox: Team-based care
This is the third in a series of articles from the National Center for Excellence in Primary Care Research (NCEPCR) in the Agency for Healthcare Research and Quality (AHRQ). This series introduces sets of tools and resources designed to help your practice.
Primary care clinicians increasingly recognize the benefits of team-based care, in which providers with complementary strengths join to the betterment of patient care. Care teams are groups of primary care staff members who collectively take responsibility for a set of patients. These teams blend multidisciplinary skills, focusing several people’s insights, rather than a single provider’s, on each patient’s problems. The composition of a care team depends on the size and resources of the practice and the needs of the patient population. Teams are generally organized around a primary care provider (for example, physician, advanced practice nurse, physician assistant) and the patient. Nurses, pharmacists, nutritionists, social workers, educators, and care coordinators also may be part of the care team. In smaller practices, care teams have fewer members, requiring creative team-based solutions. Such practices also may build virtual teams by linking themselves and their patients to providers and services in their communities. Team-based care is especially important when addressing the needs of patients with multiple chronic conditions.
AHRQ recognizes the importance that creating a team-based patient-centered culture in primary care has on improving patient outcomes. “Creating Patient-Centered Team-Based Care” is a white paper that proposes a conceptual framework to facilitate the integration of team-based care and patient-centered care in primary care settings and offers some practical strategies to support the implementation of patient-centered team-based primary care. In addition, the white paper identifies strategies that can serve as a starting point for investigations into the effectiveness of interventions to provide patient-centered team-based primary care.
One such strategy is an evidence-based teamwork practice improvement program jointly developed by AHRQ and the Department of Defense called Team Strategies & Tools to Enhance Performance and Patient Safety, better known as TeamSTEPPS. “TeamSTEPPS for Office-Based Care Version” adapts the core concepts of 20 years of evidence in the application of teamwork principles to building high-functioning teams specifically in office-based settings. The examples, discussions, videos, and exercises are tailored to the primary care environment to help any practice begin or expand its team-based care efforts.
Links from the NCEPCR site:
Tools and Resources for Research, Quality Improvement, and Practice: https://www.ahrq.gov/ncepcr/research-qi-practice/index.html
Creating Patient-Centered Team-Based Care: https://www.pcmh.ahrq.gov/page/creating-patient-centered-team-based-primary-care
TeamSTEPPS for Office-Based Care Version: https://www.ahrq.gov/teamstepps/officebasedcare/index.html
Dr. Ricciardi is director of the Division of Practice Improvement at the AHRQ. Dr. Ganiats is director of the National Center for Excellence in Primary Care Research at the AHRQ.
This is the third in a series of articles from the National Center for Excellence in Primary Care Research (NCEPCR) in the Agency for Healthcare Research and Quality (AHRQ). This series introduces sets of tools and resources designed to help your practice.
Primary care clinicians increasingly recognize the benefits of team-based care, in which providers with complementary strengths join to the betterment of patient care. Care teams are groups of primary care staff members who collectively take responsibility for a set of patients. These teams blend multidisciplinary skills, focusing several people’s insights, rather than a single provider’s, on each patient’s problems. The composition of a care team depends on the size and resources of the practice and the needs of the patient population. Teams are generally organized around a primary care provider (for example, physician, advanced practice nurse, physician assistant) and the patient. Nurses, pharmacists, nutritionists, social workers, educators, and care coordinators also may be part of the care team. In smaller practices, care teams have fewer members, requiring creative team-based solutions. Such practices also may build virtual teams by linking themselves and their patients to providers and services in their communities. Team-based care is especially important when addressing the needs of patients with multiple chronic conditions.
AHRQ recognizes the importance that creating a team-based patient-centered culture in primary care has on improving patient outcomes. “Creating Patient-Centered Team-Based Care” is a white paper that proposes a conceptual framework to facilitate the integration of team-based care and patient-centered care in primary care settings and offers some practical strategies to support the implementation of patient-centered team-based primary care. In addition, the white paper identifies strategies that can serve as a starting point for investigations into the effectiveness of interventions to provide patient-centered team-based primary care.
One such strategy is an evidence-based teamwork practice improvement program jointly developed by AHRQ and the Department of Defense called Team Strategies & Tools to Enhance Performance and Patient Safety, better known as TeamSTEPPS. “TeamSTEPPS for Office-Based Care Version” adapts the core concepts of 20 years of evidence in the application of teamwork principles to building high-functioning teams specifically in office-based settings. The examples, discussions, videos, and exercises are tailored to the primary care environment to help any practice begin or expand its team-based care efforts.
Links from the NCEPCR site:
Tools and Resources for Research, Quality Improvement, and Practice: https://www.ahrq.gov/ncepcr/research-qi-practice/index.html
Creating Patient-Centered Team-Based Care: https://www.pcmh.ahrq.gov/page/creating-patient-centered-team-based-primary-care
TeamSTEPPS for Office-Based Care Version: https://www.ahrq.gov/teamstepps/officebasedcare/index.html
Dr. Ricciardi is director of the Division of Practice Improvement at the AHRQ. Dr. Ganiats is director of the National Center for Excellence in Primary Care Research at the AHRQ.
This is the third in a series of articles from the National Center for Excellence in Primary Care Research (NCEPCR) in the Agency for Healthcare Research and Quality (AHRQ). This series introduces sets of tools and resources designed to help your practice.
Primary care clinicians increasingly recognize the benefits of team-based care, in which providers with complementary strengths join to the betterment of patient care. Care teams are groups of primary care staff members who collectively take responsibility for a set of patients. These teams blend multidisciplinary skills, focusing several people’s insights, rather than a single provider’s, on each patient’s problems. The composition of a care team depends on the size and resources of the practice and the needs of the patient population. Teams are generally organized around a primary care provider (for example, physician, advanced practice nurse, physician assistant) and the patient. Nurses, pharmacists, nutritionists, social workers, educators, and care coordinators also may be part of the care team. In smaller practices, care teams have fewer members, requiring creative team-based solutions. Such practices also may build virtual teams by linking themselves and their patients to providers and services in their communities. Team-based care is especially important when addressing the needs of patients with multiple chronic conditions.
AHRQ recognizes the importance that creating a team-based patient-centered culture in primary care has on improving patient outcomes. “Creating Patient-Centered Team-Based Care” is a white paper that proposes a conceptual framework to facilitate the integration of team-based care and patient-centered care in primary care settings and offers some practical strategies to support the implementation of patient-centered team-based primary care. In addition, the white paper identifies strategies that can serve as a starting point for investigations into the effectiveness of interventions to provide patient-centered team-based primary care.
One such strategy is an evidence-based teamwork practice improvement program jointly developed by AHRQ and the Department of Defense called Team Strategies & Tools to Enhance Performance and Patient Safety, better known as TeamSTEPPS. “TeamSTEPPS for Office-Based Care Version” adapts the core concepts of 20 years of evidence in the application of teamwork principles to building high-functioning teams specifically in office-based settings. The examples, discussions, videos, and exercises are tailored to the primary care environment to help any practice begin or expand its team-based care efforts.
Links from the NCEPCR site:
Tools and Resources for Research, Quality Improvement, and Practice: https://www.ahrq.gov/ncepcr/research-qi-practice/index.html
Creating Patient-Centered Team-Based Care: https://www.pcmh.ahrq.gov/page/creating-patient-centered-team-based-primary-care
TeamSTEPPS for Office-Based Care Version: https://www.ahrq.gov/teamstepps/officebasedcare/index.html
Dr. Ricciardi is director of the Division of Practice Improvement at the AHRQ. Dr. Ganiats is director of the National Center for Excellence in Primary Care Research at the AHRQ.
Preserving normal hematopoietic function in AML
Preclinical research has revealed a treatment that might preserve normal hematopoietic function in patients with acute myeloid leukemia (AML).
Researchers found that AML suppresses adipocytes in the bone marrow, which leads to imbalanced regulation of endogenous hematopoietic stem and progenitor cells and impaired myelo-erythroid maturation.
However, a PPARγ agonist can induce adipogenesis, which suppresses AML cells and stimulates the regeneration of healthy blood cells.
Researchers reported these findings in Nature Cell Biology.
The team found that adipocytes in the bone marrow support myelo-erythroid maturation of hematopoietic stem and progenitor cells. But AML has a negative effect on the maturation of adipocytes, which explains why deficient myelo-erythropoiesis is “a consistent feature” of AML.
The researchers also found that pro-adipogenesis therapy—treatment with the PPARγ agonist GW1929—protects healthy myelo-erythropoiesis and limits leukemic self-renewal.
“Our approach represents a different way of looking at leukemia and considers the entire bone marrow as an ecosystem, rather than the traditional approach of studying and trying to directly kill the diseased cells themselves,” said study author Allison Boyd, PhD, of McMaster University in Hamilton, Ontario, Canada.
“These traditional approaches have not delivered enough new therapeutic options for patients. The standard of care for this disease hasn’t changed in several decades.”
“The focus of chemotherapy and existing standard of care is on killing cancer cells, but, instead, we took a completely different approach, which changes the environment the cancer cells live in,” said study author Mick Bhatia, PhD, of McMaster University.
“This not only suppressed the ‘bad’ cancer cells but also bolstered the ‘good’ healthy cells, allowing them to regenerate in the new drug-induced environment. The fact that we can target one cell type in one tissue using an existing drug makes us excited about the possibilities of testing this in patients.”
“We can envision this becoming a potential new therapeutic approach that can either be added to existing treatments or even replace others in the near future. The fact that this drug activates blood regeneration may provide benefits for those waiting for bone marrow transplants by activating their own healthy cells.” 
Preclinical research has revealed a treatment that might preserve normal hematopoietic function in patients with acute myeloid leukemia (AML).
Researchers found that AML suppresses adipocytes in the bone marrow, which leads to imbalanced regulation of endogenous hematopoietic stem and progenitor cells and impaired myelo-erythroid maturation.
However, a PPARγ agonist can induce adipogenesis, which suppresses AML cells and stimulates the regeneration of healthy blood cells.
Researchers reported these findings in Nature Cell Biology.
The team found that adipocytes in the bone marrow support myelo-erythroid maturation of hematopoietic stem and progenitor cells. But AML has a negative effect on the maturation of adipocytes, which explains why deficient myelo-erythropoiesis is “a consistent feature” of AML.
The researchers also found that pro-adipogenesis therapy—treatment with the PPARγ agonist GW1929—protects healthy myelo-erythropoiesis and limits leukemic self-renewal.
“Our approach represents a different way of looking at leukemia and considers the entire bone marrow as an ecosystem, rather than the traditional approach of studying and trying to directly kill the diseased cells themselves,” said study author Allison Boyd, PhD, of McMaster University in Hamilton, Ontario, Canada.
“These traditional approaches have not delivered enough new therapeutic options for patients. The standard of care for this disease hasn’t changed in several decades.”
“The focus of chemotherapy and existing standard of care is on killing cancer cells, but, instead, we took a completely different approach, which changes the environment the cancer cells live in,” said study author Mick Bhatia, PhD, of McMaster University.
“This not only suppressed the ‘bad’ cancer cells but also bolstered the ‘good’ healthy cells, allowing them to regenerate in the new drug-induced environment. The fact that we can target one cell type in one tissue using an existing drug makes us excited about the possibilities of testing this in patients.”
“We can envision this becoming a potential new therapeutic approach that can either be added to existing treatments or even replace others in the near future. The fact that this drug activates blood regeneration may provide benefits for those waiting for bone marrow transplants by activating their own healthy cells.”
Preclinical research has revealed a treatment that might preserve normal hematopoietic function in patients with acute myeloid leukemia (AML).
Researchers found that AML suppresses adipocytes in the bone marrow, which leads to imbalanced regulation of endogenous hematopoietic stem and progenitor cells and impaired myelo-erythroid maturation.
However, a PPARγ agonist can induce adipogenesis, which suppresses AML cells and stimulates the regeneration of healthy blood cells.
Researchers reported these findings in Nature Cell Biology.
The team found that adipocytes in the bone marrow support myelo-erythroid maturation of hematopoietic stem and progenitor cells. But AML has a negative effect on the maturation of adipocytes, which explains why deficient myelo-erythropoiesis is “a consistent feature” of AML.
The researchers also found that pro-adipogenesis therapy—treatment with the PPARγ agonist GW1929—protects healthy myelo-erythropoiesis and limits leukemic self-renewal.
“Our approach represents a different way of looking at leukemia and considers the entire bone marrow as an ecosystem, rather than the traditional approach of studying and trying to directly kill the diseased cells themselves,” said study author Allison Boyd, PhD, of McMaster University in Hamilton, Ontario, Canada.
“These traditional approaches have not delivered enough new therapeutic options for patients. The standard of care for this disease hasn’t changed in several decades.”
“The focus of chemotherapy and existing standard of care is on killing cancer cells, but, instead, we took a completely different approach, which changes the environment the cancer cells live in,” said study author Mick Bhatia, PhD, of McMaster University.
“This not only suppressed the ‘bad’ cancer cells but also bolstered the ‘good’ healthy cells, allowing them to regenerate in the new drug-induced environment. The fact that we can target one cell type in one tissue using an existing drug makes us excited about the possibilities of testing this in patients.”
“We can envision this becoming a potential new therapeutic approach that can either be added to existing treatments or even replace others in the near future. The fact that this drug activates blood regeneration may provide benefits for those waiting for bone marrow transplants by activating their own healthy cells.”
Papillary thyroid microcarcinoma: Is ‘less is more’ the right approach?
Surgeons treated 95% of preoperatively diagnosed cases of papillary thyroid microcarcinoma with total thyroidectomy, compared with only 69% of postoperatively diagnosed cases, in to a single-center retrospective cohort study.
“During the study period, thyroid lobectomy was an acceptable alternative endorsed by the American Thyroid Association,” said Susan C. Pitt, MD, and her associates at the University of Wisconsin, Madison. “Nonetheless, documentation rarely stated that [thyroid lobectomy] was discussed as an option. Whether this finding indicates a true lack of discussion or a deficit in documentation is unclear, but emphasizes the need to improve the quality of the [electronic health record] and capture all elements of shared decision-making.”
Papillary thyroid microcarcinomas (PTMC) measure 1 cm or less, affect up to a third of adults, and explain about half of the recent rise in rates of papillary thyroid cancer, the investigators stated. Most cases are found incidentally and there is no evidence that they contribute to a rise in mortality, which stands at about 0.5 deaths per 100,000 diagnoses of thyroid carcinoma. Accordingly, in 2015, the American Thyroid Association (ATA) endorsed active surveillance and thyroid lobectomy as acceptable management strategies for most patients with PTMC (Thyroid. 2016 Jan 12;26[1]:1-133).
“The pendulum for the ATA guidelines has swung back and forth,” Dr. Pitt said in an interview. “I think the current 2015 ATA guidelines are still controversial – some surgeons and endocrinologists think we have swung too far [in the other direction]. Moving the field from total thyroidectomy to active surveillance is a big jump. Understanding the factors underlying current decisions will help us to implement less extensive management, like lobectomy and active surveillance.”
To do that, Dr. Pitt and her associates reviewed medical records from 125 patients with PTMC treated at the University of Wisconsin between 2008 and 2016. Most of the patients (90%) were white, 85% were female, average age was 50 years, and nearly all had classic or follicular-variant disease. Only 27% of patients underwent thyroid lobectomy; the rest underwent total thyroidectomy. Furthermore, among 19 patients diagnosed preoperatively, 95% underwent total thyroidectomy and 21% had a complication, including one (5%) case of permanent hypocalcemia that less extensive surgery might have avoided (J Surg Res. 2017;218:237-45).
“In all cases, documentation indicated that these preoperatively diagnosed patients followed the surgeon’s recommendation regarding the extent of surgery,” the researchers wrote. Surgeons cited various reasons for recommending total thyroidectomy, including – in about 20% of cases – a belief that it was the recommended treatment.
Only one of the 19 preoperatively diagnosed patients had a documented discussion of thyroid lobectomy, the researchers found.
While physicians might be concerned about recurrence or other “downstream” outcomes of a less-is-more approach to PTMC, Dr. Pitt noted that, in a recent large study, only 3.4% of these tumors metastasized over 10 years (World J Surg. 2010 Jan;34[1]:28-35).
“At the same time, I think that we have a better sense [that] patient-centered outcomes after thyroidectomy, such as health-related quality of life, swallowing, and voice outcomes, can be worse after a total thyroidectomy,” she added.
As surgical and medical therapies expand for PTMC and other nonmalignant diseases, it becomes increasingly vital that surgeons and patients undertake shared decision-making, she said. At the University of Wisconsin, physicians can enter free text in the EHR to document such discussions. She gave an example of how she does that: “‘Total thyroidectomy and lobectomy are both appropriate approaches for Ms. Smith. We discussed these options at length, including X, Y, and Z. Given Mrs. Smith’s (strong) preference to avoid X, we will proceed with a lobectomy.”
In her own practice, Dr. Pitt added, “when I look back at a note, I want to know what the decision was, and why it was made.”
Shared decision-making differs from informed consent by focusing on patient preferences, she noted. “I have used my notes in the operating room to help me decide what to do. I can look back and have a window into our conversation and what an individual patient values.” For PTMC, shared decisions should focus less on cancer risk and more on quality of life and outcomes a year later, she said.
“Patients don’t die from PTMC, and most live longer than the age-matched population. Given the risks of more extensive surgery and our current data on surgical and patient-centered outcomes, I think that thyroid lobectomy should be the initial treatment for most patients with PTMC, and surgeons should help their patients make informed decisions,” Dr. Pitt said.
The National Institutes of Health provided funding. The researchers reported having no conflicts of interest.
Surgeons treated 95% of preoperatively diagnosed cases of papillary thyroid microcarcinoma with total thyroidectomy, compared with only 69% of postoperatively diagnosed cases, in to a single-center retrospective cohort study.
“During the study period, thyroid lobectomy was an acceptable alternative endorsed by the American Thyroid Association,” said Susan C. Pitt, MD, and her associates at the University of Wisconsin, Madison. “Nonetheless, documentation rarely stated that [thyroid lobectomy] was discussed as an option. Whether this finding indicates a true lack of discussion or a deficit in documentation is unclear, but emphasizes the need to improve the quality of the [electronic health record] and capture all elements of shared decision-making.”
Papillary thyroid microcarcinomas (PTMC) measure 1 cm or less, affect up to a third of adults, and explain about half of the recent rise in rates of papillary thyroid cancer, the investigators stated. Most cases are found incidentally and there is no evidence that they contribute to a rise in mortality, which stands at about 0.5 deaths per 100,000 diagnoses of thyroid carcinoma. Accordingly, in 2015, the American Thyroid Association (ATA) endorsed active surveillance and thyroid lobectomy as acceptable management strategies for most patients with PTMC (Thyroid. 2016 Jan 12;26[1]:1-133).
“The pendulum for the ATA guidelines has swung back and forth,” Dr. Pitt said in an interview. “I think the current 2015 ATA guidelines are still controversial – some surgeons and endocrinologists think we have swung too far [in the other direction]. Moving the field from total thyroidectomy to active surveillance is a big jump. Understanding the factors underlying current decisions will help us to implement less extensive management, like lobectomy and active surveillance.”
To do that, Dr. Pitt and her associates reviewed medical records from 125 patients with PTMC treated at the University of Wisconsin between 2008 and 2016. Most of the patients (90%) were white, 85% were female, average age was 50 years, and nearly all had classic or follicular-variant disease. Only 27% of patients underwent thyroid lobectomy; the rest underwent total thyroidectomy. Furthermore, among 19 patients diagnosed preoperatively, 95% underwent total thyroidectomy and 21% had a complication, including one (5%) case of permanent hypocalcemia that less extensive surgery might have avoided (J Surg Res. 2017;218:237-45).
“In all cases, documentation indicated that these preoperatively diagnosed patients followed the surgeon’s recommendation regarding the extent of surgery,” the researchers wrote. Surgeons cited various reasons for recommending total thyroidectomy, including – in about 20% of cases – a belief that it was the recommended treatment.
Only one of the 19 preoperatively diagnosed patients had a documented discussion of thyroid lobectomy, the researchers found.
While physicians might be concerned about recurrence or other “downstream” outcomes of a less-is-more approach to PTMC, Dr. Pitt noted that, in a recent large study, only 3.4% of these tumors metastasized over 10 years (World J Surg. 2010 Jan;34[1]:28-35).
“At the same time, I think that we have a better sense [that] patient-centered outcomes after thyroidectomy, such as health-related quality of life, swallowing, and voice outcomes, can be worse after a total thyroidectomy,” she added.
As surgical and medical therapies expand for PTMC and other nonmalignant diseases, it becomes increasingly vital that surgeons and patients undertake shared decision-making, she said. At the University of Wisconsin, physicians can enter free text in the EHR to document such discussions. She gave an example of how she does that: “‘Total thyroidectomy and lobectomy are both appropriate approaches for Ms. Smith. We discussed these options at length, including X, Y, and Z. Given Mrs. Smith’s (strong) preference to avoid X, we will proceed with a lobectomy.”
In her own practice, Dr. Pitt added, “when I look back at a note, I want to know what the decision was, and why it was made.”
Shared decision-making differs from informed consent by focusing on patient preferences, she noted. “I have used my notes in the operating room to help me decide what to do. I can look back and have a window into our conversation and what an individual patient values.” For PTMC, shared decisions should focus less on cancer risk and more on quality of life and outcomes a year later, she said.
“Patients don’t die from PTMC, and most live longer than the age-matched population. Given the risks of more extensive surgery and our current data on surgical and patient-centered outcomes, I think that thyroid lobectomy should be the initial treatment for most patients with PTMC, and surgeons should help their patients make informed decisions,” Dr. Pitt said.
The National Institutes of Health provided funding. The researchers reported having no conflicts of interest.
Surgeons treated 95% of preoperatively diagnosed cases of papillary thyroid microcarcinoma with total thyroidectomy, compared with only 69% of postoperatively diagnosed cases, in to a single-center retrospective cohort study.
“During the study period, thyroid lobectomy was an acceptable alternative endorsed by the American Thyroid Association,” said Susan C. Pitt, MD, and her associates at the University of Wisconsin, Madison. “Nonetheless, documentation rarely stated that [thyroid lobectomy] was discussed as an option. Whether this finding indicates a true lack of discussion or a deficit in documentation is unclear, but emphasizes the need to improve the quality of the [electronic health record] and capture all elements of shared decision-making.”
Papillary thyroid microcarcinomas (PTMC) measure 1 cm or less, affect up to a third of adults, and explain about half of the recent rise in rates of papillary thyroid cancer, the investigators stated. Most cases are found incidentally and there is no evidence that they contribute to a rise in mortality, which stands at about 0.5 deaths per 100,000 diagnoses of thyroid carcinoma. Accordingly, in 2015, the American Thyroid Association (ATA) endorsed active surveillance and thyroid lobectomy as acceptable management strategies for most patients with PTMC (Thyroid. 2016 Jan 12;26[1]:1-133).
“The pendulum for the ATA guidelines has swung back and forth,” Dr. Pitt said in an interview. “I think the current 2015 ATA guidelines are still controversial – some surgeons and endocrinologists think we have swung too far [in the other direction]. Moving the field from total thyroidectomy to active surveillance is a big jump. Understanding the factors underlying current decisions will help us to implement less extensive management, like lobectomy and active surveillance.”
To do that, Dr. Pitt and her associates reviewed medical records from 125 patients with PTMC treated at the University of Wisconsin between 2008 and 2016. Most of the patients (90%) were white, 85% were female, average age was 50 years, and nearly all had classic or follicular-variant disease. Only 27% of patients underwent thyroid lobectomy; the rest underwent total thyroidectomy. Furthermore, among 19 patients diagnosed preoperatively, 95% underwent total thyroidectomy and 21% had a complication, including one (5%) case of permanent hypocalcemia that less extensive surgery might have avoided (J Surg Res. 2017;218:237-45).
“In all cases, documentation indicated that these preoperatively diagnosed patients followed the surgeon’s recommendation regarding the extent of surgery,” the researchers wrote. Surgeons cited various reasons for recommending total thyroidectomy, including – in about 20% of cases – a belief that it was the recommended treatment.
Only one of the 19 preoperatively diagnosed patients had a documented discussion of thyroid lobectomy, the researchers found.
While physicians might be concerned about recurrence or other “downstream” outcomes of a less-is-more approach to PTMC, Dr. Pitt noted that, in a recent large study, only 3.4% of these tumors metastasized over 10 years (World J Surg. 2010 Jan;34[1]:28-35).
“At the same time, I think that we have a better sense [that] patient-centered outcomes after thyroidectomy, such as health-related quality of life, swallowing, and voice outcomes, can be worse after a total thyroidectomy,” she added.
As surgical and medical therapies expand for PTMC and other nonmalignant diseases, it becomes increasingly vital that surgeons and patients undertake shared decision-making, she said. At the University of Wisconsin, physicians can enter free text in the EHR to document such discussions. She gave an example of how she does that: “‘Total thyroidectomy and lobectomy are both appropriate approaches for Ms. Smith. We discussed these options at length, including X, Y, and Z. Given Mrs. Smith’s (strong) preference to avoid X, we will proceed with a lobectomy.”
In her own practice, Dr. Pitt added, “when I look back at a note, I want to know what the decision was, and why it was made.”
Shared decision-making differs from informed consent by focusing on patient preferences, she noted. “I have used my notes in the operating room to help me decide what to do. I can look back and have a window into our conversation and what an individual patient values.” For PTMC, shared decisions should focus less on cancer risk and more on quality of life and outcomes a year later, she said.
“Patients don’t die from PTMC, and most live longer than the age-matched population. Given the risks of more extensive surgery and our current data on surgical and patient-centered outcomes, I think that thyroid lobectomy should be the initial treatment for most patients with PTMC, and surgeons should help their patients make informed decisions,” Dr. Pitt said.
The National Institutes of Health provided funding. The researchers reported having no conflicts of interest.
FROM THE JOURNAL OF SURGICAL RESEARCH
Key clinical point: Nearly all patients with a preoperative diagnosis of PTMC underwent total thyroidectomy, usually at their surgeon’s recommendation.
Major finding: 95% of preoperatively diagnosed patients underwent total thyroidectomy, versus 69% of those diagnosed postoperatively (P = .02). A discussion of thyroid lobectomy was documented in only one preoperatively diagnosed case.
Data source: A single-center retrospective study of 125 patients with papillary thyroid microcarcinoma.
Disclosures: The National Institutes of Health provided funding. The researchers reported having no conflicts of interest.
Reminder spurs flu vaccination of chronic disease patients
and because their parents are unaware influenza is risky for their children, reported Gilat Livni, MD, and Alina Wainstein, MD, of Tel Aviv University and their associates.
The investigators surveyed 186 parents of children attending a cardiology institute in Israel regarding flu vaccination. Over a third (37%) of the children had received a flu vaccine during the last flu season. Those who had been vaccinated were significantly more likely to have parents and siblings who were vaccinated (P less than .01).The mean age of the children was 8 years.
The main underlying cardiac diseases in the 186 children were left-to-right shunt defect in 31%, obstructive lesions in 30%, and cyanotic defect in 16%. Other cardiac abnormalities included valvular insufficiency in 11%, cardiomyopathy in 8%, and complete atrioventricular block in 4%.
More than half of parents (59%) reported that a pediatrician had recommended that their child get a flu vaccine; of these parents, 53% complied. Only 13% of parents who did not get such a recommendation had their children vaccinated – a statistically significant difference. Findings were similar regarding recommendations from pediatric cardiologists. “The failure of parents to receive information or advice from a physician regarding vaccination was strongly inversely related to vaccination of the child,” the investigators concluded.
“Our results emphasize the need to raise awareness among physicians and other medical health care personnel dealing with children with heart disease of the importance of properly counseling parents regarding influenza vaccination. Recommending the vaccine should be made part of routine patient visits in fall and winter,” concluded Dr. Livni, Dr. Wainstein, and associates.
The full text is available online (Pediatr Infect Dis J. 2017 Nov;36[11]: e268-71. doi: 10.1097/INF.0000000000001579).
and because their parents are unaware influenza is risky for their children, reported Gilat Livni, MD, and Alina Wainstein, MD, of Tel Aviv University and their associates.
The investigators surveyed 186 parents of children attending a cardiology institute in Israel regarding flu vaccination. Over a third (37%) of the children had received a flu vaccine during the last flu season. Those who had been vaccinated were significantly more likely to have parents and siblings who were vaccinated (P less than .01).The mean age of the children was 8 years.
The main underlying cardiac diseases in the 186 children were left-to-right shunt defect in 31%, obstructive lesions in 30%, and cyanotic defect in 16%. Other cardiac abnormalities included valvular insufficiency in 11%, cardiomyopathy in 8%, and complete atrioventricular block in 4%.
More than half of parents (59%) reported that a pediatrician had recommended that their child get a flu vaccine; of these parents, 53% complied. Only 13% of parents who did not get such a recommendation had their children vaccinated – a statistically significant difference. Findings were similar regarding recommendations from pediatric cardiologists. “The failure of parents to receive information or advice from a physician regarding vaccination was strongly inversely related to vaccination of the child,” the investigators concluded.
“Our results emphasize the need to raise awareness among physicians and other medical health care personnel dealing with children with heart disease of the importance of properly counseling parents regarding influenza vaccination. Recommending the vaccine should be made part of routine patient visits in fall and winter,” concluded Dr. Livni, Dr. Wainstein, and associates.
The full text is available online (Pediatr Infect Dis J. 2017 Nov;36[11]: e268-71. doi: 10.1097/INF.0000000000001579).
and because their parents are unaware influenza is risky for their children, reported Gilat Livni, MD, and Alina Wainstein, MD, of Tel Aviv University and their associates.
The investigators surveyed 186 parents of children attending a cardiology institute in Israel regarding flu vaccination. Over a third (37%) of the children had received a flu vaccine during the last flu season. Those who had been vaccinated were significantly more likely to have parents and siblings who were vaccinated (P less than .01).The mean age of the children was 8 years.
The main underlying cardiac diseases in the 186 children were left-to-right shunt defect in 31%, obstructive lesions in 30%, and cyanotic defect in 16%. Other cardiac abnormalities included valvular insufficiency in 11%, cardiomyopathy in 8%, and complete atrioventricular block in 4%.
More than half of parents (59%) reported that a pediatrician had recommended that their child get a flu vaccine; of these parents, 53% complied. Only 13% of parents who did not get such a recommendation had their children vaccinated – a statistically significant difference. Findings were similar regarding recommendations from pediatric cardiologists. “The failure of parents to receive information or advice from a physician regarding vaccination was strongly inversely related to vaccination of the child,” the investigators concluded.
“Our results emphasize the need to raise awareness among physicians and other medical health care personnel dealing with children with heart disease of the importance of properly counseling parents regarding influenza vaccination. Recommending the vaccine should be made part of routine patient visits in fall and winter,” concluded Dr. Livni, Dr. Wainstein, and associates.
The full text is available online (Pediatr Infect Dis J. 2017 Nov;36[11]: e268-71. doi: 10.1097/INF.0000000000001579).
FROM THE PEDIATRIC INFECTIOUS DISEASE JOURNAL
Low risk of bariatric surgery complications in IBD
Bariatric surgery is safe and feasible in patients with inflammatory bowel disease (IBD), with a low risk of postoperative complications vs. controls, according to results of a recent cohort study.
Besides a significantly higher risk of perioperative small-bowel obstruction and a 1-day increase in hospital stay, outcomes were comparable between patients with IBD and controls (Obes Surg. 2017 Oct 10. doi: 10.1007/s11695-017-2955-4).
Limitations of the retrospective study, according to the authors, included a potential underestimation of short-term postoperative complications, since the data set used in the study was limited to in-hospital stays and would not include events occurring after discharge.
Nevertheless, “our data show that it is reasonable to carefully proceed with bariatric interventions in obese IBD patients, especially those who are at higher risk of cardiovascular mortality and drastic need for weight reduction, to accrue benefits of weight loss,” wrote Fateh Bazerbachi, MD, of the Mayo Clinic, Rochester, Minn. and his coauthors.
Bariatric surgery is the “most effective solution” for obesity, and “appropriate candidates should not be deprived of this important, potentially life-saving procedure, if the intervention is deemed acceptably safe,” Dr. Bazerbachi and his colleagues noted.
Their cohort study included data for 314,864 adult patients in the Nationwide Inpatient Sample who underwent bariatric surgery between 2011 and 2013. Of that group, 790 patients had underlying IBD (459 Crohn’s disease, 331 ulcerative colitis). Remaining patients made up the comparator group.
The primary outcomes evaluated in the study included risks of systemic and technical complications. Risk of perioperative small-bowel obstruction was significantly higher in the IBD group (adjusted odds ratio, 4.0; 95% confidence interval, 2.2-7.4). However, the rates of other complications were similar between the two groups, data show.
Secondary outcomes in the study included length of hospital stay and mortality. Mean length of hospital stay was 3.4 days for IBD patients, vs. 2.5 days for the comparison group (P = .01), according to the report. Mortality was 0.25% for controls, while no deaths were reported in the IBD group.
In the future, bariatric surgeons may face increasing demand to treat IBD patients, given the increasing prevalence of obesity in the IBD patient population, Dr. Bazerbachi and his colleagues said.
Some surgeons may believe that bariatric intervention is more challenging in IBD patients, in part because of the underlying inflammatory state that might interfere with healing of wounds and recovery of bowel motility, they said. Bariatric surgery, however, can reduce body mass index, which in turn might make future IBD surgeries less challenging.
Another potential advantage is reduction in cardiovascular risk, which is elevated in IBD patients both due to obesity as well as the IBD condition, they added.
“Further studies are certainly needed to examine long-term outcomes of bariatric surgery on IBD and to determine whether cardiovascular mortality is reduced from these interventions in this susceptible cohort of obese IBD patients,” Dr. Bazerbachi and his colleagues wrote.
The authors declared that they had no conflicts of interest.
Bariatric surgery is safe and feasible in patients with inflammatory bowel disease (IBD), with a low risk of postoperative complications vs. controls, according to results of a recent cohort study.
Besides a significantly higher risk of perioperative small-bowel obstruction and a 1-day increase in hospital stay, outcomes were comparable between patients with IBD and controls (Obes Surg. 2017 Oct 10. doi: 10.1007/s11695-017-2955-4).
Limitations of the retrospective study, according to the authors, included a potential underestimation of short-term postoperative complications, since the data set used in the study was limited to in-hospital stays and would not include events occurring after discharge.
Nevertheless, “our data show that it is reasonable to carefully proceed with bariatric interventions in obese IBD patients, especially those who are at higher risk of cardiovascular mortality and drastic need for weight reduction, to accrue benefits of weight loss,” wrote Fateh Bazerbachi, MD, of the Mayo Clinic, Rochester, Minn. and his coauthors.
Bariatric surgery is the “most effective solution” for obesity, and “appropriate candidates should not be deprived of this important, potentially life-saving procedure, if the intervention is deemed acceptably safe,” Dr. Bazerbachi and his colleagues noted.
Their cohort study included data for 314,864 adult patients in the Nationwide Inpatient Sample who underwent bariatric surgery between 2011 and 2013. Of that group, 790 patients had underlying IBD (459 Crohn’s disease, 331 ulcerative colitis). Remaining patients made up the comparator group.
The primary outcomes evaluated in the study included risks of systemic and technical complications. Risk of perioperative small-bowel obstruction was significantly higher in the IBD group (adjusted odds ratio, 4.0; 95% confidence interval, 2.2-7.4). However, the rates of other complications were similar between the two groups, data show.
Secondary outcomes in the study included length of hospital stay and mortality. Mean length of hospital stay was 3.4 days for IBD patients, vs. 2.5 days for the comparison group (P = .01), according to the report. Mortality was 0.25% for controls, while no deaths were reported in the IBD group.
In the future, bariatric surgeons may face increasing demand to treat IBD patients, given the increasing prevalence of obesity in the IBD patient population, Dr. Bazerbachi and his colleagues said.
Some surgeons may believe that bariatric intervention is more challenging in IBD patients, in part because of the underlying inflammatory state that might interfere with healing of wounds and recovery of bowel motility, they said. Bariatric surgery, however, can reduce body mass index, which in turn might make future IBD surgeries less challenging.
Another potential advantage is reduction in cardiovascular risk, which is elevated in IBD patients both due to obesity as well as the IBD condition, they added.
“Further studies are certainly needed to examine long-term outcomes of bariatric surgery on IBD and to determine whether cardiovascular mortality is reduced from these interventions in this susceptible cohort of obese IBD patients,” Dr. Bazerbachi and his colleagues wrote.
The authors declared that they had no conflicts of interest.
Bariatric surgery is safe and feasible in patients with inflammatory bowel disease (IBD), with a low risk of postoperative complications vs. controls, according to results of a recent cohort study.
Besides a significantly higher risk of perioperative small-bowel obstruction and a 1-day increase in hospital stay, outcomes were comparable between patients with IBD and controls (Obes Surg. 2017 Oct 10. doi: 10.1007/s11695-017-2955-4).
Limitations of the retrospective study, according to the authors, included a potential underestimation of short-term postoperative complications, since the data set used in the study was limited to in-hospital stays and would not include events occurring after discharge.
Nevertheless, “our data show that it is reasonable to carefully proceed with bariatric interventions in obese IBD patients, especially those who are at higher risk of cardiovascular mortality and drastic need for weight reduction, to accrue benefits of weight loss,” wrote Fateh Bazerbachi, MD, of the Mayo Clinic, Rochester, Minn. and his coauthors.
Bariatric surgery is the “most effective solution” for obesity, and “appropriate candidates should not be deprived of this important, potentially life-saving procedure, if the intervention is deemed acceptably safe,” Dr. Bazerbachi and his colleagues noted.
Their cohort study included data for 314,864 adult patients in the Nationwide Inpatient Sample who underwent bariatric surgery between 2011 and 2013. Of that group, 790 patients had underlying IBD (459 Crohn’s disease, 331 ulcerative colitis). Remaining patients made up the comparator group.
The primary outcomes evaluated in the study included risks of systemic and technical complications. Risk of perioperative small-bowel obstruction was significantly higher in the IBD group (adjusted odds ratio, 4.0; 95% confidence interval, 2.2-7.4). However, the rates of other complications were similar between the two groups, data show.
Secondary outcomes in the study included length of hospital stay and mortality. Mean length of hospital stay was 3.4 days for IBD patients, vs. 2.5 days for the comparison group (P = .01), according to the report. Mortality was 0.25% for controls, while no deaths were reported in the IBD group.
In the future, bariatric surgeons may face increasing demand to treat IBD patients, given the increasing prevalence of obesity in the IBD patient population, Dr. Bazerbachi and his colleagues said.
Some surgeons may believe that bariatric intervention is more challenging in IBD patients, in part because of the underlying inflammatory state that might interfere with healing of wounds and recovery of bowel motility, they said. Bariatric surgery, however, can reduce body mass index, which in turn might make future IBD surgeries less challenging.
Another potential advantage is reduction in cardiovascular risk, which is elevated in IBD patients both due to obesity as well as the IBD condition, they added.
“Further studies are certainly needed to examine long-term outcomes of bariatric surgery on IBD and to determine whether cardiovascular mortality is reduced from these interventions in this susceptible cohort of obese IBD patients,” Dr. Bazerbachi and his colleagues wrote.
The authors declared that they had no conflicts of interest.
FROM OBESITY SURGERY
Key clinical point: Watch for perioperative small-bowel obstruction in IBD patients undergoing bariatric surgery.
Major finding: IBD patients had a higher risk of perioperative small bowel obstruction (adjusted odds ratio, 4.0; 95% confidence interval, 2.2-7.4) and a 1-day increase in hospital stay (P = .01), compared with controls.
Data source: Retrospective cohort study of Nationwide Inpatient Sample data including 790 patients with underlying IBD.
Disclosures: The authors declared that they had no conflicts of interest.
Symptoms fail to predict benefit of hormone therapy in older adults with subclinical hypothyroidism
VICTORIA, B.C. – , according to findings from a study reported at the annual meeting of the American Thyroid Association.
“In the U.S., individuals are frequently treated either for just a number – just because their thyroid-stimulating hormone (TSH) is elevated – or for nonspecific hypothyroid-type symptoms, such as weight gain, cold intolerance, and such. It’s extremely common,” lead investigator Douglas Bauer, MD, professor and internist at the University of California, San Francisco, commented in an interview.
“On average, this study suggests that you shouldn’t be using hypothyroid-type symptomatology to treat subclinical hypothyroidism,” he said, while also acknowledging that not writing that prescription can be challenging. “It’s hard to do nothing, I know.”
Dr. Bauer and his coinvestigators performed a subgroup analysis of the randomized controlled TRUST trial (Thyroid Hormone Replacement for Subclinical Hypothyroidism), conducted in Switzerland, Ireland, the Netherlands, and the United Kingdom. In the trial, 737 adults aged 65 years or older with persistent subclinical hypothyroidism (TSH level, 4.60-19.99 mIU/L, with normal free thyroxine level) were given either levothyroxine or placebo on a double-blind basis.
Results for the entire trial population, previously reported, showed that at 1 year, patient-reported symptoms on a thyroid-specific quality-of-life questionnaire had improved by a similar extent in both groups, with no significant differences between them (N Engl J Med. 2017;376:2534-44).
The new analysis focused on two subgroups that might be especially expected to benefit: 132 patients with a hypothyroid symptoms score greater than 30 on a 100-point scale and 209 patients with a tiredness score greater than 30 on a 100-point scale.
Results reported in a poster session showed that at 1 year, scores had improved by about 10 points with levothyroxine and placebo alike, with no significant difference, in both the group with higher hypothyroid symptoms scores (P = .90) and the group with higher tiredness scores (P = .80).
“This provides additional evidence that it’s unlikely that the treatment of subclinical hypothyroidism, at least in this population, is going to lead to symptomatic improvement,” Dr. Bauer commented.
“I would speculate that we’ve overestimated the benefit [of thyroid hormone therapy] on symptoms based on the fact that previous studies haven’t been blinded,” he said, noting that the TRUST trial used a rigorous blinding protocol, even going so far as to change the appearance of placebo pills to convince patients in the placebo group that their dose was being titrated.
A potential criticism is that the treatment was not aggressive enough, with patients in the levothyroxine group achieving a mean TSH level of 3.6 mIU/L, according to Dr. Bauer. “I think many people treating with thyroxine would like to see this TSH fall into the 2 mIU/L to 3 mIU/L range,” he acknowledged.
Taken together, the trial’s overall and subgroup findings do not rule out potential benefit for certain patients, he cautioned. For example, patients with very high symptom burden and patients with baseline TSH levels greater than 10 mIU/L were too few for separate analysis, and younger adults were not included at all.
Additionally, treatment impact on other important clinical outcomes – cardiovascular events and fractures – could not be assessed in TRUST because of insufficient enrollment.
Dr. Bauer disclosed that he had no relevant conflicts of interest. The trial was funded by the European Union, Swiss National Science Foundation, Swiss Heart Foundation, and Velux Stiftung. Merck supplied study drug.
VICTORIA, B.C. – , according to findings from a study reported at the annual meeting of the American Thyroid Association.
“In the U.S., individuals are frequently treated either for just a number – just because their thyroid-stimulating hormone (TSH) is elevated – or for nonspecific hypothyroid-type symptoms, such as weight gain, cold intolerance, and such. It’s extremely common,” lead investigator Douglas Bauer, MD, professor and internist at the University of California, San Francisco, commented in an interview.
“On average, this study suggests that you shouldn’t be using hypothyroid-type symptomatology to treat subclinical hypothyroidism,” he said, while also acknowledging that not writing that prescription can be challenging. “It’s hard to do nothing, I know.”
Dr. Bauer and his coinvestigators performed a subgroup analysis of the randomized controlled TRUST trial (Thyroid Hormone Replacement for Subclinical Hypothyroidism), conducted in Switzerland, Ireland, the Netherlands, and the United Kingdom. In the trial, 737 adults aged 65 years or older with persistent subclinical hypothyroidism (TSH level, 4.60-19.99 mIU/L, with normal free thyroxine level) were given either levothyroxine or placebo on a double-blind basis.
Results for the entire trial population, previously reported, showed that at 1 year, patient-reported symptoms on a thyroid-specific quality-of-life questionnaire had improved by a similar extent in both groups, with no significant differences between them (N Engl J Med. 2017;376:2534-44).
The new analysis focused on two subgroups that might be especially expected to benefit: 132 patients with a hypothyroid symptoms score greater than 30 on a 100-point scale and 209 patients with a tiredness score greater than 30 on a 100-point scale.
Results reported in a poster session showed that at 1 year, scores had improved by about 10 points with levothyroxine and placebo alike, with no significant difference, in both the group with higher hypothyroid symptoms scores (P = .90) and the group with higher tiredness scores (P = .80).
“This provides additional evidence that it’s unlikely that the treatment of subclinical hypothyroidism, at least in this population, is going to lead to symptomatic improvement,” Dr. Bauer commented.
“I would speculate that we’ve overestimated the benefit [of thyroid hormone therapy] on symptoms based on the fact that previous studies haven’t been blinded,” he said, noting that the TRUST trial used a rigorous blinding protocol, even going so far as to change the appearance of placebo pills to convince patients in the placebo group that their dose was being titrated.
A potential criticism is that the treatment was not aggressive enough, with patients in the levothyroxine group achieving a mean TSH level of 3.6 mIU/L, according to Dr. Bauer. “I think many people treating with thyroxine would like to see this TSH fall into the 2 mIU/L to 3 mIU/L range,” he acknowledged.
Taken together, the trial’s overall and subgroup findings do not rule out potential benefit for certain patients, he cautioned. For example, patients with very high symptom burden and patients with baseline TSH levels greater than 10 mIU/L were too few for separate analysis, and younger adults were not included at all.
Additionally, treatment impact on other important clinical outcomes – cardiovascular events and fractures – could not be assessed in TRUST because of insufficient enrollment.
Dr. Bauer disclosed that he had no relevant conflicts of interest. The trial was funded by the European Union, Swiss National Science Foundation, Swiss Heart Foundation, and Velux Stiftung. Merck supplied study drug.
VICTORIA, B.C. – , according to findings from a study reported at the annual meeting of the American Thyroid Association.
“In the U.S., individuals are frequently treated either for just a number – just because their thyroid-stimulating hormone (TSH) is elevated – or for nonspecific hypothyroid-type symptoms, such as weight gain, cold intolerance, and such. It’s extremely common,” lead investigator Douglas Bauer, MD, professor and internist at the University of California, San Francisco, commented in an interview.
“On average, this study suggests that you shouldn’t be using hypothyroid-type symptomatology to treat subclinical hypothyroidism,” he said, while also acknowledging that not writing that prescription can be challenging. “It’s hard to do nothing, I know.”
Dr. Bauer and his coinvestigators performed a subgroup analysis of the randomized controlled TRUST trial (Thyroid Hormone Replacement for Subclinical Hypothyroidism), conducted in Switzerland, Ireland, the Netherlands, and the United Kingdom. In the trial, 737 adults aged 65 years or older with persistent subclinical hypothyroidism (TSH level, 4.60-19.99 mIU/L, with normal free thyroxine level) were given either levothyroxine or placebo on a double-blind basis.
Results for the entire trial population, previously reported, showed that at 1 year, patient-reported symptoms on a thyroid-specific quality-of-life questionnaire had improved by a similar extent in both groups, with no significant differences between them (N Engl J Med. 2017;376:2534-44).
The new analysis focused on two subgroups that might be especially expected to benefit: 132 patients with a hypothyroid symptoms score greater than 30 on a 100-point scale and 209 patients with a tiredness score greater than 30 on a 100-point scale.
Results reported in a poster session showed that at 1 year, scores had improved by about 10 points with levothyroxine and placebo alike, with no significant difference, in both the group with higher hypothyroid symptoms scores (P = .90) and the group with higher tiredness scores (P = .80).
“This provides additional evidence that it’s unlikely that the treatment of subclinical hypothyroidism, at least in this population, is going to lead to symptomatic improvement,” Dr. Bauer commented.
“I would speculate that we’ve overestimated the benefit [of thyroid hormone therapy] on symptoms based on the fact that previous studies haven’t been blinded,” he said, noting that the TRUST trial used a rigorous blinding protocol, even going so far as to change the appearance of placebo pills to convince patients in the placebo group that their dose was being titrated.
A potential criticism is that the treatment was not aggressive enough, with patients in the levothyroxine group achieving a mean TSH level of 3.6 mIU/L, according to Dr. Bauer. “I think many people treating with thyroxine would like to see this TSH fall into the 2 mIU/L to 3 mIU/L range,” he acknowledged.
Taken together, the trial’s overall and subgroup findings do not rule out potential benefit for certain patients, he cautioned. For example, patients with very high symptom burden and patients with baseline TSH levels greater than 10 mIU/L were too few for separate analysis, and younger adults were not included at all.
Additionally, treatment impact on other important clinical outcomes – cardiovascular events and fractures – could not be assessed in TRUST because of insufficient enrollment.
Dr. Bauer disclosed that he had no relevant conflicts of interest. The trial was funded by the European Union, Swiss National Science Foundation, Swiss Heart Foundation, and Velux Stiftung. Merck supplied study drug.
AT ATA 2017
Key clinical point: Hypothyroid-type symptoms do not predict treatment benefit in older adults with subclinical hypothyroidism.
Major finding: Patients had statistically indistinguishable improvements at 1 year in hypothyroid symptoms scores (P = .90) and Tiredness scores (P = .80) whether given levothyroxine or placebo.
Data source: A subgroup analysis of older adults with subclinical hypothyroidism having higher baseline levels of overall hypothyroid symptoms (n = 132) or tiredness (n = 209) (TRUST trial).
Disclosures: Dr. Bauer disclosed that he had no relevant conflicts of interest. The trial was funded by the European Union, Swiss National Science Foundation, Swiss Heart Foundation, and Velux Stiftung. Merck supplied study drug.
Abnormal potassium plus suspected ACS spell trouble
BARCELONA – A serum potassium level of at least 5.0 mmol/L or 3.5 mmol/L or less at admission for suspected acute coronary syndrome is a red flag for increased risk of in-hospital mortality and cardiac arrest, according to a Swedish study of nearly 33,000 consecutive patients.
That’s true even if, as so often ultimately proves to be the case, the patient turns out not to have ACS, Jonas Faxén, MD, of the Karolinska Institute, Stockholm, reported at the annual congress of the European Society of Cardiology.
“This study highlights that, if you have a patient in the emergency department with a possible ACS and potassium imbalance, you should really be cautious,” Dr. Faxén said.
He reported on 32,955 consecutive patients admitted to Stockholm County hospitals for suspected ACS during 2006-2011 and thereby enrolled in the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry.
Overall in-hospital mortality was 2.7%. In-hospital cardiac arrest occurred in 1.5% of patients. New-onset atrial fibrillation occurred in 2.4% of patients. These key outcomes were compared between the reference group – defined as patients with an admission serum potassium of 3.5 to less than 4.0 mmol/L – and patients with an admission serum potassium above or below those cutoffs.
In a multivariate logistic regression analysis adjusted for 24 potential confounders, including demographics, presentation characteristics, main diagnosis, comorbid conditions, medications on admission, and estimated glomerular filtration rate, patients with a serum potassium of 5.0 to less than 5.5 mmol/L were at 1.8-fold increased risk of in-hospital mortality. Those with a potassium of 5.5 mmol/L or greater were at 2.3-fold increased risk.
In contrast, a low rather than a high serum potassium was an independent risk factor cardiac arrest. An admission potassium of 3.0 to less than 3.5 mmol/L carried a 1.8-fold increased risk of in-hospital cardiac arrest, while a potassium of less than 3.0 was associated with a 2.7-fold increased risk.
A serum potassium below 3.0 mmol/L at admission also was associated with a 1.7-fold increased risk of new-onset atrial fibrillation.
These elevated risks of bad outcomes didn’t differ significantly between patients with ST-elevation MI, non-STEMI ACS, and those whose final diagnosis was not ACS, Dr. Faxén noted.
Session cochair David W. Walker, MD, medical director of the East Sussex (England) Healthcare NHS Trust, observed, “When I was a junior doctor I was always taught that when patients came onto coronary care we had to get their potassium to 4.5-5.0 mmol/L. I think you might want to change that advice now.”
“The implication would be that, if you intervene quickly in a patient with an abnormal potassium level, you might make a difference. Clearly, a potassium that’s too high is much worse than too low, since patients with in-hospital cardiac arrest can often be resuscitated,” Dr. Walker commented.
Dr. Faxén reported having no financial conflicts regarding his study, which was funded by the Swedish Heart and Lung Foundation and the Stockholm County Council.
BARCELONA – A serum potassium level of at least 5.0 mmol/L or 3.5 mmol/L or less at admission for suspected acute coronary syndrome is a red flag for increased risk of in-hospital mortality and cardiac arrest, according to a Swedish study of nearly 33,000 consecutive patients.
That’s true even if, as so often ultimately proves to be the case, the patient turns out not to have ACS, Jonas Faxén, MD, of the Karolinska Institute, Stockholm, reported at the annual congress of the European Society of Cardiology.
“This study highlights that, if you have a patient in the emergency department with a possible ACS and potassium imbalance, you should really be cautious,” Dr. Faxén said.
He reported on 32,955 consecutive patients admitted to Stockholm County hospitals for suspected ACS during 2006-2011 and thereby enrolled in the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry.
Overall in-hospital mortality was 2.7%. In-hospital cardiac arrest occurred in 1.5% of patients. New-onset atrial fibrillation occurred in 2.4% of patients. These key outcomes were compared between the reference group – defined as patients with an admission serum potassium of 3.5 to less than 4.0 mmol/L – and patients with an admission serum potassium above or below those cutoffs.
In a multivariate logistic regression analysis adjusted for 24 potential confounders, including demographics, presentation characteristics, main diagnosis, comorbid conditions, medications on admission, and estimated glomerular filtration rate, patients with a serum potassium of 5.0 to less than 5.5 mmol/L were at 1.8-fold increased risk of in-hospital mortality. Those with a potassium of 5.5 mmol/L or greater were at 2.3-fold increased risk.
In contrast, a low rather than a high serum potassium was an independent risk factor cardiac arrest. An admission potassium of 3.0 to less than 3.5 mmol/L carried a 1.8-fold increased risk of in-hospital cardiac arrest, while a potassium of less than 3.0 was associated with a 2.7-fold increased risk.
A serum potassium below 3.0 mmol/L at admission also was associated with a 1.7-fold increased risk of new-onset atrial fibrillation.
These elevated risks of bad outcomes didn’t differ significantly between patients with ST-elevation MI, non-STEMI ACS, and those whose final diagnosis was not ACS, Dr. Faxén noted.
Session cochair David W. Walker, MD, medical director of the East Sussex (England) Healthcare NHS Trust, observed, “When I was a junior doctor I was always taught that when patients came onto coronary care we had to get their potassium to 4.5-5.0 mmol/L. I think you might want to change that advice now.”
“The implication would be that, if you intervene quickly in a patient with an abnormal potassium level, you might make a difference. Clearly, a potassium that’s too high is much worse than too low, since patients with in-hospital cardiac arrest can often be resuscitated,” Dr. Walker commented.
Dr. Faxén reported having no financial conflicts regarding his study, which was funded by the Swedish Heart and Lung Foundation and the Stockholm County Council.
BARCELONA – A serum potassium level of at least 5.0 mmol/L or 3.5 mmol/L or less at admission for suspected acute coronary syndrome is a red flag for increased risk of in-hospital mortality and cardiac arrest, according to a Swedish study of nearly 33,000 consecutive patients.
That’s true even if, as so often ultimately proves to be the case, the patient turns out not to have ACS, Jonas Faxén, MD, of the Karolinska Institute, Stockholm, reported at the annual congress of the European Society of Cardiology.
“This study highlights that, if you have a patient in the emergency department with a possible ACS and potassium imbalance, you should really be cautious,” Dr. Faxén said.
He reported on 32,955 consecutive patients admitted to Stockholm County hospitals for suspected ACS during 2006-2011 and thereby enrolled in the SWEDEHEART (Swedish Web System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies) registry.
Overall in-hospital mortality was 2.7%. In-hospital cardiac arrest occurred in 1.5% of patients. New-onset atrial fibrillation occurred in 2.4% of patients. These key outcomes were compared between the reference group – defined as patients with an admission serum potassium of 3.5 to less than 4.0 mmol/L – and patients with an admission serum potassium above or below those cutoffs.
In a multivariate logistic regression analysis adjusted for 24 potential confounders, including demographics, presentation characteristics, main diagnosis, comorbid conditions, medications on admission, and estimated glomerular filtration rate, patients with a serum potassium of 5.0 to less than 5.5 mmol/L were at 1.8-fold increased risk of in-hospital mortality. Those with a potassium of 5.5 mmol/L or greater were at 2.3-fold increased risk.
In contrast, a low rather than a high serum potassium was an independent risk factor cardiac arrest. An admission potassium of 3.0 to less than 3.5 mmol/L carried a 1.8-fold increased risk of in-hospital cardiac arrest, while a potassium of less than 3.0 was associated with a 2.7-fold increased risk.
A serum potassium below 3.0 mmol/L at admission also was associated with a 1.7-fold increased risk of new-onset atrial fibrillation.
These elevated risks of bad outcomes didn’t differ significantly between patients with ST-elevation MI, non-STEMI ACS, and those whose final diagnosis was not ACS, Dr. Faxén noted.
Session cochair David W. Walker, MD, medical director of the East Sussex (England) Healthcare NHS Trust, observed, “When I was a junior doctor I was always taught that when patients came onto coronary care we had to get their potassium to 4.5-5.0 mmol/L. I think you might want to change that advice now.”
“The implication would be that, if you intervene quickly in a patient with an abnormal potassium level, you might make a difference. Clearly, a potassium that’s too high is much worse than too low, since patients with in-hospital cardiac arrest can often be resuscitated,” Dr. Walker commented.
Dr. Faxén reported having no financial conflicts regarding his study, which was funded by the Swedish Heart and Lung Foundation and the Stockholm County Council.
AT THE ESC CONGRESS 2017
Key clinical point:
Major finding: Hyperkalemia of 5.0 to less than 5.5 mmol/L at admission for suspected ACS was associated with close to a twofold increased risk of in-hospital mortality.
Data source: The SWEDEHEART study is an ongoing prospective registry of patients with cardiovascular disease admitted to Stockholm County hospitals.
Disclosures: The presenter reported having no financial conflicts regarding his study, which was funded by the Swedish Heart and Lung Foundation and the Stockholm County Council.