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New guideline: Address GTCS frequency to reduce SUDEP risk
BOSTON – Generalized tonic-clonic seizures (GTCS) are a major risk factor for sudden unexpected death in epilepsy (SUDEP), which underscores the importance of advising people with epilepsy about controlling such seizures, according to a new practice guideline from the American Academy of Neurology and the American Epilepsy Society.
Though SUDEP is rare, with an incidence rate of 0.22/1,000 patient-years in children with epilepsy and 1.2/1,000 patient-years in adults with epilepsy, the guideline committee found that people with three or more GTCS per year are 15 times more likely to die suddenly than are those without this seizure type. The risk increases with increasing GTCS frequency. This translates to an absolute risk of up to 18 deaths per 1,000 patient-years for people with epilepsy who have frequent GTCS.
Specifically, the guideline recommends that , she said, adding that the guideline shows that “being free of seizures, particularly tonic-clonic seizures, is strongly associated with a decreased risk.”
Guideline coauthor, Elizabeth Donner, MD, added that, for this reason, the guideline recommends “that health professionals work with people who continue to have, specifically, these kind of seizures to try and reduce them with medications or with epilepsy surgery, actively weighing the risks and benefits of any new approach to seizure management.”
The recommendations are based on moderate (Level B) evidence.
The team also looked at numerous other risk factors for SUDEP and found that the strength of the evidence was too weak to support additional recommendations, said Dr. Donner, director of the comprehensive epilepsy program at The Hospital for Sick Children in Toronto and chair of the American Epilepsy Society SUDEP Task Force.
“More research is now needed to identify other preventable risk factors for SUDEP so that we can focus future studies on finding ways to reduce how often SUDEP occurs,” she added.
While the message regarding the importance of reducing seizure frequency is not new, it is important that this message be reiterated in the context of SUDEP, Dr. Donner said.
“It’s very important for it to be clear that the risk of frequent generalized tonic-clonic seizures – and we’re not talking about really frequent here; we’re talking about significant increased risk of death with only three per year – is not related only to maintaining a driver’s license, maintaining work, or other outcomes like that. It’s actually related to risk of death,” she said, noting that she hopes this is a motivator for pursuing treatments beyond medication when medication isn’t successful for treating seizures.
The guideline, which is endorsed by the International Child Neurology Association, is available online and in print (Neurology. 2017;88:1674–80).
Dr. Harden receives royalties from Wiley and Up-to-Date. Dr. Donner has received research support from the Canadian Institutes of Health Research, Dravet Canada, and SUDEP Aware. Other guideline authors reported numerous disclosures, including many industry sources.
BOSTON – Generalized tonic-clonic seizures (GTCS) are a major risk factor for sudden unexpected death in epilepsy (SUDEP), which underscores the importance of advising people with epilepsy about controlling such seizures, according to a new practice guideline from the American Academy of Neurology and the American Epilepsy Society.
Though SUDEP is rare, with an incidence rate of 0.22/1,000 patient-years in children with epilepsy and 1.2/1,000 patient-years in adults with epilepsy, the guideline committee found that people with three or more GTCS per year are 15 times more likely to die suddenly than are those without this seizure type. The risk increases with increasing GTCS frequency. This translates to an absolute risk of up to 18 deaths per 1,000 patient-years for people with epilepsy who have frequent GTCS.
Specifically, the guideline recommends that , she said, adding that the guideline shows that “being free of seizures, particularly tonic-clonic seizures, is strongly associated with a decreased risk.”
Guideline coauthor, Elizabeth Donner, MD, added that, for this reason, the guideline recommends “that health professionals work with people who continue to have, specifically, these kind of seizures to try and reduce them with medications or with epilepsy surgery, actively weighing the risks and benefits of any new approach to seizure management.”
The recommendations are based on moderate (Level B) evidence.
The team also looked at numerous other risk factors for SUDEP and found that the strength of the evidence was too weak to support additional recommendations, said Dr. Donner, director of the comprehensive epilepsy program at The Hospital for Sick Children in Toronto and chair of the American Epilepsy Society SUDEP Task Force.
“More research is now needed to identify other preventable risk factors for SUDEP so that we can focus future studies on finding ways to reduce how often SUDEP occurs,” she added.
While the message regarding the importance of reducing seizure frequency is not new, it is important that this message be reiterated in the context of SUDEP, Dr. Donner said.
“It’s very important for it to be clear that the risk of frequent generalized tonic-clonic seizures – and we’re not talking about really frequent here; we’re talking about significant increased risk of death with only three per year – is not related only to maintaining a driver’s license, maintaining work, or other outcomes like that. It’s actually related to risk of death,” she said, noting that she hopes this is a motivator for pursuing treatments beyond medication when medication isn’t successful for treating seizures.
The guideline, which is endorsed by the International Child Neurology Association, is available online and in print (Neurology. 2017;88:1674–80).
Dr. Harden receives royalties from Wiley and Up-to-Date. Dr. Donner has received research support from the Canadian Institutes of Health Research, Dravet Canada, and SUDEP Aware. Other guideline authors reported numerous disclosures, including many industry sources.
BOSTON – Generalized tonic-clonic seizures (GTCS) are a major risk factor for sudden unexpected death in epilepsy (SUDEP), which underscores the importance of advising people with epilepsy about controlling such seizures, according to a new practice guideline from the American Academy of Neurology and the American Epilepsy Society.
Though SUDEP is rare, with an incidence rate of 0.22/1,000 patient-years in children with epilepsy and 1.2/1,000 patient-years in adults with epilepsy, the guideline committee found that people with three or more GTCS per year are 15 times more likely to die suddenly than are those without this seizure type. The risk increases with increasing GTCS frequency. This translates to an absolute risk of up to 18 deaths per 1,000 patient-years for people with epilepsy who have frequent GTCS.
Specifically, the guideline recommends that , she said, adding that the guideline shows that “being free of seizures, particularly tonic-clonic seizures, is strongly associated with a decreased risk.”
Guideline coauthor, Elizabeth Donner, MD, added that, for this reason, the guideline recommends “that health professionals work with people who continue to have, specifically, these kind of seizures to try and reduce them with medications or with epilepsy surgery, actively weighing the risks and benefits of any new approach to seizure management.”
The recommendations are based on moderate (Level B) evidence.
The team also looked at numerous other risk factors for SUDEP and found that the strength of the evidence was too weak to support additional recommendations, said Dr. Donner, director of the comprehensive epilepsy program at The Hospital for Sick Children in Toronto and chair of the American Epilepsy Society SUDEP Task Force.
“More research is now needed to identify other preventable risk factors for SUDEP so that we can focus future studies on finding ways to reduce how often SUDEP occurs,” she added.
While the message regarding the importance of reducing seizure frequency is not new, it is important that this message be reiterated in the context of SUDEP, Dr. Donner said.
“It’s very important for it to be clear that the risk of frequent generalized tonic-clonic seizures – and we’re not talking about really frequent here; we’re talking about significant increased risk of death with only three per year – is not related only to maintaining a driver’s license, maintaining work, or other outcomes like that. It’s actually related to risk of death,” she said, noting that she hopes this is a motivator for pursuing treatments beyond medication when medication isn’t successful for treating seizures.
The guideline, which is endorsed by the International Child Neurology Association, is available online and in print (Neurology. 2017;88:1674–80).
Dr. Harden receives royalties from Wiley and Up-to-Date. Dr. Donner has received research support from the Canadian Institutes of Health Research, Dravet Canada, and SUDEP Aware. Other guideline authors reported numerous disclosures, including many industry sources.
AT AAN 2017
NCCN myelofibrosis guideline: Patient voice is key
ORLANDO – Referral to a specialized center with expertise in the management of myeloproliferative neoplasms is strongly recommended for all patients diagnosed with myelofibrosis, according to a new treatment guideline from the National Comprehensive Cancer Network.
The guideline is the first in a series addressing myeloproliferative neoplasms (MPNs), and it focuses on the diagnostic work-up of MPNs, as well as the treatment of myelofibrosis. The guideline panel, led by panel chair Ruben A. Mesa, MD, is working next on guidelines for the other two “core classic” Philadelphia chromosome–negative MPNs: polycythemia vera, and essential thrombocythemia.
Nearly two-thirds of myelofibrosis patients have intermediate-risk 2 or high-risk disease, and treatment decisions in these patients are complex and require patient input – particularly in candidates for allogeneic hematopoietic stem cell transplantation, he said.
“These diseases can be a little different than other malignant diseases,” Dr. Mesa said, explaining that while there is a clear risk of progression to acute myeloid leukemia, and from polycythemia vera and essential thrombocythemia to myelofibrosis, and while the diseases can be fatal, the burden patients face is not solely related to mortality.
There are implications in terms of health that are independent of that, such as the risk of thrombosis and bleeding, the potential for cytopenia, and severe splenomegaly that results in significant symptoms, he said.
Further, while molecular mutations and their implications for prognosis are a “rapidly moving part of the discussion,” the care of patients with MPNs involves far more than a molecular understanding of the disease.
In fact, the role of molecular changes in these patients is speculative, he said.
While such changes can be assessed and used for patient stratification, their role in myelofibrosis – unlike in other diseases such as chronic myeloid leukemia where the level of change in a target gene is highly relevant and prognostic, is not yet clear.
Thus, a core aspect of the guideline is inclusion of the voice of the patient in individualizing care, he said, noting that many factors should be considered, including how well the patient metabolizes drugs, and the symptom profile, psychosocial circumstances, support structure, and personal beliefs.
“It’s not solely about the tumor,” he stressed.
In fact, the answer to the question of whether a patient can be symptomatic enough to require a specific treatment is “no,” because of the potential for side effects, risk, expense, and other considerations.
“So the voice of the patient is always a key part [of the decision],” he said, noting also that as with all NCCN guidelines, this guideline is a partnership with the treating physician; deciding who is a transplant candidate is a nuanced issue for which the panel provides “discussion and guidance.”
“But clearly, these guidelines are the most useful and helpful in the setting of experienced providers bringing all of their experiences to bear,” he said.
In general, however, the guidelines call for allogeneic hematopoietic stem cell transplantation (HCT) in those with intermediate-risk 2 or high-risk disease who are transplant candidates, and treatment based on assessment of symptom burden (using the MPN–Symptom Assessment Form Total Symptom Score–10 Items) in those who are not HCT candidates. Those with platelets at 50,000 or below should be considered for clinical trial enrollment, and those with platelets above 50,000 should be considered for a clinical trial or treatment with the oral JAK1 and JAK2 inhibitor ruxolitinib, which has been shown to have beneficial effects on both symptoms and survival and which is approved for patients with platelets above 50,000. .
Treated patients should be monitored for response and for signs and symptoms of disease progression every 3-6 months. Treatment should continue in those who respond, as well as in those who do not – as long as there is no disease progression.
Those with progressive disease include patients who are moving toward acute leukemia, and those with overt acute leukemia.
“Here is where the key decision occurs. Are they or are they not a transplant candidate? If they are a candidate, we have a potentially curative track which would include cytoreduction followed by transplant,” Dr. Mesa said.
Cytoreduction can involve hypomethylating agents if the patient doesn’t have excess blast cells or too high a burden of disease.
Acute myeloid leukemia–like induction chemotherapy followed by allogeneic HCT is also an option in these patients.
As for treatment of low-risk myelofibrosis, the guideline states that asymptomatic patients can be observed or enrolled in a clinical trial and monitored for progression every 3-6 months, and that symptomatic patients should receive ruxolitinib or interferons (which are used off label), or be enrolled in a clinical trial. Treatment is important for patients with particularly difficult symptoms, he said, noting that some patients have had pruritus so severe that they have committed suicide. Treatment should continue unless monitoring shows signs of progression to intermediate risk 1, intermediate risk 2/high-risk, or advanced stage disease.
For those with intermediate risk 1 disease, the guideline calls for observation or ruxolitinib in those who are symptomatic, or clinical trial enrollment or allogeneic HCT. Treatment should continue unless monitoring shows disease progression, in which case the appropriate algorithm should be considered.
The guideline also addresses several special circumstances, including the management of anemia in myelofibrosis patients, which can be a difficult issue, he said.
Since the guideline was first published in December, two updates have been incorporated, and Dr. Mesa said that he anticipates regular updates given the rapidly evolving understanding of MPNs and new findings with respect to potential treatment strategies.
He noted that a number of drugs are currently in clinical trials involving patients with myelofibrosis, including the JAK2/FLT3 inhibitor pacritinib, the JAK1/JAK2 inhibitor momelotinib, the active antifibrosing agent PRM-151, and the telomerase inhibitor imetelstat, as well as numerous drug combinations.
Going forward, the guideline panel will be focusing on four different areas of assessment, including new therapies and new genetic therapies, improving transplant outcomes, MPN symptom and quality of life assessment, and nonpharmacologic interventions such as yoga.
“We certainly hope to complement things over time, to look not only at pharmacologic interventions, but others that patients may be able to utilize from a toolkit of resources,” he said.
COMFORT-1 update: ruxolitinib responses durable in myelofibrosis
To date, ruxolitinib is the only Food and Drug Administration–approved drug for the treatment of myelofibrosis.
The randomized controlled phase III COMFORT I and II trials conducted in the United States and Europe, respectively, demonstrated that the oral JAK1/JAK2 inhibitor has a rapid, beneficial impact on both survival and disease-associated enlargement of the spleen and improvement in related symptoms, Dr. Mesa said.
A 5-year update on data from 309 patients in the COMFORT-1 trial, as reported at the annual meeting of the American Society of Clinical Oncology in 2016, confirmed the durability of treatment responses to ruxolitinib in patients initially randomized to receive the drug, he said.
“We were able to demonstrate a continued survival advantage for those individuals receiving ruxolitinib,” he added.
At weeks 24 and 264, the mean spleen volume reduction was 31.6% and 37.6%, respectively, in those originally randomized to ruxolitinib. The median duration of at least 35% spleen volume reduction was 168.3 weeks.
Overall survival favored ruxolitinib (hazard ratio, 0.69). Median overall survival in the ruxolitinib group had not yet been reached.
“But we realize our work is not done. The survival curve does not plateau; we are not curing these patients. We’re having meaningful impact, but we have room to continue to improve,” he said.
Also, there is an initial drop in platelet counts that tends to stabilize, but not improve, and there is worsening of anemia (new onset grade 3 or 4 anemia was 25.2% with ruxolitinib, and 26.1% in 111 of 154 patients who crossed over from the placebo group), and although this tends to improve, these are among areas of unmet need, he added.
Further, long-term risks of treatment include cutaneous malignancies (basal cell carcinoma occurred in 7.7% and 9.0% of treatment and crossover patients, respectively), which are difficult to separate from baseline hydroxyurea use, and increased risk of herpes zoster (which occurred in 10.3% and 13.5% of treated and crossover patients).
However, there appears to be no increased risk – and there may be a slight decreased risk – of progression to acute leukemia, Dr. Mesa said.
Dr. Mesa disclosed that he has received consulting fees, honoraria, and/or grant/research support from ARIAD Pharmaceuticals, Celgene, CTI BioPharma, Galena Biopharma, Gilead Sciences, Incyte, Novartis Pharmaceuticals, and Promedior.
A step toward harmonizing treatment
Myelofibrosis is a rare chronic leukemia with a complex biology. Disease heterogeneity poses several challenges in the appropriate selection and timing of treatments in this disorder. The NCCN Practice Guidelines in Myelofibrosis is an important step towards harmonizing clinical practice for treating this disease and improving the care of patients.
Vikas Gupta, MD, FRCP, FRCPath, is Director of The Elizabeth and Tony Comper MPN Program at Princess Margaret Cancer Centre in Toronto and a member of the editorial advisory board of Hematology News.
A step toward harmonizing treatment
Myelofibrosis is a rare chronic leukemia with a complex biology. Disease heterogeneity poses several challenges in the appropriate selection and timing of treatments in this disorder. The NCCN Practice Guidelines in Myelofibrosis is an important step towards harmonizing clinical practice for treating this disease and improving the care of patients.
Vikas Gupta, MD, FRCP, FRCPath, is Director of The Elizabeth and Tony Comper MPN Program at Princess Margaret Cancer Centre in Toronto and a member of the editorial advisory board of Hematology News.
A step toward harmonizing treatment
Myelofibrosis is a rare chronic leukemia with a complex biology. Disease heterogeneity poses several challenges in the appropriate selection and timing of treatments in this disorder. The NCCN Practice Guidelines in Myelofibrosis is an important step towards harmonizing clinical practice for treating this disease and improving the care of patients.
Vikas Gupta, MD, FRCP, FRCPath, is Director of The Elizabeth and Tony Comper MPN Program at Princess Margaret Cancer Centre in Toronto and a member of the editorial advisory board of Hematology News.
ORLANDO – Referral to a specialized center with expertise in the management of myeloproliferative neoplasms is strongly recommended for all patients diagnosed with myelofibrosis, according to a new treatment guideline from the National Comprehensive Cancer Network.
The guideline is the first in a series addressing myeloproliferative neoplasms (MPNs), and it focuses on the diagnostic work-up of MPNs, as well as the treatment of myelofibrosis. The guideline panel, led by panel chair Ruben A. Mesa, MD, is working next on guidelines for the other two “core classic” Philadelphia chromosome–negative MPNs: polycythemia vera, and essential thrombocythemia.
Nearly two-thirds of myelofibrosis patients have intermediate-risk 2 or high-risk disease, and treatment decisions in these patients are complex and require patient input – particularly in candidates for allogeneic hematopoietic stem cell transplantation, he said.
“These diseases can be a little different than other malignant diseases,” Dr. Mesa said, explaining that while there is a clear risk of progression to acute myeloid leukemia, and from polycythemia vera and essential thrombocythemia to myelofibrosis, and while the diseases can be fatal, the burden patients face is not solely related to mortality.
There are implications in terms of health that are independent of that, such as the risk of thrombosis and bleeding, the potential for cytopenia, and severe splenomegaly that results in significant symptoms, he said.
Further, while molecular mutations and their implications for prognosis are a “rapidly moving part of the discussion,” the care of patients with MPNs involves far more than a molecular understanding of the disease.
In fact, the role of molecular changes in these patients is speculative, he said.
While such changes can be assessed and used for patient stratification, their role in myelofibrosis – unlike in other diseases such as chronic myeloid leukemia where the level of change in a target gene is highly relevant and prognostic, is not yet clear.
Thus, a core aspect of the guideline is inclusion of the voice of the patient in individualizing care, he said, noting that many factors should be considered, including how well the patient metabolizes drugs, and the symptom profile, psychosocial circumstances, support structure, and personal beliefs.
“It’s not solely about the tumor,” he stressed.
In fact, the answer to the question of whether a patient can be symptomatic enough to require a specific treatment is “no,” because of the potential for side effects, risk, expense, and other considerations.
“So the voice of the patient is always a key part [of the decision],” he said, noting also that as with all NCCN guidelines, this guideline is a partnership with the treating physician; deciding who is a transplant candidate is a nuanced issue for which the panel provides “discussion and guidance.”
“But clearly, these guidelines are the most useful and helpful in the setting of experienced providers bringing all of their experiences to bear,” he said.
In general, however, the guidelines call for allogeneic hematopoietic stem cell transplantation (HCT) in those with intermediate-risk 2 or high-risk disease who are transplant candidates, and treatment based on assessment of symptom burden (using the MPN–Symptom Assessment Form Total Symptom Score–10 Items) in those who are not HCT candidates. Those with platelets at 50,000 or below should be considered for clinical trial enrollment, and those with platelets above 50,000 should be considered for a clinical trial or treatment with the oral JAK1 and JAK2 inhibitor ruxolitinib, which has been shown to have beneficial effects on both symptoms and survival and which is approved for patients with platelets above 50,000. .
Treated patients should be monitored for response and for signs and symptoms of disease progression every 3-6 months. Treatment should continue in those who respond, as well as in those who do not – as long as there is no disease progression.
Those with progressive disease include patients who are moving toward acute leukemia, and those with overt acute leukemia.
“Here is where the key decision occurs. Are they or are they not a transplant candidate? If they are a candidate, we have a potentially curative track which would include cytoreduction followed by transplant,” Dr. Mesa said.
Cytoreduction can involve hypomethylating agents if the patient doesn’t have excess blast cells or too high a burden of disease.
Acute myeloid leukemia–like induction chemotherapy followed by allogeneic HCT is also an option in these patients.
As for treatment of low-risk myelofibrosis, the guideline states that asymptomatic patients can be observed or enrolled in a clinical trial and monitored for progression every 3-6 months, and that symptomatic patients should receive ruxolitinib or interferons (which are used off label), or be enrolled in a clinical trial. Treatment is important for patients with particularly difficult symptoms, he said, noting that some patients have had pruritus so severe that they have committed suicide. Treatment should continue unless monitoring shows signs of progression to intermediate risk 1, intermediate risk 2/high-risk, or advanced stage disease.
For those with intermediate risk 1 disease, the guideline calls for observation or ruxolitinib in those who are symptomatic, or clinical trial enrollment or allogeneic HCT. Treatment should continue unless monitoring shows disease progression, in which case the appropriate algorithm should be considered.
The guideline also addresses several special circumstances, including the management of anemia in myelofibrosis patients, which can be a difficult issue, he said.
Since the guideline was first published in December, two updates have been incorporated, and Dr. Mesa said that he anticipates regular updates given the rapidly evolving understanding of MPNs and new findings with respect to potential treatment strategies.
He noted that a number of drugs are currently in clinical trials involving patients with myelofibrosis, including the JAK2/FLT3 inhibitor pacritinib, the JAK1/JAK2 inhibitor momelotinib, the active antifibrosing agent PRM-151, and the telomerase inhibitor imetelstat, as well as numerous drug combinations.
Going forward, the guideline panel will be focusing on four different areas of assessment, including new therapies and new genetic therapies, improving transplant outcomes, MPN symptom and quality of life assessment, and nonpharmacologic interventions such as yoga.
“We certainly hope to complement things over time, to look not only at pharmacologic interventions, but others that patients may be able to utilize from a toolkit of resources,” he said.
COMFORT-1 update: ruxolitinib responses durable in myelofibrosis
To date, ruxolitinib is the only Food and Drug Administration–approved drug for the treatment of myelofibrosis.
The randomized controlled phase III COMFORT I and II trials conducted in the United States and Europe, respectively, demonstrated that the oral JAK1/JAK2 inhibitor has a rapid, beneficial impact on both survival and disease-associated enlargement of the spleen and improvement in related symptoms, Dr. Mesa said.
A 5-year update on data from 309 patients in the COMFORT-1 trial, as reported at the annual meeting of the American Society of Clinical Oncology in 2016, confirmed the durability of treatment responses to ruxolitinib in patients initially randomized to receive the drug, he said.
“We were able to demonstrate a continued survival advantage for those individuals receiving ruxolitinib,” he added.
At weeks 24 and 264, the mean spleen volume reduction was 31.6% and 37.6%, respectively, in those originally randomized to ruxolitinib. The median duration of at least 35% spleen volume reduction was 168.3 weeks.
Overall survival favored ruxolitinib (hazard ratio, 0.69). Median overall survival in the ruxolitinib group had not yet been reached.
“But we realize our work is not done. The survival curve does not plateau; we are not curing these patients. We’re having meaningful impact, but we have room to continue to improve,” he said.
Also, there is an initial drop in platelet counts that tends to stabilize, but not improve, and there is worsening of anemia (new onset grade 3 or 4 anemia was 25.2% with ruxolitinib, and 26.1% in 111 of 154 patients who crossed over from the placebo group), and although this tends to improve, these are among areas of unmet need, he added.
Further, long-term risks of treatment include cutaneous malignancies (basal cell carcinoma occurred in 7.7% and 9.0% of treatment and crossover patients, respectively), which are difficult to separate from baseline hydroxyurea use, and increased risk of herpes zoster (which occurred in 10.3% and 13.5% of treated and crossover patients).
However, there appears to be no increased risk – and there may be a slight decreased risk – of progression to acute leukemia, Dr. Mesa said.
Dr. Mesa disclosed that he has received consulting fees, honoraria, and/or grant/research support from ARIAD Pharmaceuticals, Celgene, CTI BioPharma, Galena Biopharma, Gilead Sciences, Incyte, Novartis Pharmaceuticals, and Promedior.
ORLANDO – Referral to a specialized center with expertise in the management of myeloproliferative neoplasms is strongly recommended for all patients diagnosed with myelofibrosis, according to a new treatment guideline from the National Comprehensive Cancer Network.
The guideline is the first in a series addressing myeloproliferative neoplasms (MPNs), and it focuses on the diagnostic work-up of MPNs, as well as the treatment of myelofibrosis. The guideline panel, led by panel chair Ruben A. Mesa, MD, is working next on guidelines for the other two “core classic” Philadelphia chromosome–negative MPNs: polycythemia vera, and essential thrombocythemia.
Nearly two-thirds of myelofibrosis patients have intermediate-risk 2 or high-risk disease, and treatment decisions in these patients are complex and require patient input – particularly in candidates for allogeneic hematopoietic stem cell transplantation, he said.
“These diseases can be a little different than other malignant diseases,” Dr. Mesa said, explaining that while there is a clear risk of progression to acute myeloid leukemia, and from polycythemia vera and essential thrombocythemia to myelofibrosis, and while the diseases can be fatal, the burden patients face is not solely related to mortality.
There are implications in terms of health that are independent of that, such as the risk of thrombosis and bleeding, the potential for cytopenia, and severe splenomegaly that results in significant symptoms, he said.
Further, while molecular mutations and their implications for prognosis are a “rapidly moving part of the discussion,” the care of patients with MPNs involves far more than a molecular understanding of the disease.
In fact, the role of molecular changes in these patients is speculative, he said.
While such changes can be assessed and used for patient stratification, their role in myelofibrosis – unlike in other diseases such as chronic myeloid leukemia where the level of change in a target gene is highly relevant and prognostic, is not yet clear.
Thus, a core aspect of the guideline is inclusion of the voice of the patient in individualizing care, he said, noting that many factors should be considered, including how well the patient metabolizes drugs, and the symptom profile, psychosocial circumstances, support structure, and personal beliefs.
“It’s not solely about the tumor,” he stressed.
In fact, the answer to the question of whether a patient can be symptomatic enough to require a specific treatment is “no,” because of the potential for side effects, risk, expense, and other considerations.
“So the voice of the patient is always a key part [of the decision],” he said, noting also that as with all NCCN guidelines, this guideline is a partnership with the treating physician; deciding who is a transplant candidate is a nuanced issue for which the panel provides “discussion and guidance.”
“But clearly, these guidelines are the most useful and helpful in the setting of experienced providers bringing all of their experiences to bear,” he said.
In general, however, the guidelines call for allogeneic hematopoietic stem cell transplantation (HCT) in those with intermediate-risk 2 or high-risk disease who are transplant candidates, and treatment based on assessment of symptom burden (using the MPN–Symptom Assessment Form Total Symptom Score–10 Items) in those who are not HCT candidates. Those with platelets at 50,000 or below should be considered for clinical trial enrollment, and those with platelets above 50,000 should be considered for a clinical trial or treatment with the oral JAK1 and JAK2 inhibitor ruxolitinib, which has been shown to have beneficial effects on both symptoms and survival and which is approved for patients with platelets above 50,000. .
Treated patients should be monitored for response and for signs and symptoms of disease progression every 3-6 months. Treatment should continue in those who respond, as well as in those who do not – as long as there is no disease progression.
Those with progressive disease include patients who are moving toward acute leukemia, and those with overt acute leukemia.
“Here is where the key decision occurs. Are they or are they not a transplant candidate? If they are a candidate, we have a potentially curative track which would include cytoreduction followed by transplant,” Dr. Mesa said.
Cytoreduction can involve hypomethylating agents if the patient doesn’t have excess blast cells or too high a burden of disease.
Acute myeloid leukemia–like induction chemotherapy followed by allogeneic HCT is also an option in these patients.
As for treatment of low-risk myelofibrosis, the guideline states that asymptomatic patients can be observed or enrolled in a clinical trial and monitored for progression every 3-6 months, and that symptomatic patients should receive ruxolitinib or interferons (which are used off label), or be enrolled in a clinical trial. Treatment is important for patients with particularly difficult symptoms, he said, noting that some patients have had pruritus so severe that they have committed suicide. Treatment should continue unless monitoring shows signs of progression to intermediate risk 1, intermediate risk 2/high-risk, or advanced stage disease.
For those with intermediate risk 1 disease, the guideline calls for observation or ruxolitinib in those who are symptomatic, or clinical trial enrollment or allogeneic HCT. Treatment should continue unless monitoring shows disease progression, in which case the appropriate algorithm should be considered.
The guideline also addresses several special circumstances, including the management of anemia in myelofibrosis patients, which can be a difficult issue, he said.
Since the guideline was first published in December, two updates have been incorporated, and Dr. Mesa said that he anticipates regular updates given the rapidly evolving understanding of MPNs and new findings with respect to potential treatment strategies.
He noted that a number of drugs are currently in clinical trials involving patients with myelofibrosis, including the JAK2/FLT3 inhibitor pacritinib, the JAK1/JAK2 inhibitor momelotinib, the active antifibrosing agent PRM-151, and the telomerase inhibitor imetelstat, as well as numerous drug combinations.
Going forward, the guideline panel will be focusing on four different areas of assessment, including new therapies and new genetic therapies, improving transplant outcomes, MPN symptom and quality of life assessment, and nonpharmacologic interventions such as yoga.
“We certainly hope to complement things over time, to look not only at pharmacologic interventions, but others that patients may be able to utilize from a toolkit of resources,” he said.
COMFORT-1 update: ruxolitinib responses durable in myelofibrosis
To date, ruxolitinib is the only Food and Drug Administration–approved drug for the treatment of myelofibrosis.
The randomized controlled phase III COMFORT I and II trials conducted in the United States and Europe, respectively, demonstrated that the oral JAK1/JAK2 inhibitor has a rapid, beneficial impact on both survival and disease-associated enlargement of the spleen and improvement in related symptoms, Dr. Mesa said.
A 5-year update on data from 309 patients in the COMFORT-1 trial, as reported at the annual meeting of the American Society of Clinical Oncology in 2016, confirmed the durability of treatment responses to ruxolitinib in patients initially randomized to receive the drug, he said.
“We were able to demonstrate a continued survival advantage for those individuals receiving ruxolitinib,” he added.
At weeks 24 and 264, the mean spleen volume reduction was 31.6% and 37.6%, respectively, in those originally randomized to ruxolitinib. The median duration of at least 35% spleen volume reduction was 168.3 weeks.
Overall survival favored ruxolitinib (hazard ratio, 0.69). Median overall survival in the ruxolitinib group had not yet been reached.
“But we realize our work is not done. The survival curve does not plateau; we are not curing these patients. We’re having meaningful impact, but we have room to continue to improve,” he said.
Also, there is an initial drop in platelet counts that tends to stabilize, but not improve, and there is worsening of anemia (new onset grade 3 or 4 anemia was 25.2% with ruxolitinib, and 26.1% in 111 of 154 patients who crossed over from the placebo group), and although this tends to improve, these are among areas of unmet need, he added.
Further, long-term risks of treatment include cutaneous malignancies (basal cell carcinoma occurred in 7.7% and 9.0% of treatment and crossover patients, respectively), which are difficult to separate from baseline hydroxyurea use, and increased risk of herpes zoster (which occurred in 10.3% and 13.5% of treated and crossover patients).
However, there appears to be no increased risk – and there may be a slight decreased risk – of progression to acute leukemia, Dr. Mesa said.
Dr. Mesa disclosed that he has received consulting fees, honoraria, and/or grant/research support from ARIAD Pharmaceuticals, Celgene, CTI BioPharma, Galena Biopharma, Gilead Sciences, Incyte, Novartis Pharmaceuticals, and Promedior.
EXPERT ANALYSIS AT THE NCCN ANNUAL CONFERENCE
Eliminating hepatitis in the United States: A road map
An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.
The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.
The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.
But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”
They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.
Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”
Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.
As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.
Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”
Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.”
Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”
Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”
But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”
Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.
“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”
Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”
Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.
One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.
“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.
But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.
Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”
An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.
The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.
The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.
But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”
They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.
Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”
Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.
As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.
Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”
Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.”
Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”
Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”
But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”
Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.
“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”
Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”
Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.
One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.
“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.
But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.
Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”
An ambitious new report by the National Academies of Sciences, Engineering, and Medicine lays out a detailed path by which some 90,000 deaths from hepatitis B and C infection could be prevented by 2030.
The National Academies, a group of nongovernmental advisory bodies that includes the former Institute of Medicine, said that “the tools to prevent these deaths” exist – namely vaccination to prevent new hepatitis B infections and antiviral drugs, including new oral medications that can cure chronic hepatitis C infections within months.
The authors of the 200-plus-page report, led by Brian Strom, MD, MPH, of Rutgers University in Newark, NJ, calculate that deaths from hepatitis B infection could be halved by 2030 if 90% of patients are diagnosed, if 90% of those diagnosed are connected to care, and if 80% of those for whom treatment is indicated receive it. Treating everyone with chronic hepatitis C would reduce new infections by 90% by 2030, while reducing related deaths by 65%, Dr. Strom and his colleagues estimate.
But the authors also concede that drastic changes to current health policy would be required to reach these goals. These include the adoption of “aggressive testing, diagnosis, treatment, and prevention methods, such as needle exchange.”
They propose that the federal government seek a unique licensing arrangement with one or more manufacturers to bring down the notoriously high cost of direct-acting drugs used in hepatitis C, as a way of raising treatment rates. Currently, fewer than half the patients on Medicaid who are eligible for hepatitis C treatment receive it, and fewer than 1% of prisoners, who have high rates of infection.
Dr. Joseph Lim, director of the viral hepatitis program at Yale University in New Haven. Conn., who was not involved in the National Academies report, called it helpful in the sense that “it casts a spotlight on something that those of us involved in the care of people with viral hepatitis have long known – which is that this is a national and global public health burden that has been under the radar and in the shadow of other important health priorities.”
Both hepatitis B and C increase the risk of liver cancer and are associated with significant morbidity and mortality. Though approximately 4 million people in the United States are estimated to be infected with chronic hepatitis B (1.3 million) or C (2.7 million), these diseases account for less than 1% of the research budget at the National Institutes of Health, the report said. This compares unfavorably to funding for HIV, which affects about 1 million Americans.
As the report states, the tools to radically reduce hepatitis B and C deaths already exist. However, Dr. Lim cautioned in an interview, “the public health infrastructure to address viral hepatitis has been woefully inadequate.” In the United States, he noted, most states receive federal funding for at most a single person in charge of viral hepatitis epidemiology. “The resources currently available are in no way adequate to achieve the very aggressive goals described in the report,” he said.
Even among people with a known diagnosis of hepatitis B or C, only some receive confirmatory testing, Dr. Lim said. And of those with confirmed infections, “only a fraction are linked to care from the diagnosing clinician to a provider with the capacity to assess the state of liver disease and determine whether antiviral therapy is warranted.” Finally, he said, “many patients continue to face barriers to curative therapy due to cost and restrictions by public and private payers.”
Among the recommendations contained in the report is that unrestricted, mass treatment of hepatitis C infections be undertaken – regardless of disease stage. Currently, direct-acting antiviral agents remain costly and are poorly covered, notably by Medicaid. The National Academies advise that the government rectify this by purchasing “a license or assignment to the patent on a direct-acting antiviral drug, and use it only in those market segments where the government pays for treatment and access is now limited, such as Medicaid and prisons.”
Dr. Lim called the licensing proposal “very novel and bold,” but noted that there is no precedent in the United States for diseases such as hepatitis C. “If it could be done it would be an incredible model of government-pharma partnership for the public health good, and have a very significant impact.”
Steven Flamm, MD, chief of the liver transplantation program at Northwestern University in Chicago, who like Dr. Lim was not involved in the creation of the report, said in an interview that it contained innovative ideas and helped underscore the fact that “hepatitis has been given short shrift. The NIH and other agencies do not devote time and energy to this particular medical issue for reasons that are not completely clear.”
But “the problem with these kinds of analyses,” he said, “is that carrying them out is harder than making the recommendations.”
Dr. Flamm echoed Dr. Lim’s concerns about the practicability of implementing some of the recommendations in what he considers a resource-deprived health care environment for viral hepatitis.
“Is elimination possible or can you take a big bite out of it? The answer to that question is yes. We now have agents that can treat chronic viral hepatitis well, which we didn’t have a few years ago.”
Still, he emphasized, having the tools is only one part of the picture. Hepatitis C diagnostic tests have been available since the early 1990s. Yet, Dr. Flamm pointed out, fewer than half of patients have been diagnosed. “If the new CDC screening guidelines gain traction, we will do better than that.”
Dr. Flamm said that he considered the report’s call for a unique government licensing agreement for hepatitis C drugs a tall order. The drugs are already heavily discounted by manufacturers in many cases, he said, yet remain unavailable to those in need of them. In Illinois, Dr. Flamm said, few Medicaid patients with confirmed hepatitis C are given the short-acting antivirals that have revolutionized treatment. “The vast majority have no access to the therapy at all,” he said.
One of the report’s strengths, he said, is in detailing innovative prevention strategies such as delivering and promoting hepatitis B vaccinations to adults through local pharmacies, after the model of influenza vaccinations, and also conducting needle exchanges through pharmacies for intravenous drug users, who are at high risk of contracting both hepatitis B and C.
“Many of these strategies are not very costly,” he said. “The problem is you run into moral platitudes – to eliminate hepatitis, we will have to overcome that,” Dr. Flamm said, something that cannot be taken for granted in the current political environment.
But even if the goals outlined in the report seem ambitious, its authors have done an important service in underscoring the burden of viral hepatitis and laying out how some barriers to prevention, diagnosis, and treatment might be broken, he said.
Viral hepatitis “is a big deal, and it does cost a tremendous amount of money,” he added. “Everybody focuses on the therapeutic cost, but nobody focuses on the costs, direct and indirect, of all the sick people that are out there.”
FROM THE NATIONAL ACADEMIES OF SCIENCES, ENGINEERING, AND MEDICINE
USPSTF: No recommendation on screening for celiac disease
The current evidence is insufficient for the U.S. Preventive Services Task Force to recommend either for or against routine screening of asymptomatic people for celiac disease, according to a Recommendation Statement published online March 28 in JAMA.
The USPSTF is tasked with making recommendations regarding the effectiveness of specific preventive health care services for patients who have no related signs or symptoms. In this case, the group commissioned a systematic review of the literature on celiac disease from 1946 through June 2016, which became the basis for the evidence report informing their Recommendation Statement, said Kirsten Bibbins-Domingo, PhD, MD, chair of the USPSTF and lead author of the statement, and her associates.
However, only 4 studies out of the 3,036 that were examined addressed the question of screening adequately, and they offered few data of use. According to Roger Chou, MD, lead author of the Evidence Report, and his associates, no trials assessed the screening of asymptomatic children, adolescents, or adults for celiac disease with regard to morbidity, mortality, or quality of life. The evidence also was inadequate concerning targeted screening of at-risk individuals, and there were no studies of the effectiveness of treatment after screen-detected celiac disease was found.
There was some evidence supporting the diagnostic accuracy of the tissue transglutaminase-IgA test to detect celiac disease, but “little or no evidence ... to inform most of the key questions related to benefits and harms of screening for celiac disease in asymptomatic individuals,” said Dr. Chou, of the Pacific Northwest Evidence-Based Practice Center and Oregon Health & Science University, both in Portland, and his associates (JAMA. 2017 Mar 28. doi: 10.1001/jama.2016.10395).
Dr. Bibbins-Domingo noted that the American Academy of Family Physicians also has concluded that the evidence is insufficient to assess the balance of screening’s benefits and harms. In contrast, the American College of Gastroenterology recommends that screening be considered in asymptomatic people who have a first-degree relative with a confirmed diagnosis of celiac disease (JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.1462).
In addition, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommends screening at age 3 years for asymptomatic children who have conditions associated with celiac disease, including type 1 diabetes, autoimmune thyroiditis, Down syndrome, Turner syndrome, William’s syndrome, or selective IgA deficiency, said Dr. Bobbins-Domingo, who is also professor of medicine at the University of California, San Francisco.
Copies of the Recommendation Statement, the Evidence Report, the authors’ disclosures, and other materials are available at www.uspreventiveservicestaskforce.org.
Even though the current evidence on the effectiveness of screening for celiac disease is scarce or absent, it remains reasonable for clinicians to have a low threshold for testing patients, especially in high-risk populations such as those with an affected family member or a related autoimmune disorder.
This is because most celiac disease is unrecognized, and patients can present with diverse symptoms rather than the classic triad of abdominal pain, diarrhea, and weight loss.
Rok Seon Choung, MD, and Joseph A. Murray, MD , are in the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn. Dr. Murray reported ties to Alvine Pharmaceuticals, Alba Therapeutics, Celimmune, BioLineRx, and numerous others. Dr. Choung and Dr. Murray made these remarks in an editorial accompanying the USPSTF reports (JAMA. 2017 Mar 28;317:1221-3).
Even though the current evidence on the effectiveness of screening for celiac disease is scarce or absent, it remains reasonable for clinicians to have a low threshold for testing patients, especially in high-risk populations such as those with an affected family member or a related autoimmune disorder.
This is because most celiac disease is unrecognized, and patients can present with diverse symptoms rather than the classic triad of abdominal pain, diarrhea, and weight loss.
Rok Seon Choung, MD, and Joseph A. Murray, MD , are in the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn. Dr. Murray reported ties to Alvine Pharmaceuticals, Alba Therapeutics, Celimmune, BioLineRx, and numerous others. Dr. Choung and Dr. Murray made these remarks in an editorial accompanying the USPSTF reports (JAMA. 2017 Mar 28;317:1221-3).
Even though the current evidence on the effectiveness of screening for celiac disease is scarce or absent, it remains reasonable for clinicians to have a low threshold for testing patients, especially in high-risk populations such as those with an affected family member or a related autoimmune disorder.
This is because most celiac disease is unrecognized, and patients can present with diverse symptoms rather than the classic triad of abdominal pain, diarrhea, and weight loss.
Rok Seon Choung, MD, and Joseph A. Murray, MD , are in the division of gastroenterology and hepatology at Mayo Clinic, Rochester, Minn. Dr. Murray reported ties to Alvine Pharmaceuticals, Alba Therapeutics, Celimmune, BioLineRx, and numerous others. Dr. Choung and Dr. Murray made these remarks in an editorial accompanying the USPSTF reports (JAMA. 2017 Mar 28;317:1221-3).
The current evidence is insufficient for the U.S. Preventive Services Task Force to recommend either for or against routine screening of asymptomatic people for celiac disease, according to a Recommendation Statement published online March 28 in JAMA.
The USPSTF is tasked with making recommendations regarding the effectiveness of specific preventive health care services for patients who have no related signs or symptoms. In this case, the group commissioned a systematic review of the literature on celiac disease from 1946 through June 2016, which became the basis for the evidence report informing their Recommendation Statement, said Kirsten Bibbins-Domingo, PhD, MD, chair of the USPSTF and lead author of the statement, and her associates.
However, only 4 studies out of the 3,036 that were examined addressed the question of screening adequately, and they offered few data of use. According to Roger Chou, MD, lead author of the Evidence Report, and his associates, no trials assessed the screening of asymptomatic children, adolescents, or adults for celiac disease with regard to morbidity, mortality, or quality of life. The evidence also was inadequate concerning targeted screening of at-risk individuals, and there were no studies of the effectiveness of treatment after screen-detected celiac disease was found.
There was some evidence supporting the diagnostic accuracy of the tissue transglutaminase-IgA test to detect celiac disease, but “little or no evidence ... to inform most of the key questions related to benefits and harms of screening for celiac disease in asymptomatic individuals,” said Dr. Chou, of the Pacific Northwest Evidence-Based Practice Center and Oregon Health & Science University, both in Portland, and his associates (JAMA. 2017 Mar 28. doi: 10.1001/jama.2016.10395).
Dr. Bibbins-Domingo noted that the American Academy of Family Physicians also has concluded that the evidence is insufficient to assess the balance of screening’s benefits and harms. In contrast, the American College of Gastroenterology recommends that screening be considered in asymptomatic people who have a first-degree relative with a confirmed diagnosis of celiac disease (JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.1462).
In addition, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommends screening at age 3 years for asymptomatic children who have conditions associated with celiac disease, including type 1 diabetes, autoimmune thyroiditis, Down syndrome, Turner syndrome, William’s syndrome, or selective IgA deficiency, said Dr. Bobbins-Domingo, who is also professor of medicine at the University of California, San Francisco.
Copies of the Recommendation Statement, the Evidence Report, the authors’ disclosures, and other materials are available at www.uspreventiveservicestaskforce.org.
The current evidence is insufficient for the U.S. Preventive Services Task Force to recommend either for or against routine screening of asymptomatic people for celiac disease, according to a Recommendation Statement published online March 28 in JAMA.
The USPSTF is tasked with making recommendations regarding the effectiveness of specific preventive health care services for patients who have no related signs or symptoms. In this case, the group commissioned a systematic review of the literature on celiac disease from 1946 through June 2016, which became the basis for the evidence report informing their Recommendation Statement, said Kirsten Bibbins-Domingo, PhD, MD, chair of the USPSTF and lead author of the statement, and her associates.
However, only 4 studies out of the 3,036 that were examined addressed the question of screening adequately, and they offered few data of use. According to Roger Chou, MD, lead author of the Evidence Report, and his associates, no trials assessed the screening of asymptomatic children, adolescents, or adults for celiac disease with regard to morbidity, mortality, or quality of life. The evidence also was inadequate concerning targeted screening of at-risk individuals, and there were no studies of the effectiveness of treatment after screen-detected celiac disease was found.
There was some evidence supporting the diagnostic accuracy of the tissue transglutaminase-IgA test to detect celiac disease, but “little or no evidence ... to inform most of the key questions related to benefits and harms of screening for celiac disease in asymptomatic individuals,” said Dr. Chou, of the Pacific Northwest Evidence-Based Practice Center and Oregon Health & Science University, both in Portland, and his associates (JAMA. 2017 Mar 28. doi: 10.1001/jama.2016.10395).
Dr. Bibbins-Domingo noted that the American Academy of Family Physicians also has concluded that the evidence is insufficient to assess the balance of screening’s benefits and harms. In contrast, the American College of Gastroenterology recommends that screening be considered in asymptomatic people who have a first-degree relative with a confirmed diagnosis of celiac disease (JAMA. 2017 Mar 28. doi: 10.1001/jama.2017.1462).
In addition, the North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition recommends screening at age 3 years for asymptomatic children who have conditions associated with celiac disease, including type 1 diabetes, autoimmune thyroiditis, Down syndrome, Turner syndrome, William’s syndrome, or selective IgA deficiency, said Dr. Bobbins-Domingo, who is also professor of medicine at the University of California, San Francisco.
Copies of the Recommendation Statement, the Evidence Report, the authors’ disclosures, and other materials are available at www.uspreventiveservicestaskforce.org.
FROM JAMA
Key clinical point: The current evidence is insufficient for the USPSTF to recommend either for or against routine screening of asymptomatic people for celiac disease.
Major finding: Only 4 studies out of the 3,036 that were examined addressed the question of screening adequately.
Data source: An assessment of the benefits and harms of screening based on a review of four studies.
Disclosures: The USPSTF’s work is supported by the U.S. Agency for Healthcare Research and Quality. The authors’ financial disclosures are available at www.uspreventiveservicestaskforce.org.
USPSTF affirms optional pelvic screening
Current evidence fails to support or reject routine screening pelvic exams for asymptomatic, low-risk, nonpregnant adult women, the U.S. Preventive Services Task Force concluded after reviewing the evidence on the accuracy, benefits, and potential harms.
The USPSTF issued an inconclusive “I” statement that was published online March 7 (JAMA. 2017;317[9]:947-53).
Researchers found no data comparing the impact of no screening versus screening pelvic examinations on patient health outcomes including reducing all-cause mortality, reducing cancer-specific and disease-specific morbidity and mortality, and improving quality of life.
“No direct evidence was identified for overall benefits and harms of the pelvic examination as a one-time or periodic screening test,” Janelle M. Guirguis-Blake, MD, of the University of Washington, Tacoma, and colleagues wrote in the accompanying evidence report (JAMA. 2017;317[9]:954-66). The review comprised nine studies: one addressing the harms of screening and eight addressing both harms and accuracy.
Although screening pelvic exams may identify serious conditions as well as benign ones, the potential remains for false-positive and false-negative results that might lead to invasive surgery and unnecessary testing and procedures, the researchers noted. However, the recommendations do not apply to certain conditions for which screening is already recommended, including cervical cancer (via Pap smear), gonorrhea, and chlamydia.
The recommendations are primarily a call for more research rather than a clear guide for clinicians, according to the USPSTF. The research gaps include studies on the physical and psychological harms of pelvic screening for asymptomatic women in primary care; the ability of screening to detect conditions beyond ovarian cancer, genital herpes, bacterial vaginosis, and trichomoniasis; and the impact of screening on a variety of health outcomes, including quality of life.
Given the inadequate evidence to recommend for or against screening, the USPSTF cited the recommendations of other organizations. Both the American College of Physicians and the American Academy of Family Physicians recommend against performing screening pelvic exams in asymptomatic, nonpregnant adult women. The American College of Obstetricians and Gynecologists recommends annual pelvic exams for women 21 years and older but acknowledges a lack of evidence and has said it should be a shared decision between the patient and clinician.
The USPSTF members reported having no relevant financial conflicts.
The USPSTF task force finding of insufficient evidence to support or refute screening pelvic exams conflicts with the views of other organizations, George F. Sawaya, MD, wrote in an editorial (JAMA 2017 Mar 7. doi: 10.1001/jamainternmed.2017.0271).
The American College of Physicians currently recommends against routine screening in asymptomatic, nonpregnant women, while the American College of Obstetricians and Gynecologists recommends in favor of an annual pelvic exam “based on expert opinion” despite the lack of evidence, he said.
“The USPSTF believes that in the setting of an ‘I’ statement, clinicians should be forthright with patients about the uncertainty concerning the balance of benefits and harms,” Dr. Sawaya wrote.
“But perhaps the conversation should focus on the uncertainty among the three professional groups,” he added. “Women should know the facts: that all three groups agree there is no scientific evidence that these examinations are beneficial; that there is evidence of harms including ‘false alarms,’ further testing, and even unnecessary surgery; and that one group strongly recommends against screening examinations, believing them to be more harmful than beneficial,” he said.
The USPSTF recommendation is not a surprise, Colleen McNicholas, DO, MSCI, and Jeffrey F. Peipert, MD, PhD, noted in a second editorial (JAMA 2017;317[9]:910-11). “Despite lack of rigorous research, many would argue that the periodic examination provides opportunity for counseling and trust building between the patient and physician and thus should be universally implemented,” they wrote. However, many women express fear and anxiety before the exam and discomfort, pain, or embarrassment during the exam. “To ignore this aspect when comparing individual parts of the examination seems insensitive and inappropriate,” they added.
“Women, as patients, should be involved in the decision regarding whether to perform a pelvic examination, and clinicians should not require that the patient undergo this procedure to obtain screening, counseling, and age-appropriate health services,” they concluded.
Dr. Sawaya is affiliated with the University of California, San Francisco. He reported having no financial conflicts. Dr. Peipert is affiliated with Indiana University School of Medicine, Indianapolis, and disclosed receiving grants from Teva Pharmaceuticals, Bayer Healthcare Pharmaceuticals, and Merck, as well as serving on the advisory boards of Perrigo and Teva. Dr. McNicholas is affiliated with Washington University, St. Louis, and reported having no financial conflicts.
The USPSTF task force finding of insufficient evidence to support or refute screening pelvic exams conflicts with the views of other organizations, George F. Sawaya, MD, wrote in an editorial (JAMA 2017 Mar 7. doi: 10.1001/jamainternmed.2017.0271).
The American College of Physicians currently recommends against routine screening in asymptomatic, nonpregnant women, while the American College of Obstetricians and Gynecologists recommends in favor of an annual pelvic exam “based on expert opinion” despite the lack of evidence, he said.
“The USPSTF believes that in the setting of an ‘I’ statement, clinicians should be forthright with patients about the uncertainty concerning the balance of benefits and harms,” Dr. Sawaya wrote.
“But perhaps the conversation should focus on the uncertainty among the three professional groups,” he added. “Women should know the facts: that all three groups agree there is no scientific evidence that these examinations are beneficial; that there is evidence of harms including ‘false alarms,’ further testing, and even unnecessary surgery; and that one group strongly recommends against screening examinations, believing them to be more harmful than beneficial,” he said.
The USPSTF recommendation is not a surprise, Colleen McNicholas, DO, MSCI, and Jeffrey F. Peipert, MD, PhD, noted in a second editorial (JAMA 2017;317[9]:910-11). “Despite lack of rigorous research, many would argue that the periodic examination provides opportunity for counseling and trust building between the patient and physician and thus should be universally implemented,” they wrote. However, many women express fear and anxiety before the exam and discomfort, pain, or embarrassment during the exam. “To ignore this aspect when comparing individual parts of the examination seems insensitive and inappropriate,” they added.
“Women, as patients, should be involved in the decision regarding whether to perform a pelvic examination, and clinicians should not require that the patient undergo this procedure to obtain screening, counseling, and age-appropriate health services,” they concluded.
Dr. Sawaya is affiliated with the University of California, San Francisco. He reported having no financial conflicts. Dr. Peipert is affiliated with Indiana University School of Medicine, Indianapolis, and disclosed receiving grants from Teva Pharmaceuticals, Bayer Healthcare Pharmaceuticals, and Merck, as well as serving on the advisory boards of Perrigo and Teva. Dr. McNicholas is affiliated with Washington University, St. Louis, and reported having no financial conflicts.
The USPSTF task force finding of insufficient evidence to support or refute screening pelvic exams conflicts with the views of other organizations, George F. Sawaya, MD, wrote in an editorial (JAMA 2017 Mar 7. doi: 10.1001/jamainternmed.2017.0271).
The American College of Physicians currently recommends against routine screening in asymptomatic, nonpregnant women, while the American College of Obstetricians and Gynecologists recommends in favor of an annual pelvic exam “based on expert opinion” despite the lack of evidence, he said.
“The USPSTF believes that in the setting of an ‘I’ statement, clinicians should be forthright with patients about the uncertainty concerning the balance of benefits and harms,” Dr. Sawaya wrote.
“But perhaps the conversation should focus on the uncertainty among the three professional groups,” he added. “Women should know the facts: that all three groups agree there is no scientific evidence that these examinations are beneficial; that there is evidence of harms including ‘false alarms,’ further testing, and even unnecessary surgery; and that one group strongly recommends against screening examinations, believing them to be more harmful than beneficial,” he said.
The USPSTF recommendation is not a surprise, Colleen McNicholas, DO, MSCI, and Jeffrey F. Peipert, MD, PhD, noted in a second editorial (JAMA 2017;317[9]:910-11). “Despite lack of rigorous research, many would argue that the periodic examination provides opportunity for counseling and trust building between the patient and physician and thus should be universally implemented,” they wrote. However, many women express fear and anxiety before the exam and discomfort, pain, or embarrassment during the exam. “To ignore this aspect when comparing individual parts of the examination seems insensitive and inappropriate,” they added.
“Women, as patients, should be involved in the decision regarding whether to perform a pelvic examination, and clinicians should not require that the patient undergo this procedure to obtain screening, counseling, and age-appropriate health services,” they concluded.
Dr. Sawaya is affiliated with the University of California, San Francisco. He reported having no financial conflicts. Dr. Peipert is affiliated with Indiana University School of Medicine, Indianapolis, and disclosed receiving grants from Teva Pharmaceuticals, Bayer Healthcare Pharmaceuticals, and Merck, as well as serving on the advisory boards of Perrigo and Teva. Dr. McNicholas is affiliated with Washington University, St. Louis, and reported having no financial conflicts.
Current evidence fails to support or reject routine screening pelvic exams for asymptomatic, low-risk, nonpregnant adult women, the U.S. Preventive Services Task Force concluded after reviewing the evidence on the accuracy, benefits, and potential harms.
The USPSTF issued an inconclusive “I” statement that was published online March 7 (JAMA. 2017;317[9]:947-53).
Researchers found no data comparing the impact of no screening versus screening pelvic examinations on patient health outcomes including reducing all-cause mortality, reducing cancer-specific and disease-specific morbidity and mortality, and improving quality of life.
“No direct evidence was identified for overall benefits and harms of the pelvic examination as a one-time or periodic screening test,” Janelle M. Guirguis-Blake, MD, of the University of Washington, Tacoma, and colleagues wrote in the accompanying evidence report (JAMA. 2017;317[9]:954-66). The review comprised nine studies: one addressing the harms of screening and eight addressing both harms and accuracy.
Although screening pelvic exams may identify serious conditions as well as benign ones, the potential remains for false-positive and false-negative results that might lead to invasive surgery and unnecessary testing and procedures, the researchers noted. However, the recommendations do not apply to certain conditions for which screening is already recommended, including cervical cancer (via Pap smear), gonorrhea, and chlamydia.
The recommendations are primarily a call for more research rather than a clear guide for clinicians, according to the USPSTF. The research gaps include studies on the physical and psychological harms of pelvic screening for asymptomatic women in primary care; the ability of screening to detect conditions beyond ovarian cancer, genital herpes, bacterial vaginosis, and trichomoniasis; and the impact of screening on a variety of health outcomes, including quality of life.
Given the inadequate evidence to recommend for or against screening, the USPSTF cited the recommendations of other organizations. Both the American College of Physicians and the American Academy of Family Physicians recommend against performing screening pelvic exams in asymptomatic, nonpregnant adult women. The American College of Obstetricians and Gynecologists recommends annual pelvic exams for women 21 years and older but acknowledges a lack of evidence and has said it should be a shared decision between the patient and clinician.
The USPSTF members reported having no relevant financial conflicts.
Current evidence fails to support or reject routine screening pelvic exams for asymptomatic, low-risk, nonpregnant adult women, the U.S. Preventive Services Task Force concluded after reviewing the evidence on the accuracy, benefits, and potential harms.
The USPSTF issued an inconclusive “I” statement that was published online March 7 (JAMA. 2017;317[9]:947-53).
Researchers found no data comparing the impact of no screening versus screening pelvic examinations on patient health outcomes including reducing all-cause mortality, reducing cancer-specific and disease-specific morbidity and mortality, and improving quality of life.
“No direct evidence was identified for overall benefits and harms of the pelvic examination as a one-time or periodic screening test,” Janelle M. Guirguis-Blake, MD, of the University of Washington, Tacoma, and colleagues wrote in the accompanying evidence report (JAMA. 2017;317[9]:954-66). The review comprised nine studies: one addressing the harms of screening and eight addressing both harms and accuracy.
Although screening pelvic exams may identify serious conditions as well as benign ones, the potential remains for false-positive and false-negative results that might lead to invasive surgery and unnecessary testing and procedures, the researchers noted. However, the recommendations do not apply to certain conditions for which screening is already recommended, including cervical cancer (via Pap smear), gonorrhea, and chlamydia.
The recommendations are primarily a call for more research rather than a clear guide for clinicians, according to the USPSTF. The research gaps include studies on the physical and psychological harms of pelvic screening for asymptomatic women in primary care; the ability of screening to detect conditions beyond ovarian cancer, genital herpes, bacterial vaginosis, and trichomoniasis; and the impact of screening on a variety of health outcomes, including quality of life.
Given the inadequate evidence to recommend for or against screening, the USPSTF cited the recommendations of other organizations. Both the American College of Physicians and the American Academy of Family Physicians recommend against performing screening pelvic exams in asymptomatic, nonpregnant adult women. The American College of Obstetricians and Gynecologists recommends annual pelvic exams for women 21 years and older but acknowledges a lack of evidence and has said it should be a shared decision between the patient and clinician.
The USPSTF members reported having no relevant financial conflicts.
FROM JAMA
Guidelines tackle long-term screening, management of myeloma
New guidelines recommend proactively screening for the late-term effects of both myeloma itself and the multiple therapies many patients receive.
“We are entering a watershed period in which patients are expecting to live in excess of 5 to 10 years after a diagnosis of myeloma, and issues of survivorship are becoming increasingly important,” wrote John A. Snowden, MD, of Sheffield (England) Teaching Hospitals NHS Foundation Trust and his associates on behalf of the UK Myeloma Forum and the British Society for Haematology.
Late effects of myeloma and therapies “constitute a unique syndrome,” the guideline authors emphasized. “Survivorship in myeloma therefore requires specialized screening, coordinated management and multidisciplinary care” (Br J Haematol. 2017 Jan 20. doi: 10.1111/bjh.14514).
Patients with myeloma should not receive live attenuated vaccines, the guidelines noted. Inactivated vaccinations should be timed to periods of minimal disease and after treatment recovery. The authors recommended influenza and varicella-zoster vaccines for both patients and household contacts. For patients, they also recommended Haemophilus influenzae type b vaccine and conjugate pneumococcal vaccine, followed by polysaccharide PPV23 at least 2 months later. They also suggested revaccination after HSCT.
About half of myeloma patients have renal impairment and should undergo routine tests of serum calcium, parathyroid hormone, and vitamin D, the authors stated. Moderate to severe renal impairment, renal-related hyperparathyroidism, and nephrotic syndrome merit specialty referrals, they added. They also advised carefully managing diabetes and hypertension to delay end-stage kidney disease, modifying doses of lenalidomide and bisphosphonate doses in renally impaired patients, avoiding nephrotoxic drugs when possible, and considering erythropoiesis-stimulating agents and iron supplementation for anemia.
Endocrine disorders are also common in myeloma, and the authors recommended annual screening for hypothyroidism, hypogonadism in males, and menopausal symptoms in younger females, especially after HSCT. They emphasized annual measurements of weight, height, body mass index, waist circumference, strength and frailty, blood pressure, HbA1c, and serum lipids, with referral to primary care when needed. For bone loss, they emphasized weight-bearing exercise, bisphosphonates, dietary changes, and calcium and vitamin D supplementation. They recommended specialist input on hormone therapy, if indicated.
Spinal cord or nerve-root compression often accompanies myeloma, and long-term survivors also may have peripheral neuropathy secondary to chemotherapy and other drug treatments, the guidelines noted. They recommended testing thyroid function and vitamin B12 levels, reducing or eliminating neurotoxic agents, offering gabapentin or pregabalin for symptom control, and referring patients to pain specialists and neurologists for peripheral neuropathy beyond grade I. They also advised annual ophthalmic screening because even intermittent high-dose corticosteroid therapy can lead to cataracts.
Cardiopulmonary abnormalities affect about half of myeloma patients and deserve heightened attention, the authors stressed. They recommended routinely screening cardiovascular risk factors, testing natriuretic peptide annually, and performing electrocardiograms, echocardiography, and pulmonary function tests in at-risk patients. They also advised diet, weight control, smoking cessation, physical activity, and specialist referral for patients with established cardiovascular or pulmonary disease.
Bisphosphonates can cause osteonecrosis of the jaw, and chemotherapy and other therapies can cause oral dryness. The guidelines emphasized – in addition to monitoring for these adverse outcomes – the importance of oral hygiene, artificial saliva rinses, annual dental exams, and specialty evaluations for nonhealing lesions.
Novel myeloma therapies often cause diarrhea, but chronic diarrhea should be evaluated by a gastroenterologist to rule out malignancies, underlying bowel disease, AL amyloidosis, and bile acid malabsorption, the authors stressed. They also recommended annual assessments of liver function tests, drug and alcohol history, and vitamin D, B12, folate, and ferritin levels. Nutritionists should provide input if patients are losing weight, they added.
Myeloma confers at least eight times the risk of myelodysplastic syndrome and acute myeloid leukemia, compared with the general population, the guidelines noted. Second primary malignancies can result from long-term exposure to lenalidomide and to such alkylating agents as melphalan. They advised considering myelodysplastic syndrome and acute myeloid leukemia in patients with persistent or worsening cytopenias, investigating symptoms that could indicate other malignancies, participating in cancer screening registries, and developing formal surveillance for second primary malignancies.
Additional recommendations included baseline geriatric assessment in elderly and frail patients; holistic assessments at the start of each line of treatment to pinpoint needs and concerns and to plan support services; and regular assessments of mood, anxiety, and cognitive status, with referrals for therapy, psychiatry, and support groups as needed. The authors also stressed the role of routine holistic needs-assessments to detect and track both pain and fatigue. Therapy should always include prehabilitation and rehabilitation, and clinicians should recommend ongoing regular physical activity and a healthy lifestyle, they emphasized.
To develop the guidelines, the experts searched Medline and the Cochrane databases for literature published between 2006 and March 31, 2016. They based key recommendations on evidence from randomized, controlled trials. When those data were not available, they resorted to other studies and to consensus expert opinion. The recommendations take cost-effectiveness into account, but are not based on formal health economic assessments, the experts noted.
Myeloma UK paid for an independent medical writer to help search the literature and draft the manuscript. Dr. Snowden also disclosed support from Sheffield Hospitals Charity.
New guidelines recommend proactively screening for the late-term effects of both myeloma itself and the multiple therapies many patients receive.
“We are entering a watershed period in which patients are expecting to live in excess of 5 to 10 years after a diagnosis of myeloma, and issues of survivorship are becoming increasingly important,” wrote John A. Snowden, MD, of Sheffield (England) Teaching Hospitals NHS Foundation Trust and his associates on behalf of the UK Myeloma Forum and the British Society for Haematology.
Late effects of myeloma and therapies “constitute a unique syndrome,” the guideline authors emphasized. “Survivorship in myeloma therefore requires specialized screening, coordinated management and multidisciplinary care” (Br J Haematol. 2017 Jan 20. doi: 10.1111/bjh.14514).
Patients with myeloma should not receive live attenuated vaccines, the guidelines noted. Inactivated vaccinations should be timed to periods of minimal disease and after treatment recovery. The authors recommended influenza and varicella-zoster vaccines for both patients and household contacts. For patients, they also recommended Haemophilus influenzae type b vaccine and conjugate pneumococcal vaccine, followed by polysaccharide PPV23 at least 2 months later. They also suggested revaccination after HSCT.
About half of myeloma patients have renal impairment and should undergo routine tests of serum calcium, parathyroid hormone, and vitamin D, the authors stated. Moderate to severe renal impairment, renal-related hyperparathyroidism, and nephrotic syndrome merit specialty referrals, they added. They also advised carefully managing diabetes and hypertension to delay end-stage kidney disease, modifying doses of lenalidomide and bisphosphonate doses in renally impaired patients, avoiding nephrotoxic drugs when possible, and considering erythropoiesis-stimulating agents and iron supplementation for anemia.
Endocrine disorders are also common in myeloma, and the authors recommended annual screening for hypothyroidism, hypogonadism in males, and menopausal symptoms in younger females, especially after HSCT. They emphasized annual measurements of weight, height, body mass index, waist circumference, strength and frailty, blood pressure, HbA1c, and serum lipids, with referral to primary care when needed. For bone loss, they emphasized weight-bearing exercise, bisphosphonates, dietary changes, and calcium and vitamin D supplementation. They recommended specialist input on hormone therapy, if indicated.
Spinal cord or nerve-root compression often accompanies myeloma, and long-term survivors also may have peripheral neuropathy secondary to chemotherapy and other drug treatments, the guidelines noted. They recommended testing thyroid function and vitamin B12 levels, reducing or eliminating neurotoxic agents, offering gabapentin or pregabalin for symptom control, and referring patients to pain specialists and neurologists for peripheral neuropathy beyond grade I. They also advised annual ophthalmic screening because even intermittent high-dose corticosteroid therapy can lead to cataracts.
Cardiopulmonary abnormalities affect about half of myeloma patients and deserve heightened attention, the authors stressed. They recommended routinely screening cardiovascular risk factors, testing natriuretic peptide annually, and performing electrocardiograms, echocardiography, and pulmonary function tests in at-risk patients. They also advised diet, weight control, smoking cessation, physical activity, and specialist referral for patients with established cardiovascular or pulmonary disease.
Bisphosphonates can cause osteonecrosis of the jaw, and chemotherapy and other therapies can cause oral dryness. The guidelines emphasized – in addition to monitoring for these adverse outcomes – the importance of oral hygiene, artificial saliva rinses, annual dental exams, and specialty evaluations for nonhealing lesions.
Novel myeloma therapies often cause diarrhea, but chronic diarrhea should be evaluated by a gastroenterologist to rule out malignancies, underlying bowel disease, AL amyloidosis, and bile acid malabsorption, the authors stressed. They also recommended annual assessments of liver function tests, drug and alcohol history, and vitamin D, B12, folate, and ferritin levels. Nutritionists should provide input if patients are losing weight, they added.
Myeloma confers at least eight times the risk of myelodysplastic syndrome and acute myeloid leukemia, compared with the general population, the guidelines noted. Second primary malignancies can result from long-term exposure to lenalidomide and to such alkylating agents as melphalan. They advised considering myelodysplastic syndrome and acute myeloid leukemia in patients with persistent or worsening cytopenias, investigating symptoms that could indicate other malignancies, participating in cancer screening registries, and developing formal surveillance for second primary malignancies.
Additional recommendations included baseline geriatric assessment in elderly and frail patients; holistic assessments at the start of each line of treatment to pinpoint needs and concerns and to plan support services; and regular assessments of mood, anxiety, and cognitive status, with referrals for therapy, psychiatry, and support groups as needed. The authors also stressed the role of routine holistic needs-assessments to detect and track both pain and fatigue. Therapy should always include prehabilitation and rehabilitation, and clinicians should recommend ongoing regular physical activity and a healthy lifestyle, they emphasized.
To develop the guidelines, the experts searched Medline and the Cochrane databases for literature published between 2006 and March 31, 2016. They based key recommendations on evidence from randomized, controlled trials. When those data were not available, they resorted to other studies and to consensus expert opinion. The recommendations take cost-effectiveness into account, but are not based on formal health economic assessments, the experts noted.
Myeloma UK paid for an independent medical writer to help search the literature and draft the manuscript. Dr. Snowden also disclosed support from Sheffield Hospitals Charity.
New guidelines recommend proactively screening for the late-term effects of both myeloma itself and the multiple therapies many patients receive.
“We are entering a watershed period in which patients are expecting to live in excess of 5 to 10 years after a diagnosis of myeloma, and issues of survivorship are becoming increasingly important,” wrote John A. Snowden, MD, of Sheffield (England) Teaching Hospitals NHS Foundation Trust and his associates on behalf of the UK Myeloma Forum and the British Society for Haematology.
Late effects of myeloma and therapies “constitute a unique syndrome,” the guideline authors emphasized. “Survivorship in myeloma therefore requires specialized screening, coordinated management and multidisciplinary care” (Br J Haematol. 2017 Jan 20. doi: 10.1111/bjh.14514).
Patients with myeloma should not receive live attenuated vaccines, the guidelines noted. Inactivated vaccinations should be timed to periods of minimal disease and after treatment recovery. The authors recommended influenza and varicella-zoster vaccines for both patients and household contacts. For patients, they also recommended Haemophilus influenzae type b vaccine and conjugate pneumococcal vaccine, followed by polysaccharide PPV23 at least 2 months later. They also suggested revaccination after HSCT.
About half of myeloma patients have renal impairment and should undergo routine tests of serum calcium, parathyroid hormone, and vitamin D, the authors stated. Moderate to severe renal impairment, renal-related hyperparathyroidism, and nephrotic syndrome merit specialty referrals, they added. They also advised carefully managing diabetes and hypertension to delay end-stage kidney disease, modifying doses of lenalidomide and bisphosphonate doses in renally impaired patients, avoiding nephrotoxic drugs when possible, and considering erythropoiesis-stimulating agents and iron supplementation for anemia.
Endocrine disorders are also common in myeloma, and the authors recommended annual screening for hypothyroidism, hypogonadism in males, and menopausal symptoms in younger females, especially after HSCT. They emphasized annual measurements of weight, height, body mass index, waist circumference, strength and frailty, blood pressure, HbA1c, and serum lipids, with referral to primary care when needed. For bone loss, they emphasized weight-bearing exercise, bisphosphonates, dietary changes, and calcium and vitamin D supplementation. They recommended specialist input on hormone therapy, if indicated.
Spinal cord or nerve-root compression often accompanies myeloma, and long-term survivors also may have peripheral neuropathy secondary to chemotherapy and other drug treatments, the guidelines noted. They recommended testing thyroid function and vitamin B12 levels, reducing or eliminating neurotoxic agents, offering gabapentin or pregabalin for symptom control, and referring patients to pain specialists and neurologists for peripheral neuropathy beyond grade I. They also advised annual ophthalmic screening because even intermittent high-dose corticosteroid therapy can lead to cataracts.
Cardiopulmonary abnormalities affect about half of myeloma patients and deserve heightened attention, the authors stressed. They recommended routinely screening cardiovascular risk factors, testing natriuretic peptide annually, and performing electrocardiograms, echocardiography, and pulmonary function tests in at-risk patients. They also advised diet, weight control, smoking cessation, physical activity, and specialist referral for patients with established cardiovascular or pulmonary disease.
Bisphosphonates can cause osteonecrosis of the jaw, and chemotherapy and other therapies can cause oral dryness. The guidelines emphasized – in addition to monitoring for these adverse outcomes – the importance of oral hygiene, artificial saliva rinses, annual dental exams, and specialty evaluations for nonhealing lesions.
Novel myeloma therapies often cause diarrhea, but chronic diarrhea should be evaluated by a gastroenterologist to rule out malignancies, underlying bowel disease, AL amyloidosis, and bile acid malabsorption, the authors stressed. They also recommended annual assessments of liver function tests, drug and alcohol history, and vitamin D, B12, folate, and ferritin levels. Nutritionists should provide input if patients are losing weight, they added.
Myeloma confers at least eight times the risk of myelodysplastic syndrome and acute myeloid leukemia, compared with the general population, the guidelines noted. Second primary malignancies can result from long-term exposure to lenalidomide and to such alkylating agents as melphalan. They advised considering myelodysplastic syndrome and acute myeloid leukemia in patients with persistent or worsening cytopenias, investigating symptoms that could indicate other malignancies, participating in cancer screening registries, and developing formal surveillance for second primary malignancies.
Additional recommendations included baseline geriatric assessment in elderly and frail patients; holistic assessments at the start of each line of treatment to pinpoint needs and concerns and to plan support services; and regular assessments of mood, anxiety, and cognitive status, with referrals for therapy, psychiatry, and support groups as needed. The authors also stressed the role of routine holistic needs-assessments to detect and track both pain and fatigue. Therapy should always include prehabilitation and rehabilitation, and clinicians should recommend ongoing regular physical activity and a healthy lifestyle, they emphasized.
To develop the guidelines, the experts searched Medline and the Cochrane databases for literature published between 2006 and March 31, 2016. They based key recommendations on evidence from randomized, controlled trials. When those data were not available, they resorted to other studies and to consensus expert opinion. The recommendations take cost-effectiveness into account, but are not based on formal health economic assessments, the experts noted.
Myeloma UK paid for an independent medical writer to help search the literature and draft the manuscript. Dr. Snowden also disclosed support from Sheffield Hospitals Charity.
FROM BRITISH JOURNAL OF HAEMATOLOGY
Guideline: Prioritize nondrug therapies for low back pain
Clinicians and patients should prioritize nonpharmacologic therapies for low back pain of any duration, according to an updated guideline from the American College of Physicians.
For acute and subacute low back pain, first-line choices include heat, massage, acupuncture, and spinal manipulation, Amir Qaseem, MD, PhD, and his associates wrote in the Annals of Internal Medicine. Patients with chronic low back pain have many nondrug options, ranging from exercise and tai chi to mindfulness-based stress reduction and spinal manipulation, the authors add (Ann Intern Med. 2017 Feb 14. doi: 10.7326/M16-2367).
The updated therapeutic recommendations focus on clinical presentations. They define acute low back pain as lasting less than 4 weeks, subacute low back pain as lasting 4-12 weeks, and chronic low back pain as lasting more than 12 weeks. For acute and subacute low back pain, low to moderate quality evidence supports the efficacy of acupuncture, massage, spinal manipulation, superficial heat, lumbar supports, and low-level laser therapy, the guideline authors conclude.
They recommend considering nonsteroidal anti-inflammatory drugs or skeletal muscle relaxants for patients who want medications for acute or subacute low back pain. There is moderate-quality evidence that NSAIDs confer a small analgesic benefit, compared with placebo, but their renal and gastrointestinal risks call for careful patient selection and use of the lowest possible doses and treatment durations, the authors emphasized.
Likewise, moderate-quality evidence supports the use of skeletal muscle relaxants for short-term pain relief, but patients should know that these drugs can lead to sedation and other adverse effects on the central nervous system, they stated.
Acetaminophen is no longer recommended for low back pain, having failed to shorten time to recovery, compared with placebo, in a large, multicenter, randomized trial (Lancet. 2014 Nov 1;384[9954]:1586-96).
Likewise, short-term oral or intramuscular corticosteroids have been found ineffective for acute low back pain, while benzodiazepines are ineffective for radiculopathy, the experts noted.
“Evidence was insufficient to determine effectiveness of antidepressants, benzodiazepines, antiseizure medications, or opioids, versus placebo, in patients with acute or subacute low back pain,” they added.
The guideline authors also noted insufficient evidence for many nondrug therapies for acute and subacute low back pain, including transcutaneous electrical nerve stimulation, electrical muscle stimulation, inferential therapy, short-wave diathermy, traction, superficial cold, motor control exercise, Pilates, tai chi, yoga, psychological therapies, multidisciplinary rehabilitation, ultrasound, and taping.
For chronic low back pain, the guideline strongly recommends starting with nondrug therapies, including exercise, multidisciplinary rehabilitation, acupuncture, mindfulness-based stress reduction, tai chi, yoga, motor control exercise, progressive relaxation, electromyography biofeedback, low-level laser therapy, operant therapy, cognitive behavioral therapy, or spinal manipulation.
Despite low-quality evidence for these modalities, “fewer harms are associated with these types of therapies than with pharmacologic options,” the authors wrote.
If nonpharmacologic interventions fail to improve chronic low back pain, the experts recommended NSAIDs in the first line, followed by second-line therapy with tramadol or duloxetine (Cymbalta). Recent evidence suggests that NSAIDs are less effective for low back pain than previously thought, while the trials that reported a modest analgesic benefit of duloxetine over placebo were industry funded, the authors note.
Opioids should only be considered for chronic low back pain that fails both nondrug and nonopioid therapies, “and only if the potential benefits outweigh the risks for individual patients, and after a discussion of known risks and realistic benefits,” the guideline authors emphasized.
This update does not cover topical therapies or epidural injections. Epidural steroid injections decreased pain associated with radiculopathy in the short term but did not confer long-term benefits, according to a recent separate review (Ann Intern Med. 2015 Sep 1;163[5]:373-81).
The Agency for Healthcare Research and Quality funded the work. One coauthor disclosed personal fees from Takeda Pharmaceuticals outside the submitted work, and membership in the American College of Physicians Clinical Guidelines Committee and the American College of Rheumatology Quality of Care Committee. The other authors had no conflicts. Two members of the ACP Clinical Guidelines Committee disclosed ties to Healthwise and UpToDate outside the submitted work.
Despite the considerable effort invested in these systematic reviews and in providing clinicians with rational recommendations for care, doubts exist as to whether simply publishing this work will be sufficient to drive guideline-concordant care.
Systematic reviews and recommendations from governmental organizations and professional societies are not new and predate large increases in diagnostic and therapeutic services.
For example, the lack of evidence supporting opiates for low back pain did not prevent their dramatic increase in use. Moreover, these updated reviews and recommendations do not focus on diagnostic tests, such as magnetic resonance imaging, and invasive therapies, such as injections and surgery, which are major drivers of health care spending for low back pain.
If clinicians and their professional societies cannot demonstrate that their recommendations are improving the delivery of high-value services, what are the alternatives?
Likely what is needed is an “all of the above” approach: more pragmatic trials to evaluate proven therapies and their combinations in real-world settings; efforts to reduce the use of low-value services, such as payer coverage policies based on guideline recommendations; patient engagement through shared decision making; and pressure on insurers to cover nonpharmacologic, noninvasive therapies that have shown benefit.
Steven J. Atlas, MD, MPH, is at Massachusetts General Hospital in Boston. He disclosed royalties from UpToDate and personal fees from Healthwise. These comments are from his editorial (Ann Intern Med. 2017 Feb 14. doi: 10.7326/M17-0923).
Despite the considerable effort invested in these systematic reviews and in providing clinicians with rational recommendations for care, doubts exist as to whether simply publishing this work will be sufficient to drive guideline-concordant care.
Systematic reviews and recommendations from governmental organizations and professional societies are not new and predate large increases in diagnostic and therapeutic services.
For example, the lack of evidence supporting opiates for low back pain did not prevent their dramatic increase in use. Moreover, these updated reviews and recommendations do not focus on diagnostic tests, such as magnetic resonance imaging, and invasive therapies, such as injections and surgery, which are major drivers of health care spending for low back pain.
If clinicians and their professional societies cannot demonstrate that their recommendations are improving the delivery of high-value services, what are the alternatives?
Likely what is needed is an “all of the above” approach: more pragmatic trials to evaluate proven therapies and their combinations in real-world settings; efforts to reduce the use of low-value services, such as payer coverage policies based on guideline recommendations; patient engagement through shared decision making; and pressure on insurers to cover nonpharmacologic, noninvasive therapies that have shown benefit.
Steven J. Atlas, MD, MPH, is at Massachusetts General Hospital in Boston. He disclosed royalties from UpToDate and personal fees from Healthwise. These comments are from his editorial (Ann Intern Med. 2017 Feb 14. doi: 10.7326/M17-0923).
Despite the considerable effort invested in these systematic reviews and in providing clinicians with rational recommendations for care, doubts exist as to whether simply publishing this work will be sufficient to drive guideline-concordant care.
Systematic reviews and recommendations from governmental organizations and professional societies are not new and predate large increases in diagnostic and therapeutic services.
For example, the lack of evidence supporting opiates for low back pain did not prevent their dramatic increase in use. Moreover, these updated reviews and recommendations do not focus on diagnostic tests, such as magnetic resonance imaging, and invasive therapies, such as injections and surgery, which are major drivers of health care spending for low back pain.
If clinicians and their professional societies cannot demonstrate that their recommendations are improving the delivery of high-value services, what are the alternatives?
Likely what is needed is an “all of the above” approach: more pragmatic trials to evaluate proven therapies and their combinations in real-world settings; efforts to reduce the use of low-value services, such as payer coverage policies based on guideline recommendations; patient engagement through shared decision making; and pressure on insurers to cover nonpharmacologic, noninvasive therapies that have shown benefit.
Steven J. Atlas, MD, MPH, is at Massachusetts General Hospital in Boston. He disclosed royalties from UpToDate and personal fees from Healthwise. These comments are from his editorial (Ann Intern Med. 2017 Feb 14. doi: 10.7326/M17-0923).
Clinicians and patients should prioritize nonpharmacologic therapies for low back pain of any duration, according to an updated guideline from the American College of Physicians.
For acute and subacute low back pain, first-line choices include heat, massage, acupuncture, and spinal manipulation, Amir Qaseem, MD, PhD, and his associates wrote in the Annals of Internal Medicine. Patients with chronic low back pain have many nondrug options, ranging from exercise and tai chi to mindfulness-based stress reduction and spinal manipulation, the authors add (Ann Intern Med. 2017 Feb 14. doi: 10.7326/M16-2367).
The updated therapeutic recommendations focus on clinical presentations. They define acute low back pain as lasting less than 4 weeks, subacute low back pain as lasting 4-12 weeks, and chronic low back pain as lasting more than 12 weeks. For acute and subacute low back pain, low to moderate quality evidence supports the efficacy of acupuncture, massage, spinal manipulation, superficial heat, lumbar supports, and low-level laser therapy, the guideline authors conclude.
They recommend considering nonsteroidal anti-inflammatory drugs or skeletal muscle relaxants for patients who want medications for acute or subacute low back pain. There is moderate-quality evidence that NSAIDs confer a small analgesic benefit, compared with placebo, but their renal and gastrointestinal risks call for careful patient selection and use of the lowest possible doses and treatment durations, the authors emphasized.
Likewise, moderate-quality evidence supports the use of skeletal muscle relaxants for short-term pain relief, but patients should know that these drugs can lead to sedation and other adverse effects on the central nervous system, they stated.
Acetaminophen is no longer recommended for low back pain, having failed to shorten time to recovery, compared with placebo, in a large, multicenter, randomized trial (Lancet. 2014 Nov 1;384[9954]:1586-96).
Likewise, short-term oral or intramuscular corticosteroids have been found ineffective for acute low back pain, while benzodiazepines are ineffective for radiculopathy, the experts noted.
“Evidence was insufficient to determine effectiveness of antidepressants, benzodiazepines, antiseizure medications, or opioids, versus placebo, in patients with acute or subacute low back pain,” they added.
The guideline authors also noted insufficient evidence for many nondrug therapies for acute and subacute low back pain, including transcutaneous electrical nerve stimulation, electrical muscle stimulation, inferential therapy, short-wave diathermy, traction, superficial cold, motor control exercise, Pilates, tai chi, yoga, psychological therapies, multidisciplinary rehabilitation, ultrasound, and taping.
For chronic low back pain, the guideline strongly recommends starting with nondrug therapies, including exercise, multidisciplinary rehabilitation, acupuncture, mindfulness-based stress reduction, tai chi, yoga, motor control exercise, progressive relaxation, electromyography biofeedback, low-level laser therapy, operant therapy, cognitive behavioral therapy, or spinal manipulation.
Despite low-quality evidence for these modalities, “fewer harms are associated with these types of therapies than with pharmacologic options,” the authors wrote.
If nonpharmacologic interventions fail to improve chronic low back pain, the experts recommended NSAIDs in the first line, followed by second-line therapy with tramadol or duloxetine (Cymbalta). Recent evidence suggests that NSAIDs are less effective for low back pain than previously thought, while the trials that reported a modest analgesic benefit of duloxetine over placebo were industry funded, the authors note.
Opioids should only be considered for chronic low back pain that fails both nondrug and nonopioid therapies, “and only if the potential benefits outweigh the risks for individual patients, and after a discussion of known risks and realistic benefits,” the guideline authors emphasized.
This update does not cover topical therapies or epidural injections. Epidural steroid injections decreased pain associated with radiculopathy in the short term but did not confer long-term benefits, according to a recent separate review (Ann Intern Med. 2015 Sep 1;163[5]:373-81).
The Agency for Healthcare Research and Quality funded the work. One coauthor disclosed personal fees from Takeda Pharmaceuticals outside the submitted work, and membership in the American College of Physicians Clinical Guidelines Committee and the American College of Rheumatology Quality of Care Committee. The other authors had no conflicts. Two members of the ACP Clinical Guidelines Committee disclosed ties to Healthwise and UpToDate outside the submitted work.
Clinicians and patients should prioritize nonpharmacologic therapies for low back pain of any duration, according to an updated guideline from the American College of Physicians.
For acute and subacute low back pain, first-line choices include heat, massage, acupuncture, and spinal manipulation, Amir Qaseem, MD, PhD, and his associates wrote in the Annals of Internal Medicine. Patients with chronic low back pain have many nondrug options, ranging from exercise and tai chi to mindfulness-based stress reduction and spinal manipulation, the authors add (Ann Intern Med. 2017 Feb 14. doi: 10.7326/M16-2367).
The updated therapeutic recommendations focus on clinical presentations. They define acute low back pain as lasting less than 4 weeks, subacute low back pain as lasting 4-12 weeks, and chronic low back pain as lasting more than 12 weeks. For acute and subacute low back pain, low to moderate quality evidence supports the efficacy of acupuncture, massage, spinal manipulation, superficial heat, lumbar supports, and low-level laser therapy, the guideline authors conclude.
They recommend considering nonsteroidal anti-inflammatory drugs or skeletal muscle relaxants for patients who want medications for acute or subacute low back pain. There is moderate-quality evidence that NSAIDs confer a small analgesic benefit, compared with placebo, but their renal and gastrointestinal risks call for careful patient selection and use of the lowest possible doses and treatment durations, the authors emphasized.
Likewise, moderate-quality evidence supports the use of skeletal muscle relaxants for short-term pain relief, but patients should know that these drugs can lead to sedation and other adverse effects on the central nervous system, they stated.
Acetaminophen is no longer recommended for low back pain, having failed to shorten time to recovery, compared with placebo, in a large, multicenter, randomized trial (Lancet. 2014 Nov 1;384[9954]:1586-96).
Likewise, short-term oral or intramuscular corticosteroids have been found ineffective for acute low back pain, while benzodiazepines are ineffective for radiculopathy, the experts noted.
“Evidence was insufficient to determine effectiveness of antidepressants, benzodiazepines, antiseizure medications, or opioids, versus placebo, in patients with acute or subacute low back pain,” they added.
The guideline authors also noted insufficient evidence for many nondrug therapies for acute and subacute low back pain, including transcutaneous electrical nerve stimulation, electrical muscle stimulation, inferential therapy, short-wave diathermy, traction, superficial cold, motor control exercise, Pilates, tai chi, yoga, psychological therapies, multidisciplinary rehabilitation, ultrasound, and taping.
For chronic low back pain, the guideline strongly recommends starting with nondrug therapies, including exercise, multidisciplinary rehabilitation, acupuncture, mindfulness-based stress reduction, tai chi, yoga, motor control exercise, progressive relaxation, electromyography biofeedback, low-level laser therapy, operant therapy, cognitive behavioral therapy, or spinal manipulation.
Despite low-quality evidence for these modalities, “fewer harms are associated with these types of therapies than with pharmacologic options,” the authors wrote.
If nonpharmacologic interventions fail to improve chronic low back pain, the experts recommended NSAIDs in the first line, followed by second-line therapy with tramadol or duloxetine (Cymbalta). Recent evidence suggests that NSAIDs are less effective for low back pain than previously thought, while the trials that reported a modest analgesic benefit of duloxetine over placebo were industry funded, the authors note.
Opioids should only be considered for chronic low back pain that fails both nondrug and nonopioid therapies, “and only if the potential benefits outweigh the risks for individual patients, and after a discussion of known risks and realistic benefits,” the guideline authors emphasized.
This update does not cover topical therapies or epidural injections. Epidural steroid injections decreased pain associated with radiculopathy in the short term but did not confer long-term benefits, according to a recent separate review (Ann Intern Med. 2015 Sep 1;163[5]:373-81).
The Agency for Healthcare Research and Quality funded the work. One coauthor disclosed personal fees from Takeda Pharmaceuticals outside the submitted work, and membership in the American College of Physicians Clinical Guidelines Committee and the American College of Rheumatology Quality of Care Committee. The other authors had no conflicts. Two members of the ACP Clinical Guidelines Committee disclosed ties to Healthwise and UpToDate outside the submitted work.
FROM ANNALS OF INTERNAL MEDICINE
Complex congenital heart conditions call for complex care in pregnancy
A new scientific statement from the American Heart Association (AHA) brings together recommendations for management of pregnancy for women with serious congenital heart disease. The 38-page document addresses a wide range of complex congenital heart conditions, presenting a newly unified set of recommendations for care that ranges from preconception counseling, through pregnancy, labor, and delivery, to the postpartum period.
Caring for women with complex congenital heart lesions is becoming more commonplace, as more infants undergo successful repairs of previously-unsurvivable cardiac anomalies. “More moms with congenital heart disease are showing up pregnant, having survived the tumultuous peripartum and neonatal period, and are now facing a new set of risks in pregnancy,” Michael Foley, MD, chair of the department of obstetrics and gynecology at the University of Arizona, Phoenix, said in an interview.
Joseph Kay, MD, a cardiologist and professor of medicine and pediatrics at the University of Colorado, Aurora, said that one big benefit of the new scientific statement is having a single reference point for care of these patients. “The scientific statement brings all of the information about caring for these patients together into one document. This will be a very valuable resource for trainees to get a sense of what’s important; it also represents a platform for new programs to understand the scope of services needed,” said Dr. Kay in an interview.
The document provides a thorough review of the physiologic changes of pregnancy and the intrapartum and postpartum periods, noting that the heterogeneity of congenital heart disease means that women who have different lesions carry different risks in pregnancy.
Examples of lesions presenting intermediate risk include most arrhythmias (category II), hypertrophic cardiomyopathy, and a repaired coarctation (both category II-III). The most severe lesions carry a contraindication for pregnancy; the WHO guidelines suggest discussing termination should women with a category IV lesion become pregnant. Severe mitral stenosis, severe symptomatic aortic stenosis, and severe systemic ventricular dysfunction all place women into category IV.
Beginning with pregnancy risk category III, the WHO guidelines recommend intensive cardiac and obstetric monitoring throughout pregnancy, childbirth, and the puerperium. Several maternal-fetal medicine specialists interviewed all agreed that an interdisciplinary team is a must for good obstetric care in this population.
How interdisciplinary care plays out can depend on geography and facility-dependent resources. Dr. Kay said that his facility is the referral site for pregnant women with complex congenital lesions in an area that spans the Canadian and the Mexican borders from north to south, and ranges from parts of Kansas to eastern Montana from east to west. Still, Dr. Kay said that even for patients with lower-risk lesions, “We will see patients at least once, at approximately the midpoint of pregnancy, and again during the third trimester if possible.” The specifics of care depend on “the nature of the lesion and the complexity of the disease,” said Dr. Kay.
In his facility, said Dr. Kay, telemetry is available for all of the labor and delivery unit beds. This means that the mother and infant can usually stay together and receive postpartum nursing and lactation care from a skilled staff.
In no circumstances should ob.gyns. go it alone, said Dr. Foley. “The conversation with the ob.gyn. needs to be about comanaging these patients, at the very least. Even the most learned maternal-fetal medicine specialist needs to be working with a cardiologist and an anesthesiologist to create a delivery plan that includes pain management, fluid management, and consideration for intrapartum hemodynamic monitoring,” he said.
And the team needs to be in place long before delivery, Dr. Foley pointed out. “In many hospitals, the care delivery gap may be the inability to have this consistent proactive approach. You can’t expect the best outcomes when you have to hurriedly assemble an unfamiliar ad hoc team when a woman with congenital heart disease presents in labor. Despite their best intentions, inconsistent team members may not have the knowledge and experience to provide the safest care for these patients,” he said.
Though an individualized labor and delivery plan is a must, and a multispecialty team should be assembled, maternal congenital heart disease doesn’t necessarily consign a woman to cesarean delivery. “Most women can and should have a vaginal delivery. It’s safer for them. If a natural delivery may increase risk of issues, we may consider a facilitated second stage of labor with epidural anesthesia and forceps- or vacuum-assisted delivery,” said Dr. Kay.
It’s important to understand the nuances of an individual patient’s health and risk status, said Dr. Norton. “A simplified view is often bad. It’s not the case that ‘it’s always better to deliver’ or ‘it’s always better to have a cesarean delivery.’”
Especially for women who need anticoagulation or who may have lesions that put them at great risk should pregnancy occur, preconception counseling is a vital part of their care, and guidance in the scientific statement can help specialists avoid the complications that can occur in the absence of evidence-based treatment. Said Dr. Kay, “I have seen an unfortunate case or two of patients whose anticoagulation was stopped or changed, contrary to guidelines, and who suffered strokes. I hope more people will see this document.”
Ms. Canobbio echoed the sentiment: “You don’t want to have to backpedal once a young woman presents with a pregnancy. Appropriate contraceptive counseling needs to be part of the conversation.”
One key concept underscored in the scientific statement is that elevated risk persists into the postpartum period. “Following delivery, the mother is still at risk for an extended period of time. The greatest risk for mortality in these patients is post delivery, when a large volume of blood is expelled from the uterus back into the maternal circulation,” said Ms. Canobbio. “These women need close follow-up; we can’t say they are home free until several weeks to 2 months after delivery. The need for vigilance and surveillance continues.”
Since the scientific statement is not a new set of guidelines, but rather a compilation of currently existing reference documents, the authors noted that management differences may exist in some cases, but did not assign greater value to one practice than another. “We addressed that there are differences between the European and the American guidelines. For example, with regard to anticoagulation, both would agree to use Lovenox [enoxaparin], but the difference is whether it should be used for the entire pregnancy or for parts of the pregnancy,” said Ms. Canobbio.
Looking forward, more women with complex congenital heart disease will bear children, but their future is not certain. Said Ms. Canobbio: “The data are growing that if the patient is clinically stable at the time of pregnancy, it’s likely we can get them through safely. What’s not yet known is whether the burden of pregnancy in a woman who is otherwise healthy will shorten her lifespan. However, early data are promising, and it’s looking like these women can fare well.”
Topics covered in the scientific statement include:
- Defining which patients are at increased risk in pregnancy.
- Physiological adaptations of pregnancy, the puerperium, and the postpartum period, with an emphasis on hemodynamic changes.
- Assessment and evaluation in the preconception and early prenatal periods.
- Pregnancy management, including appropriate testing.
- Medications in pregnancy, including a table of common cardiac drugs and their pregnancy categories and lactation risks.
- Breakdown of suggested prenatal care by trimester.
- Intrapartum care, including indications for fluid management, ECG and hemodynamic monitoring, and management of the second stage of delivery.
- Postpartum care, with attention to the very rapid increase in blood volume and concomitant leap in stroke volume and cardiac output.
- Considerations when choosing contraceptive method.
- Cardiac complications seen in pregnancy, including arrhythmias, managing mechanical valves and anticoagulation, heart failure, and cyanosis.
- Indications for and risks associated with interventional therapies during pregnancy.
- Detailed discussion of management of pregnancy for women with specific lesions.
None of the members of the writing committee for the scientific statement had relevant disclosures. Dr. Foley and Dr. Kay reported no disclosures. Dr. Norton reported that she has received research funding from Natera and Ultragenyx.
[email protected]
On Twitter @karioakes
A new scientific statement from the American Heart Association (AHA) brings together recommendations for management of pregnancy for women with serious congenital heart disease. The 38-page document addresses a wide range of complex congenital heart conditions, presenting a newly unified set of recommendations for care that ranges from preconception counseling, through pregnancy, labor, and delivery, to the postpartum period.
Caring for women with complex congenital heart lesions is becoming more commonplace, as more infants undergo successful repairs of previously-unsurvivable cardiac anomalies. “More moms with congenital heart disease are showing up pregnant, having survived the tumultuous peripartum and neonatal period, and are now facing a new set of risks in pregnancy,” Michael Foley, MD, chair of the department of obstetrics and gynecology at the University of Arizona, Phoenix, said in an interview.
Joseph Kay, MD, a cardiologist and professor of medicine and pediatrics at the University of Colorado, Aurora, said that one big benefit of the new scientific statement is having a single reference point for care of these patients. “The scientific statement brings all of the information about caring for these patients together into one document. This will be a very valuable resource for trainees to get a sense of what’s important; it also represents a platform for new programs to understand the scope of services needed,” said Dr. Kay in an interview.
The document provides a thorough review of the physiologic changes of pregnancy and the intrapartum and postpartum periods, noting that the heterogeneity of congenital heart disease means that women who have different lesions carry different risks in pregnancy.
Examples of lesions presenting intermediate risk include most arrhythmias (category II), hypertrophic cardiomyopathy, and a repaired coarctation (both category II-III). The most severe lesions carry a contraindication for pregnancy; the WHO guidelines suggest discussing termination should women with a category IV lesion become pregnant. Severe mitral stenosis, severe symptomatic aortic stenosis, and severe systemic ventricular dysfunction all place women into category IV.
Beginning with pregnancy risk category III, the WHO guidelines recommend intensive cardiac and obstetric monitoring throughout pregnancy, childbirth, and the puerperium. Several maternal-fetal medicine specialists interviewed all agreed that an interdisciplinary team is a must for good obstetric care in this population.
How interdisciplinary care plays out can depend on geography and facility-dependent resources. Dr. Kay said that his facility is the referral site for pregnant women with complex congenital lesions in an area that spans the Canadian and the Mexican borders from north to south, and ranges from parts of Kansas to eastern Montana from east to west. Still, Dr. Kay said that even for patients with lower-risk lesions, “We will see patients at least once, at approximately the midpoint of pregnancy, and again during the third trimester if possible.” The specifics of care depend on “the nature of the lesion and the complexity of the disease,” said Dr. Kay.
In his facility, said Dr. Kay, telemetry is available for all of the labor and delivery unit beds. This means that the mother and infant can usually stay together and receive postpartum nursing and lactation care from a skilled staff.
In no circumstances should ob.gyns. go it alone, said Dr. Foley. “The conversation with the ob.gyn. needs to be about comanaging these patients, at the very least. Even the most learned maternal-fetal medicine specialist needs to be working with a cardiologist and an anesthesiologist to create a delivery plan that includes pain management, fluid management, and consideration for intrapartum hemodynamic monitoring,” he said.
And the team needs to be in place long before delivery, Dr. Foley pointed out. “In many hospitals, the care delivery gap may be the inability to have this consistent proactive approach. You can’t expect the best outcomes when you have to hurriedly assemble an unfamiliar ad hoc team when a woman with congenital heart disease presents in labor. Despite their best intentions, inconsistent team members may not have the knowledge and experience to provide the safest care for these patients,” he said.
Though an individualized labor and delivery plan is a must, and a multispecialty team should be assembled, maternal congenital heart disease doesn’t necessarily consign a woman to cesarean delivery. “Most women can and should have a vaginal delivery. It’s safer for them. If a natural delivery may increase risk of issues, we may consider a facilitated second stage of labor with epidural anesthesia and forceps- or vacuum-assisted delivery,” said Dr. Kay.
It’s important to understand the nuances of an individual patient’s health and risk status, said Dr. Norton. “A simplified view is often bad. It’s not the case that ‘it’s always better to deliver’ or ‘it’s always better to have a cesarean delivery.’”
Especially for women who need anticoagulation or who may have lesions that put them at great risk should pregnancy occur, preconception counseling is a vital part of their care, and guidance in the scientific statement can help specialists avoid the complications that can occur in the absence of evidence-based treatment. Said Dr. Kay, “I have seen an unfortunate case or two of patients whose anticoagulation was stopped or changed, contrary to guidelines, and who suffered strokes. I hope more people will see this document.”
Ms. Canobbio echoed the sentiment: “You don’t want to have to backpedal once a young woman presents with a pregnancy. Appropriate contraceptive counseling needs to be part of the conversation.”
One key concept underscored in the scientific statement is that elevated risk persists into the postpartum period. “Following delivery, the mother is still at risk for an extended period of time. The greatest risk for mortality in these patients is post delivery, when a large volume of blood is expelled from the uterus back into the maternal circulation,” said Ms. Canobbio. “These women need close follow-up; we can’t say they are home free until several weeks to 2 months after delivery. The need for vigilance and surveillance continues.”
Since the scientific statement is not a new set of guidelines, but rather a compilation of currently existing reference documents, the authors noted that management differences may exist in some cases, but did not assign greater value to one practice than another. “We addressed that there are differences between the European and the American guidelines. For example, with regard to anticoagulation, both would agree to use Lovenox [enoxaparin], but the difference is whether it should be used for the entire pregnancy or for parts of the pregnancy,” said Ms. Canobbio.
Looking forward, more women with complex congenital heart disease will bear children, but their future is not certain. Said Ms. Canobbio: “The data are growing that if the patient is clinically stable at the time of pregnancy, it’s likely we can get them through safely. What’s not yet known is whether the burden of pregnancy in a woman who is otherwise healthy will shorten her lifespan. However, early data are promising, and it’s looking like these women can fare well.”
Topics covered in the scientific statement include:
- Defining which patients are at increased risk in pregnancy.
- Physiological adaptations of pregnancy, the puerperium, and the postpartum period, with an emphasis on hemodynamic changes.
- Assessment and evaluation in the preconception and early prenatal periods.
- Pregnancy management, including appropriate testing.
- Medications in pregnancy, including a table of common cardiac drugs and their pregnancy categories and lactation risks.
- Breakdown of suggested prenatal care by trimester.
- Intrapartum care, including indications for fluid management, ECG and hemodynamic monitoring, and management of the second stage of delivery.
- Postpartum care, with attention to the very rapid increase in blood volume and concomitant leap in stroke volume and cardiac output.
- Considerations when choosing contraceptive method.
- Cardiac complications seen in pregnancy, including arrhythmias, managing mechanical valves and anticoagulation, heart failure, and cyanosis.
- Indications for and risks associated with interventional therapies during pregnancy.
- Detailed discussion of management of pregnancy for women with specific lesions.
None of the members of the writing committee for the scientific statement had relevant disclosures. Dr. Foley and Dr. Kay reported no disclosures. Dr. Norton reported that she has received research funding from Natera and Ultragenyx.
[email protected]
On Twitter @karioakes
A new scientific statement from the American Heart Association (AHA) brings together recommendations for management of pregnancy for women with serious congenital heart disease. The 38-page document addresses a wide range of complex congenital heart conditions, presenting a newly unified set of recommendations for care that ranges from preconception counseling, through pregnancy, labor, and delivery, to the postpartum period.
Caring for women with complex congenital heart lesions is becoming more commonplace, as more infants undergo successful repairs of previously-unsurvivable cardiac anomalies. “More moms with congenital heart disease are showing up pregnant, having survived the tumultuous peripartum and neonatal period, and are now facing a new set of risks in pregnancy,” Michael Foley, MD, chair of the department of obstetrics and gynecology at the University of Arizona, Phoenix, said in an interview.
Joseph Kay, MD, a cardiologist and professor of medicine and pediatrics at the University of Colorado, Aurora, said that one big benefit of the new scientific statement is having a single reference point for care of these patients. “The scientific statement brings all of the information about caring for these patients together into one document. This will be a very valuable resource for trainees to get a sense of what’s important; it also represents a platform for new programs to understand the scope of services needed,” said Dr. Kay in an interview.
The document provides a thorough review of the physiologic changes of pregnancy and the intrapartum and postpartum periods, noting that the heterogeneity of congenital heart disease means that women who have different lesions carry different risks in pregnancy.
Examples of lesions presenting intermediate risk include most arrhythmias (category II), hypertrophic cardiomyopathy, and a repaired coarctation (both category II-III). The most severe lesions carry a contraindication for pregnancy; the WHO guidelines suggest discussing termination should women with a category IV lesion become pregnant. Severe mitral stenosis, severe symptomatic aortic stenosis, and severe systemic ventricular dysfunction all place women into category IV.
Beginning with pregnancy risk category III, the WHO guidelines recommend intensive cardiac and obstetric monitoring throughout pregnancy, childbirth, and the puerperium. Several maternal-fetal medicine specialists interviewed all agreed that an interdisciplinary team is a must for good obstetric care in this population.
How interdisciplinary care plays out can depend on geography and facility-dependent resources. Dr. Kay said that his facility is the referral site for pregnant women with complex congenital lesions in an area that spans the Canadian and the Mexican borders from north to south, and ranges from parts of Kansas to eastern Montana from east to west. Still, Dr. Kay said that even for patients with lower-risk lesions, “We will see patients at least once, at approximately the midpoint of pregnancy, and again during the third trimester if possible.” The specifics of care depend on “the nature of the lesion and the complexity of the disease,” said Dr. Kay.
In his facility, said Dr. Kay, telemetry is available for all of the labor and delivery unit beds. This means that the mother and infant can usually stay together and receive postpartum nursing and lactation care from a skilled staff.
In no circumstances should ob.gyns. go it alone, said Dr. Foley. “The conversation with the ob.gyn. needs to be about comanaging these patients, at the very least. Even the most learned maternal-fetal medicine specialist needs to be working with a cardiologist and an anesthesiologist to create a delivery plan that includes pain management, fluid management, and consideration for intrapartum hemodynamic monitoring,” he said.
And the team needs to be in place long before delivery, Dr. Foley pointed out. “In many hospitals, the care delivery gap may be the inability to have this consistent proactive approach. You can’t expect the best outcomes when you have to hurriedly assemble an unfamiliar ad hoc team when a woman with congenital heart disease presents in labor. Despite their best intentions, inconsistent team members may not have the knowledge and experience to provide the safest care for these patients,” he said.
Though an individualized labor and delivery plan is a must, and a multispecialty team should be assembled, maternal congenital heart disease doesn’t necessarily consign a woman to cesarean delivery. “Most women can and should have a vaginal delivery. It’s safer for them. If a natural delivery may increase risk of issues, we may consider a facilitated second stage of labor with epidural anesthesia and forceps- or vacuum-assisted delivery,” said Dr. Kay.
It’s important to understand the nuances of an individual patient’s health and risk status, said Dr. Norton. “A simplified view is often bad. It’s not the case that ‘it’s always better to deliver’ or ‘it’s always better to have a cesarean delivery.’”
Especially for women who need anticoagulation or who may have lesions that put them at great risk should pregnancy occur, preconception counseling is a vital part of their care, and guidance in the scientific statement can help specialists avoid the complications that can occur in the absence of evidence-based treatment. Said Dr. Kay, “I have seen an unfortunate case or two of patients whose anticoagulation was stopped or changed, contrary to guidelines, and who suffered strokes. I hope more people will see this document.”
Ms. Canobbio echoed the sentiment: “You don’t want to have to backpedal once a young woman presents with a pregnancy. Appropriate contraceptive counseling needs to be part of the conversation.”
One key concept underscored in the scientific statement is that elevated risk persists into the postpartum period. “Following delivery, the mother is still at risk for an extended period of time. The greatest risk for mortality in these patients is post delivery, when a large volume of blood is expelled from the uterus back into the maternal circulation,” said Ms. Canobbio. “These women need close follow-up; we can’t say they are home free until several weeks to 2 months after delivery. The need for vigilance and surveillance continues.”
Since the scientific statement is not a new set of guidelines, but rather a compilation of currently existing reference documents, the authors noted that management differences may exist in some cases, but did not assign greater value to one practice than another. “We addressed that there are differences between the European and the American guidelines. For example, with regard to anticoagulation, both would agree to use Lovenox [enoxaparin], but the difference is whether it should be used for the entire pregnancy or for parts of the pregnancy,” said Ms. Canobbio.
Looking forward, more women with complex congenital heart disease will bear children, but their future is not certain. Said Ms. Canobbio: “The data are growing that if the patient is clinically stable at the time of pregnancy, it’s likely we can get them through safely. What’s not yet known is whether the burden of pregnancy in a woman who is otherwise healthy will shorten her lifespan. However, early data are promising, and it’s looking like these women can fare well.”
Topics covered in the scientific statement include:
- Defining which patients are at increased risk in pregnancy.
- Physiological adaptations of pregnancy, the puerperium, and the postpartum period, with an emphasis on hemodynamic changes.
- Assessment and evaluation in the preconception and early prenatal periods.
- Pregnancy management, including appropriate testing.
- Medications in pregnancy, including a table of common cardiac drugs and their pregnancy categories and lactation risks.
- Breakdown of suggested prenatal care by trimester.
- Intrapartum care, including indications for fluid management, ECG and hemodynamic monitoring, and management of the second stage of delivery.
- Postpartum care, with attention to the very rapid increase in blood volume and concomitant leap in stroke volume and cardiac output.
- Considerations when choosing contraceptive method.
- Cardiac complications seen in pregnancy, including arrhythmias, managing mechanical valves and anticoagulation, heart failure, and cyanosis.
- Indications for and risks associated with interventional therapies during pregnancy.
- Detailed discussion of management of pregnancy for women with specific lesions.
None of the members of the writing committee for the scientific statement had relevant disclosures. Dr. Foley and Dr. Kay reported no disclosures. Dr. Norton reported that she has received research funding from Natera and Ultragenyx.
[email protected]
On Twitter @karioakes
AGA Clinical Practice Update: Treatment for severe alcohol hepatitis challenging
Acute alcoholic hepatitis carries a high risk of mortality, yet only a minority of patients admitted to the hospital with the condition receive appropriate treatment, said the authors of an expert review.
Writing in the January 2017 issue of Clinical Gastroenterology and Hepatology, Mack C. Mitchell Jr., MD, of the University of Texas Southwestern Medical Center, Dallas, and Craig J. McClain, MD, of the University of Louisville (Ky.), described the challenges associated with treating acute alcoholic hepatitis and its consequences.
Acute alcohol hepatitis develops in heavy drinkers and presents with rapid onset of malaise, anorexia, tender hepatomegaly, and features of the systemic inflammatory response syndrome. Patients with alcoholic hepatitis also are at high risk of nutritional deficiency, infection, acute kidney injury, and multiorgan failure.
The two most widely used therapies are glucocorticoids – generally considered the standard of care for severe alcoholic hepatitis – and the phosphodiesterase inhibitor pentoxifylline (Clin Gastroenterol Hepatol. 2017. doi: 10.1016/j.cgh.2016.08.047).
“Although in its most severe form AH has a high short-term mortality rate if untreated, in 2011, only 28% of more than 1,600 patients admitted to U.S. hospitals were treated with glucocorticoids and 17% with pentoxifylline (PTX), suggesting a lack of widespread confidence in the two most frequently used therapies for AH,” the authors wrote.
Both drugs work by addressing the underlying inflammation that plays a key role in liver injury, but the evidence for both is mixed: A 2008 Cochrane systematic review of 15 trials concluded there was no benefit from glucocorticoids, largely because of substantial variability in bias across the trials, while two meta-analyses of pentoxifylline trials concluded that there were no differences in short-term mortality between those who received it and those who did not.
Some patients are unsuitable for glucocorticoids and others may develop resistance. There is also the possibility that, while glucocorticoids may improve short-term survival, the associated increase in infection risk removes that advantage at 90 days and 1 year after diagnosis. These infections, in turn, often precede the development of acute kidney injury and multiorgan failure.
The authors, however, did suggest that the approach of very high, short-term bursts of glucocorticoids to induce “immune paralysis” – an approach taken for lupus nephritis – might be considered.
They stressed that abstinence was the cornerstone of treatment for acute alcoholic hepatitis, with studies showing that patients with alcoholic hepatitis who resume heavy drinking have significantly worse outcomes than those who don’t.
“Although abstinence is important at all stages, it is particularly important to emphasize abstinence beyond 90 days when many patients are regaining normal functioning,” Dr. Mitchell and Dr. McClain wrote.
Infection, kidney injury, and malnutrition are all significant concerns in patients with acute alcoholic hepatitis.
With respect to infection, the authors said considerable suspicion is required to pick up bacterial and fungal infections, as patients may not always have a fever and an elevated white blood cell count is an unreliable indicator. Infection also can lead to acute kidney injury.
Malnutrition is not only common in patients with alcohol hepatitis, but it has a significant negative impact on recovery. All patients should be encouraged to meet nutritional goals as early as possible, but just how to achieve this is controversial, the authors stressed.
For example, one study suggested that enteral nutrition was as good as glucocorticoids in reducing 28-day mortality, while another found enteral nutrition via nasogastric tube – in addition to glucocorticoids – was no better than glucocorticoids alone. “Whether [nasogastric] tubes should be used to provide enteral nutrition is a subject of controversy,” the authors wrote. “Normal- to high-protein diets are safe and do not increase the risk of encephalopathy in patients with AH.”
No conflicts of interest were declared.
Acute alcoholic hepatitis carries a high risk of mortality, yet only a minority of patients admitted to the hospital with the condition receive appropriate treatment, said the authors of an expert review.
Writing in the January 2017 issue of Clinical Gastroenterology and Hepatology, Mack C. Mitchell Jr., MD, of the University of Texas Southwestern Medical Center, Dallas, and Craig J. McClain, MD, of the University of Louisville (Ky.), described the challenges associated with treating acute alcoholic hepatitis and its consequences.
Acute alcohol hepatitis develops in heavy drinkers and presents with rapid onset of malaise, anorexia, tender hepatomegaly, and features of the systemic inflammatory response syndrome. Patients with alcoholic hepatitis also are at high risk of nutritional deficiency, infection, acute kidney injury, and multiorgan failure.
The two most widely used therapies are glucocorticoids – generally considered the standard of care for severe alcoholic hepatitis – and the phosphodiesterase inhibitor pentoxifylline (Clin Gastroenterol Hepatol. 2017. doi: 10.1016/j.cgh.2016.08.047).
“Although in its most severe form AH has a high short-term mortality rate if untreated, in 2011, only 28% of more than 1,600 patients admitted to U.S. hospitals were treated with glucocorticoids and 17% with pentoxifylline (PTX), suggesting a lack of widespread confidence in the two most frequently used therapies for AH,” the authors wrote.
Both drugs work by addressing the underlying inflammation that plays a key role in liver injury, but the evidence for both is mixed: A 2008 Cochrane systematic review of 15 trials concluded there was no benefit from glucocorticoids, largely because of substantial variability in bias across the trials, while two meta-analyses of pentoxifylline trials concluded that there were no differences in short-term mortality between those who received it and those who did not.
Some patients are unsuitable for glucocorticoids and others may develop resistance. There is also the possibility that, while glucocorticoids may improve short-term survival, the associated increase in infection risk removes that advantage at 90 days and 1 year after diagnosis. These infections, in turn, often precede the development of acute kidney injury and multiorgan failure.
The authors, however, did suggest that the approach of very high, short-term bursts of glucocorticoids to induce “immune paralysis” – an approach taken for lupus nephritis – might be considered.
They stressed that abstinence was the cornerstone of treatment for acute alcoholic hepatitis, with studies showing that patients with alcoholic hepatitis who resume heavy drinking have significantly worse outcomes than those who don’t.
“Although abstinence is important at all stages, it is particularly important to emphasize abstinence beyond 90 days when many patients are regaining normal functioning,” Dr. Mitchell and Dr. McClain wrote.
Infection, kidney injury, and malnutrition are all significant concerns in patients with acute alcoholic hepatitis.
With respect to infection, the authors said considerable suspicion is required to pick up bacterial and fungal infections, as patients may not always have a fever and an elevated white blood cell count is an unreliable indicator. Infection also can lead to acute kidney injury.
Malnutrition is not only common in patients with alcohol hepatitis, but it has a significant negative impact on recovery. All patients should be encouraged to meet nutritional goals as early as possible, but just how to achieve this is controversial, the authors stressed.
For example, one study suggested that enteral nutrition was as good as glucocorticoids in reducing 28-day mortality, while another found enteral nutrition via nasogastric tube – in addition to glucocorticoids – was no better than glucocorticoids alone. “Whether [nasogastric] tubes should be used to provide enteral nutrition is a subject of controversy,” the authors wrote. “Normal- to high-protein diets are safe and do not increase the risk of encephalopathy in patients with AH.”
No conflicts of interest were declared.
Acute alcoholic hepatitis carries a high risk of mortality, yet only a minority of patients admitted to the hospital with the condition receive appropriate treatment, said the authors of an expert review.
Writing in the January 2017 issue of Clinical Gastroenterology and Hepatology, Mack C. Mitchell Jr., MD, of the University of Texas Southwestern Medical Center, Dallas, and Craig J. McClain, MD, of the University of Louisville (Ky.), described the challenges associated with treating acute alcoholic hepatitis and its consequences.
Acute alcohol hepatitis develops in heavy drinkers and presents with rapid onset of malaise, anorexia, tender hepatomegaly, and features of the systemic inflammatory response syndrome. Patients with alcoholic hepatitis also are at high risk of nutritional deficiency, infection, acute kidney injury, and multiorgan failure.
The two most widely used therapies are glucocorticoids – generally considered the standard of care for severe alcoholic hepatitis – and the phosphodiesterase inhibitor pentoxifylline (Clin Gastroenterol Hepatol. 2017. doi: 10.1016/j.cgh.2016.08.047).
“Although in its most severe form AH has a high short-term mortality rate if untreated, in 2011, only 28% of more than 1,600 patients admitted to U.S. hospitals were treated with glucocorticoids and 17% with pentoxifylline (PTX), suggesting a lack of widespread confidence in the two most frequently used therapies for AH,” the authors wrote.
Both drugs work by addressing the underlying inflammation that plays a key role in liver injury, but the evidence for both is mixed: A 2008 Cochrane systematic review of 15 trials concluded there was no benefit from glucocorticoids, largely because of substantial variability in bias across the trials, while two meta-analyses of pentoxifylline trials concluded that there were no differences in short-term mortality between those who received it and those who did not.
Some patients are unsuitable for glucocorticoids and others may develop resistance. There is also the possibility that, while glucocorticoids may improve short-term survival, the associated increase in infection risk removes that advantage at 90 days and 1 year after diagnosis. These infections, in turn, often precede the development of acute kidney injury and multiorgan failure.
The authors, however, did suggest that the approach of very high, short-term bursts of glucocorticoids to induce “immune paralysis” – an approach taken for lupus nephritis – might be considered.
They stressed that abstinence was the cornerstone of treatment for acute alcoholic hepatitis, with studies showing that patients with alcoholic hepatitis who resume heavy drinking have significantly worse outcomes than those who don’t.
“Although abstinence is important at all stages, it is particularly important to emphasize abstinence beyond 90 days when many patients are regaining normal functioning,” Dr. Mitchell and Dr. McClain wrote.
Infection, kidney injury, and malnutrition are all significant concerns in patients with acute alcoholic hepatitis.
With respect to infection, the authors said considerable suspicion is required to pick up bacterial and fungal infections, as patients may not always have a fever and an elevated white blood cell count is an unreliable indicator. Infection also can lead to acute kidney injury.
Malnutrition is not only common in patients with alcohol hepatitis, but it has a significant negative impact on recovery. All patients should be encouraged to meet nutritional goals as early as possible, but just how to achieve this is controversial, the authors stressed.
For example, one study suggested that enteral nutrition was as good as glucocorticoids in reducing 28-day mortality, while another found enteral nutrition via nasogastric tube – in addition to glucocorticoids – was no better than glucocorticoids alone. “Whether [nasogastric] tubes should be used to provide enteral nutrition is a subject of controversy,” the authors wrote. “Normal- to high-protein diets are safe and do not increase the risk of encephalopathy in patients with AH.”
No conflicts of interest were declared.
FROM CLINICAL GASTROENTEROLOGY AND HEPATOLOGY
ADA: Empagliflozin and liraglutide reduce type 2 CV death
to reduce the risk of CV death, according to the American Diabetes Association 2017 Standards of Medical Care.
ADA updates it standards annually based on new information and research; like its predecessors, the 2017 guidance is comprehensive, addressing mental, social, and other challenges faced by patients with diabetes, along with clinical care (Diabetes Care. 2017 Jan;40(Suppl 1):S4-S5).
The 2017 guidance contains a great deal of new information. At 135 pages, there are 22 more pages than in 2016. “They did a really nice job. This guide is useful for anyone helping patients with diabetes,” including diabetologists, dietitians, educators, psychologists, and social workers, Richard Hellman, MD, a clinical endocrinologist in North Kansas City, Mo., said in an interview.
The empagliflozin and liraglutide recommendation applies to any patient with type 2 diabetes who has a history of stroke, heart attack, acute coronary syndrome, angina, or peripheral arterial disease. Data from recent trials have shown use of the drugs modestly reduces cardiovascular mortality in this population.
It’s unclear if the benefits are drug specific or group effects. “We anxiously await the results of several ongoing cardiovascular outcomes trials” to find out, said Helena Rodbard, MD, a clinical endocrinologist in Rockville, Md., who also commented on the new standards.
Basal insulin plus a GLP-1 receptor agonist, like liraglutide, are also now recommended for insulin-dependent type 2 disease. “This combination gives rise to a markedly reduced risk of hypoglycemia compared with basal insulin ... basal bolus insulin, or premixed insulins,” according to the ADA.
The newer drugs and insulins are expensive. To help doctors and patients negotiate the price hurdle, ADA added tables on how much the various options cost per month. It was a good move; “the cost of care is going up so fast” in diabetes “that many patients can no longer afford” what’s prescribed. “It’s a major problem,” said Dr. Hellman, clinical professor at the University of Missouri–Kansas City.
The ADA also set a blood glucose level of 54 mg/dL to trigger aggressive hypoglycemia treatment. “There has been confusion over when to treat aggressively. It was a good choice to land on 54 mg/dL” a safe, conservative number a bit higher than others have suggested, Dr. Hellman said.
Meanwhile, the group lowered its metabolic surgery cut point – the ADA has stopped using the term “bariatric surgery” – to type 2 patients with a body mass index of 30 kg/m2 when medications don’t work. The group also set a new hypertension treatment target of 120-160/80-105 mm Hg in pregnancy, and said that insulin is the treatment of choice for gestational diabetes, given concerns about metformin crossing the placenta and glyburide in cord blood.
The ADA expanded its list of diabetes comorbidities to include autoimmune disease, HIV, anxiety, depression, and disordered eating. In addition, doctors should ask patients how well they sleep – since sleep problems affect glycemic control – and should intervene when there’s a problem, according to the guidance.
The group updated its combination injection algorithm for type 2 diabetes “to reflect studies demonstrating the noninferiority of basal insulin plus” liraglutide and its class members “versus basal insulin plus rapid-acting insulin” or two daily injections of premixed insulin. The ADA added a section on the role of newly available biosimilar insulins, as well, and clarified that either basal insulin or basal plus bolus correctional insulin can be used to treat noncritical inpatients, but noted that “sole use of sliding scale insulin in the inpatient hospital setting is strongly discouraged.”
People on long-term metformin should have their vitamin B12 checked periodically, because of new evidence about the risk of B12 deficiency, the group said, and “due to the risk of malformations associated with unplanned pregnancies and poor metabolic control.” The group added “a new recommendation ... encouraging preconception counseling starting at puberty for all girls of childbearing potential.”
“Even though most of this information should be well known to practitioners treating patients, [it’s] a worthwhile read for everyone who treats people with diabetes,” Dr. Rodbard said.
The majority of the people on the ADA’s update committee had no disclosures, but a few reported ties to various companies, including Novo Nordisk, the maker of liraglutide, and Boehringer Ingelheim and Lilly, the companies that developed and/or marketed empagliflozin. Dr. Hellman had no conflicts. Dr. Rodbard is an adviser or researcher for AstraZeneca, Lilly, Janssen, Merck, Novo Nordisk, Sanofi, and Regeneron.
to reduce the risk of CV death, according to the American Diabetes Association 2017 Standards of Medical Care.
ADA updates it standards annually based on new information and research; like its predecessors, the 2017 guidance is comprehensive, addressing mental, social, and other challenges faced by patients with diabetes, along with clinical care (Diabetes Care. 2017 Jan;40(Suppl 1):S4-S5).
The 2017 guidance contains a great deal of new information. At 135 pages, there are 22 more pages than in 2016. “They did a really nice job. This guide is useful for anyone helping patients with diabetes,” including diabetologists, dietitians, educators, psychologists, and social workers, Richard Hellman, MD, a clinical endocrinologist in North Kansas City, Mo., said in an interview.
The empagliflozin and liraglutide recommendation applies to any patient with type 2 diabetes who has a history of stroke, heart attack, acute coronary syndrome, angina, or peripheral arterial disease. Data from recent trials have shown use of the drugs modestly reduces cardiovascular mortality in this population.
It’s unclear if the benefits are drug specific or group effects. “We anxiously await the results of several ongoing cardiovascular outcomes trials” to find out, said Helena Rodbard, MD, a clinical endocrinologist in Rockville, Md., who also commented on the new standards.
Basal insulin plus a GLP-1 receptor agonist, like liraglutide, are also now recommended for insulin-dependent type 2 disease. “This combination gives rise to a markedly reduced risk of hypoglycemia compared with basal insulin ... basal bolus insulin, or premixed insulins,” according to the ADA.
The newer drugs and insulins are expensive. To help doctors and patients negotiate the price hurdle, ADA added tables on how much the various options cost per month. It was a good move; “the cost of care is going up so fast” in diabetes “that many patients can no longer afford” what’s prescribed. “It’s a major problem,” said Dr. Hellman, clinical professor at the University of Missouri–Kansas City.
The ADA also set a blood glucose level of 54 mg/dL to trigger aggressive hypoglycemia treatment. “There has been confusion over when to treat aggressively. It was a good choice to land on 54 mg/dL” a safe, conservative number a bit higher than others have suggested, Dr. Hellman said.
Meanwhile, the group lowered its metabolic surgery cut point – the ADA has stopped using the term “bariatric surgery” – to type 2 patients with a body mass index of 30 kg/m2 when medications don’t work. The group also set a new hypertension treatment target of 120-160/80-105 mm Hg in pregnancy, and said that insulin is the treatment of choice for gestational diabetes, given concerns about metformin crossing the placenta and glyburide in cord blood.
The ADA expanded its list of diabetes comorbidities to include autoimmune disease, HIV, anxiety, depression, and disordered eating. In addition, doctors should ask patients how well they sleep – since sleep problems affect glycemic control – and should intervene when there’s a problem, according to the guidance.
The group updated its combination injection algorithm for type 2 diabetes “to reflect studies demonstrating the noninferiority of basal insulin plus” liraglutide and its class members “versus basal insulin plus rapid-acting insulin” or two daily injections of premixed insulin. The ADA added a section on the role of newly available biosimilar insulins, as well, and clarified that either basal insulin or basal plus bolus correctional insulin can be used to treat noncritical inpatients, but noted that “sole use of sliding scale insulin in the inpatient hospital setting is strongly discouraged.”
People on long-term metformin should have their vitamin B12 checked periodically, because of new evidence about the risk of B12 deficiency, the group said, and “due to the risk of malformations associated with unplanned pregnancies and poor metabolic control.” The group added “a new recommendation ... encouraging preconception counseling starting at puberty for all girls of childbearing potential.”
“Even though most of this information should be well known to practitioners treating patients, [it’s] a worthwhile read for everyone who treats people with diabetes,” Dr. Rodbard said.
The majority of the people on the ADA’s update committee had no disclosures, but a few reported ties to various companies, including Novo Nordisk, the maker of liraglutide, and Boehringer Ingelheim and Lilly, the companies that developed and/or marketed empagliflozin. Dr. Hellman had no conflicts. Dr. Rodbard is an adviser or researcher for AstraZeneca, Lilly, Janssen, Merck, Novo Nordisk, Sanofi, and Regeneron.
to reduce the risk of CV death, according to the American Diabetes Association 2017 Standards of Medical Care.
ADA updates it standards annually based on new information and research; like its predecessors, the 2017 guidance is comprehensive, addressing mental, social, and other challenges faced by patients with diabetes, along with clinical care (Diabetes Care. 2017 Jan;40(Suppl 1):S4-S5).
The 2017 guidance contains a great deal of new information. At 135 pages, there are 22 more pages than in 2016. “They did a really nice job. This guide is useful for anyone helping patients with diabetes,” including diabetologists, dietitians, educators, psychologists, and social workers, Richard Hellman, MD, a clinical endocrinologist in North Kansas City, Mo., said in an interview.
The empagliflozin and liraglutide recommendation applies to any patient with type 2 diabetes who has a history of stroke, heart attack, acute coronary syndrome, angina, or peripheral arterial disease. Data from recent trials have shown use of the drugs modestly reduces cardiovascular mortality in this population.
It’s unclear if the benefits are drug specific or group effects. “We anxiously await the results of several ongoing cardiovascular outcomes trials” to find out, said Helena Rodbard, MD, a clinical endocrinologist in Rockville, Md., who also commented on the new standards.
Basal insulin plus a GLP-1 receptor agonist, like liraglutide, are also now recommended for insulin-dependent type 2 disease. “This combination gives rise to a markedly reduced risk of hypoglycemia compared with basal insulin ... basal bolus insulin, or premixed insulins,” according to the ADA.
The newer drugs and insulins are expensive. To help doctors and patients negotiate the price hurdle, ADA added tables on how much the various options cost per month. It was a good move; “the cost of care is going up so fast” in diabetes “that many patients can no longer afford” what’s prescribed. “It’s a major problem,” said Dr. Hellman, clinical professor at the University of Missouri–Kansas City.
The ADA also set a blood glucose level of 54 mg/dL to trigger aggressive hypoglycemia treatment. “There has been confusion over when to treat aggressively. It was a good choice to land on 54 mg/dL” a safe, conservative number a bit higher than others have suggested, Dr. Hellman said.
Meanwhile, the group lowered its metabolic surgery cut point – the ADA has stopped using the term “bariatric surgery” – to type 2 patients with a body mass index of 30 kg/m2 when medications don’t work. The group also set a new hypertension treatment target of 120-160/80-105 mm Hg in pregnancy, and said that insulin is the treatment of choice for gestational diabetes, given concerns about metformin crossing the placenta and glyburide in cord blood.
The ADA expanded its list of diabetes comorbidities to include autoimmune disease, HIV, anxiety, depression, and disordered eating. In addition, doctors should ask patients how well they sleep – since sleep problems affect glycemic control – and should intervene when there’s a problem, according to the guidance.
The group updated its combination injection algorithm for type 2 diabetes “to reflect studies demonstrating the noninferiority of basal insulin plus” liraglutide and its class members “versus basal insulin plus rapid-acting insulin” or two daily injections of premixed insulin. The ADA added a section on the role of newly available biosimilar insulins, as well, and clarified that either basal insulin or basal plus bolus correctional insulin can be used to treat noncritical inpatients, but noted that “sole use of sliding scale insulin in the inpatient hospital setting is strongly discouraged.”
People on long-term metformin should have their vitamin B12 checked periodically, because of new evidence about the risk of B12 deficiency, the group said, and “due to the risk of malformations associated with unplanned pregnancies and poor metabolic control.” The group added “a new recommendation ... encouraging preconception counseling starting at puberty for all girls of childbearing potential.”
“Even though most of this information should be well known to practitioners treating patients, [it’s] a worthwhile read for everyone who treats people with diabetes,” Dr. Rodbard said.
The majority of the people on the ADA’s update committee had no disclosures, but a few reported ties to various companies, including Novo Nordisk, the maker of liraglutide, and Boehringer Ingelheim and Lilly, the companies that developed and/or marketed empagliflozin. Dr. Hellman had no conflicts. Dr. Rodbard is an adviser or researcher for AstraZeneca, Lilly, Janssen, Merck, Novo Nordisk, Sanofi, and Regeneron.
