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Selinexor trials placed on partial hold
The US Food and Drug Administration (FDA) has placed a partial clinical hold on all trials of selinexor (KPT-330).
Selinexor is an inhibitor being evaluated in multiple trials of patients with relapsed and/or refractory hematologic and solid tumor malignancies.
While the partial clinical hold remains in effect, patients with stable disease or better may remain on selinexor.
However, no new patients may be enrolled in selinexor trials until the hold is lifted.
The FDA has indicated that the partial clinical hold is due to incomplete information in the existing version of the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.
Karyopharm Therapeutics Inc., the company developing selinexor, said it has amended the brochure, updated the informed consent documents accordingly, and submitted the documents to the FDA as requested.
As of March 10, Karyopharm had provided all requested materials to the FDA believed to be required to lift the partial clinical hold. By regulation, the FDA has 30 days from the receipt of Karyopharm’s submission to notify the company whether the partial clinical hold is lifted.
Karyopharm said it is working with the FDA to seek the release of the hold and resume enrollment in its selinexor trials as expeditiously as possible. The company believes its previously disclosed enrollment rates and timelines for its ongoing trials will remain materially unchanged.
About selinexor
Selinexor is a selective inhibitor of nuclear export (SINE) XPO1 antagonist. The drug binds with and inhibits XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to induce apoptosis in cancer cells while largely sparing normal cells.
To date, more than 1900 patients have been treated with selinexor. The drug is currently being evaluated in several trials across multiple cancer indications.
One of these is the phase 2 SOPRA trial, in which selinexor is being compared to investigator’s choice of therapy (1 of 3 potential salvage therapies). The trial is enrolling patients 60 years of age or older with relapsed or refractory acute myeloid leukemia who are ineligible for standard intensive chemotherapy and/or transplant.
The SADAL study is a phase 2b trial comparing high and low doses of selinexor in patients with relapsed and/or refractory de novo diffuse large B-cell lymphoma who have no therapeutic options of demonstrated clinical benefit.
STORM is a phase 2b trial evaluating selinexor and low-dose dexamethasone in patients with heavily pretreated multiple myeloma (MM). And STOMP is a phase 1b/2 study evaluating selinexor in combination with existing therapies across the broader population in MM.
Karyopharm is also planning a randomized, phase 3 study known as BOSTON. In this trial, researchers will compare selinexor plus bortezomib and low-dose dexamethasone to bortezomib and low-dose dexamethasone in MM patients who have had 1 to 3 prior lines of therapy.
Additional phase 1, 2, and 3 studies are ongoing or currently planned.
The US Food and Drug Administration (FDA) has placed a partial clinical hold on all trials of selinexor (KPT-330).
Selinexor is an inhibitor being evaluated in multiple trials of patients with relapsed and/or refractory hematologic and solid tumor malignancies.
While the partial clinical hold remains in effect, patients with stable disease or better may remain on selinexor.
However, no new patients may be enrolled in selinexor trials until the hold is lifted.
The FDA has indicated that the partial clinical hold is due to incomplete information in the existing version of the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.
Karyopharm Therapeutics Inc., the company developing selinexor, said it has amended the brochure, updated the informed consent documents accordingly, and submitted the documents to the FDA as requested.
As of March 10, Karyopharm had provided all requested materials to the FDA believed to be required to lift the partial clinical hold. By regulation, the FDA has 30 days from the receipt of Karyopharm’s submission to notify the company whether the partial clinical hold is lifted.
Karyopharm said it is working with the FDA to seek the release of the hold and resume enrollment in its selinexor trials as expeditiously as possible. The company believes its previously disclosed enrollment rates and timelines for its ongoing trials will remain materially unchanged.
About selinexor
Selinexor is a selective inhibitor of nuclear export (SINE) XPO1 antagonist. The drug binds with and inhibits XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to induce apoptosis in cancer cells while largely sparing normal cells.
To date, more than 1900 patients have been treated with selinexor. The drug is currently being evaluated in several trials across multiple cancer indications.
One of these is the phase 2 SOPRA trial, in which selinexor is being compared to investigator’s choice of therapy (1 of 3 potential salvage therapies). The trial is enrolling patients 60 years of age or older with relapsed or refractory acute myeloid leukemia who are ineligible for standard intensive chemotherapy and/or transplant.
The SADAL study is a phase 2b trial comparing high and low doses of selinexor in patients with relapsed and/or refractory de novo diffuse large B-cell lymphoma who have no therapeutic options of demonstrated clinical benefit.
STORM is a phase 2b trial evaluating selinexor and low-dose dexamethasone in patients with heavily pretreated multiple myeloma (MM). And STOMP is a phase 1b/2 study evaluating selinexor in combination with existing therapies across the broader population in MM.
Karyopharm is also planning a randomized, phase 3 study known as BOSTON. In this trial, researchers will compare selinexor plus bortezomib and low-dose dexamethasone to bortezomib and low-dose dexamethasone in MM patients who have had 1 to 3 prior lines of therapy.
Additional phase 1, 2, and 3 studies are ongoing or currently planned.
The US Food and Drug Administration (FDA) has placed a partial clinical hold on all trials of selinexor (KPT-330).
Selinexor is an inhibitor being evaluated in multiple trials of patients with relapsed and/or refractory hematologic and solid tumor malignancies.
While the partial clinical hold remains in effect, patients with stable disease or better may remain on selinexor.
However, no new patients may be enrolled in selinexor trials until the hold is lifted.
The FDA has indicated that the partial clinical hold is due to incomplete information in the existing version of the investigator’s brochure, including an incomplete list of serious adverse events associated with selinexor.
Karyopharm Therapeutics Inc., the company developing selinexor, said it has amended the brochure, updated the informed consent documents accordingly, and submitted the documents to the FDA as requested.
As of March 10, Karyopharm had provided all requested materials to the FDA believed to be required to lift the partial clinical hold. By regulation, the FDA has 30 days from the receipt of Karyopharm’s submission to notify the company whether the partial clinical hold is lifted.
Karyopharm said it is working with the FDA to seek the release of the hold and resume enrollment in its selinexor trials as expeditiously as possible. The company believes its previously disclosed enrollment rates and timelines for its ongoing trials will remain materially unchanged.
About selinexor
Selinexor is a selective inhibitor of nuclear export (SINE) XPO1 antagonist. The drug binds with and inhibits XPO1, leading to the accumulation of tumor suppressor proteins in the cell nucleus. This reinitiates and amplifies their tumor suppressor function and is believed to induce apoptosis in cancer cells while largely sparing normal cells.
To date, more than 1900 patients have been treated with selinexor. The drug is currently being evaluated in several trials across multiple cancer indications.
One of these is the phase 2 SOPRA trial, in which selinexor is being compared to investigator’s choice of therapy (1 of 3 potential salvage therapies). The trial is enrolling patients 60 years of age or older with relapsed or refractory acute myeloid leukemia who are ineligible for standard intensive chemotherapy and/or transplant.
The SADAL study is a phase 2b trial comparing high and low doses of selinexor in patients with relapsed and/or refractory de novo diffuse large B-cell lymphoma who have no therapeutic options of demonstrated clinical benefit.
STORM is a phase 2b trial evaluating selinexor and low-dose dexamethasone in patients with heavily pretreated multiple myeloma (MM). And STOMP is a phase 1b/2 study evaluating selinexor in combination with existing therapies across the broader population in MM.
Karyopharm is also planning a randomized, phase 3 study known as BOSTON. In this trial, researchers will compare selinexor plus bortezomib and low-dose dexamethasone to bortezomib and low-dose dexamethasone in MM patients who have had 1 to 3 prior lines of therapy.
Additional phase 1, 2, and 3 studies are ongoing or currently planned.
Sickle cell trait linked to end-stage renal disease
Black individuals with sickle cell trait (SCT) have an increased risk of developing end-stage renal disease (ESRD), according to new research.
The study indicates that having SCT actually doubles the risk of ESRD.
And the trait confers a similar degree of risk as APOL1 gene variants, which are currently the most widely recognized genetic contributors to kidney disease in blacks.
Researchers believe this finding may have important public policy implications for genetic counseling for individuals with SCT.
Rakhi P. Naik, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and her colleagues reported this finding in the Journal of the American Society of Nephrology.
Previous research suggested there is an association between SCT and chronic kidney disease, but it hasn’t been clear if that extends to ESRD. Studies have also suggested a possible association between kidney disease and hemoglobin C trait, but the link has not been confirmed.
So Dr Naik and her colleagues decided to investigate these potential links. To do so, the researchers analyzed data from a large, population-based study, the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.
The team evaluated information on 9909 black individuals, 739 of whom had SCT and 243 of whom had hemoglobin C trait.
The data indicate that individuals with SCT have a 2-fold higher risk of developing ESRD when compared to those without SCT. But there is no association between hemoglobin C trait and ESRD.
At a median follow-up of 6.5 years, the incidence of ESRD was 5.4% (40/739) in participants with SCT, 2.5% (6/243) in subjects with hemoglobin C trait, and 2.6% (234/8927) in individuals without either trait.
The incidence rate for ESRD was 8.5 per 1000 person-years for participants with SCT, 3.9 per 1000 person-years for subjects with hemoglobin C trait, and 4.0 per 1000 person-years for individuals without either trait.
The researchers noted that SCT conferred a similar degree of ESRD risk as APOL1 gene variants. The hazard ratio for subjects with SCT was 2.03, and the hazard ratio for those with APOL1 high-risk genotypes was 1.77.
“Although you cannot change the genes you are born with, doctors can use this information to start screening for kidney disease earlier and to aggressively treat any other risk factors you may have, such as diabetes or high blood pressure,” Dr Naik said.
“We still need more studies to determine if there are other treatments that can be used to slow the progression of kidney disease, specifically in individuals with sickle cell trait.” 
Black individuals with sickle cell trait (SCT) have an increased risk of developing end-stage renal disease (ESRD), according to new research.
The study indicates that having SCT actually doubles the risk of ESRD.
And the trait confers a similar degree of risk as APOL1 gene variants, which are currently the most widely recognized genetic contributors to kidney disease in blacks.
Researchers believe this finding may have important public policy implications for genetic counseling for individuals with SCT.
Rakhi P. Naik, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and her colleagues reported this finding in the Journal of the American Society of Nephrology.
Previous research suggested there is an association between SCT and chronic kidney disease, but it hasn’t been clear if that extends to ESRD. Studies have also suggested a possible association between kidney disease and hemoglobin C trait, but the link has not been confirmed.
So Dr Naik and her colleagues decided to investigate these potential links. To do so, the researchers analyzed data from a large, population-based study, the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.
The team evaluated information on 9909 black individuals, 739 of whom had SCT and 243 of whom had hemoglobin C trait.
The data indicate that individuals with SCT have a 2-fold higher risk of developing ESRD when compared to those without SCT. But there is no association between hemoglobin C trait and ESRD.
At a median follow-up of 6.5 years, the incidence of ESRD was 5.4% (40/739) in participants with SCT, 2.5% (6/243) in subjects with hemoglobin C trait, and 2.6% (234/8927) in individuals without either trait.
The incidence rate for ESRD was 8.5 per 1000 person-years for participants with SCT, 3.9 per 1000 person-years for subjects with hemoglobin C trait, and 4.0 per 1000 person-years for individuals without either trait.
The researchers noted that SCT conferred a similar degree of ESRD risk as APOL1 gene variants. The hazard ratio for subjects with SCT was 2.03, and the hazard ratio for those with APOL1 high-risk genotypes was 1.77.
“Although you cannot change the genes you are born with, doctors can use this information to start screening for kidney disease earlier and to aggressively treat any other risk factors you may have, such as diabetes or high blood pressure,” Dr Naik said.
“We still need more studies to determine if there are other treatments that can be used to slow the progression of kidney disease, specifically in individuals with sickle cell trait.”
Black individuals with sickle cell trait (SCT) have an increased risk of developing end-stage renal disease (ESRD), according to new research.
The study indicates that having SCT actually doubles the risk of ESRD.
And the trait confers a similar degree of risk as APOL1 gene variants, which are currently the most widely recognized genetic contributors to kidney disease in blacks.
Researchers believe this finding may have important public policy implications for genetic counseling for individuals with SCT.
Rakhi P. Naik, MD, of Johns Hopkins University School of Medicine in Baltimore, Maryland, and her colleagues reported this finding in the Journal of the American Society of Nephrology.
Previous research suggested there is an association between SCT and chronic kidney disease, but it hasn’t been clear if that extends to ESRD. Studies have also suggested a possible association between kidney disease and hemoglobin C trait, but the link has not been confirmed.
So Dr Naik and her colleagues decided to investigate these potential links. To do so, the researchers analyzed data from a large, population-based study, the REasons for Geographic and Racial Differences in Stroke (REGARDS) study.
The team evaluated information on 9909 black individuals, 739 of whom had SCT and 243 of whom had hemoglobin C trait.
The data indicate that individuals with SCT have a 2-fold higher risk of developing ESRD when compared to those without SCT. But there is no association between hemoglobin C trait and ESRD.
At a median follow-up of 6.5 years, the incidence of ESRD was 5.4% (40/739) in participants with SCT, 2.5% (6/243) in subjects with hemoglobin C trait, and 2.6% (234/8927) in individuals without either trait.
The incidence rate for ESRD was 8.5 per 1000 person-years for participants with SCT, 3.9 per 1000 person-years for subjects with hemoglobin C trait, and 4.0 per 1000 person-years for individuals without either trait.
The researchers noted that SCT conferred a similar degree of ESRD risk as APOL1 gene variants. The hazard ratio for subjects with SCT was 2.03, and the hazard ratio for those with APOL1 high-risk genotypes was 1.77.
“Although you cannot change the genes you are born with, doctors can use this information to start screening for kidney disease earlier and to aggressively treat any other risk factors you may have, such as diabetes or high blood pressure,” Dr Naik said.
“We still need more studies to determine if there are other treatments that can be used to slow the progression of kidney disease, specifically in individuals with sickle cell trait.”
PRAC recommends suspending gadolinium agents
The European Medicines Agency’s (EMA) Pharmacovigilance and Risk Assessment Committee (PRAC) has recommended suspending marketing authorizations for 4 linear gadolinium contrast agents because of evidence that small amounts of the gadolinium they contain are deposited in the brain.
The agents concerned are intravenous injections of gadobenic acid, gadodiamide, gadopentetic acid, and gadoversetamide, which are given to patients to enhance images from magnetic resonance imaging (MRI) body scans.
The PRAC’s review of gadolinium agents found “convincing evidence” of accumulation of gadolinium in the brain from studies directly measuring gadolinium in brain tissues and areas of increased signal intensity seen on MRI scan images many months after the last injection of a gadolinium contrast agent.
Although no symptoms or diseases linked to gadolinium in the brain have been reported, the PRAC took a precautionary approach, noting that data on the long-term effects in the brain are limited.
Companies concerned by this review have the right to request that the PRAC re-examine its recommendations.
The PRAC’s recommendations will be sent to the Committee for Medicinal Products for Human Use (CHMP) for its opinion. Further details will be published at the time of the CHMP opinion.
The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all European Union member states.
Details of the review, recommendations
The PRAC’s review was initiated on March 17, 2016, at the request of the European Commission, under Article 31 of Directive 2001/83/EC.
The review covers agents containing the following active substances: gadobenic acid, gadobutrol, gadodiamide, gadopentetic acid, gadoteric acid, gadoteridol, gadoversetamide, and gadoxetic acid.
The 4 agents recommended for suspension (gadobenic acid, gadodiamide, gadopentetic acid, and gadoversetamide) are linear agents. They have a structure more likely to release gadolinium, which can build up in body tissues.
Other agents, known as macrocyclic agents, are more stable and have a much lower propensity to release gadolinium.
The PRAC recommends that macrocyclic agents (gadobutrol, gadoteric acid, and gadoteridol) be used at the lowest dose that enhances images sufficiently to make diagnoses and only when unenhanced body scans are not suitable.
The PRAC has recommended that some linear agents remain available. The committee said that gadoxetic acid, a linear agent used at a low dose for liver scans, can remain on the market as it meets an important diagnostic need in patients with few alternatives.
In addition, a formulation of gadopentetic acid injected directly into joints should remain available because its gadolinium concentration is very low—around 200 times lower than those of intravenous products.
Both agents should be used at the lowest dose that enhances images sufficiently to make diagnoses and only if unenhanced scans are not suitable.
For those marketing authorizations recommended for suspension, the suspensions can be lifted if the respective companies provide evidence of new benefits in an identified patient group that outweigh its risks or show that their product (modified or not) does not release gadolinium significantly or lead to its retention in tissues.
The European Medicines Agency’s (EMA) Pharmacovigilance and Risk Assessment Committee (PRAC) has recommended suspending marketing authorizations for 4 linear gadolinium contrast agents because of evidence that small amounts of the gadolinium they contain are deposited in the brain.
The agents concerned are intravenous injections of gadobenic acid, gadodiamide, gadopentetic acid, and gadoversetamide, which are given to patients to enhance images from magnetic resonance imaging (MRI) body scans.
The PRAC’s review of gadolinium agents found “convincing evidence” of accumulation of gadolinium in the brain from studies directly measuring gadolinium in brain tissues and areas of increased signal intensity seen on MRI scan images many months after the last injection of a gadolinium contrast agent.
Although no symptoms or diseases linked to gadolinium in the brain have been reported, the PRAC took a precautionary approach, noting that data on the long-term effects in the brain are limited.
Companies concerned by this review have the right to request that the PRAC re-examine its recommendations.
The PRAC’s recommendations will be sent to the Committee for Medicinal Products for Human Use (CHMP) for its opinion. Further details will be published at the time of the CHMP opinion.
The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all European Union member states.
Details of the review, recommendations
The PRAC’s review was initiated on March 17, 2016, at the request of the European Commission, under Article 31 of Directive 2001/83/EC.
The review covers agents containing the following active substances: gadobenic acid, gadobutrol, gadodiamide, gadopentetic acid, gadoteric acid, gadoteridol, gadoversetamide, and gadoxetic acid.
The 4 agents recommended for suspension (gadobenic acid, gadodiamide, gadopentetic acid, and gadoversetamide) are linear agents. They have a structure more likely to release gadolinium, which can build up in body tissues.
Other agents, known as macrocyclic agents, are more stable and have a much lower propensity to release gadolinium.
The PRAC recommends that macrocyclic agents (gadobutrol, gadoteric acid, and gadoteridol) be used at the lowest dose that enhances images sufficiently to make diagnoses and only when unenhanced body scans are not suitable.
The PRAC has recommended that some linear agents remain available. The committee said that gadoxetic acid, a linear agent used at a low dose for liver scans, can remain on the market as it meets an important diagnostic need in patients with few alternatives.
In addition, a formulation of gadopentetic acid injected directly into joints should remain available because its gadolinium concentration is very low—around 200 times lower than those of intravenous products.
Both agents should be used at the lowest dose that enhances images sufficiently to make diagnoses and only if unenhanced scans are not suitable.
For those marketing authorizations recommended for suspension, the suspensions can be lifted if the respective companies provide evidence of new benefits in an identified patient group that outweigh its risks or show that their product (modified or not) does not release gadolinium significantly or lead to its retention in tissues.
The European Medicines Agency’s (EMA) Pharmacovigilance and Risk Assessment Committee (PRAC) has recommended suspending marketing authorizations for 4 linear gadolinium contrast agents because of evidence that small amounts of the gadolinium they contain are deposited in the brain.
The agents concerned are intravenous injections of gadobenic acid, gadodiamide, gadopentetic acid, and gadoversetamide, which are given to patients to enhance images from magnetic resonance imaging (MRI) body scans.
The PRAC’s review of gadolinium agents found “convincing evidence” of accumulation of gadolinium in the brain from studies directly measuring gadolinium in brain tissues and areas of increased signal intensity seen on MRI scan images many months after the last injection of a gadolinium contrast agent.
Although no symptoms or diseases linked to gadolinium in the brain have been reported, the PRAC took a precautionary approach, noting that data on the long-term effects in the brain are limited.
Companies concerned by this review have the right to request that the PRAC re-examine its recommendations.
The PRAC’s recommendations will be sent to the Committee for Medicinal Products for Human Use (CHMP) for its opinion. Further details will be published at the time of the CHMP opinion.
The final stage of the review procedure is the adoption by the European Commission of a legally binding decision applicable in all European Union member states.
Details of the review, recommendations
The PRAC’s review was initiated on March 17, 2016, at the request of the European Commission, under Article 31 of Directive 2001/83/EC.
The review covers agents containing the following active substances: gadobenic acid, gadobutrol, gadodiamide, gadopentetic acid, gadoteric acid, gadoteridol, gadoversetamide, and gadoxetic acid.
The 4 agents recommended for suspension (gadobenic acid, gadodiamide, gadopentetic acid, and gadoversetamide) are linear agents. They have a structure more likely to release gadolinium, which can build up in body tissues.
Other agents, known as macrocyclic agents, are more stable and have a much lower propensity to release gadolinium.
The PRAC recommends that macrocyclic agents (gadobutrol, gadoteric acid, and gadoteridol) be used at the lowest dose that enhances images sufficiently to make diagnoses and only when unenhanced body scans are not suitable.
The PRAC has recommended that some linear agents remain available. The committee said that gadoxetic acid, a linear agent used at a low dose for liver scans, can remain on the market as it meets an important diagnostic need in patients with few alternatives.
In addition, a formulation of gadopentetic acid injected directly into joints should remain available because its gadolinium concentration is very low—around 200 times lower than those of intravenous products.
Both agents should be used at the lowest dose that enhances images sufficiently to make diagnoses and only if unenhanced scans are not suitable.
For those marketing authorizations recommended for suspension, the suspensions can be lifted if the respective companies provide evidence of new benefits in an identified patient group that outweigh its risks or show that their product (modified or not) does not release gadolinium significantly or lead to its retention in tissues.
Is Vitamin D Beneficial for MS Patients?
Q) What is the role of vitamin D in multiple sclerosis? Is it beneficial?
The exact etiology and pathophysiology of multiple sclerosis (MS) is still not fully understood. Research strongly suggests that there are two major causative factors: one genetic, and the other, environmental. From an environmental standpoint, multiple studies have shown that living farther from the equator, not being exposed to sunlight, and having a low vitamin D level are all correlated with increased risk for MS and MS relapse.1
Our bodies need sunlight to successfully synthesize vitamin D in the skin. Research has found that individuals with lightly pigmented skin are five times more efficient at synthesizing vitamin D in the presence of sunlight than those with darker skin.2 However, the ability to absorb sunlight is also correlated with the earth’s latitude; worse absorption occurs in areas beyond the 40th parallel (in either hemisphere), where UVB levels are too low to synthesize vitamin D four to six months out of the year.2
When exposed to UVB rays, our bodies start to synthesize vitamin D; it undergoes a transformation in the liver and then the kidneys and ultimately becomes the hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol).2 Calcitriol is recognized by multiple tissues throughout the body that contain vitamin D receptors. Specifically, in the central nervous system, receptors are located on microglia, activated monocytes, and B and T lymphocytes.1 In MS, myelin (the coating around the nerves) is destroyed by an immune-mediated inflammatory process involving the microglia and B and T lymphocytes. Vitamin D quiets down this inflammation, thereby reducing disability accumulation and relapse risk and resulting in fewer changes on MRI.
Vitamin D is also believed to shift the immune response to an anti-inflammatory state by focusing the response on the cytotoxic T cells often found in MS lesions, which attack neurons and oligodendrocytes.2 This theory was tested by Munger and colleagues, who used a pooled cohort of 187,000 women from the Nurses’ Health Study and Nurses’ Health Study II to assess vitamin D intake and risk for MS. Compared to women with lower vitamin D intake, those who took 700 IU/d had a 41% lower incidence of MS. Women who took ≥ 400 IU/d had a 33% lower risk for MS, compared to nonusers.3 In another evaluation of 7 million US military personnel, individuals with a serum vitamin D level of 40 ng/mL were 62% less likely to develop MS.4
In light of the anti-inflammatory effects of vitamin D and its purported reduction of MS risk, it is possible that patients with MS should begin vitamin D supplementation early to obtain maximum anti-inflammatory effects. While an optimal vitamin D goal has not been established in the literature, some studies suggest 30 to 55 ng/mL as a target range for serum vitamin D level.1
While vitamin D has been found to be well-tolerated, patients should be cautioned that very high doses can cause fatigue, abdominal cramps, nausea, vomiting, kidney damage, hypertension, hypercalcemia, and oth
Lisa Marie Fox, MSPAS, PA-C
Division of Multiple Sclerosis, Department of Neurology, Johns Hopkins Hosptial, Baltimore
1. Waubant E, Mowry E, Bowling A. The role of vitamin D in multiple sclerosis pathology and treatment: answers and opportunities. Int J MS Care. 2015;17(2):1-24.
2. Pierrot-Deseilligny C. Clinical implications of a possible role of vitamin D in multiple sclerosis. J Neurol. 2009;256(9):1468-1478.3. Munger KL, Zhang SM, O’Reilly E, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004;62(1):60-65.
4. Munger KL, Levin LI, Hollis BW, et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006; 296(23):2832-2838.
5. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53-58.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month’s responses were authored by Bryan Walker and Lisa Marie Fox, MSPAS, PA-C, who is in the Division of Multiple Sclerosis, Department of Neurology, at Johns Hopkins Hospital in Baltimore.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month’s responses were authored by Bryan Walker and Lisa Marie Fox, MSPAS, PA-C, who is in the Division of Multiple Sclerosis, Department of Neurology, at Johns Hopkins Hospital in Baltimore.
Clinician Reviews in partnership with
MS Consult is edited by Colleen J. Harris, MN, NP, MSCN, Nurse Practitioner/Manager of the Multiple Sclerosis Clinic at Foothills Medical Centre in Calgary, Alberta, Canada, and Bryan Walker, MHS, PA-C, who is in the Department of Neurology, Division of MS and Neuroimmunology, at Duke University Medical Center in Durham, North Carolina. This month’s responses were authored by Bryan Walker and Lisa Marie Fox, MSPAS, PA-C, who is in the Division of Multiple Sclerosis, Department of Neurology, at Johns Hopkins Hospital in Baltimore.
Q) What is the role of vitamin D in multiple sclerosis? Is it beneficial?
The exact etiology and pathophysiology of multiple sclerosis (MS) is still not fully understood. Research strongly suggests that there are two major causative factors: one genetic, and the other, environmental. From an environmental standpoint, multiple studies have shown that living farther from the equator, not being exposed to sunlight, and having a low vitamin D level are all correlated with increased risk for MS and MS relapse.1
Our bodies need sunlight to successfully synthesize vitamin D in the skin. Research has found that individuals with lightly pigmented skin are five times more efficient at synthesizing vitamin D in the presence of sunlight than those with darker skin.2 However, the ability to absorb sunlight is also correlated with the earth’s latitude; worse absorption occurs in areas beyond the 40th parallel (in either hemisphere), where UVB levels are too low to synthesize vitamin D four to six months out of the year.2
When exposed to UVB rays, our bodies start to synthesize vitamin D; it undergoes a transformation in the liver and then the kidneys and ultimately becomes the hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol).2 Calcitriol is recognized by multiple tissues throughout the body that contain vitamin D receptors. Specifically, in the central nervous system, receptors are located on microglia, activated monocytes, and B and T lymphocytes.1 In MS, myelin (the coating around the nerves) is destroyed by an immune-mediated inflammatory process involving the microglia and B and T lymphocytes. Vitamin D quiets down this inflammation, thereby reducing disability accumulation and relapse risk and resulting in fewer changes on MRI.
Vitamin D is also believed to shift the immune response to an anti-inflammatory state by focusing the response on the cytotoxic T cells often found in MS lesions, which attack neurons and oligodendrocytes.2 This theory was tested by Munger and colleagues, who used a pooled cohort of 187,000 women from the Nurses’ Health Study and Nurses’ Health Study II to assess vitamin D intake and risk for MS. Compared to women with lower vitamin D intake, those who took 700 IU/d had a 41% lower incidence of MS. Women who took ≥ 400 IU/d had a 33% lower risk for MS, compared to nonusers.3 In another evaluation of 7 million US military personnel, individuals with a serum vitamin D level of 40 ng/mL were 62% less likely to develop MS.4
In light of the anti-inflammatory effects of vitamin D and its purported reduction of MS risk, it is possible that patients with MS should begin vitamin D supplementation early to obtain maximum anti-inflammatory effects. While an optimal vitamin D goal has not been established in the literature, some studies suggest 30 to 55 ng/mL as a target range for serum vitamin D level.1
While vitamin D has been found to be well-tolerated, patients should be cautioned that very high doses can cause fatigue, abdominal cramps, nausea, vomiting, kidney damage, hypertension, hypercalcemia, and oth
Lisa Marie Fox, MSPAS, PA-C
Division of Multiple Sclerosis, Department of Neurology, Johns Hopkins Hosptial, Baltimore
Q) What is the role of vitamin D in multiple sclerosis? Is it beneficial?
The exact etiology and pathophysiology of multiple sclerosis (MS) is still not fully understood. Research strongly suggests that there are two major causative factors: one genetic, and the other, environmental. From an environmental standpoint, multiple studies have shown that living farther from the equator, not being exposed to sunlight, and having a low vitamin D level are all correlated with increased risk for MS and MS relapse.1
Our bodies need sunlight to successfully synthesize vitamin D in the skin. Research has found that individuals with lightly pigmented skin are five times more efficient at synthesizing vitamin D in the presence of sunlight than those with darker skin.2 However, the ability to absorb sunlight is also correlated with the earth’s latitude; worse absorption occurs in areas beyond the 40th parallel (in either hemisphere), where UVB levels are too low to synthesize vitamin D four to six months out of the year.2
When exposed to UVB rays, our bodies start to synthesize vitamin D; it undergoes a transformation in the liver and then the kidneys and ultimately becomes the hormonally active form of vitamin D, 1,25-dihydroxyvitamin D3 (calcitriol).2 Calcitriol is recognized by multiple tissues throughout the body that contain vitamin D receptors. Specifically, in the central nervous system, receptors are located on microglia, activated monocytes, and B and T lymphocytes.1 In MS, myelin (the coating around the nerves) is destroyed by an immune-mediated inflammatory process involving the microglia and B and T lymphocytes. Vitamin D quiets down this inflammation, thereby reducing disability accumulation and relapse risk and resulting in fewer changes on MRI.
Vitamin D is also believed to shift the immune response to an anti-inflammatory state by focusing the response on the cytotoxic T cells often found in MS lesions, which attack neurons and oligodendrocytes.2 This theory was tested by Munger and colleagues, who used a pooled cohort of 187,000 women from the Nurses’ Health Study and Nurses’ Health Study II to assess vitamin D intake and risk for MS. Compared to women with lower vitamin D intake, those who took 700 IU/d had a 41% lower incidence of MS. Women who took ≥ 400 IU/d had a 33% lower risk for MS, compared to nonusers.3 In another evaluation of 7 million US military personnel, individuals with a serum vitamin D level of 40 ng/mL were 62% less likely to develop MS.4
In light of the anti-inflammatory effects of vitamin D and its purported reduction of MS risk, it is possible that patients with MS should begin vitamin D supplementation early to obtain maximum anti-inflammatory effects. While an optimal vitamin D goal has not been established in the literature, some studies suggest 30 to 55 ng/mL as a target range for serum vitamin D level.1
While vitamin D has been found to be well-tolerated, patients should be cautioned that very high doses can cause fatigue, abdominal cramps, nausea, vomiting, kidney damage, hypertension, hypercalcemia, and oth
Lisa Marie Fox, MSPAS, PA-C
Division of Multiple Sclerosis, Department of Neurology, Johns Hopkins Hosptial, Baltimore
1. Waubant E, Mowry E, Bowling A. The role of vitamin D in multiple sclerosis pathology and treatment: answers and opportunities. Int J MS Care. 2015;17(2):1-24.
2. Pierrot-Deseilligny C. Clinical implications of a possible role of vitamin D in multiple sclerosis. J Neurol. 2009;256(9):1468-1478.3. Munger KL, Zhang SM, O’Reilly E, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004;62(1):60-65.
4. Munger KL, Levin LI, Hollis BW, et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006; 296(23):2832-2838.
5. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53-58.
1. Waubant E, Mowry E, Bowling A. The role of vitamin D in multiple sclerosis pathology and treatment: answers and opportunities. Int J MS Care. 2015;17(2):1-24.
2. Pierrot-Deseilligny C. Clinical implications of a possible role of vitamin D in multiple sclerosis. J Neurol. 2009;256(9):1468-1478.3. Munger KL, Zhang SM, O’Reilly E, et al. Vitamin D intake and incidence of multiple sclerosis. Neurology. 2004;62(1):60-65.
4. Munger KL, Levin LI, Hollis BW, et al. Serum 25-hydroxyvitamin D levels and risk of multiple sclerosis. JAMA. 2006; 296(23):2832-2838.
5. Ross AC, Manson JE, Abrams SA, et al. The 2011 report on dietary reference intakes for calcium and vitamin D from the Institute of Medicine: what clinicians need to know. J Clin Endocrinol Metab. 2011;96(1):53-58.
Esophageal variceal bleeding, portal hypertension tied to recurrent pediatric GI bleeds
Readmission to the hospital after acute GI bleeding in children is most often associated with an initial diagnosis of portal hypertension or esophageal variceal hemorrhage, based on data from a retrospective study of 9,902 patients.
Rebleeding in adults may be predicted by endoscopic characteristics of the bleeding source in some cases, but “there is still a considerable subgroup of children admitted with acute gastrointestinal bleeding and not endoscoped but in whom we do not have any measure to predict rebleeding including after discharge,” Thomas M. Attard, MD, Children’s Mercy Hospital, Kansas City, Mo., and his colleagues said.
The study included children aged 1-21 years with upper or indeterminate GI bleeding who were discharged from 49 pediatric hospitals between January 1, 2007 and September 30, 2015. Overall, 1,460 children (16%) were readmitted at least once within 30 days, with 72 readmitted twice and an average of 10 days’ time to readmission.
Readmission for recurrent bleeding was most frequently associated with an initial diagnosis of portal hypertension (20%) or esophageal variceal hemorrhage (20%). Children who had undergone endoscopy (odds ratio, 0.77) or Meckel’s scan (OR, 0.51) on initial admission were least likely to require readmission.
Children with one or two complex chronic conditions were almost twice as likely to be readmitted than were those with no complex chronic conditions, and a longer initial hospital stay and early treatment with proton pump inhibitors were associated with increased likelihood of readmission. “These may be indicative of more medically frail patients and greater severity of initial illness, respectively,” the researchers said. They found no association between increased risk of readmission and demographic factors including age, sex, race, and urban vs. rural residence (J Pediatr. 2017 Feb. doi: 10.1016/j.jpeds.2017.01.044).
Readmission to the hospital after acute GI bleeding in children is most often associated with an initial diagnosis of portal hypertension or esophageal variceal hemorrhage, based on data from a retrospective study of 9,902 patients.
Rebleeding in adults may be predicted by endoscopic characteristics of the bleeding source in some cases, but “there is still a considerable subgroup of children admitted with acute gastrointestinal bleeding and not endoscoped but in whom we do not have any measure to predict rebleeding including after discharge,” Thomas M. Attard, MD, Children’s Mercy Hospital, Kansas City, Mo., and his colleagues said.
The study included children aged 1-21 years with upper or indeterminate GI bleeding who were discharged from 49 pediatric hospitals between January 1, 2007 and September 30, 2015. Overall, 1,460 children (16%) were readmitted at least once within 30 days, with 72 readmitted twice and an average of 10 days’ time to readmission.
Readmission for recurrent bleeding was most frequently associated with an initial diagnosis of portal hypertension (20%) or esophageal variceal hemorrhage (20%). Children who had undergone endoscopy (odds ratio, 0.77) or Meckel’s scan (OR, 0.51) on initial admission were least likely to require readmission.
Children with one or two complex chronic conditions were almost twice as likely to be readmitted than were those with no complex chronic conditions, and a longer initial hospital stay and early treatment with proton pump inhibitors were associated with increased likelihood of readmission. “These may be indicative of more medically frail patients and greater severity of initial illness, respectively,” the researchers said. They found no association between increased risk of readmission and demographic factors including age, sex, race, and urban vs. rural residence (J Pediatr. 2017 Feb. doi: 10.1016/j.jpeds.2017.01.044).
Readmission to the hospital after acute GI bleeding in children is most often associated with an initial diagnosis of portal hypertension or esophageal variceal hemorrhage, based on data from a retrospective study of 9,902 patients.
Rebleeding in adults may be predicted by endoscopic characteristics of the bleeding source in some cases, but “there is still a considerable subgroup of children admitted with acute gastrointestinal bleeding and not endoscoped but in whom we do not have any measure to predict rebleeding including after discharge,” Thomas M. Attard, MD, Children’s Mercy Hospital, Kansas City, Mo., and his colleagues said.
The study included children aged 1-21 years with upper or indeterminate GI bleeding who were discharged from 49 pediatric hospitals between January 1, 2007 and September 30, 2015. Overall, 1,460 children (16%) were readmitted at least once within 30 days, with 72 readmitted twice and an average of 10 days’ time to readmission.
Readmission for recurrent bleeding was most frequently associated with an initial diagnosis of portal hypertension (20%) or esophageal variceal hemorrhage (20%). Children who had undergone endoscopy (odds ratio, 0.77) or Meckel’s scan (OR, 0.51) on initial admission were least likely to require readmission.
Children with one or two complex chronic conditions were almost twice as likely to be readmitted than were those with no complex chronic conditions, and a longer initial hospital stay and early treatment with proton pump inhibitors were associated with increased likelihood of readmission. “These may be indicative of more medically frail patients and greater severity of initial illness, respectively,” the researchers said. They found no association between increased risk of readmission and demographic factors including age, sex, race, and urban vs. rural residence (J Pediatr. 2017 Feb. doi: 10.1016/j.jpeds.2017.01.044).
FROM THE JOURNAL OF PEDIATRICS
ICD-10 Update: Report From the AAD Meeting
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Hair Disorders in the Skin of Color Population: Report From the AAD Meeting
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Bipartisan Budget Act (BBA) of 2015 threatens growth of pulmonary rehab
In late 2015, Congress passed the Bipartisan Budget Act (BBA) to address numerous wide-ranging budget concerns, including issues related to agriculture, pensions, the strategic petroleum reserve, along with some Medicare issues. Section 603 of BBA is now coming back to haunt pulmonary rehabilitation services.
The intent of Section 603 is reasonable – to address the phenomenon of hospitals purchasing physician practices to take advantage of payment differentials between identical or virtually identical services when comparing the hospital outpatient prospective payment system (HOPPS) and the physician fee schedule (PFS). For example, an orthopedic practice might own its own MRI and related support services. It will bill for those services under the PFS. However, if the practice sells that segment of the revenue stream (the MRI assets, etc) to a hospital, the hospital can bill Medicare for those same services under the hospital outpatient prospective payment system at an amount notably higher than the PFS payment.
To address this payment aberration, Congress instructed the Centers for Medicare & Medicaid Services to craft a system to preclude a hospital from such behavior. If a hospital offers new or expanded outpatient services, it could NOT bill Medicare under the hospital outpatient services methodology and would be required to bill under the PFS payment methodology. Importantly, a few exemptions exist. If the new or expanded service is within 250 yards of the main hospital campus, the outpatient billing methodology is permitted. Likewise, if expansion of a current off-campus service occurs at the same location of the current off-site service, the hospital may continue to bill under the outpatient rules. Several other technical exceptions are permitted, for example construction planned prior to passage of BBA.
The implications for pulmonary rehabilitation are critical to its growth. A hospital that wishes to expand its current program and bill under the hospital outpatient methodology MUST do so by expanding at its current location. An expansion at a new location that is not within 250 yards of the main hospital campus triggers Section 603 provisions, and the hospital will bill at the physician fee schedule rate. Because the PFS payment rate is just over half of the payment rate for HOPPS payment, it is unlikely that a hospital would expand an existing program or establish a new one if it would be forced to bill under the lower rate.
While congressional logic may be relatively understandable, for pulmonary medicine, it is based on the premise that a hospital would purchase a pulmonary practice because that practice had a lucrative pulmonary rehabilitation services cash flow. NAMDRC and other societies were able to document major flaws in the basic premise, resulting in very problematic unintended consequences. A detailed review of Medicare claims data provides strong evidence that pulmonary practices simply do not provide pulmonary rehab services.
These data strongly indicate that G0424 pulmonary practice physician office billing for the most recent year data are available ($230K), compared with hospital outpatient allowed charges ($119M), is less than two-tenths of 1% of billing through the hospital setting. To argue that hospitals are purchasing pulmonary practices for financial gain tied to pulmonary rehab services defies Medicare data, as well as financial logic. If the CMS premise was valid, one would expect the aggregate physician office billing to be much greater than $535K. In discussions with CMS, the Agency did agree that there are likely to be unintended consequences related to Section 603 implementation. The Agency also emphasizes that it does not have the statutory authority for a “carve out” exemption. CMS stated that even if it agreed with us, it simply lacked the authority to exempt pulmonary rehab services. CMS also agreed that there is growing evidence that pulmonary rehab is a underutilized service that may very well save the program money through reduced hospitalizations and rehospitalizations, but it has little choice to implement the statute as Congress so mandated.
Therefore, the only solution is a legislative one. NAMDRC and other societies are seriously considering approaching Congress for such resolution.
In late 2015, Congress passed the Bipartisan Budget Act (BBA) to address numerous wide-ranging budget concerns, including issues related to agriculture, pensions, the strategic petroleum reserve, along with some Medicare issues. Section 603 of BBA is now coming back to haunt pulmonary rehabilitation services.
The intent of Section 603 is reasonable – to address the phenomenon of hospitals purchasing physician practices to take advantage of payment differentials between identical or virtually identical services when comparing the hospital outpatient prospective payment system (HOPPS) and the physician fee schedule (PFS). For example, an orthopedic practice might own its own MRI and related support services. It will bill for those services under the PFS. However, if the practice sells that segment of the revenue stream (the MRI assets, etc) to a hospital, the hospital can bill Medicare for those same services under the hospital outpatient prospective payment system at an amount notably higher than the PFS payment.
To address this payment aberration, Congress instructed the Centers for Medicare & Medicaid Services to craft a system to preclude a hospital from such behavior. If a hospital offers new or expanded outpatient services, it could NOT bill Medicare under the hospital outpatient services methodology and would be required to bill under the PFS payment methodology. Importantly, a few exemptions exist. If the new or expanded service is within 250 yards of the main hospital campus, the outpatient billing methodology is permitted. Likewise, if expansion of a current off-campus service occurs at the same location of the current off-site service, the hospital may continue to bill under the outpatient rules. Several other technical exceptions are permitted, for example construction planned prior to passage of BBA.
The implications for pulmonary rehabilitation are critical to its growth. A hospital that wishes to expand its current program and bill under the hospital outpatient methodology MUST do so by expanding at its current location. An expansion at a new location that is not within 250 yards of the main hospital campus triggers Section 603 provisions, and the hospital will bill at the physician fee schedule rate. Because the PFS payment rate is just over half of the payment rate for HOPPS payment, it is unlikely that a hospital would expand an existing program or establish a new one if it would be forced to bill under the lower rate.
While congressional logic may be relatively understandable, for pulmonary medicine, it is based on the premise that a hospital would purchase a pulmonary practice because that practice had a lucrative pulmonary rehabilitation services cash flow. NAMDRC and other societies were able to document major flaws in the basic premise, resulting in very problematic unintended consequences. A detailed review of Medicare claims data provides strong evidence that pulmonary practices simply do not provide pulmonary rehab services.
These data strongly indicate that G0424 pulmonary practice physician office billing for the most recent year data are available ($230K), compared with hospital outpatient allowed charges ($119M), is less than two-tenths of 1% of billing through the hospital setting. To argue that hospitals are purchasing pulmonary practices for financial gain tied to pulmonary rehab services defies Medicare data, as well as financial logic. If the CMS premise was valid, one would expect the aggregate physician office billing to be much greater than $535K. In discussions with CMS, the Agency did agree that there are likely to be unintended consequences related to Section 603 implementation. The Agency also emphasizes that it does not have the statutory authority for a “carve out” exemption. CMS stated that even if it agreed with us, it simply lacked the authority to exempt pulmonary rehab services. CMS also agreed that there is growing evidence that pulmonary rehab is a underutilized service that may very well save the program money through reduced hospitalizations and rehospitalizations, but it has little choice to implement the statute as Congress so mandated.
Therefore, the only solution is a legislative one. NAMDRC and other societies are seriously considering approaching Congress for such resolution.
In late 2015, Congress passed the Bipartisan Budget Act (BBA) to address numerous wide-ranging budget concerns, including issues related to agriculture, pensions, the strategic petroleum reserve, along with some Medicare issues. Section 603 of BBA is now coming back to haunt pulmonary rehabilitation services.
The intent of Section 603 is reasonable – to address the phenomenon of hospitals purchasing physician practices to take advantage of payment differentials between identical or virtually identical services when comparing the hospital outpatient prospective payment system (HOPPS) and the physician fee schedule (PFS). For example, an orthopedic practice might own its own MRI and related support services. It will bill for those services under the PFS. However, if the practice sells that segment of the revenue stream (the MRI assets, etc) to a hospital, the hospital can bill Medicare for those same services under the hospital outpatient prospective payment system at an amount notably higher than the PFS payment.
To address this payment aberration, Congress instructed the Centers for Medicare & Medicaid Services to craft a system to preclude a hospital from such behavior. If a hospital offers new or expanded outpatient services, it could NOT bill Medicare under the hospital outpatient services methodology and would be required to bill under the PFS payment methodology. Importantly, a few exemptions exist. If the new or expanded service is within 250 yards of the main hospital campus, the outpatient billing methodology is permitted. Likewise, if expansion of a current off-campus service occurs at the same location of the current off-site service, the hospital may continue to bill under the outpatient rules. Several other technical exceptions are permitted, for example construction planned prior to passage of BBA.
The implications for pulmonary rehabilitation are critical to its growth. A hospital that wishes to expand its current program and bill under the hospital outpatient methodology MUST do so by expanding at its current location. An expansion at a new location that is not within 250 yards of the main hospital campus triggers Section 603 provisions, and the hospital will bill at the physician fee schedule rate. Because the PFS payment rate is just over half of the payment rate for HOPPS payment, it is unlikely that a hospital would expand an existing program or establish a new one if it would be forced to bill under the lower rate.
While congressional logic may be relatively understandable, for pulmonary medicine, it is based on the premise that a hospital would purchase a pulmonary practice because that practice had a lucrative pulmonary rehabilitation services cash flow. NAMDRC and other societies were able to document major flaws in the basic premise, resulting in very problematic unintended consequences. A detailed review of Medicare claims data provides strong evidence that pulmonary practices simply do not provide pulmonary rehab services.
These data strongly indicate that G0424 pulmonary practice physician office billing for the most recent year data are available ($230K), compared with hospital outpatient allowed charges ($119M), is less than two-tenths of 1% of billing through the hospital setting. To argue that hospitals are purchasing pulmonary practices for financial gain tied to pulmonary rehab services defies Medicare data, as well as financial logic. If the CMS premise was valid, one would expect the aggregate physician office billing to be much greater than $535K. In discussions with CMS, the Agency did agree that there are likely to be unintended consequences related to Section 603 implementation. The Agency also emphasizes that it does not have the statutory authority for a “carve out” exemption. CMS stated that even if it agreed with us, it simply lacked the authority to exempt pulmonary rehab services. CMS also agreed that there is growing evidence that pulmonary rehab is a underutilized service that may very well save the program money through reduced hospitalizations and rehospitalizations, but it has little choice to implement the statute as Congress so mandated.
Therefore, the only solution is a legislative one. NAMDRC and other societies are seriously considering approaching Congress for such resolution.
Survey: Most military family physicians wary of transgender treatments
The U.S. military now allows transgender people to serve openly, and all medical personnel are supposed to be trained in their treatment – including care related to gender transition – by June 2017.
But a new survey of 204 family physicians who work for the military shows that most aren’t willing to prescribe cross-hormone treatment to eligible adult transgender patients.
In addition, “we found that most military clinicians did not receive any formal training on transgender care during their medical education, most had not treated a patient with gender dysphoria, and most had not received sufficient training to prescribe cross-hormone therapy,” said Natasha A. Schvey, PhD, an assistant professor with the medical and clinical psychology department at the Uniformed Services University of the Health Sciences, Bethesda, Md., and lead author of a new study that summarizes the survey findings.
An estimated 12,800 transgender people serve in the U.S. military, and researchers believe that they make up a larger proportion of the military population than in the general population.
In October 2016, the Department of Defense ended its ban on service by transgender troops. A policy statement says: “Service members with a diagnosis from a military medical provider indicating that gender transition is medically necessary will be provided medical care and treatment for the diagnosed medical condition, in the same manner as other medical care and treatment.”
For the new study, Dr. Schvey and her associates surveyed 204 of the approximately 1,700 family physicians who serve the military (JAMA Intern Med. 2017 Mar 13. doi: 10.1001/jamainternmed.2017.0136). The survey respondents had all attended an annual meeting in March 2016.
Most respondents were male (62.8%) and white (85.5%); 21.7% were residents. The highest number of respondents (42.6%) worked for the U.S. Air Force.
Almost three-quarters of the respondents said that they had received no training or medical education in gender dysphoria, and 62.7% said they had never treated a transgender patient as a physician.
Just under half (47.1%) of respondents – 82 – said they would prescribe cross-hormone therapy to eligible adult patients, but only one would do so independently. The others would only do so with additional education (7.5% of all responding physicians), the help of an experienced clinician (17.2%), or both (21.8%).
The other 52.9% said they wouldn’t prescribe the hormone therapy. Eight percent of all responding physicians blamed ethical concerns, 19.5% pointed to lack of comfort, and 25.3% mentioned both, the investigators reported.
Why are so many physicians so uncomfortable?
Dr. Schvey said the survey design doesn’t allow for speculation about what the ethical concerns might be, but “the data did indicate that hours of training on transgender care were directly associated with the likelihood of prescribing cross-hormone therapy. Therefore, some of the lack of comfort may be due to lack of experience and adequate training.”
Although family physicians are generally used to treating patients with hormones for contraception and to treat perimenopausal symptoms and hypogonadism, many don’t know about dosing regimens and other information regarding their use in transgender patients, study coauthor David A. Klein, MD, assistant professor of family medicine and pediatrics at the Uniformed Services University of the Health Sciences, said in an interview. And, he noted, “some are unaware that provision of cross-hormone therapy is within their scope of care.”
Going forward, “given that greater education in transgender care is associated with increased competency,” Dr. Schvey said in an interview, “it will be important to assess the training of military physicians to ensure skill and sensitivity in treating patients who identify as transgender.”
The study had no specific funding, and the authors reported no relevant conflicts of interest.
I first learned the term transsexual from a 1972 publication by the American Medical Association titled “Human Sexuality.” I found the textbook on my father’s bookshelf as a 10-year-old and for the first time found a word to describe my inner world.
Up until 2016, transgender individuals in the military were not given appropriate medical or psychological assistance. They were forced to seek help in secret, outside the military health care system, or to await discharge proceedings.
Although the situation has improved markedly, there is still a long way to go. We need better protocols for individuals who wish to transition while active duty, for retirees, and their family members. We need to aid them in preserving their fertility, and we need to foster an environment of openness where no soldier feels like he or she is isolated from fellow service members owing to gender identity.
Although I completed my medical training as a male, today I serve as a female physician in every respect within the Department of Defense. Last month, I graduated the Army Medical Department’s Advanced Course with honors, and now I look forward to the second half of my military career being treated like any other capable military physician. My hope is that over time all clinicians gain comfort and skill in treating transgender persons.
Jamie L. Henry, MD, is with the Walter Reed National Military Medical Center in Bethesda, Md. These comments were taken from an editorial (JAMA Intern Med. 2017 Mar 13. doi: 10.1001/jamainternmed.2017.0140) accompanying the report by Dr. Schvey and her associates.
I first learned the term transsexual from a 1972 publication by the American Medical Association titled “Human Sexuality.” I found the textbook on my father’s bookshelf as a 10-year-old and for the first time found a word to describe my inner world.
Up until 2016, transgender individuals in the military were not given appropriate medical or psychological assistance. They were forced to seek help in secret, outside the military health care system, or to await discharge proceedings.
Although the situation has improved markedly, there is still a long way to go. We need better protocols for individuals who wish to transition while active duty, for retirees, and their family members. We need to aid them in preserving their fertility, and we need to foster an environment of openness where no soldier feels like he or she is isolated from fellow service members owing to gender identity.
Although I completed my medical training as a male, today I serve as a female physician in every respect within the Department of Defense. Last month, I graduated the Army Medical Department’s Advanced Course with honors, and now I look forward to the second half of my military career being treated like any other capable military physician. My hope is that over time all clinicians gain comfort and skill in treating transgender persons.
Jamie L. Henry, MD, is with the Walter Reed National Military Medical Center in Bethesda, Md. These comments were taken from an editorial (JAMA Intern Med. 2017 Mar 13. doi: 10.1001/jamainternmed.2017.0140) accompanying the report by Dr. Schvey and her associates.
I first learned the term transsexual from a 1972 publication by the American Medical Association titled “Human Sexuality.” I found the textbook on my father’s bookshelf as a 10-year-old and for the first time found a word to describe my inner world.
Up until 2016, transgender individuals in the military were not given appropriate medical or psychological assistance. They were forced to seek help in secret, outside the military health care system, or to await discharge proceedings.
Although the situation has improved markedly, there is still a long way to go. We need better protocols for individuals who wish to transition while active duty, for retirees, and their family members. We need to aid them in preserving their fertility, and we need to foster an environment of openness where no soldier feels like he or she is isolated from fellow service members owing to gender identity.
Although I completed my medical training as a male, today I serve as a female physician in every respect within the Department of Defense. Last month, I graduated the Army Medical Department’s Advanced Course with honors, and now I look forward to the second half of my military career being treated like any other capable military physician. My hope is that over time all clinicians gain comfort and skill in treating transgender persons.
Jamie L. Henry, MD, is with the Walter Reed National Military Medical Center in Bethesda, Md. These comments were taken from an editorial (JAMA Intern Med. 2017 Mar 13. doi: 10.1001/jamainternmed.2017.0140) accompanying the report by Dr. Schvey and her associates.
The U.S. military now allows transgender people to serve openly, and all medical personnel are supposed to be trained in their treatment – including care related to gender transition – by June 2017.
But a new survey of 204 family physicians who work for the military shows that most aren’t willing to prescribe cross-hormone treatment to eligible adult transgender patients.
In addition, “we found that most military clinicians did not receive any formal training on transgender care during their medical education, most had not treated a patient with gender dysphoria, and most had not received sufficient training to prescribe cross-hormone therapy,” said Natasha A. Schvey, PhD, an assistant professor with the medical and clinical psychology department at the Uniformed Services University of the Health Sciences, Bethesda, Md., and lead author of a new study that summarizes the survey findings.
An estimated 12,800 transgender people serve in the U.S. military, and researchers believe that they make up a larger proportion of the military population than in the general population.
In October 2016, the Department of Defense ended its ban on service by transgender troops. A policy statement says: “Service members with a diagnosis from a military medical provider indicating that gender transition is medically necessary will be provided medical care and treatment for the diagnosed medical condition, in the same manner as other medical care and treatment.”
For the new study, Dr. Schvey and her associates surveyed 204 of the approximately 1,700 family physicians who serve the military (JAMA Intern Med. 2017 Mar 13. doi: 10.1001/jamainternmed.2017.0136). The survey respondents had all attended an annual meeting in March 2016.
Most respondents were male (62.8%) and white (85.5%); 21.7% were residents. The highest number of respondents (42.6%) worked for the U.S. Air Force.
Almost three-quarters of the respondents said that they had received no training or medical education in gender dysphoria, and 62.7% said they had never treated a transgender patient as a physician.
Just under half (47.1%) of respondents – 82 – said they would prescribe cross-hormone therapy to eligible adult patients, but only one would do so independently. The others would only do so with additional education (7.5% of all responding physicians), the help of an experienced clinician (17.2%), or both (21.8%).
The other 52.9% said they wouldn’t prescribe the hormone therapy. Eight percent of all responding physicians blamed ethical concerns, 19.5% pointed to lack of comfort, and 25.3% mentioned both, the investigators reported.
Why are so many physicians so uncomfortable?
Dr. Schvey said the survey design doesn’t allow for speculation about what the ethical concerns might be, but “the data did indicate that hours of training on transgender care were directly associated with the likelihood of prescribing cross-hormone therapy. Therefore, some of the lack of comfort may be due to lack of experience and adequate training.”
Although family physicians are generally used to treating patients with hormones for contraception and to treat perimenopausal symptoms and hypogonadism, many don’t know about dosing regimens and other information regarding their use in transgender patients, study coauthor David A. Klein, MD, assistant professor of family medicine and pediatrics at the Uniformed Services University of the Health Sciences, said in an interview. And, he noted, “some are unaware that provision of cross-hormone therapy is within their scope of care.”
Going forward, “given that greater education in transgender care is associated with increased competency,” Dr. Schvey said in an interview, “it will be important to assess the training of military physicians to ensure skill and sensitivity in treating patients who identify as transgender.”
The study had no specific funding, and the authors reported no relevant conflicts of interest.
The U.S. military now allows transgender people to serve openly, and all medical personnel are supposed to be trained in their treatment – including care related to gender transition – by June 2017.
But a new survey of 204 family physicians who work for the military shows that most aren’t willing to prescribe cross-hormone treatment to eligible adult transgender patients.
In addition, “we found that most military clinicians did not receive any formal training on transgender care during their medical education, most had not treated a patient with gender dysphoria, and most had not received sufficient training to prescribe cross-hormone therapy,” said Natasha A. Schvey, PhD, an assistant professor with the medical and clinical psychology department at the Uniformed Services University of the Health Sciences, Bethesda, Md., and lead author of a new study that summarizes the survey findings.
An estimated 12,800 transgender people serve in the U.S. military, and researchers believe that they make up a larger proportion of the military population than in the general population.
In October 2016, the Department of Defense ended its ban on service by transgender troops. A policy statement says: “Service members with a diagnosis from a military medical provider indicating that gender transition is medically necessary will be provided medical care and treatment for the diagnosed medical condition, in the same manner as other medical care and treatment.”
For the new study, Dr. Schvey and her associates surveyed 204 of the approximately 1,700 family physicians who serve the military (JAMA Intern Med. 2017 Mar 13. doi: 10.1001/jamainternmed.2017.0136). The survey respondents had all attended an annual meeting in March 2016.
Most respondents were male (62.8%) and white (85.5%); 21.7% were residents. The highest number of respondents (42.6%) worked for the U.S. Air Force.
Almost three-quarters of the respondents said that they had received no training or medical education in gender dysphoria, and 62.7% said they had never treated a transgender patient as a physician.
Just under half (47.1%) of respondents – 82 – said they would prescribe cross-hormone therapy to eligible adult patients, but only one would do so independently. The others would only do so with additional education (7.5% of all responding physicians), the help of an experienced clinician (17.2%), or both (21.8%).
The other 52.9% said they wouldn’t prescribe the hormone therapy. Eight percent of all responding physicians blamed ethical concerns, 19.5% pointed to lack of comfort, and 25.3% mentioned both, the investigators reported.
Why are so many physicians so uncomfortable?
Dr. Schvey said the survey design doesn’t allow for speculation about what the ethical concerns might be, but “the data did indicate that hours of training on transgender care were directly associated with the likelihood of prescribing cross-hormone therapy. Therefore, some of the lack of comfort may be due to lack of experience and adequate training.”
Although family physicians are generally used to treating patients with hormones for contraception and to treat perimenopausal symptoms and hypogonadism, many don’t know about dosing regimens and other information regarding their use in transgender patients, study coauthor David A. Klein, MD, assistant professor of family medicine and pediatrics at the Uniformed Services University of the Health Sciences, said in an interview. And, he noted, “some are unaware that provision of cross-hormone therapy is within their scope of care.”
Going forward, “given that greater education in transgender care is associated with increased competency,” Dr. Schvey said in an interview, “it will be important to assess the training of military physicians to ensure skill and sensitivity in treating patients who identify as transgender.”
The study had no specific funding, and the authors reported no relevant conflicts of interest.
AKI seen in 64% of children hospitalized with diabetic ketoacidosis
A high proportion of children with type 1 diabetes who are hospitalized for diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), according to results from a study.
Researchers reviewing records from a Canadian hospital found that in a cohort of 165 children hospitalized for DKA during a 5-year period (2008-2013), 64% developed the complication. Severe forms of AKI (stage 2 or 3) were common, representing 45% and 20%, respectively, of children with AKI. Two patients in the cohort required dialysis.
“We hypothesized that, because DKA is associated with both volume depletion and conservative fluid administration upon presentation, these children are potentially at high risk for AKI, above the level of risk expected by the rare reported cases in the literature,” Dr. Hursh and his colleagues wrote (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0020).
The investigators found that lower serum bicarbonate levels and elevated heart rates were indeed associated with increased risk of severe AKI. Serum bicarbonate level of less than 10 mEq/L was associated with a fivefold increase in the odds of severe (stage 2 or 3) AKI (adjusted odds ratio, 5.22; 95% confidence interval, 1.35-20.22). Each increase of 5 bpm in initial heart rate was associated with a 22% increase in the odds of severe AKI (aOR, 1.22; 95% CI, 1.07-1.39).
Dr. Hursh and his colleagues defined AKI using serum creatinine values. As baseline values prior to hospital admission were not available, the researchers used estimated normal value ranges from published studies, choosing a glomerular filtration rate of 120 mL/min per 1.73 m2 as a standard baseline value. Urine output was not used as a measure because of inconsistent records.
Of particular concern was that more than 40% of patients with AKI “did not have documented resolution of AKI prior to discharge or arrangements for follow-up in the nephrology clinic. Of note, the final AKI stage was severe for 50% of these children,” the researchers wrote in their analysis.
The findings suggest that clinicians “should consider AKI as a frequent complication that accompanies pediatric DKA and should be especially alert to its presence in severe presentations of DKA,” they said. AKI is underrecognized “both because of a lack of awareness of AKI as a complication of DKA and because the serum creatinine level in pediatric patients must be interpreted in the context of the child’s age and height. It is crucial to develop or have in place systems that identify and monitor abnormal markers of renal function in this population.”
The researchers acknowledged as limitations of their study its retrospective design, the absence of baseline serum creatinine values, and the lack of urine output data for use in AKI severity grading. And prospective longitudinal studies, they wrote, “are needed to assess the effect of these AKI episodes on the trajectory of renal disease in children with diabetes.”
The researchers reported no outside funding or relevant financial disclosures.
With the lack of targeted therapies to prevent AKI or decrease its associated consequences, supportive care is the mainstay of treatment and focuses on fluid and electrolyte management, nutrition, prevention of further injury through close attention to medication dosing, and, when needed, renal replacement therapy. At first glance, these findings may not appear to be overly surprising or significant; children with volume depletion have decreased renal blood flow, leading to AKI, which corrects with fluid administration. However, the authors appropriately suggest that this issue is not a simple one and that fluid management should be carefully considered in these patients. Because of severe hyperglycemia and derangements in serum sodium concentration, children with DKA are at risk of potentially catastrophic cerebral edema, leading to recommendations for cautious administration of fluids in this high-risk population.
These findings may lead clinicians and investigators to question established practices related to aggressive fluid administration in the sickest children. While awaiting more research to determine the sweet spot for fluid management in children with AKI, it seems reasonable to give fluids to patients with AKI secondary to volume depletion while quickly shifting to more restrictive strategies in those who do not respond to volume and have decreasing urine output. This may be especially important for children with DKA, as conservative fluid management may decrease central nervous system complications.
We commend the authors for exploring AKI in a novel pediatric population, expanding our knowledge on whom kidney function should be more diligently examined, providing insights on relevant fluid strategies, and increasing awareness for a group of patients who may benefit from closer long-term nephrology follow-up.
Benjamin L. Laskin, MD , is at the Children’s Hospital of Philadelphia, and Jens Goebel, MD , is at Children’s Hospital Colorado, Aurora. Dr. Laskin’s and Dr. Goebel’s comments are excerpted from an editorial accompanying the study by Hursh et al. (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0009). Dr Laskin is supported by a National Institutes of Health grant. The editorialists had no other relevant financial disclosures.
With the lack of targeted therapies to prevent AKI or decrease its associated consequences, supportive care is the mainstay of treatment and focuses on fluid and electrolyte management, nutrition, prevention of further injury through close attention to medication dosing, and, when needed, renal replacement therapy. At first glance, these findings may not appear to be overly surprising or significant; children with volume depletion have decreased renal blood flow, leading to AKI, which corrects with fluid administration. However, the authors appropriately suggest that this issue is not a simple one and that fluid management should be carefully considered in these patients. Because of severe hyperglycemia and derangements in serum sodium concentration, children with DKA are at risk of potentially catastrophic cerebral edema, leading to recommendations for cautious administration of fluids in this high-risk population.
These findings may lead clinicians and investigators to question established practices related to aggressive fluid administration in the sickest children. While awaiting more research to determine the sweet spot for fluid management in children with AKI, it seems reasonable to give fluids to patients with AKI secondary to volume depletion while quickly shifting to more restrictive strategies in those who do not respond to volume and have decreasing urine output. This may be especially important for children with DKA, as conservative fluid management may decrease central nervous system complications.
We commend the authors for exploring AKI in a novel pediatric population, expanding our knowledge on whom kidney function should be more diligently examined, providing insights on relevant fluid strategies, and increasing awareness for a group of patients who may benefit from closer long-term nephrology follow-up.
Benjamin L. Laskin, MD , is at the Children’s Hospital of Philadelphia, and Jens Goebel, MD , is at Children’s Hospital Colorado, Aurora. Dr. Laskin’s and Dr. Goebel’s comments are excerpted from an editorial accompanying the study by Hursh et al. (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0009). Dr Laskin is supported by a National Institutes of Health grant. The editorialists had no other relevant financial disclosures.
With the lack of targeted therapies to prevent AKI or decrease its associated consequences, supportive care is the mainstay of treatment and focuses on fluid and electrolyte management, nutrition, prevention of further injury through close attention to medication dosing, and, when needed, renal replacement therapy. At first glance, these findings may not appear to be overly surprising or significant; children with volume depletion have decreased renal blood flow, leading to AKI, which corrects with fluid administration. However, the authors appropriately suggest that this issue is not a simple one and that fluid management should be carefully considered in these patients. Because of severe hyperglycemia and derangements in serum sodium concentration, children with DKA are at risk of potentially catastrophic cerebral edema, leading to recommendations for cautious administration of fluids in this high-risk population.
These findings may lead clinicians and investigators to question established practices related to aggressive fluid administration in the sickest children. While awaiting more research to determine the sweet spot for fluid management in children with AKI, it seems reasonable to give fluids to patients with AKI secondary to volume depletion while quickly shifting to more restrictive strategies in those who do not respond to volume and have decreasing urine output. This may be especially important for children with DKA, as conservative fluid management may decrease central nervous system complications.
We commend the authors for exploring AKI in a novel pediatric population, expanding our knowledge on whom kidney function should be more diligently examined, providing insights on relevant fluid strategies, and increasing awareness for a group of patients who may benefit from closer long-term nephrology follow-up.
Benjamin L. Laskin, MD , is at the Children’s Hospital of Philadelphia, and Jens Goebel, MD , is at Children’s Hospital Colorado, Aurora. Dr. Laskin’s and Dr. Goebel’s comments are excerpted from an editorial accompanying the study by Hursh et al. (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0009). Dr Laskin is supported by a National Institutes of Health grant. The editorialists had no other relevant financial disclosures.
A high proportion of children with type 1 diabetes who are hospitalized for diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), according to results from a study.
Researchers reviewing records from a Canadian hospital found that in a cohort of 165 children hospitalized for DKA during a 5-year period (2008-2013), 64% developed the complication. Severe forms of AKI (stage 2 or 3) were common, representing 45% and 20%, respectively, of children with AKI. Two patients in the cohort required dialysis.
“We hypothesized that, because DKA is associated with both volume depletion and conservative fluid administration upon presentation, these children are potentially at high risk for AKI, above the level of risk expected by the rare reported cases in the literature,” Dr. Hursh and his colleagues wrote (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0020).
The investigators found that lower serum bicarbonate levels and elevated heart rates were indeed associated with increased risk of severe AKI. Serum bicarbonate level of less than 10 mEq/L was associated with a fivefold increase in the odds of severe (stage 2 or 3) AKI (adjusted odds ratio, 5.22; 95% confidence interval, 1.35-20.22). Each increase of 5 bpm in initial heart rate was associated with a 22% increase in the odds of severe AKI (aOR, 1.22; 95% CI, 1.07-1.39).
Dr. Hursh and his colleagues defined AKI using serum creatinine values. As baseline values prior to hospital admission were not available, the researchers used estimated normal value ranges from published studies, choosing a glomerular filtration rate of 120 mL/min per 1.73 m2 as a standard baseline value. Urine output was not used as a measure because of inconsistent records.
Of particular concern was that more than 40% of patients with AKI “did not have documented resolution of AKI prior to discharge or arrangements for follow-up in the nephrology clinic. Of note, the final AKI stage was severe for 50% of these children,” the researchers wrote in their analysis.
The findings suggest that clinicians “should consider AKI as a frequent complication that accompanies pediatric DKA and should be especially alert to its presence in severe presentations of DKA,” they said. AKI is underrecognized “both because of a lack of awareness of AKI as a complication of DKA and because the serum creatinine level in pediatric patients must be interpreted in the context of the child’s age and height. It is crucial to develop or have in place systems that identify and monitor abnormal markers of renal function in this population.”
The researchers acknowledged as limitations of their study its retrospective design, the absence of baseline serum creatinine values, and the lack of urine output data for use in AKI severity grading. And prospective longitudinal studies, they wrote, “are needed to assess the effect of these AKI episodes on the trajectory of renal disease in children with diabetes.”
The researchers reported no outside funding or relevant financial disclosures.
A high proportion of children with type 1 diabetes who are hospitalized for diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), according to results from a study.
Researchers reviewing records from a Canadian hospital found that in a cohort of 165 children hospitalized for DKA during a 5-year period (2008-2013), 64% developed the complication. Severe forms of AKI (stage 2 or 3) were common, representing 45% and 20%, respectively, of children with AKI. Two patients in the cohort required dialysis.
“We hypothesized that, because DKA is associated with both volume depletion and conservative fluid administration upon presentation, these children are potentially at high risk for AKI, above the level of risk expected by the rare reported cases in the literature,” Dr. Hursh and his colleagues wrote (JAMA Pediatr. 2017 Mar 13. doi: 10.1001/jamapediatrics.2017.0020).
The investigators found that lower serum bicarbonate levels and elevated heart rates were indeed associated with increased risk of severe AKI. Serum bicarbonate level of less than 10 mEq/L was associated with a fivefold increase in the odds of severe (stage 2 or 3) AKI (adjusted odds ratio, 5.22; 95% confidence interval, 1.35-20.22). Each increase of 5 bpm in initial heart rate was associated with a 22% increase in the odds of severe AKI (aOR, 1.22; 95% CI, 1.07-1.39).
Dr. Hursh and his colleagues defined AKI using serum creatinine values. As baseline values prior to hospital admission were not available, the researchers used estimated normal value ranges from published studies, choosing a glomerular filtration rate of 120 mL/min per 1.73 m2 as a standard baseline value. Urine output was not used as a measure because of inconsistent records.
Of particular concern was that more than 40% of patients with AKI “did not have documented resolution of AKI prior to discharge or arrangements for follow-up in the nephrology clinic. Of note, the final AKI stage was severe for 50% of these children,” the researchers wrote in their analysis.
The findings suggest that clinicians “should consider AKI as a frequent complication that accompanies pediatric DKA and should be especially alert to its presence in severe presentations of DKA,” they said. AKI is underrecognized “both because of a lack of awareness of AKI as a complication of DKA and because the serum creatinine level in pediatric patients must be interpreted in the context of the child’s age and height. It is crucial to develop or have in place systems that identify and monitor abnormal markers of renal function in this population.”
The researchers acknowledged as limitations of their study its retrospective design, the absence of baseline serum creatinine values, and the lack of urine output data for use in AKI severity grading. And prospective longitudinal studies, they wrote, “are needed to assess the effect of these AKI episodes on the trajectory of renal disease in children with diabetes.”
The researchers reported no outside funding or relevant financial disclosures.
FROM JAMA PEDIATRICS
Key clinical point: Acute kidney injury may occur in up to two-thirds of children hospitalized for diabetic ketoacidosis.
Major finding: In a cohort of 165 children hospitalized with DKA, 64% developed AKI. Of these, 45% had stage 2 AKI and 20% had stage 3.
Data source: A retrospective single-site cohort study of records from 165 children with DKA hospitalized from 2008 to 2013.
Disclosures: The researchers disclosed no outside funding or relevant financial conflicts of interest.