The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have published a guideline to offer up-to-date, evidence-based recommendations for the treatment of adult patients with MS. The guideline is intended to fill a perceived need for a comprehensive document that includes information about recently approved MS therapies and helps clinicians and patients resolve difficulties in everyday clinical practice. It was published in the February issue of Multiple Sclerosis.

Authors Addressed 10 Questions

Xavier Montalban, MD, PhD, Chair and Director of the Department of Neurology and Neuroimmunology at Vall d’Hebron University Hospital in Barcelona, and colleagues agreed to investigate 10 questions related to treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns, and treatment of MS in pregnancy. They developed the guideline following the recommendations of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group, along with EAN recommendations for writing a neurologic management guideline. Literature searches relied upon databases such as the Cochrane Central Register of Controlled Trials, Excerpta Medica, and Medical Literature Analysis and Retrieval System Online.

The authors evaluated data for all disease-modifying treatments (DMTs) approved by the European Medicines Agency at the time of publication. They did not consider combination therapies, complementary or alternative medicine, or symptomatic treatment. Although focused on Europe, the guideline does not account for regulatory or organizational issues specific to any European country.

Strong Recommendations

Dr. Montalban and colleagues agreed upon 21 recommendations and consensus statements. The recommendations were categorized as strong or weak, according to the quality of evidence and the risk–benefit balance. The authors formulated consensus statements on questions for which evidence was insufficient to support a formal recommendation.

The first of the guideline’s three strong recommendations is that neurologists offer interferon or glatiramer acetate to patients with clinically isolated syndrome (CIS) and an abnormal MRI with lesions suggestive of MS who do not fulfill criteria for MS. The second is to offer early treatment with DMTs to patients with active relapsing-remitting MS, as defined by clinical relapses or MRI activity. The authors defined active lesions as contrast-enhancing lesions or new or unequivocally enlarging T2 lesions assessed at least annually. This recommendation also applies to patients with CIS who fulfill current diagnostic criteria for MS. The third strong recommendation is to offer a more efficacious drug to patients treated with interferon or glatiramer acetate who show evidence of disease activity.

Weak Recommendations

Nine of the guideline’s recommendations are categorized as weak. For example, neurologists should consider treating patients with active secondary progressive MS with interferon beta-1a or -1b, taking into account the treatments’ “dubious efficacy,” as well as their safety and tolerability, according to the authors. Neurologists should consider mitoxantrone, ocrelizumab, and cladribine for this population. The authors recommend considering ocrelizumab as a treatment for patients with primary progressive MS.

As a way of monitoring treatment response, the authors recommend that neurologists consider combining MRI with clinical measures when evaluating disease evolution in treated patients. When making treatment decisions in the event of safety concerns, neurologists should consider the possibility that disease activity may resume or rebound if treatment is stopped, particularly with natalizumab, said Dr. Montalban and colleagues. Continuation of DMT treatment should be considered for patients who are clinically stable, who have stable MRI, and who have no problems with safety or tolerability, according to the guideline.

“For women planning a pregnancy, if there is a high risk of disease reactivation, consider using interferon or glatiramer acetate until pregnancy is confirmed,” said the authors. “In some very specific (active) cases, continuing this treatment during pregnancy could also be considered.” Delaying pregnancy is advisable for women with persistent high disease activity. If such a woman decides to become pregnant or has an unplanned pregnancy, neurologists may consider treatment with natalizumab throughout pregnancy after a full discussion with the patient of the potential implications. “Treatment with alemtuzumab could be an alternative therapeutic option for planned pregnancy in very active cases, provided that a four-month interval is strictly observed from the latest infusion until conception,” said Dr. Montalban and colleagues.

Consensus Statements

Several of the guideline’s consensus statements relate to the monitoring of treatment response. For patients treated with DMTs, the authors recommend performing a standardized reference brain MRI within six months of treatment onset, and comparing it with a subsequent brain MRI performed 12 months after starting treatment. The measurement of new or unequivocally enlarging T2 lesions is the preferred MRI method of gauging treatment response, supplemented by gadolinium-enhancing lesions. To monitor treatment safety, the authors recommend performing a standardized reference brain MRI every year in patients at low risk for progressive multifocal leukoencephalopathy (PML), and every three to six months in patients at high risk for PML.

If the neurologist and patient have decided to switch therapies, they should consider the patient’s characteristics and comorbidities, drug safety profiles, and disease severity when choosing a new DMT. If treatment of a highly efficacious drug is stopped because of safety or efficacy problems, the neurologist should consider starting another highly efficacious drug, according to the guideline. Disease activity, the drug’s half-life and biologic activity, and the potential for resumed disease activity or rebound should be considered when choosing a new therapy, said Dr. Montalban and colleagues.

—Erik Greb

Suggested Reading

Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler. 2018;24(2):96-120.

The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have published a guideline to offer up-to-date, evidence-based recommendations for the treatment of adult patients with MS. The guideline is intended to fill a perceived need for a comprehensive document that includes information about recently approved MS therapies and helps clinicians and patients resolve difficulties in everyday clinical practice. It was published in the February issue of Multiple Sclerosis.

Authors Addressed 10 Questions

Xavier Montalban, MD, PhD, Chair and Director of the Department of Neurology and Neuroimmunology at Vall d’Hebron University Hospital in Barcelona, and colleagues agreed to investigate 10 questions related to treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns, and treatment of MS in pregnancy. They developed the guideline following the recommendations of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group, along with EAN recommendations for writing a neurologic management guideline. Literature searches relied upon databases such as the Cochrane Central Register of Controlled Trials, Excerpta Medica, and Medical Literature Analysis and Retrieval System Online.

The authors evaluated data for all disease-modifying treatments (DMTs) approved by the European Medicines Agency at the time of publication. They did not consider combination therapies, complementary or alternative medicine, or symptomatic treatment. Although focused on Europe, the guideline does not account for regulatory or organizational issues specific to any European country.

Strong Recommendations

Dr. Montalban and colleagues agreed upon 21 recommendations and consensus statements. The recommendations were categorized as strong or weak, according to the quality of evidence and the risk–benefit balance. The authors formulated consensus statements on questions for which evidence was insufficient to support a formal recommendation.

The first of the guideline’s three strong recommendations is that neurologists offer interferon or glatiramer acetate to patients with clinically isolated syndrome (CIS) and an abnormal MRI with lesions suggestive of MS who do not fulfill criteria for MS. The second is to offer early treatment with DMTs to patients with active relapsing-remitting MS, as defined by clinical relapses or MRI activity. The authors defined active lesions as contrast-enhancing lesions or new or unequivocally enlarging T2 lesions assessed at least annually. This recommendation also applies to patients with CIS who fulfill current diagnostic criteria for MS. The third strong recommendation is to offer a more efficacious drug to patients treated with interferon or glatiramer acetate who show evidence of disease activity.

Weak Recommendations

Nine of the guideline’s recommendations are categorized as weak. For example, neurologists should consider treating patients with active secondary progressive MS with interferon beta-1a or -1b, taking into account the treatments’ “dubious efficacy,” as well as their safety and tolerability, according to the authors. Neurologists should consider mitoxantrone, ocrelizumab, and cladribine for this population. The authors recommend considering ocrelizumab as a treatment for patients with primary progressive MS.

As a way of monitoring treatment response, the authors recommend that neurologists consider combining MRI with clinical measures when evaluating disease evolution in treated patients. When making treatment decisions in the event of safety concerns, neurologists should consider the possibility that disease activity may resume or rebound if treatment is stopped, particularly with natalizumab, said Dr. Montalban and colleagues. Continuation of DMT treatment should be considered for patients who are clinically stable, who have stable MRI, and who have no problems with safety or tolerability, according to the guideline.

“For women planning a pregnancy, if there is a high risk of disease reactivation, consider using interferon or glatiramer acetate until pregnancy is confirmed,” said the authors. “In some very specific (active) cases, continuing this treatment during pregnancy could also be considered.” Delaying pregnancy is advisable for women with persistent high disease activity. If such a woman decides to become pregnant or has an unplanned pregnancy, neurologists may consider treatment with natalizumab throughout pregnancy after a full discussion with the patient of the potential implications. “Treatment with alemtuzumab could be an alternative therapeutic option for planned pregnancy in very active cases, provided that a four-month interval is strictly observed from the latest infusion until conception,” said Dr. Montalban and colleagues.

Consensus Statements

Several of the guideline’s consensus statements relate to the monitoring of treatment response. For patients treated with DMTs, the authors recommend performing a standardized reference brain MRI within six months of treatment onset, and comparing it with a subsequent brain MRI performed 12 months after starting treatment. The measurement of new or unequivocally enlarging T2 lesions is the preferred MRI method of gauging treatment response, supplemented by gadolinium-enhancing lesions. To monitor treatment safety, the authors recommend performing a standardized reference brain MRI every year in patients at low risk for progressive multifocal leukoencephalopathy (PML), and every three to six months in patients at high risk for PML.

If the neurologist and patient have decided to switch therapies, they should consider the patient’s characteristics and comorbidities, drug safety profiles, and disease severity when choosing a new DMT. If treatment of a highly efficacious drug is stopped because of safety or efficacy problems, the neurologist should consider starting another highly efficacious drug, according to the guideline. Disease activity, the drug’s half-life and biologic activity, and the potential for resumed disease activity or rebound should be considered when choosing a new therapy, said Dr. Montalban and colleagues.

—Erik Greb

Suggested Reading

Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler. 2018;24(2):96-120.

The European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) and the European Academy of Neurology (EAN) have published a guideline to offer up-to-date, evidence-based recommendations for the treatment of adult patients with MS. The guideline is intended to fill a perceived need for a comprehensive document that includes information about recently approved MS therapies and helps clinicians and patients resolve difficulties in everyday clinical practice. It was published in the February issue of Multiple Sclerosis.

Authors Addressed 10 Questions

Xavier Montalban, MD, PhD, Chair and Director of the Department of Neurology and Neuroimmunology at Vall d’Hebron University Hospital in Barcelona, and colleagues agreed to investigate 10 questions related to treatment efficacy, response criteria, strategies to address suboptimal response and safety concerns, and treatment of MS in pregnancy. They developed the guideline following the recommendations of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group, along with EAN recommendations for writing a neurologic management guideline. Literature searches relied upon databases such as the Cochrane Central Register of Controlled Trials, Excerpta Medica, and Medical Literature Analysis and Retrieval System Online.

The authors evaluated data for all disease-modifying treatments (DMTs) approved by the European Medicines Agency at the time of publication. They did not consider combination therapies, complementary or alternative medicine, or symptomatic treatment. Although focused on Europe, the guideline does not account for regulatory or organizational issues specific to any European country.

Strong Recommendations

Dr. Montalban and colleagues agreed upon 21 recommendations and consensus statements. The recommendations were categorized as strong or weak, according to the quality of evidence and the risk–benefit balance. The authors formulated consensus statements on questions for which evidence was insufficient to support a formal recommendation.

The first of the guideline’s three strong recommendations is that neurologists offer interferon or glatiramer acetate to patients with clinically isolated syndrome (CIS) and an abnormal MRI with lesions suggestive of MS who do not fulfill criteria for MS. The second is to offer early treatment with DMTs to patients with active relapsing-remitting MS, as defined by clinical relapses or MRI activity. The authors defined active lesions as contrast-enhancing lesions or new or unequivocally enlarging T2 lesions assessed at least annually. This recommendation also applies to patients with CIS who fulfill current diagnostic criteria for MS. The third strong recommendation is to offer a more efficacious drug to patients treated with interferon or glatiramer acetate who show evidence of disease activity.

Weak Recommendations

Nine of the guideline’s recommendations are categorized as weak. For example, neurologists should consider treating patients with active secondary progressive MS with interferon beta-1a or -1b, taking into account the treatments’ “dubious efficacy,” as well as their safety and tolerability, according to the authors. Neurologists should consider mitoxantrone, ocrelizumab, and cladribine for this population. The authors recommend considering ocrelizumab as a treatment for patients with primary progressive MS.

As a way of monitoring treatment response, the authors recommend that neurologists consider combining MRI with clinical measures when evaluating disease evolution in treated patients. When making treatment decisions in the event of safety concerns, neurologists should consider the possibility that disease activity may resume or rebound if treatment is stopped, particularly with natalizumab, said Dr. Montalban and colleagues. Continuation of DMT treatment should be considered for patients who are clinically stable, who have stable MRI, and who have no problems with safety or tolerability, according to the guideline.

“For women planning a pregnancy, if there is a high risk of disease reactivation, consider using interferon or glatiramer acetate until pregnancy is confirmed,” said the authors. “In some very specific (active) cases, continuing this treatment during pregnancy could also be considered.” Delaying pregnancy is advisable for women with persistent high disease activity. If such a woman decides to become pregnant or has an unplanned pregnancy, neurologists may consider treatment with natalizumab throughout pregnancy after a full discussion with the patient of the potential implications. “Treatment with alemtuzumab could be an alternative therapeutic option for planned pregnancy in very active cases, provided that a four-month interval is strictly observed from the latest infusion until conception,” said Dr. Montalban and colleagues.

Consensus Statements

Several of the guideline’s consensus statements relate to the monitoring of treatment response. For patients treated with DMTs, the authors recommend performing a standardized reference brain MRI within six months of treatment onset, and comparing it with a subsequent brain MRI performed 12 months after starting treatment. The measurement of new or unequivocally enlarging T2 lesions is the preferred MRI method of gauging treatment response, supplemented by gadolinium-enhancing lesions. To monitor treatment safety, the authors recommend performing a standardized reference brain MRI every year in patients at low risk for progressive multifocal leukoencephalopathy (PML), and every three to six months in patients at high risk for PML.

If the neurologist and patient have decided to switch therapies, they should consider the patient’s characteristics and comorbidities, drug safety profiles, and disease severity when choosing a new DMT. If treatment of a highly efficacious drug is stopped because of safety or efficacy problems, the neurologist should consider starting another highly efficacious drug, according to the guideline. Disease activity, the drug’s half-life and biologic activity, and the potential for resumed disease activity or rebound should be considered when choosing a new therapy, said Dr. Montalban and colleagues.

—Erik Greb

Suggested Reading

Montalban X, Gold R, Thompson AJ, et al. ECTRIMS/EAN Guideline on the pharmacological treatment of people with multiple sclerosis. Mult Scler. 2018;24(2):96-120.

Consider thalassemia traits in patients with iron deficiency

The editorial is an excellent review of iron deficiency as an associated finding with adverse health and pregnancy outcomes. However, one genetic issue appears to have escaped comment. In Florida, our African American patients have a commonly found association with microcytic anemia at least as often as iron deficiency: a variety of α- and ß-thalassemia traits that may occur individually or together. Other racial groups, including Mediterranean and Asian patients, also may carry both the α- and ß-thalassemia traits.

Your recommendation to routinely screen for ferritin deficit is laudable as a general health care practice. If the screening result is normal, however, consider thalassemia carrier states as a secondary explanation as well as a genetic issue requiring partner testing. Aggressive iron loading of a nondeficient anemic patient can risk excess absorption, storage, and ultimate organ compromise in later life if continued indefinitely.

Richard P. Perkins, MD
Fort Myers, Florida
 

Patient education is key to managing iron deficiency

Forty years ago, my professors expounded on how some people could not absorb iron and that the answer was intravenous iron infusion. After writing a few prescriptions, however, I found that I no longer had patients with absorptive problems once I learned to carefully, and with visual aids, explain the iron story and meticulously monitor compliance. I have been through the “slow Fe” and the “prenatal vitamins have iron” nonsense. Ferrous sulfate is about as good as anything. I have explained the theory of vitamin C−assist and found that telling people to avoid taking iron with meals is folly.

I suggest that the iron story is complete. Rather than wasting money on further research, we should spend funds on teaching young physicians to educate patients and monitor compliance. In recent years, I have found that a daily text message to the patient frequently is very helpful.

Robert W. Jackson, MD
Washougal, Washington

Dr. Barbieri responds

I thank Drs. Perkins and Jackson for their helpful recommendations for the management of iron deficiency anemia. I agree with Dr. Perkins that screening for thalassemia is an important part of preconception and prenatal care. In the editorial’s table on page 10 discussing the differential diagnosis of anemia, we mentioned the importance of hemoglobin electrophoresis and measurement of vitamin B12 and folate levels to identify cases of anemia caused by thalassemia or vitamin deficiency. I agree with Dr. Jackson that oral iron supplementation along with patient education can resolve most cases of iron deficiency in early and mid-pregnancy. However, in the last few weeks of pregnancy there may not be sufficient time for oral iron supplementation to be effective in resolving iron deficiency anemia. In this situation and in patients at high risk for malabsorption, including women with prior gastric bypass, intravenous iron might be the best approach to resolving the anemia.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Consider thalassemia traits in patients with iron deficiency

The editorial is an excellent review of iron deficiency as an associated finding with adverse health and pregnancy outcomes. However, one genetic issue appears to have escaped comment. In Florida, our African American patients have a commonly found association with microcytic anemia at least as often as iron deficiency: a variety of α- and ß-thalassemia traits that may occur individually or together. Other racial groups, including Mediterranean and Asian patients, also may carry both the α- and ß-thalassemia traits.

Your recommendation to routinely screen for ferritin deficit is laudable as a general health care practice. If the screening result is normal, however, consider thalassemia carrier states as a secondary explanation as well as a genetic issue requiring partner testing. Aggressive iron loading of a nondeficient anemic patient can risk excess absorption, storage, and ultimate organ compromise in later life if continued indefinitely.

Richard P. Perkins, MD
Fort Myers, Florida
 

Patient education is key to managing iron deficiency

Forty years ago, my professors expounded on how some people could not absorb iron and that the answer was intravenous iron infusion. After writing a few prescriptions, however, I found that I no longer had patients with absorptive problems once I learned to carefully, and with visual aids, explain the iron story and meticulously monitor compliance. I have been through the “slow Fe” and the “prenatal vitamins have iron” nonsense. Ferrous sulfate is about as good as anything. I have explained the theory of vitamin C−assist and found that telling people to avoid taking iron with meals is folly.

I suggest that the iron story is complete. Rather than wasting money on further research, we should spend funds on teaching young physicians to educate patients and monitor compliance. In recent years, I have found that a daily text message to the patient frequently is very helpful.

Robert W. Jackson, MD
Washougal, Washington

Dr. Barbieri responds

I thank Drs. Perkins and Jackson for their helpful recommendations for the management of iron deficiency anemia. I agree with Dr. Perkins that screening for thalassemia is an important part of preconception and prenatal care. In the editorial’s table on page 10 discussing the differential diagnosis of anemia, we mentioned the importance of hemoglobin electrophoresis and measurement of vitamin B12 and folate levels to identify cases of anemia caused by thalassemia or vitamin deficiency. I agree with Dr. Jackson that oral iron supplementation along with patient education can resolve most cases of iron deficiency in early and mid-pregnancy. However, in the last few weeks of pregnancy there may not be sufficient time for oral iron supplementation to be effective in resolving iron deficiency anemia. In this situation and in patients at high risk for malabsorption, including women with prior gastric bypass, intravenous iron might be the best approach to resolving the anemia.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

Consider thalassemia traits in patients with iron deficiency

The editorial is an excellent review of iron deficiency as an associated finding with adverse health and pregnancy outcomes. However, one genetic issue appears to have escaped comment. In Florida, our African American patients have a commonly found association with microcytic anemia at least as often as iron deficiency: a variety of α- and ß-thalassemia traits that may occur individually or together. Other racial groups, including Mediterranean and Asian patients, also may carry both the α- and ß-thalassemia traits.

Your recommendation to routinely screen for ferritin deficit is laudable as a general health care practice. If the screening result is normal, however, consider thalassemia carrier states as a secondary explanation as well as a genetic issue requiring partner testing. Aggressive iron loading of a nondeficient anemic patient can risk excess absorption, storage, and ultimate organ compromise in later life if continued indefinitely.

Richard P. Perkins, MD
Fort Myers, Florida
 

Patient education is key to managing iron deficiency

Forty years ago, my professors expounded on how some people could not absorb iron and that the answer was intravenous iron infusion. After writing a few prescriptions, however, I found that I no longer had patients with absorptive problems once I learned to carefully, and with visual aids, explain the iron story and meticulously monitor compliance. I have been through the “slow Fe” and the “prenatal vitamins have iron” nonsense. Ferrous sulfate is about as good as anything. I have explained the theory of vitamin C−assist and found that telling people to avoid taking iron with meals is folly.

I suggest that the iron story is complete. Rather than wasting money on further research, we should spend funds on teaching young physicians to educate patients and monitor compliance. In recent years, I have found that a daily text message to the patient frequently is very helpful.

Robert W. Jackson, MD
Washougal, Washington

Dr. Barbieri responds

I thank Drs. Perkins and Jackson for their helpful recommendations for the management of iron deficiency anemia. I agree with Dr. Perkins that screening for thalassemia is an important part of preconception and prenatal care. In the editorial’s table on page 10 discussing the differential diagnosis of anemia, we mentioned the importance of hemoglobin electrophoresis and measurement of vitamin B12 and folate levels to identify cases of anemia caused by thalassemia or vitamin deficiency. I agree with Dr. Jackson that oral iron supplementation along with patient education can resolve most cases of iron deficiency in early and mid-pregnancy. However, in the last few weeks of pregnancy there may not be sufficient time for oral iron supplementation to be effective in resolving iron deficiency anemia. In this situation and in patients at high risk for malabsorption, including women with prior gastric bypass, intravenous iron might be the best approach to resolving the anemia.

Share your thoughts! Send your Letter to the Editor to [email protected]. Please include your name and the city and state in which you practice.

SAN DIEGO – Online consultations between dermatologists, patients with psoriasis, and the patients’ primary care physicians were as effective as in-person consultations in successfully treating the disease in a multicenter, randomized study of 296 patients.

“Innovative telehealth delivery models that emphasize collaboration, quality, and efficiency can be transformative to improving patient-centered outcomes in chronic disease,” April W. Armstrong, MD, said at the annual meeting of the American Academy of Dermatology. The online model she tested fostered “increased patient engagement” and provided “comprehensive specialist support,” said Dr. Armstrong, director of the psoriasis program at the University of Southern California, Los Angeles.

To objectively assess whether online consultations are as effective as in-person examinations, Dr. Armstrong and her associates at three U.S. centers randomized adult psoriasis patients from across the disease spectrum to receive 1 year of dermatology care either in person or online. Patients enrolled in the online arm received training in taking digital images of their skin lesions and uploading the data for remote access by their dermatologist and primary care physician. The frequency of in-person and online consultations was left to the discretion of each patient and his or her physician.

Among the 148 patients randomized to each arm, 17 in the online group and 13 in the in-person group withdrew from the study or were lost to follow-up. The researchers analyzed the results on an intention-to-treat basis.

They assessed three parameters of treatment efficacy that they measured at baseline and then every 3 months out to 1 year: Psoriasis Area and Severity Index, body surface area score, and patient global self-assessment. A comparison of changes between the two treatment arms after 1 year for the first two measures met the study’s prespecified definition of equivalence, Dr. Armstrong reported. The third measure, a patient’s global self-assessment, showed lower patient-assessed disease severity after 1 year among the patients managed online, compared with those managed in person.

The incidence of adverse events and serious adverse events was similar in the two treatment arms.

Dr. Armstrong had no relevant financial disclosures.

[email protected]

Source: Armstrong A et al. AAD 2018, abstract 6730..

SAN DIEGO – Online consultations between dermatologists, patients with psoriasis, and the patients’ primary care physicians were as effective as in-person consultations in successfully treating the disease in a multicenter, randomized study of 296 patients.

“Innovative telehealth delivery models that emphasize collaboration, quality, and efficiency can be transformative to improving patient-centered outcomes in chronic disease,” April W. Armstrong, MD, said at the annual meeting of the American Academy of Dermatology. The online model she tested fostered “increased patient engagement” and provided “comprehensive specialist support,” said Dr. Armstrong, director of the psoriasis program at the University of Southern California, Los Angeles.

To objectively assess whether online consultations are as effective as in-person examinations, Dr. Armstrong and her associates at three U.S. centers randomized adult psoriasis patients from across the disease spectrum to receive 1 year of dermatology care either in person or online. Patients enrolled in the online arm received training in taking digital images of their skin lesions and uploading the data for remote access by their dermatologist and primary care physician. The frequency of in-person and online consultations was left to the discretion of each patient and his or her physician.

Among the 148 patients randomized to each arm, 17 in the online group and 13 in the in-person group withdrew from the study or were lost to follow-up. The researchers analyzed the results on an intention-to-treat basis.

They assessed three parameters of treatment efficacy that they measured at baseline and then every 3 months out to 1 year: Psoriasis Area and Severity Index, body surface area score, and patient global self-assessment. A comparison of changes between the two treatment arms after 1 year for the first two measures met the study’s prespecified definition of equivalence, Dr. Armstrong reported. The third measure, a patient’s global self-assessment, showed lower patient-assessed disease severity after 1 year among the patients managed online, compared with those managed in person.

The incidence of adverse events and serious adverse events was similar in the two treatment arms.

Dr. Armstrong had no relevant financial disclosures.

[email protected]

Source: Armstrong A et al. AAD 2018, abstract 6730..

SAN DIEGO – Online consultations between dermatologists, patients with psoriasis, and the patients’ primary care physicians were as effective as in-person consultations in successfully treating the disease in a multicenter, randomized study of 296 patients.

“Innovative telehealth delivery models that emphasize collaboration, quality, and efficiency can be transformative to improving patient-centered outcomes in chronic disease,” April W. Armstrong, MD, said at the annual meeting of the American Academy of Dermatology. The online model she tested fostered “increased patient engagement” and provided “comprehensive specialist support,” said Dr. Armstrong, director of the psoriasis program at the University of Southern California, Los Angeles.

To objectively assess whether online consultations are as effective as in-person examinations, Dr. Armstrong and her associates at three U.S. centers randomized adult psoriasis patients from across the disease spectrum to receive 1 year of dermatology care either in person or online. Patients enrolled in the online arm received training in taking digital images of their skin lesions and uploading the data for remote access by their dermatologist and primary care physician. The frequency of in-person and online consultations was left to the discretion of each patient and his or her physician.

Among the 148 patients randomized to each arm, 17 in the online group and 13 in the in-person group withdrew from the study or were lost to follow-up. The researchers analyzed the results on an intention-to-treat basis.

They assessed three parameters of treatment efficacy that they measured at baseline and then every 3 months out to 1 year: Psoriasis Area and Severity Index, body surface area score, and patient global self-assessment. A comparison of changes between the two treatment arms after 1 year for the first two measures met the study’s prespecified definition of equivalence, Dr. Armstrong reported. The third measure, a patient’s global self-assessment, showed lower patient-assessed disease severity after 1 year among the patients managed online, compared with those managed in person.

The incidence of adverse events and serious adverse events was similar in the two treatment arms.

Dr. Armstrong had no relevant financial disclosures.

[email protected]

Source: Armstrong A et al. AAD 2018, abstract 6730..

TAMPA, FLA. – Gender bias that disadvantages women from rising in academic medicine might require specific habit-changing strategies rather than efforts that draw on goodwill alone, according to new follow-up data from a randomized trial discussed and reevaluated at the annual meeting of the American College of Psychiatrists.

One premise of this trial, supported by other research, is that entrenched gender stereotypes drive both male and female behavior and must be addressed directly for change, said Molly Carnes, MD, professor of psychiatry at the University of Wisconsin, Madison.

The initial results of the trial, which randomized academic departments at the University of Wisconsin to participate in habit-changing workshops or to serve as controls, were published almost 3 years ago (Acad Med. 2015 Feb;90[2]:221-30). It is the most recent follow-up (Devine et al. J Exp Soc Psychol. 2017 Nov;73:211-5) that corroborates that long-term changes are possible with intervention.

The published findings showed that when 1,137 faculty members from 46 departments in the experimental arm were compared with 1,153 faculty members from 46 departments in the control arm, there were significant improvements in the experimental arm in surveyed attitudes reflecting personal bias awareness (P = .001) and willingness to support gender equity (P = .013).

These changes in attitude translated into concrete changes in new female faculty hires in the most recent analysis. From 32% in a 2-year period before the workshops, the new female hires climbed to 46% in the 2-year period after the workshops – a relative increase of 44% in the departments participating in the experimental arm. In the control departments, female new faculty hires remained at 32% in both time periods.

“Basically, there are 20 new women faculty members at the University of Wisconsin because of this study,” Dr. Carnes said.

The training was not designed to change just male faculty perceptions but perceptions of both males and females. The result was a fundamental change in culture within departments randomized to the experimental arm, according to data generated by a variety of study analyses.

“When we looked at questions about department climate, we found that both male and female faculty members in the experimental groups were significantly more likely to say they fit in their department, they felt respected for their research and scholarship by their colleagues, and they felt comfortable raising personal and family issues even if they conflicted with departmental activities,” Dr. Carnes said.

This general attitude change is important, because Dr. Carnes emphasized that women share the cultural biases that can result in reduced female career opportunities in clinical and academic medicine. In addition, women generally are aware that stereotypical positive “agentic” adjectives for men, such as decisive, competitive, and ambitious, often are viewed negatively and generate backlash when applied to women. They therefore act on this awareness.

“Stereotype-based bias is a habit that can be broken, but it requires more than good intentions,” said Dr. Carnes, who emphasized that “gender-based assumptions and stereotypes are deeply embedded in the patterns of thinking of both men and women.”

As one example, Dr. Carnes cited her work evaluating female resident behavior when leading in-hospital code resuscitations. There are data to show that there is no difference in the effectiveness of male and female resident code leaders, but women typically feel that the assertive, aggressive behavior required for code leadership is “counternormative.” After the code, some women feel compelled to apologize to team members for being demanding or assertive, a step that Dr. Carnes attributed at least in part to fear of backlash from stepping out of gender-expected behavior.

The fix is not necessarily suppression of gender-related attributes. Dr. Carnes cited evidence that the stereotypical positive communal adjectives for women, such as nurturing, supportive, and sympathetic, might explain why studies suggest that women are more likely than men to be transformational leaders who inspire team members to contribute beyond their own self-interest in achieving goals.

Ultimately, the fix is replacement of stereotypes that impair men as well as women from defusing biases that “lead to subtle unintentional advantages in academic career advancement for Jack not afforded to Jill,” Dr. Carnes said. Based on the low numbers of female leaders in academic medicine decades after medical schools began enrolling women in substantial numbers, she concluded that meaningful change in gender bias is not likely to occur without implementation of specific proactive strategies aimed at challenging current perceptions. Her published study confirms that such strategies can help.

Dr. Carnes reported no conflicts of interest.

[email protected]

TAMPA, FLA. – Gender bias that disadvantages women from rising in academic medicine might require specific habit-changing strategies rather than efforts that draw on goodwill alone, according to new follow-up data from a randomized trial discussed and reevaluated at the annual meeting of the American College of Psychiatrists.

One premise of this trial, supported by other research, is that entrenched gender stereotypes drive both male and female behavior and must be addressed directly for change, said Molly Carnes, MD, professor of psychiatry at the University of Wisconsin, Madison.

The initial results of the trial, which randomized academic departments at the University of Wisconsin to participate in habit-changing workshops or to serve as controls, were published almost 3 years ago (Acad Med. 2015 Feb;90[2]:221-30). It is the most recent follow-up (Devine et al. J Exp Soc Psychol. 2017 Nov;73:211-5) that corroborates that long-term changes are possible with intervention.

The published findings showed that when 1,137 faculty members from 46 departments in the experimental arm were compared with 1,153 faculty members from 46 departments in the control arm, there were significant improvements in the experimental arm in surveyed attitudes reflecting personal bias awareness (P = .001) and willingness to support gender equity (P = .013).

These changes in attitude translated into concrete changes in new female faculty hires in the most recent analysis. From 32% in a 2-year period before the workshops, the new female hires climbed to 46% in the 2-year period after the workshops – a relative increase of 44% in the departments participating in the experimental arm. In the control departments, female new faculty hires remained at 32% in both time periods.

“Basically, there are 20 new women faculty members at the University of Wisconsin because of this study,” Dr. Carnes said.

The training was not designed to change just male faculty perceptions but perceptions of both males and females. The result was a fundamental change in culture within departments randomized to the experimental arm, according to data generated by a variety of study analyses.

“When we looked at questions about department climate, we found that both male and female faculty members in the experimental groups were significantly more likely to say they fit in their department, they felt respected for their research and scholarship by their colleagues, and they felt comfortable raising personal and family issues even if they conflicted with departmental activities,” Dr. Carnes said.

This general attitude change is important, because Dr. Carnes emphasized that women share the cultural biases that can result in reduced female career opportunities in clinical and academic medicine. In addition, women generally are aware that stereotypical positive “agentic” adjectives for men, such as decisive, competitive, and ambitious, often are viewed negatively and generate backlash when applied to women. They therefore act on this awareness.

“Stereotype-based bias is a habit that can be broken, but it requires more than good intentions,” said Dr. Carnes, who emphasized that “gender-based assumptions and stereotypes are deeply embedded in the patterns of thinking of both men and women.”

As one example, Dr. Carnes cited her work evaluating female resident behavior when leading in-hospital code resuscitations. There are data to show that there is no difference in the effectiveness of male and female resident code leaders, but women typically feel that the assertive, aggressive behavior required for code leadership is “counternormative.” After the code, some women feel compelled to apologize to team members for being demanding or assertive, a step that Dr. Carnes attributed at least in part to fear of backlash from stepping out of gender-expected behavior.

The fix is not necessarily suppression of gender-related attributes. Dr. Carnes cited evidence that the stereotypical positive communal adjectives for women, such as nurturing, supportive, and sympathetic, might explain why studies suggest that women are more likely than men to be transformational leaders who inspire team members to contribute beyond their own self-interest in achieving goals.

Ultimately, the fix is replacement of stereotypes that impair men as well as women from defusing biases that “lead to subtle unintentional advantages in academic career advancement for Jack not afforded to Jill,” Dr. Carnes said. Based on the low numbers of female leaders in academic medicine decades after medical schools began enrolling women in substantial numbers, she concluded that meaningful change in gender bias is not likely to occur without implementation of specific proactive strategies aimed at challenging current perceptions. Her published study confirms that such strategies can help.

Dr. Carnes reported no conflicts of interest.

[email protected]

TAMPA, FLA. – Gender bias that disadvantages women from rising in academic medicine might require specific habit-changing strategies rather than efforts that draw on goodwill alone, according to new follow-up data from a randomized trial discussed and reevaluated at the annual meeting of the American College of Psychiatrists.

One premise of this trial, supported by other research, is that entrenched gender stereotypes drive both male and female behavior and must be addressed directly for change, said Molly Carnes, MD, professor of psychiatry at the University of Wisconsin, Madison.

The initial results of the trial, which randomized academic departments at the University of Wisconsin to participate in habit-changing workshops or to serve as controls, were published almost 3 years ago (Acad Med. 2015 Feb;90[2]:221-30). It is the most recent follow-up (Devine et al. J Exp Soc Psychol. 2017 Nov;73:211-5) that corroborates that long-term changes are possible with intervention.

The published findings showed that when 1,137 faculty members from 46 departments in the experimental arm were compared with 1,153 faculty members from 46 departments in the control arm, there were significant improvements in the experimental arm in surveyed attitudes reflecting personal bias awareness (P = .001) and willingness to support gender equity (P = .013).

These changes in attitude translated into concrete changes in new female faculty hires in the most recent analysis. From 32% in a 2-year period before the workshops, the new female hires climbed to 46% in the 2-year period after the workshops – a relative increase of 44% in the departments participating in the experimental arm. In the control departments, female new faculty hires remained at 32% in both time periods.

“Basically, there are 20 new women faculty members at the University of Wisconsin because of this study,” Dr. Carnes said.

The training was not designed to change just male faculty perceptions but perceptions of both males and females. The result was a fundamental change in culture within departments randomized to the experimental arm, according to data generated by a variety of study analyses.

“When we looked at questions about department climate, we found that both male and female faculty members in the experimental groups were significantly more likely to say they fit in their department, they felt respected for their research and scholarship by their colleagues, and they felt comfortable raising personal and family issues even if they conflicted with departmental activities,” Dr. Carnes said.

This general attitude change is important, because Dr. Carnes emphasized that women share the cultural biases that can result in reduced female career opportunities in clinical and academic medicine. In addition, women generally are aware that stereotypical positive “agentic” adjectives for men, such as decisive, competitive, and ambitious, often are viewed negatively and generate backlash when applied to women. They therefore act on this awareness.

“Stereotype-based bias is a habit that can be broken, but it requires more than good intentions,” said Dr. Carnes, who emphasized that “gender-based assumptions and stereotypes are deeply embedded in the patterns of thinking of both men and women.”

As one example, Dr. Carnes cited her work evaluating female resident behavior when leading in-hospital code resuscitations. There are data to show that there is no difference in the effectiveness of male and female resident code leaders, but women typically feel that the assertive, aggressive behavior required for code leadership is “counternormative.” After the code, some women feel compelled to apologize to team members for being demanding or assertive, a step that Dr. Carnes attributed at least in part to fear of backlash from stepping out of gender-expected behavior.

The fix is not necessarily suppression of gender-related attributes. Dr. Carnes cited evidence that the stereotypical positive communal adjectives for women, such as nurturing, supportive, and sympathetic, might explain why studies suggest that women are more likely than men to be transformational leaders who inspire team members to contribute beyond their own self-interest in achieving goals.

Ultimately, the fix is replacement of stereotypes that impair men as well as women from defusing biases that “lead to subtle unintentional advantages in academic career advancement for Jack not afforded to Jill,” Dr. Carnes said. Based on the low numbers of female leaders in academic medicine decades after medical schools began enrolling women in substantial numbers, she concluded that meaningful change in gender bias is not likely to occur without implementation of specific proactive strategies aimed at challenging current perceptions. Her published study confirms that such strategies can help.

Dr. Carnes reported no conflicts of interest.

[email protected]

Insomnia is prevalent among U.S. soldiers, and the highest prevalence rate is among those with current major depressive episode, according to a cross-sectional analysis.

“Psychiatric disorders moderated the relationship between insomnia and memory/concentration problems, suggesting the psychiatric disorders contribute unique variance to cognitive problems,” wrote Janeese A. Brownlow, PhD, of the University of Pennsylvania, Philadelphia, and her associates. “Results highlight the importance of considering both insomnia and psychiatric disorders in the diagnosis and treatment of cognitive deficits in military soldiers.”

The researchers used the All Army Study of the Army Study to Assess Risk and Resilience in Servicemembers as their data source. They used the Composite International Diagnostic Interview (CIDI) and the Posttraumatic Stress Disorder Checklist to assess psychiatric disorders; the CIDI also helped assess cognitive problems. One of the strengths of this study was its large sample size: It had an unweighted sample of 21,449 soldiers.

[email protected]

Insomnia is prevalent among U.S. soldiers, and the highest prevalence rate is among those with current major depressive episode, according to a cross-sectional analysis.

“Psychiatric disorders moderated the relationship between insomnia and memory/concentration problems, suggesting the psychiatric disorders contribute unique variance to cognitive problems,” wrote Janeese A. Brownlow, PhD, of the University of Pennsylvania, Philadelphia, and her associates. “Results highlight the importance of considering both insomnia and psychiatric disorders in the diagnosis and treatment of cognitive deficits in military soldiers.”

The researchers used the All Army Study of the Army Study to Assess Risk and Resilience in Servicemembers as their data source. They used the Composite International Diagnostic Interview (CIDI) and the Posttraumatic Stress Disorder Checklist to assess psychiatric disorders; the CIDI also helped assess cognitive problems. One of the strengths of this study was its large sample size: It had an unweighted sample of 21,449 soldiers.

[email protected]

Insomnia is prevalent among U.S. soldiers, and the highest prevalence rate is among those with current major depressive episode, according to a cross-sectional analysis.

“Psychiatric disorders moderated the relationship between insomnia and memory/concentration problems, suggesting the psychiatric disorders contribute unique variance to cognitive problems,” wrote Janeese A. Brownlow, PhD, of the University of Pennsylvania, Philadelphia, and her associates. “Results highlight the importance of considering both insomnia and psychiatric disorders in the diagnosis and treatment of cognitive deficits in military soldiers.”

The researchers used the All Army Study of the Army Study to Assess Risk and Resilience in Servicemembers as their data source. They used the Composite International Diagnostic Interview (CIDI) and the Posttraumatic Stress Disorder Checklist to assess psychiatric disorders; the CIDI also helped assess cognitive problems. One of the strengths of this study was its large sample size: It had an unweighted sample of 21,449 soldiers.

[email protected]

The tragic Feb. 14 massacre at Marjory Stoneman Douglas High School in Parkland, Fla., which left 17 people dead and 15 hospitalized, was the 34th¹ U.S. mass shooting of 2018. Last year was a record year, with 346 mass shootings.² In response to these tragedies, mental health providers are being looked at to help solve the problem. In fact, the day after the Florida shooting, President Trump tweeted: “So many signs that the Florida shooter was mentally disturbed ... Must always report such instances to authorities, again and again!”³

This response is reminiscent of how the state of New York reacted to the 2012 Sandy Hook massacre in Newtown, Conn. One month after the shooting, the NY SAFE (New York Secure Ammunition and Firearms Enforcement) Act was passed, which, among its measures, requires mental health providers to report individuals “likely” to engage in harm.⁴ The act represented an attempt to empower mental health providers to report high-risk, potentially violent individuals to the appropriate authorities.

Second, these types of mandates can perpetuate stigma in mental health, both potentially driving away patients who could benefit from therapy, and straining the relationships between patient and provider for those in treatment. Given the high degree of effort it takes for some populations to engage in mental health services, we can imagine a prohibitive additional hesitation if patients worry that their rights and liberties may be taken away if they said “the wrong thing.” Indeed, it has been demonstrated many times that nothing matters more to the outcome of mental health treatment than the relationship between the providers and their patients,11 an effect that is true even for medication management.¹² Being more wary of one’s treating provider may, therefore, limit the effect of treatment from the patient’s perspective. In the same vein, some therapists may rightly pause to consider whether they should be more vigilant and dutifully extract statements confirming a nonviolent mindset at every meeting, much in the way we perform suicide risk assessment to assess safety. Or, therapists could hesitate to probe for violent themes out of an underlying wish to avoid discovering something that they would have to report. Such tensions created within the therapist also may lend to suboptimal treatment.

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Joshi is a research track psychiatry resident at the University of California, San Diego. His current research focuses on developing novel therapeutic strategies to target cognitive impairment in schizophrenia. His interests include graduate medical education and applied bioethics.

References

1. Gun Violence Archive http://www.gunviolencearchive.org/reports/mass-shooting

2. https://www.abc15.com/news/data/mass-shootings-in-the-us-when-where-they-have-occurred-in-2018

3. https://twitter.com/realDonaldTrump/status/964110212885106689

4. http://www.nyspsych.org/index.php?option=com_content&view=article&id=73

5. https://www.politico.com/states/new-york/albany/story/2018/02/15/after-florida-school-shooting-cuomo-again-touts-safe-act-256104

6. MMWR 2004;53(2):1-96

7. J Affect Disord. 1999 Jul;54(1-2):21-8

8. Ethol Sociobiol. 1993;14(4):231-48

9. http://www.dcf.state.fl.us/newsroom/publicdocuments/Headquarters/Records20180219/Petition%20to%20Publically%20Release%20DCF%20Records.pdf

10. Ann Rev Clin Psychol. 2017 May 8;13:445-69

11. Psychotherapy Theory Res Prac. 2001;38(4):357-61

12. J Affect Disord. 2006 Jun;92(2-3):287-90

The tragic Feb. 14 massacre at Marjory Stoneman Douglas High School in Parkland, Fla., which left 17 people dead and 15 hospitalized, was the 34th¹ U.S. mass shooting of 2018. Last year was a record year, with 346 mass shootings.² In response to these tragedies, mental health providers are being looked at to help solve the problem. In fact, the day after the Florida shooting, President Trump tweeted: “So many signs that the Florida shooter was mentally disturbed ... Must always report such instances to authorities, again and again!”³

This response is reminiscent of how the state of New York reacted to the 2012 Sandy Hook massacre in Newtown, Conn. One month after the shooting, the NY SAFE (New York Secure Ammunition and Firearms Enforcement) Act was passed, which, among its measures, requires mental health providers to report individuals “likely” to engage in harm.⁴ The act represented an attempt to empower mental health providers to report high-risk, potentially violent individuals to the appropriate authorities.

Second, these types of mandates can perpetuate stigma in mental health, both potentially driving away patients who could benefit from therapy, and straining the relationships between patient and provider for those in treatment. Given the high degree of effort it takes for some populations to engage in mental health services, we can imagine a prohibitive additional hesitation if patients worry that their rights and liberties may be taken away if they said “the wrong thing.” Indeed, it has been demonstrated many times that nothing matters more to the outcome of mental health treatment than the relationship between the providers and their patients,11 an effect that is true even for medication management.¹² Being more wary of one’s treating provider may, therefore, limit the effect of treatment from the patient’s perspective. In the same vein, some therapists may rightly pause to consider whether they should be more vigilant and dutifully extract statements confirming a nonviolent mindset at every meeting, much in the way we perform suicide risk assessment to assess safety. Or, therapists could hesitate to probe for violent themes out of an underlying wish to avoid discovering something that they would have to report. Such tensions created within the therapist also may lend to suboptimal treatment.

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Joshi is a research track psychiatry resident at the University of California, San Diego. His current research focuses on developing novel therapeutic strategies to target cognitive impairment in schizophrenia. His interests include graduate medical education and applied bioethics.

References

1. Gun Violence Archive http://www.gunviolencearchive.org/reports/mass-shooting

2. https://www.abc15.com/news/data/mass-shootings-in-the-us-when-where-they-have-occurred-in-2018

3. https://twitter.com/realDonaldTrump/status/964110212885106689

4. http://www.nyspsych.org/index.php?option=com_content&view=article&id=73

5. https://www.politico.com/states/new-york/albany/story/2018/02/15/after-florida-school-shooting-cuomo-again-touts-safe-act-256104

6. MMWR 2004;53(2):1-96

7. J Affect Disord. 1999 Jul;54(1-2):21-8

8. Ethol Sociobiol. 1993;14(4):231-48

9. http://www.dcf.state.fl.us/newsroom/publicdocuments/Headquarters/Records20180219/Petition%20to%20Publically%20Release%20DCF%20Records.pdf

10. Ann Rev Clin Psychol. 2017 May 8;13:445-69

11. Psychotherapy Theory Res Prac. 2001;38(4):357-61

12. J Affect Disord. 2006 Jun;92(2-3):287-90

The tragic Feb. 14 massacre at Marjory Stoneman Douglas High School in Parkland, Fla., which left 17 people dead and 15 hospitalized, was the 34th¹ U.S. mass shooting of 2018. Last year was a record year, with 346 mass shootings.² In response to these tragedies, mental health providers are being looked at to help solve the problem. In fact, the day after the Florida shooting, President Trump tweeted: “So many signs that the Florida shooter was mentally disturbed ... Must always report such instances to authorities, again and again!”³

This response is reminiscent of how the state of New York reacted to the 2012 Sandy Hook massacre in Newtown, Conn. One month after the shooting, the NY SAFE (New York Secure Ammunition and Firearms Enforcement) Act was passed, which, among its measures, requires mental health providers to report individuals “likely” to engage in harm.⁴ The act represented an attempt to empower mental health providers to report high-risk, potentially violent individuals to the appropriate authorities.

Second, these types of mandates can perpetuate stigma in mental health, both potentially driving away patients who could benefit from therapy, and straining the relationships between patient and provider for those in treatment. Given the high degree of effort it takes for some populations to engage in mental health services, we can imagine a prohibitive additional hesitation if patients worry that their rights and liberties may be taken away if they said “the wrong thing.” Indeed, it has been demonstrated many times that nothing matters more to the outcome of mental health treatment than the relationship between the providers and their patients,11 an effect that is true even for medication management.¹² Being more wary of one’s treating provider may, therefore, limit the effect of treatment from the patient’s perspective. In the same vein, some therapists may rightly pause to consider whether they should be more vigilant and dutifully extract statements confirming a nonviolent mindset at every meeting, much in the way we perform suicide risk assessment to assess safety. Or, therapists could hesitate to probe for violent themes out of an underlying wish to avoid discovering something that they would have to report. Such tensions created within the therapist also may lend to suboptimal treatment.

Dr. Badre is a forensic psychiatrist in San Diego and an expert in correctional mental health. He holds teaching positions at the University of California, San Diego, and the University of San Diego. He teaches medical education, psychopharmacology, ethics in psychiatry, and correctional care. Dr. Joshi is a research track psychiatry resident at the University of California, San Diego. His current research focuses on developing novel therapeutic strategies to target cognitive impairment in schizophrenia. His interests include graduate medical education and applied bioethics.

References

1. Gun Violence Archive http://www.gunviolencearchive.org/reports/mass-shooting

2. https://www.abc15.com/news/data/mass-shootings-in-the-us-when-where-they-have-occurred-in-2018

3. https://twitter.com/realDonaldTrump/status/964110212885106689

4. http://www.nyspsych.org/index.php?option=com_content&view=article&id=73

5. https://www.politico.com/states/new-york/albany/story/2018/02/15/after-florida-school-shooting-cuomo-again-touts-safe-act-256104

6. MMWR 2004;53(2):1-96

7. J Affect Disord. 1999 Jul;54(1-2):21-8

8. Ethol Sociobiol. 1993;14(4):231-48

9. http://www.dcf.state.fl.us/newsroom/publicdocuments/Headquarters/Records20180219/Petition%20to%20Publically%20Release%20DCF%20Records.pdf

10. Ann Rev Clin Psychol. 2017 May 8;13:445-69

11. Psychotherapy Theory Res Prac. 2001;38(4):357-61

12. J Affect Disord. 2006 Jun;92(2-3):287-90

SAN DIEGO—Developments in strategies based on CRISPR and antisense oligonucleotides (ASOs) have raised the prospect that these therapies targeting genetically caused diseases could one day benefit patients with Huntington’s disease, according to an overview provided at the 142nd Annual Meeting of the American Neurological Association. Researchers aspire to conduct clinical trials in people who carry the risk gene for Huntington’s disease, but for whom disease onset is 20 or 30 years away. “If we can dose them early enough, we might be able to … delay or prevent onset,” said Sarah Tabrizi, MBChB, PhD, Joint Head of the Department of Neurodegenerative Disease at University College London.

A Rare, Progressive Dementia

Huntington’s disease is the most common genetic dementia. Its prevalence is approximately one in 8,000. The disease is caused by a mutation in the first exon of HTT that influences the number of CAG trinucleotide repeats. A person with more than 40 CAG repeats will develop the disease. This number of repeats results in the production of an elongated version of the huntingtin protein, which subsequently is cleaved into toxic segments that accumulate in neurons. Disease onset typically occurs between the mid-30s and 40s.

Initial symptoms of Huntington’s disease include irritability, poor coordination, indecision, and chorea. Symptoms worsen as the disease progresses, and patients may develop personality changes and difficulty walking, swallowing, and thinking. Survival ranges from 15 to 20 years from symptom onset.

New Drug Modalities Have Many Potential Targets

Many pathogenic mechanisms contribute to the onset of Huntington’s disease and could be therapeutic targets. “Targeting DNA or RNA is absolutely critical,” said Dr. Tabrizi. “It does not matter what the downstream cellular pathway is. If you target proximally, you have more chance of achieving a therapeutic benefit in neurodegeneration.”

Many efforts to develop a therapy for Huntington’s disease focus on huntingtin transcription and translation. The aim is to lower the amount of mutant huntingtin in the brain. For example, studies of zinc finger proteins targeting DNA are in early preclinical development. Other investigators are using RNA interference to target huntingtin messenger RNA (mRNA) or ASOs to target huntingtin mRNA.

Data suggest that the CRISPR technique can remove the excess CAG repeats in cell lines. This technique is based on a naturally occurring genome-editing system that identifies viruses and cleaves their DNA, but it may be decades before this method is able to treat the whole human brain, said Dr. Tabrizi.

ASOs

She and her colleagues are studying an ASO as a therapy for Huntington’s disease. These molecules are short pieces of chemically modified DNA or RNA that can be diffused rapidly and easily enter cells in the CNS. They are stable, their effects are reversible, and they allow for dose titration. Dr. Tabrizi’s group is analyzing an ASO with 20 base pairs that recognizes and degrades the huntingtin mRNA transcript. The molecule’s chemical modifications give it high affinity, stability, and tolerability, and it is delivered intrathecally.

A preclinical study in nonhuman primates provided valuable pharmacokinetic and pharmacodynamic information that influenced the dosing of Dr. Tabrizi’s current, ongoing trial in humans. The investigators gave monkeys four intrathecal doses of therapy at monthly intervals before sacrificing them. They found that treatment significantly lowered huntingtin RNA levels in the frontal cortex and occipital cortex. The levels were about 50% lower in the caudate and thalamus after treatment, and approximately 75% lower in the hippocampus. Suppression of huntingtin RNA was sustained in the frontal cortex and the caudate for eight weeks, and the reduction was approximately 15% at that time. The ASO reached the deep structures of the brain, but had a predominantly cortical pharmacodynamic effect, said Dr. Tabrizi.

First-in-Man Study Is Complete

Dr. Tabrizi and colleagues have recently completed the first-in-man clinical trial. Their objective was primarily to evaluate the safety and tolerability of multiple intrathecal administrations of the therapy in ascending doses. They intended to obtain more information about the drug’s pharmacokinetics and to look at its effects on mutant huntingtin.

The trial was designed as a phase Ib–IIa study that could lead to a phase III clinical trial if enough data on dosing were obtained. Participants were randomized 3:1 to antisense drug or placebo. Including a placebo group in a first-in-man study was important for investigating drug effects, procedure effects, and the placebo effect, which is large in Huntington’s disease, said Dr. Tabrizi.

Patients received the ASO by a push bolus intrathecal injection through a small-gauge atraumatic needle. Each patient received four doses delivered at 28-day intervals. The follow-up period was 15 weeks.

The first participant received the first dose in September 2015, and enrollment was complete in June 2017. Dr. Tabrizi and colleagues enrolled 46 patients with early-stage Huntington’s disease into the study. Mean age at baseline was 47. Approximately 60% of participants were men. Participants’ mean number of CAG repeats was 44, and the baseline CSF level of mutant huntingtin, mean total functional capacity, and total motor score were consistent with early stage Huntington’s disease.

Intrathecal dosing was well tolerated. “We chose a small-gauge atraumatic needle because … we did not want to have to stop [the trial] because of headaches,” said Dr. Tabrizi. The researchers have not recorded any safety concerns to date, and the results seem to support further development of the therapy, she added.

The follow-up visits are complete, and patients are entering an open-label extension in which all participants will receive active treatment. The extension also will generate long-term safety data. In December 2017, Ionis Pharmaceuticals, which designed the ASO treatment and sponsored the first-in-man clinical study, announced that the study results provide clear evidence of target engagement and reduction in mutant huntingtin protein. Roche, Ionis’s partner in developing the treatment, licensed the drug and will be responsible for all future development. Such activities may include larger, longer studies aimed at determining whether lowering mutant huntingtin protein benefits patients, said Dr. Tabrizi.

—Erik Greb

Suggested Reading

Aronin N, DiFiglia M. Huntingtin-lowering strategies in Huntington’s disease: antisense oligonucleotides, small RNAs, and gene editing. Mov Disord. 2014;29(11):1455-1461.

Kordasiewicz HB, Stanek LM, Wancewicz EV, et al. Sustained therapeutic reversal of Huntington’s disease by transient repression of huntingtin synthesis. Neuron. 2012;74(6):1031-1044.

Skotte NH, Southwell AL, Østergaard ME, et al. Allele-specific suppression of mutant huntingtin using antisense oligonucleotides: providing a therapeutic option for all Huntington disease patients. PLoS One. 2014;9(9):e107434.

Wild EJ, Tabrizi SJ. Therapies targeting DNA and RNA in Huntington’s disease. Lancet Neurol. 2017;16(10):837-847.

SAN DIEGO—Developments in strategies based on CRISPR and antisense oligonucleotides (ASOs) have raised the prospect that these therapies targeting genetically caused diseases could one day benefit patients with Huntington’s disease, according to an overview provided at the 142nd Annual Meeting of the American Neurological Association. Researchers aspire to conduct clinical trials in people who carry the risk gene for Huntington’s disease, but for whom disease onset is 20 or 30 years away. “If we can dose them early enough, we might be able to … delay or prevent onset,” said Sarah Tabrizi, MBChB, PhD, Joint Head of the Department of Neurodegenerative Disease at University College London.

A Rare, Progressive Dementia

Huntington’s disease is the most common genetic dementia. Its prevalence is approximately one in 8,000. The disease is caused by a mutation in the first exon of HTT that influences the number of CAG trinucleotide repeats. A person with more than 40 CAG repeats will develop the disease. This number of repeats results in the production of an elongated version of the huntingtin protein, which subsequently is cleaved into toxic segments that accumulate in neurons. Disease onset typically occurs between the mid-30s and 40s.

Initial symptoms of Huntington’s disease include irritability, poor coordination, indecision, and chorea. Symptoms worsen as the disease progresses, and patients may develop personality changes and difficulty walking, swallowing, and thinking. Survival ranges from 15 to 20 years from symptom onset.

New Drug Modalities Have Many Potential Targets

Many pathogenic mechanisms contribute to the onset of Huntington’s disease and could be therapeutic targets. “Targeting DNA or RNA is absolutely critical,” said Dr. Tabrizi. “It does not matter what the downstream cellular pathway is. If you target proximally, you have more chance of achieving a therapeutic benefit in neurodegeneration.”

Many efforts to develop a therapy for Huntington’s disease focus on huntingtin transcription and translation. The aim is to lower the amount of mutant huntingtin in the brain. For example, studies of zinc finger proteins targeting DNA are in early preclinical development. Other investigators are using RNA interference to target huntingtin messenger RNA (mRNA) or ASOs to target huntingtin mRNA.

Data suggest that the CRISPR technique can remove the excess CAG repeats in cell lines. This technique is based on a naturally occurring genome-editing system that identifies viruses and cleaves their DNA, but it may be decades before this method is able to treat the whole human brain, said Dr. Tabrizi.

ASOs

She and her colleagues are studying an ASO as a therapy for Huntington’s disease. These molecules are short pieces of chemically modified DNA or RNA that can be diffused rapidly and easily enter cells in the CNS. They are stable, their effects are reversible, and they allow for dose titration. Dr. Tabrizi’s group is analyzing an ASO with 20 base pairs that recognizes and degrades the huntingtin mRNA transcript. The molecule’s chemical modifications give it high affinity, stability, and tolerability, and it is delivered intrathecally.

A preclinical study in nonhuman primates provided valuable pharmacokinetic and pharmacodynamic information that influenced the dosing of Dr. Tabrizi’s current, ongoing trial in humans. The investigators gave monkeys four intrathecal doses of therapy at monthly intervals before sacrificing them. They found that treatment significantly lowered huntingtin RNA levels in the frontal cortex and occipital cortex. The levels were about 50% lower in the caudate and thalamus after treatment, and approximately 75% lower in the hippocampus. Suppression of huntingtin RNA was sustained in the frontal cortex and the caudate for eight weeks, and the reduction was approximately 15% at that time. The ASO reached the deep structures of the brain, but had a predominantly cortical pharmacodynamic effect, said Dr. Tabrizi.

First-in-Man Study Is Complete

Dr. Tabrizi and colleagues have recently completed the first-in-man clinical trial. Their objective was primarily to evaluate the safety and tolerability of multiple intrathecal administrations of the therapy in ascending doses. They intended to obtain more information about the drug’s pharmacokinetics and to look at its effects on mutant huntingtin.

The trial was designed as a phase Ib–IIa study that could lead to a phase III clinical trial if enough data on dosing were obtained. Participants were randomized 3:1 to antisense drug or placebo. Including a placebo group in a first-in-man study was important for investigating drug effects, procedure effects, and the placebo effect, which is large in Huntington’s disease, said Dr. Tabrizi.

Patients received the ASO by a push bolus intrathecal injection through a small-gauge atraumatic needle. Each patient received four doses delivered at 28-day intervals. The follow-up period was 15 weeks.

The first participant received the first dose in September 2015, and enrollment was complete in June 2017. Dr. Tabrizi and colleagues enrolled 46 patients with early-stage Huntington’s disease into the study. Mean age at baseline was 47. Approximately 60% of participants were men. Participants’ mean number of CAG repeats was 44, and the baseline CSF level of mutant huntingtin, mean total functional capacity, and total motor score were consistent with early stage Huntington’s disease.

Intrathecal dosing was well tolerated. “We chose a small-gauge atraumatic needle because … we did not want to have to stop [the trial] because of headaches,” said Dr. Tabrizi. The researchers have not recorded any safety concerns to date, and the results seem to support further development of the therapy, she added.

The follow-up visits are complete, and patients are entering an open-label extension in which all participants will receive active treatment. The extension also will generate long-term safety data. In December 2017, Ionis Pharmaceuticals, which designed the ASO treatment and sponsored the first-in-man clinical study, announced that the study results provide clear evidence of target engagement and reduction in mutant huntingtin protein. Roche, Ionis’s partner in developing the treatment, licensed the drug and will be responsible for all future development. Such activities may include larger, longer studies aimed at determining whether lowering mutant huntingtin protein benefits patients, said Dr. Tabrizi.

—Erik Greb

Suggested Reading

Aronin N, DiFiglia M. Huntingtin-lowering strategies in Huntington’s disease: antisense oligonucleotides, small RNAs, and gene editing. Mov Disord. 2014;29(11):1455-1461.

Kordasiewicz HB, Stanek LM, Wancewicz EV, et al. Sustained therapeutic reversal of Huntington’s disease by transient repression of huntingtin synthesis. Neuron. 2012;74(6):1031-1044.

Skotte NH, Southwell AL, Østergaard ME, et al. Allele-specific suppression of mutant huntingtin using antisense oligonucleotides: providing a therapeutic option for all Huntington disease patients. PLoS One. 2014;9(9):e107434.

Wild EJ, Tabrizi SJ. Therapies targeting DNA and RNA in Huntington’s disease. Lancet Neurol. 2017;16(10):837-847.

SAN DIEGO—Developments in strategies based on CRISPR and antisense oligonucleotides (ASOs) have raised the prospect that these therapies targeting genetically caused diseases could one day benefit patients with Huntington’s disease, according to an overview provided at the 142nd Annual Meeting of the American Neurological Association. Researchers aspire to conduct clinical trials in people who carry the risk gene for Huntington’s disease, but for whom disease onset is 20 or 30 years away. “If we can dose them early enough, we might be able to … delay or prevent onset,” said Sarah Tabrizi, MBChB, PhD, Joint Head of the Department of Neurodegenerative Disease at University College London.

A Rare, Progressive Dementia

Huntington’s disease is the most common genetic dementia. Its prevalence is approximately one in 8,000. The disease is caused by a mutation in the first exon of HTT that influences the number of CAG trinucleotide repeats. A person with more than 40 CAG repeats will develop the disease. This number of repeats results in the production of an elongated version of the huntingtin protein, which subsequently is cleaved into toxic segments that accumulate in neurons. Disease onset typically occurs between the mid-30s and 40s.

Initial symptoms of Huntington’s disease include irritability, poor coordination, indecision, and chorea. Symptoms worsen as the disease progresses, and patients may develop personality changes and difficulty walking, swallowing, and thinking. Survival ranges from 15 to 20 years from symptom onset.

New Drug Modalities Have Many Potential Targets

Many pathogenic mechanisms contribute to the onset of Huntington’s disease and could be therapeutic targets. “Targeting DNA or RNA is absolutely critical,” said Dr. Tabrizi. “It does not matter what the downstream cellular pathway is. If you target proximally, you have more chance of achieving a therapeutic benefit in neurodegeneration.”

Many efforts to develop a therapy for Huntington’s disease focus on huntingtin transcription and translation. The aim is to lower the amount of mutant huntingtin in the brain. For example, studies of zinc finger proteins targeting DNA are in early preclinical development. Other investigators are using RNA interference to target huntingtin messenger RNA (mRNA) or ASOs to target huntingtin mRNA.

Data suggest that the CRISPR technique can remove the excess CAG repeats in cell lines. This technique is based on a naturally occurring genome-editing system that identifies viruses and cleaves their DNA, but it may be decades before this method is able to treat the whole human brain, said Dr. Tabrizi.

ASOs

She and her colleagues are studying an ASO as a therapy for Huntington’s disease. These molecules are short pieces of chemically modified DNA or RNA that can be diffused rapidly and easily enter cells in the CNS. They are stable, their effects are reversible, and they allow for dose titration. Dr. Tabrizi’s group is analyzing an ASO with 20 base pairs that recognizes and degrades the huntingtin mRNA transcript. The molecule’s chemical modifications give it high affinity, stability, and tolerability, and it is delivered intrathecally.

A preclinical study in nonhuman primates provided valuable pharmacokinetic and pharmacodynamic information that influenced the dosing of Dr. Tabrizi’s current, ongoing trial in humans. The investigators gave monkeys four intrathecal doses of therapy at monthly intervals before sacrificing them. They found that treatment significantly lowered huntingtin RNA levels in the frontal cortex and occipital cortex. The levels were about 50% lower in the caudate and thalamus after treatment, and approximately 75% lower in the hippocampus. Suppression of huntingtin RNA was sustained in the frontal cortex and the caudate for eight weeks, and the reduction was approximately 15% at that time. The ASO reached the deep structures of the brain, but had a predominantly cortical pharmacodynamic effect, said Dr. Tabrizi.

First-in-Man Study Is Complete

Dr. Tabrizi and colleagues have recently completed the first-in-man clinical trial. Their objective was primarily to evaluate the safety and tolerability of multiple intrathecal administrations of the therapy in ascending doses. They intended to obtain more information about the drug’s pharmacokinetics and to look at its effects on mutant huntingtin.

The trial was designed as a phase Ib–IIa study that could lead to a phase III clinical trial if enough data on dosing were obtained. Participants were randomized 3:1 to antisense drug or placebo. Including a placebo group in a first-in-man study was important for investigating drug effects, procedure effects, and the placebo effect, which is large in Huntington’s disease, said Dr. Tabrizi.

Patients received the ASO by a push bolus intrathecal injection through a small-gauge atraumatic needle. Each patient received four doses delivered at 28-day intervals. The follow-up period was 15 weeks.

The first participant received the first dose in September 2015, and enrollment was complete in June 2017. Dr. Tabrizi and colleagues enrolled 46 patients with early-stage Huntington’s disease into the study. Mean age at baseline was 47. Approximately 60% of participants were men. Participants’ mean number of CAG repeats was 44, and the baseline CSF level of mutant huntingtin, mean total functional capacity, and total motor score were consistent with early stage Huntington’s disease.

Intrathecal dosing was well tolerated. “We chose a small-gauge atraumatic needle because … we did not want to have to stop [the trial] because of headaches,” said Dr. Tabrizi. The researchers have not recorded any safety concerns to date, and the results seem to support further development of the therapy, she added.

The follow-up visits are complete, and patients are entering an open-label extension in which all participants will receive active treatment. The extension also will generate long-term safety data. In December 2017, Ionis Pharmaceuticals, which designed the ASO treatment and sponsored the first-in-man clinical study, announced that the study results provide clear evidence of target engagement and reduction in mutant huntingtin protein. Roche, Ionis’s partner in developing the treatment, licensed the drug and will be responsible for all future development. Such activities may include larger, longer studies aimed at determining whether lowering mutant huntingtin protein benefits patients, said Dr. Tabrizi.

—Erik Greb

Suggested Reading

Aronin N, DiFiglia M. Huntingtin-lowering strategies in Huntington’s disease: antisense oligonucleotides, small RNAs, and gene editing. Mov Disord. 2014;29(11):1455-1461.

Kordasiewicz HB, Stanek LM, Wancewicz EV, et al. Sustained therapeutic reversal of Huntington’s disease by transient repression of huntingtin synthesis. Neuron. 2012;74(6):1031-1044.

Skotte NH, Southwell AL, Østergaard ME, et al. Allele-specific suppression of mutant huntingtin using antisense oligonucleotides: providing a therapeutic option for all Huntington disease patients. PLoS One. 2014;9(9):e107434.

Wild EJ, Tabrizi SJ. Therapies targeting DNA and RNA in Huntington’s disease. Lancet Neurol. 2017;16(10):837-847.

Case

A 55-year-old woman with diabetes, hypertension, and chronic kidney disease (CKD) stage 4 is admitted to the hospital for treatment of left lower-extremity cellulitis. Laboratory studies on admission show a creatinine level of 2.5 mg/dL (glomerular filtration rate [GFR] is 20 mL/min per 1.73 m²; baseline creatinine is between 2.2 and 2.6 mg/dL), potassium level of 3.0 mEq/L, magnesium level of 1.5 mEq/L, bicarbonate level of 18 mEq/L, phosphate level of 6.5 mg/dL, and calcium level of 7.5 mg/dL.

She is put on renally dosed vancomycin to treat her cellulitis. As the hospitalist, how should you manage her multiple electrolyte abnormalities?
 

Overview of the issue

CKD is also an important risk factor for acute kidney injury. Additionally, rates of readmission for CKD patients are higher than those without CKD. Given that CKD is a “silent disease” that many patients do not realize they have, it is very possible that the first documentation of CKD could happen during an acute hospitalization.

Among the various manifestations of CKD, electrolyte abnormalities are the most likely ones hospitalists will run into.
 

Overview of the data

Hypokalemia and Hypomagnesemia

Hypokalemia (potassium levels less than 3.5 mEq/L) is not as common as hyperkalemia (potassium levels greater than 5.0 mEq/L) in CKD, which is the result of impaired renal excretion of potassium. Hypokalemia can occur as a result of GI losses, urinary losses, or decreased intake and can be worsened by the use of certain drugs, such as non–K-sparing diuretics.

In the setting of diuretic use involving thiazides and loop diuretics, hypokalemia is dose and sodium-intake dependent. Potassium deficiency worsens the effects of detrimental sodium excess, which plays a role in hypertension and its associated complications. Potassium also has a protective vascular effect, which is a major reason why potassium should be kept normal in patients with CKD.

Acutely, hypokalemia can cause arrhythmias, ileus, and paralysis, which are all indications for immediate repletion. In these cases, hypokalemia must be repleted carefully in small increments (some suggest 20 mEq doses), and the patient must be monitored frequently to avoid hyperkalemia. If patients are persistently hypokalemic, several options can be considered based on the underlying cause. Dietary modifications with foods rich in potassium (containing 250mg/100g) can be suggested. Daily potassium chloride supplementation can be used in those on diuretic therapy who have hypokalemia and metabolic alkalosis (bicarbonate levels greater than 30 mEq/L). Alkalinizing salts, containing citrate or bicarbonate, can be used in hypokalemia without metabolic alkalosis. Initiation of angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-adrenergic blockers, and K-sparing diuretics can be used as well.

Potassium supplementation and K-sparing diuretics should be used with extreme caution in CKD 3 and 4 given the risk of overcorrection. If potassium supplements or drugs to raise serum potassium are initiated in house, potassium should be rechecked within a week. These treatments should be avoided in individuals with diabetes, who are at highest risk for hyperkalemia given hyporeninemic hypoaldosteronism (type IV renal tubular acidosis).

Metabolic acidosis

Acid-base balance is maintained by the kidney through urinary excretion of hydrogen ions both as titratable acids and ammonium. In CKD, renal excretion of the daily acid load is impaired, primarily from decreased ammonium excretion caused by there being too few functioning nephrons.

Metabolic acidosis in CKD is defined as a serum bicarbonate concentration of persistently less than 22 mEq/L. The overall prevalence of metabolic acidosis in cases of CKD that don’t require dialysis is about 15% and increases linearly with a decline in GFR. In the Chronic Renal Insufficiency Cohort study, 7%, 13%, and 37% of participants with CKD stages 2, 3, and 4 respectively had metabolic acidosis.

Metabolic acidosis has a variety of adverse outcomes, including bone demineralization, increased protein catabolism and muscle wasting, impaired cardiac function, impaired glucose homeostasis, and systemic inflammation. Additionally, multiple studies have shown an association between metabolic acidosis and progression of CKD and increased mortality.

The 2013 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend maintaining the serum bicarbonate level within the reference range (23-29 mEq/L) with alkali therapy. Options include sodium bicarbonate or sodium citrate (which is rapidly metabolized to bicarbonate) in doses of 0.5-1.0 mEq/kg once per day. Sodium bicarbonate is inexpensive; however, it can lead to gastrointestinal upset as the bicarbonate is converted into CO₂ in the stomach. This side effect is usually self-limited and improves with time. Typical starting doses are 650 mg twice a day if the serum bicarbonate level is 19-21 mEq/L or 1300 mg twice a day if the serum bicarbonate level is less than or equal to 18 mEq/L.

Sodium citrate can be used if gastrointestinal upset occurs, although caution should be used in those on aluminum binders or with liver disease. Alkali treatment should be started when bicarbonate levels are persistently low (for weeks or months) or if very low (less than or equal to 18 mEq/L) without an acute reversible cause. After patients have begun therapy, they should be monitored for the development of worsening hypertension or edema caused by sodium-mediated fluid retention, although this rarely occurs.
 

Hyperphosphatemia and Hypocalcemia

Hyperphosphatemia (phosphate levels greater than 4.6 mg/dL) develops early in CKD because of a reduced filtered-phosphate load. Hypocalcemia and hyperphosphatemia can lead to secondary hyperparathyroidism. Given that hyperphosphatemia has been associated with an increased mortality among patients with CKD, treatment is warranted, but the optimal phosphorus range is unknown. According to the KDIGO guidelines, the goal phosphorus level is less than 4.5 mg/dL in patients with CKD who are not on dialysis.

Treatment includes dietary restriction to 900 mg/day and phosphate binders. There is a high phosphate load in processed foods and colas because of food additives. It is therefore recommended to reduce consumption of these foods while encouraging consumption of meat and eggs, which offer additional nutritional value. Those who have failed dietary restrictions should be put on a phosphate binder, either calcium containing (calcium carbonate, calcium acetate) or non–calcium containing (Sevelamer, lanthanum). Non–calcium-containing binders are recommended for patients with hypercalcemia (levels greater than 9.5 mg/dL). There is some data that suggests that non–calcium-containing binders are superior to calcium-containing binders in terms of vascular disease outcomes, but non–calcium-containing binders are sometimes difficult to obtain because of cost and insurance coverage.

Hypocalcemia (calcium levels below 8.4 mg/dL) occurs in the setting of late stage untreated CKD because of decreased GI uptake of calcium from diet in the context of vitamin D deficiency (less than 30 ng/mL) in addition to hyperphosphatemia. Phosphate and vitamin D correction is preferred to calcium supplementation because hyperphosphatemia and vitamin D deficiency occur earlier in CKD. Phosphate reduction is described above.

Regarding vitamin D deficiency, it is recommended to start supplementation with either vitamin D2 or D3. Doses should be adjusted if GFR is less than 30 mL/min per 1.73 m². It is important to monitor for hypercalcemia, which can also occur in CKD in this context, because it has also been associated with increased morbidity and mortality. If calcium levels are greater than 10.2 mg/dL, all vitamin D supplementation should be discontinued.
 

Back to the case

Our patient who was admitted for cellulitis has concomitant hypokalemia, hypomagnesemia, acidosis, and hyperphosphatemia with related hypocalcemia. She revealed that her diet was poor prior to her admission for her infection. She was given 20 mEq of potassium orally and placed on a potassium rich diet until potassium levels normalized. She was also given magnesium oxide orally on the first and second day of admission, with repeat levels that were normal. Her acidosis was treated with sodium bicarbonate – 1,300 mg orally twice daily. For her hyperphosphatemia and hypocalcemia, she was placed on phosphate restriction with nutritional counseling with plans to follow up as an outpatient to determine need for phosphate binders. In addition, vitamin D levels were checked, and she was started on repletion for vitamin D deficiency (27 ng/mL). Daily BMP, magnesium, and phosphorus were checked while in house until they were normal for 2 days, and follow-up lab work was requested with her nephrology appointment, which was scheduled for within 1 week.

Bottom line

Electrolyte abnormalities in CKD are numerous and have multiple adverse clinical outcomes. Early intervention and management, especially of metabolic acidosis and hyperphosphatemia, can have a significant effect, including prevention of progression of CKD and possibly reduced mortality.

Dr. Daya, Dr. Apgar, and Dr. Eniasivam are assistant clinical professors in the division of hospital medicine at the University of California, San Francisco.

References

1. Coresh J et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007 Nov 7;298(17):2038-47.

2. Dhondup T et al. Electrolyte and acid-base disorders in chronic kidney disease and end-stage kidney failure. Blood Purif. 2017;43(1-3):179-188.

3. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004 May;43(5 Suppl 1):S1-290.

4. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl (2011). 2013 Jan;3(1):1–150.

5. Sakaguchi Y et al. Hypomagnesemia in type 2 diabetic nephropathy: A novel predictor of end-stage renal disease. Diabetes Care. 2012 Jul;35(7):1591-7.

6. Palmer SC et al. Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: A systematic review and meta-analysis. JAMA. 2011 Mar 16;305(11):1119-27.

7. Patel L et al. Sevelamer versus calcium-based binders for treatment of hyperphosphatemia in CKD: A meta-analysis of randomized controlled trials. Clin J Am Soc Nephrol. 2016 Feb 5;11(2):232-44.

8. Raphael KL. Approach to the treatment of chronic metabolic acidosis in CKD. Am J Kidney Dis. 2016 Apr;67(4):696-702.

9. Raphael KL et al. Prevalence of and risk factors for reduced serum bicarbonate in chronic kidney disease. Nephrology (Carlton). 2014 Oct;19(10):648-54.

Additional reading

1. Chapter 3: Management of Progression and Complications of CKD. Kidney Int Suppl (2011). 2013 Jan:3(1):73-90.

2. Raphael KL. Approach to the treatment of chronic metabolic acidosis in CKD. Am J Kidney Dis. 2016 Apr;67(4):696-702.

Quiz

A 75-year-old male with hypertension and CKD Stage 4 is admitted to the hospital for a hip fracture following a fall. Laboratory studies on admission show a potassium level of 3.2 mEq/L, vitamin D level of 45 ng/mL, bicarbonate level of 17 mEq/L, phosphate level of 5.0 mg/dL, and calcium level of 10.3 mg/dL.

What electrolyte replacements should be initiated?

A. Dietary restriction of phosphate, sodium bicarbonate, potassium chloride, and vitamin D.

B. Non–calcium-containing phosphate binder, vitamin D, and potassium chloride.

C. Calcium-containing phosphate binder and sodium bicarbonate.

D. Non–calcium-containing phosphate binder, sodium bicarbonate, and potassium chloride.

Answer: D. Given the patient’s hypokalemia, potassium supplementation should be considered. Additionally, given his hyperphosphatemia and hypercalcemia, a non–calcium-containing phosphate binder like Sevelamer should be started. His metabolic acidosis should be corrected with sodium bicarbonate. There is no indication to supplement vitamin D based on his current lab values.
 

Key Points

• Identify and treat underlying causes of hypokalemia and hypomagnesemia.
• Do not hesitate to treat metabolic acidosis in CKD.
• Manage hyperphosphatemia and hypocalcemia by ordering appropriate lab studies and providing nutritional consultation with outpatient nephrology follow-up as indicated.

Case

A 55-year-old woman with diabetes, hypertension, and chronic kidney disease (CKD) stage 4 is admitted to the hospital for treatment of left lower-extremity cellulitis. Laboratory studies on admission show a creatinine level of 2.5 mg/dL (glomerular filtration rate [GFR] is 20 mL/min per 1.73 m²; baseline creatinine is between 2.2 and 2.6 mg/dL), potassium level of 3.0 mEq/L, magnesium level of 1.5 mEq/L, bicarbonate level of 18 mEq/L, phosphate level of 6.5 mg/dL, and calcium level of 7.5 mg/dL.

She is put on renally dosed vancomycin to treat her cellulitis. As the hospitalist, how should you manage her multiple electrolyte abnormalities?
 

Overview of the issue

CKD is also an important risk factor for acute kidney injury. Additionally, rates of readmission for CKD patients are higher than those without CKD. Given that CKD is a “silent disease” that many patients do not realize they have, it is very possible that the first documentation of CKD could happen during an acute hospitalization.

Among the various manifestations of CKD, electrolyte abnormalities are the most likely ones hospitalists will run into.
 

Overview of the data

Hypokalemia and Hypomagnesemia

Hypokalemia (potassium levels less than 3.5 mEq/L) is not as common as hyperkalemia (potassium levels greater than 5.0 mEq/L) in CKD, which is the result of impaired renal excretion of potassium. Hypokalemia can occur as a result of GI losses, urinary losses, or decreased intake and can be worsened by the use of certain drugs, such as non–K-sparing diuretics.

In the setting of diuretic use involving thiazides and loop diuretics, hypokalemia is dose and sodium-intake dependent. Potassium deficiency worsens the effects of detrimental sodium excess, which plays a role in hypertension and its associated complications. Potassium also has a protective vascular effect, which is a major reason why potassium should be kept normal in patients with CKD.

Acutely, hypokalemia can cause arrhythmias, ileus, and paralysis, which are all indications for immediate repletion. In these cases, hypokalemia must be repleted carefully in small increments (some suggest 20 mEq doses), and the patient must be monitored frequently to avoid hyperkalemia. If patients are persistently hypokalemic, several options can be considered based on the underlying cause. Dietary modifications with foods rich in potassium (containing 250mg/100g) can be suggested. Daily potassium chloride supplementation can be used in those on diuretic therapy who have hypokalemia and metabolic alkalosis (bicarbonate levels greater than 30 mEq/L). Alkalinizing salts, containing citrate or bicarbonate, can be used in hypokalemia without metabolic alkalosis. Initiation of angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-adrenergic blockers, and K-sparing diuretics can be used as well.

Potassium supplementation and K-sparing diuretics should be used with extreme caution in CKD 3 and 4 given the risk of overcorrection. If potassium supplements or drugs to raise serum potassium are initiated in house, potassium should be rechecked within a week. These treatments should be avoided in individuals with diabetes, who are at highest risk for hyperkalemia given hyporeninemic hypoaldosteronism (type IV renal tubular acidosis).

Metabolic acidosis

Acid-base balance is maintained by the kidney through urinary excretion of hydrogen ions both as titratable acids and ammonium. In CKD, renal excretion of the daily acid load is impaired, primarily from decreased ammonium excretion caused by there being too few functioning nephrons.

Metabolic acidosis in CKD is defined as a serum bicarbonate concentration of persistently less than 22 mEq/L. The overall prevalence of metabolic acidosis in cases of CKD that don’t require dialysis is about 15% and increases linearly with a decline in GFR. In the Chronic Renal Insufficiency Cohort study, 7%, 13%, and 37% of participants with CKD stages 2, 3, and 4 respectively had metabolic acidosis.

Metabolic acidosis has a variety of adverse outcomes, including bone demineralization, increased protein catabolism and muscle wasting, impaired cardiac function, impaired glucose homeostasis, and systemic inflammation. Additionally, multiple studies have shown an association between metabolic acidosis and progression of CKD and increased mortality.

The 2013 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend maintaining the serum bicarbonate level within the reference range (23-29 mEq/L) with alkali therapy. Options include sodium bicarbonate or sodium citrate (which is rapidly metabolized to bicarbonate) in doses of 0.5-1.0 mEq/kg once per day. Sodium bicarbonate is inexpensive; however, it can lead to gastrointestinal upset as the bicarbonate is converted into CO₂ in the stomach. This side effect is usually self-limited and improves with time. Typical starting doses are 650 mg twice a day if the serum bicarbonate level is 19-21 mEq/L or 1300 mg twice a day if the serum bicarbonate level is less than or equal to 18 mEq/L.

Sodium citrate can be used if gastrointestinal upset occurs, although caution should be used in those on aluminum binders or with liver disease. Alkali treatment should be started when bicarbonate levels are persistently low (for weeks or months) or if very low (less than or equal to 18 mEq/L) without an acute reversible cause. After patients have begun therapy, they should be monitored for the development of worsening hypertension or edema caused by sodium-mediated fluid retention, although this rarely occurs.
 

Hyperphosphatemia and Hypocalcemia

Hyperphosphatemia (phosphate levels greater than 4.6 mg/dL) develops early in CKD because of a reduced filtered-phosphate load. Hypocalcemia and hyperphosphatemia can lead to secondary hyperparathyroidism. Given that hyperphosphatemia has been associated with an increased mortality among patients with CKD, treatment is warranted, but the optimal phosphorus range is unknown. According to the KDIGO guidelines, the goal phosphorus level is less than 4.5 mg/dL in patients with CKD who are not on dialysis.

Treatment includes dietary restriction to 900 mg/day and phosphate binders. There is a high phosphate load in processed foods and colas because of food additives. It is therefore recommended to reduce consumption of these foods while encouraging consumption of meat and eggs, which offer additional nutritional value. Those who have failed dietary restrictions should be put on a phosphate binder, either calcium containing (calcium carbonate, calcium acetate) or non–calcium containing (Sevelamer, lanthanum). Non–calcium-containing binders are recommended for patients with hypercalcemia (levels greater than 9.5 mg/dL). There is some data that suggests that non–calcium-containing binders are superior to calcium-containing binders in terms of vascular disease outcomes, but non–calcium-containing binders are sometimes difficult to obtain because of cost and insurance coverage.

Hypocalcemia (calcium levels below 8.4 mg/dL) occurs in the setting of late stage untreated CKD because of decreased GI uptake of calcium from diet in the context of vitamin D deficiency (less than 30 ng/mL) in addition to hyperphosphatemia. Phosphate and vitamin D correction is preferred to calcium supplementation because hyperphosphatemia and vitamin D deficiency occur earlier in CKD. Phosphate reduction is described above.

Regarding vitamin D deficiency, it is recommended to start supplementation with either vitamin D2 or D3. Doses should be adjusted if GFR is less than 30 mL/min per 1.73 m². It is important to monitor for hypercalcemia, which can also occur in CKD in this context, because it has also been associated with increased morbidity and mortality. If calcium levels are greater than 10.2 mg/dL, all vitamin D supplementation should be discontinued.
 

Back to the case

Our patient who was admitted for cellulitis has concomitant hypokalemia, hypomagnesemia, acidosis, and hyperphosphatemia with related hypocalcemia. She revealed that her diet was poor prior to her admission for her infection. She was given 20 mEq of potassium orally and placed on a potassium rich diet until potassium levels normalized. She was also given magnesium oxide orally on the first and second day of admission, with repeat levels that were normal. Her acidosis was treated with sodium bicarbonate – 1,300 mg orally twice daily. For her hyperphosphatemia and hypocalcemia, she was placed on phosphate restriction with nutritional counseling with plans to follow up as an outpatient to determine need for phosphate binders. In addition, vitamin D levels were checked, and she was started on repletion for vitamin D deficiency (27 ng/mL). Daily BMP, magnesium, and phosphorus were checked while in house until they were normal for 2 days, and follow-up lab work was requested with her nephrology appointment, which was scheduled for within 1 week.

Bottom line

Electrolyte abnormalities in CKD are numerous and have multiple adverse clinical outcomes. Early intervention and management, especially of metabolic acidosis and hyperphosphatemia, can have a significant effect, including prevention of progression of CKD and possibly reduced mortality.

Dr. Daya, Dr. Apgar, and Dr. Eniasivam are assistant clinical professors in the division of hospital medicine at the University of California, San Francisco.

References

1. Coresh J et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007 Nov 7;298(17):2038-47.

2. Dhondup T et al. Electrolyte and acid-base disorders in chronic kidney disease and end-stage kidney failure. Blood Purif. 2017;43(1-3):179-188.

3. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004 May;43(5 Suppl 1):S1-290.

4. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl (2011). 2013 Jan;3(1):1–150.

5. Sakaguchi Y et al. Hypomagnesemia in type 2 diabetic nephropathy: A novel predictor of end-stage renal disease. Diabetes Care. 2012 Jul;35(7):1591-7.

6. Palmer SC et al. Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: A systematic review and meta-analysis. JAMA. 2011 Mar 16;305(11):1119-27.

7. Patel L et al. Sevelamer versus calcium-based binders for treatment of hyperphosphatemia in CKD: A meta-analysis of randomized controlled trials. Clin J Am Soc Nephrol. 2016 Feb 5;11(2):232-44.

8. Raphael KL. Approach to the treatment of chronic metabolic acidosis in CKD. Am J Kidney Dis. 2016 Apr;67(4):696-702.

9. Raphael KL et al. Prevalence of and risk factors for reduced serum bicarbonate in chronic kidney disease. Nephrology (Carlton). 2014 Oct;19(10):648-54.

Additional reading

1. Chapter 3: Management of Progression and Complications of CKD. Kidney Int Suppl (2011). 2013 Jan:3(1):73-90.

2. Raphael KL. Approach to the treatment of chronic metabolic acidosis in CKD. Am J Kidney Dis. 2016 Apr;67(4):696-702.

Quiz

A 75-year-old male with hypertension and CKD Stage 4 is admitted to the hospital for a hip fracture following a fall. Laboratory studies on admission show a potassium level of 3.2 mEq/L, vitamin D level of 45 ng/mL, bicarbonate level of 17 mEq/L, phosphate level of 5.0 mg/dL, and calcium level of 10.3 mg/dL.

What electrolyte replacements should be initiated?

A. Dietary restriction of phosphate, sodium bicarbonate, potassium chloride, and vitamin D.

B. Non–calcium-containing phosphate binder, vitamin D, and potassium chloride.

C. Calcium-containing phosphate binder and sodium bicarbonate.

D. Non–calcium-containing phosphate binder, sodium bicarbonate, and potassium chloride.

Answer: D. Given the patient’s hypokalemia, potassium supplementation should be considered. Additionally, given his hyperphosphatemia and hypercalcemia, a non–calcium-containing phosphate binder like Sevelamer should be started. His metabolic acidosis should be corrected with sodium bicarbonate. There is no indication to supplement vitamin D based on his current lab values.
 

Key Points

• Identify and treat underlying causes of hypokalemia and hypomagnesemia.
• Do not hesitate to treat metabolic acidosis in CKD.
• Manage hyperphosphatemia and hypocalcemia by ordering appropriate lab studies and providing nutritional consultation with outpatient nephrology follow-up as indicated.

Case

A 55-year-old woman with diabetes, hypertension, and chronic kidney disease (CKD) stage 4 is admitted to the hospital for treatment of left lower-extremity cellulitis. Laboratory studies on admission show a creatinine level of 2.5 mg/dL (glomerular filtration rate [GFR] is 20 mL/min per 1.73 m²; baseline creatinine is between 2.2 and 2.6 mg/dL), potassium level of 3.0 mEq/L, magnesium level of 1.5 mEq/L, bicarbonate level of 18 mEq/L, phosphate level of 6.5 mg/dL, and calcium level of 7.5 mg/dL.

She is put on renally dosed vancomycin to treat her cellulitis. As the hospitalist, how should you manage her multiple electrolyte abnormalities?
 

Overview of the issue

CKD is also an important risk factor for acute kidney injury. Additionally, rates of readmission for CKD patients are higher than those without CKD. Given that CKD is a “silent disease” that many patients do not realize they have, it is very possible that the first documentation of CKD could happen during an acute hospitalization.

Among the various manifestations of CKD, electrolyte abnormalities are the most likely ones hospitalists will run into.
 

Overview of the data

Hypokalemia and Hypomagnesemia

Hypokalemia (potassium levels less than 3.5 mEq/L) is not as common as hyperkalemia (potassium levels greater than 5.0 mEq/L) in CKD, which is the result of impaired renal excretion of potassium. Hypokalemia can occur as a result of GI losses, urinary losses, or decreased intake and can be worsened by the use of certain drugs, such as non–K-sparing diuretics.

In the setting of diuretic use involving thiazides and loop diuretics, hypokalemia is dose and sodium-intake dependent. Potassium deficiency worsens the effects of detrimental sodium excess, which plays a role in hypertension and its associated complications. Potassium also has a protective vascular effect, which is a major reason why potassium should be kept normal in patients with CKD.

Acutely, hypokalemia can cause arrhythmias, ileus, and paralysis, which are all indications for immediate repletion. In these cases, hypokalemia must be repleted carefully in small increments (some suggest 20 mEq doses), and the patient must be monitored frequently to avoid hyperkalemia. If patients are persistently hypokalemic, several options can be considered based on the underlying cause. Dietary modifications with foods rich in potassium (containing 250mg/100g) can be suggested. Daily potassium chloride supplementation can be used in those on diuretic therapy who have hypokalemia and metabolic alkalosis (bicarbonate levels greater than 30 mEq/L). Alkalinizing salts, containing citrate or bicarbonate, can be used in hypokalemia without metabolic alkalosis. Initiation of angiotensin-converting-enzyme (ACE) inhibitors, angiotensin II receptor blockers (ARBs), beta-adrenergic blockers, and K-sparing diuretics can be used as well.

Potassium supplementation and K-sparing diuretics should be used with extreme caution in CKD 3 and 4 given the risk of overcorrection. If potassium supplements or drugs to raise serum potassium are initiated in house, potassium should be rechecked within a week. These treatments should be avoided in individuals with diabetes, who are at highest risk for hyperkalemia given hyporeninemic hypoaldosteronism (type IV renal tubular acidosis).

Metabolic acidosis

Acid-base balance is maintained by the kidney through urinary excretion of hydrogen ions both as titratable acids and ammonium. In CKD, renal excretion of the daily acid load is impaired, primarily from decreased ammonium excretion caused by there being too few functioning nephrons.

Metabolic acidosis in CKD is defined as a serum bicarbonate concentration of persistently less than 22 mEq/L. The overall prevalence of metabolic acidosis in cases of CKD that don’t require dialysis is about 15% and increases linearly with a decline in GFR. In the Chronic Renal Insufficiency Cohort study, 7%, 13%, and 37% of participants with CKD stages 2, 3, and 4 respectively had metabolic acidosis.

Metabolic acidosis has a variety of adverse outcomes, including bone demineralization, increased protein catabolism and muscle wasting, impaired cardiac function, impaired glucose homeostasis, and systemic inflammation. Additionally, multiple studies have shown an association between metabolic acidosis and progression of CKD and increased mortality.

The 2013 Kidney Disease Improving Global Outcomes (KDIGO) guidelines recommend maintaining the serum bicarbonate level within the reference range (23-29 mEq/L) with alkali therapy. Options include sodium bicarbonate or sodium citrate (which is rapidly metabolized to bicarbonate) in doses of 0.5-1.0 mEq/kg once per day. Sodium bicarbonate is inexpensive; however, it can lead to gastrointestinal upset as the bicarbonate is converted into CO₂ in the stomach. This side effect is usually self-limited and improves with time. Typical starting doses are 650 mg twice a day if the serum bicarbonate level is 19-21 mEq/L or 1300 mg twice a day if the serum bicarbonate level is less than or equal to 18 mEq/L.

Sodium citrate can be used if gastrointestinal upset occurs, although caution should be used in those on aluminum binders or with liver disease. Alkali treatment should be started when bicarbonate levels are persistently low (for weeks or months) or if very low (less than or equal to 18 mEq/L) without an acute reversible cause. After patients have begun therapy, they should be monitored for the development of worsening hypertension or edema caused by sodium-mediated fluid retention, although this rarely occurs.
 

Hyperphosphatemia and Hypocalcemia

Hyperphosphatemia (phosphate levels greater than 4.6 mg/dL) develops early in CKD because of a reduced filtered-phosphate load. Hypocalcemia and hyperphosphatemia can lead to secondary hyperparathyroidism. Given that hyperphosphatemia has been associated with an increased mortality among patients with CKD, treatment is warranted, but the optimal phosphorus range is unknown. According to the KDIGO guidelines, the goal phosphorus level is less than 4.5 mg/dL in patients with CKD who are not on dialysis.

Treatment includes dietary restriction to 900 mg/day and phosphate binders. There is a high phosphate load in processed foods and colas because of food additives. It is therefore recommended to reduce consumption of these foods while encouraging consumption of meat and eggs, which offer additional nutritional value. Those who have failed dietary restrictions should be put on a phosphate binder, either calcium containing (calcium carbonate, calcium acetate) or non–calcium containing (Sevelamer, lanthanum). Non–calcium-containing binders are recommended for patients with hypercalcemia (levels greater than 9.5 mg/dL). There is some data that suggests that non–calcium-containing binders are superior to calcium-containing binders in terms of vascular disease outcomes, but non–calcium-containing binders are sometimes difficult to obtain because of cost and insurance coverage.

Hypocalcemia (calcium levels below 8.4 mg/dL) occurs in the setting of late stage untreated CKD because of decreased GI uptake of calcium from diet in the context of vitamin D deficiency (less than 30 ng/mL) in addition to hyperphosphatemia. Phosphate and vitamin D correction is preferred to calcium supplementation because hyperphosphatemia and vitamin D deficiency occur earlier in CKD. Phosphate reduction is described above.

Regarding vitamin D deficiency, it is recommended to start supplementation with either vitamin D2 or D3. Doses should be adjusted if GFR is less than 30 mL/min per 1.73 m². It is important to monitor for hypercalcemia, which can also occur in CKD in this context, because it has also been associated with increased morbidity and mortality. If calcium levels are greater than 10.2 mg/dL, all vitamin D supplementation should be discontinued.
 

Back to the case

Our patient who was admitted for cellulitis has concomitant hypokalemia, hypomagnesemia, acidosis, and hyperphosphatemia with related hypocalcemia. She revealed that her diet was poor prior to her admission for her infection. She was given 20 mEq of potassium orally and placed on a potassium rich diet until potassium levels normalized. She was also given magnesium oxide orally on the first and second day of admission, with repeat levels that were normal. Her acidosis was treated with sodium bicarbonate – 1,300 mg orally twice daily. For her hyperphosphatemia and hypocalcemia, she was placed on phosphate restriction with nutritional counseling with plans to follow up as an outpatient to determine need for phosphate binders. In addition, vitamin D levels were checked, and she was started on repletion for vitamin D deficiency (27 ng/mL). Daily BMP, magnesium, and phosphorus were checked while in house until they were normal for 2 days, and follow-up lab work was requested with her nephrology appointment, which was scheduled for within 1 week.

Bottom line

Electrolyte abnormalities in CKD are numerous and have multiple adverse clinical outcomes. Early intervention and management, especially of metabolic acidosis and hyperphosphatemia, can have a significant effect, including prevention of progression of CKD and possibly reduced mortality.

Dr. Daya, Dr. Apgar, and Dr. Eniasivam are assistant clinical professors in the division of hospital medicine at the University of California, San Francisco.

References

1. Coresh J et al. Prevalence of chronic kidney disease in the United States. JAMA. 2007 Nov 7;298(17):2038-47.

2. Dhondup T et al. Electrolyte and acid-base disorders in chronic kidney disease and end-stage kidney failure. Blood Purif. 2017;43(1-3):179-188.

3. K/DOQI clinical practice guidelines on hypertension and antihypertensive agents in chronic kidney disease. Am J Kidney Dis. 2004 May;43(5 Suppl 1):S1-290.

4. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl (2011). 2013 Jan;3(1):1–150.

5. Sakaguchi Y et al. Hypomagnesemia in type 2 diabetic nephropathy: A novel predictor of end-stage renal disease. Diabetes Care. 2012 Jul;35(7):1591-7.

6. Palmer SC et al. Serum levels of phosphorus, parathyroid hormone, and calcium and risks of death and cardiovascular disease in individuals with chronic kidney disease: A systematic review and meta-analysis. JAMA. 2011 Mar 16;305(11):1119-27.

7. Patel L et al. Sevelamer versus calcium-based binders for treatment of hyperphosphatemia in CKD: A meta-analysis of randomized controlled trials. Clin J Am Soc Nephrol. 2016 Feb 5;11(2):232-44.

8. Raphael KL. Approach to the treatment of chronic metabolic acidosis in CKD. Am J Kidney Dis. 2016 Apr;67(4):696-702.

9. Raphael KL et al. Prevalence of and risk factors for reduced serum bicarbonate in chronic kidney disease. Nephrology (Carlton). 2014 Oct;19(10):648-54.

Additional reading

1. Chapter 3: Management of Progression and Complications of CKD. Kidney Int Suppl (2011). 2013 Jan:3(1):73-90.

2. Raphael KL. Approach to the treatment of chronic metabolic acidosis in CKD. Am J Kidney Dis. 2016 Apr;67(4):696-702.

Quiz

A 75-year-old male with hypertension and CKD Stage 4 is admitted to the hospital for a hip fracture following a fall. Laboratory studies on admission show a potassium level of 3.2 mEq/L, vitamin D level of 45 ng/mL, bicarbonate level of 17 mEq/L, phosphate level of 5.0 mg/dL, and calcium level of 10.3 mg/dL.

What electrolyte replacements should be initiated?

A. Dietary restriction of phosphate, sodium bicarbonate, potassium chloride, and vitamin D.

B. Non–calcium-containing phosphate binder, vitamin D, and potassium chloride.

C. Calcium-containing phosphate binder and sodium bicarbonate.

D. Non–calcium-containing phosphate binder, sodium bicarbonate, and potassium chloride.

Answer: D. Given the patient’s hypokalemia, potassium supplementation should be considered. Additionally, given his hyperphosphatemia and hypercalcemia, a non–calcium-containing phosphate binder like Sevelamer should be started. His metabolic acidosis should be corrected with sodium bicarbonate. There is no indication to supplement vitamin D based on his current lab values.
 

Key Points

• Identify and treat underlying causes of hypokalemia and hypomagnesemia.
• Do not hesitate to treat metabolic acidosis in CKD.
• Manage hyperphosphatemia and hypocalcemia by ordering appropriate lab studies and providing nutritional consultation with outpatient nephrology follow-up as indicated.

Nutrition during a child’s first 1,000 days—from conception to age 2—is pivotal for a child’s neurodevelopment and lifelong health, according to an American Academy of Pediatrics (AAP) policy statement.

“Healthy, normal neurodevelopment is a complex process involving cellular and structural changes in the brain that proceed in a specified sequence,” said Sara Jane Schwarzenberg, MD, and Michael K. Georgieff, MD, both of the University of Minnesota Masonic Children’s Hospital, Minneapolis, and the AAP Committee on Nutrition, in the statement. “Changes that are too rapid or too slow in one part of the brain may result in the failure of crucial pathway connections to other parts of the brain. Timing is crucial; once a particular developmental sequence fails, it may not be possible to retrieve all the lost function.”

The policy statement was published in the February issue of Pediatrics.

A Crucial Period

Research shows that the most active period of neural development is in the first 1,000 days. During this time, structures and processes develop that influence behavior and provide a basis for later-developing structures, including auditory and visual systems, myelination, and brain circuits involved in social development.

The importance of macronutrients for development was highlighted in a study of rural Guatemalan children between 1969 and 1989. Children in some villages received a high-calorie, high-protein supplement, and some children received a low-calorie supplement without protein. Both supplements contained vitamins and minerals. Children who received the high-calorie, high-protein supplements before age 2 had higher test scores, better reading and vocabulary skills, and faster information processing, compared with children who received the low-calorie supplements.

Many populations lack access to high-quality macronutrient sources, however. In the United States in 2015, 16.6% of households (6.4 million) were food insecure (ie, their access to adequate food was limited by a lack of money or other resources). In households with incomes below 185% of the poverty line, 36.8% were food insecure, according to the Department of Agriculture.

Food insecurity extends to micronutrients such as vitamins and minerals like zinc; iron; choline; folate; iodine; vitamins A, D, B6, and B12; and long-chain polyunsaturated fatty acids. A lack of any of these micronutrients in early childhood can lead to neurodevelopmental issues later in life, the authors said. An important source of micronutrients is human milk, provided by breastfeeding. Studies have shown that infants who are fed human milk have improved cognitive performance, compared with infants who consume formula.

Government-sponsored programs exist that provide nutritional support to women, infants, and young children. The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is one of the most important programs, helping 53% of children under age 1, the authors said. The Supplemental Nutrition Assistance Program (SNAP) provides economic aid to buy food; it kept approximately 4.9 million children out of poverty in 2012, the authors said. SNAP Nutrition Education is intended to help people make healthy food choices with limited money.

10 Recommendations

The AAP policy statement includes the following 10 recommendations:

• Be knowledgeable about breastfeeding, and help breastfeeding mothers. The AAP recommends exclusive breastfeeding for the first six months and continued breastfeeding with the addition of food for at least the first year.
• Advocate at the local, state, and federal levels to preserve and strengthen programs focused on maternal, fetal, and neonatal nutrition.
• Be familiar with food sources that supply nutrients necessary for brain development, and make appropriate dietary recommendations. Know which nutrients are at risk in the breastfed infant after six months, such as zinc, iron, and vitamin D.
• Nutritional advice should convey that eating healthy is a positive choice, not just an avoidance of unhealthy foods.
• Existing assistance programs should aim to improve micro- and macronutrient offerings. For example, food pantries and soup kitchens can create food packages and meals that target the needs of pregnant women, breastfeeding women, and children up to age 2.
• Encourage parents to use programs that provide early childhood nutrition (eg, WIC), and advocate for the removal of barriers to enrolling or staying enrolled in these programs.
• Oppose changes in eligibility or financing structures that would adversely affect programs providing early childhood nutrition.
• Anticipate neurodevelopmental issues in children with early nutrient deficiency.
• Work with obstetricians and family physicians to encourage improvements in maternal diet and identify clinical situations that may limit the availability of crucial micronutrients to the fetus.
• Advocate to reduce hunger at the local, national, and global levels. The statement lists organizations focused on hunger, such as Feeding America, 1,000 Days, and Share Our Strength.

—Ian Lacy

Suggested Reading

Schwarzenberg SJ, Georgieff MK; Committee on Nutrition. Advocacy for improving nutrition in the first 1000 days to support childhood development and adult health. Pediatrics. 2018;141(2). pii: e20173716.

Nutrition during a child’s first 1,000 days—from conception to age 2—is pivotal for a child’s neurodevelopment and lifelong health, according to an American Academy of Pediatrics (AAP) policy statement.

“Healthy, normal neurodevelopment is a complex process involving cellular and structural changes in the brain that proceed in a specified sequence,” said Sara Jane Schwarzenberg, MD, and Michael K. Georgieff, MD, both of the University of Minnesota Masonic Children’s Hospital, Minneapolis, and the AAP Committee on Nutrition, in the statement. “Changes that are too rapid or too slow in one part of the brain may result in the failure of crucial pathway connections to other parts of the brain. Timing is crucial; once a particular developmental sequence fails, it may not be possible to retrieve all the lost function.”

The policy statement was published in the February issue of Pediatrics.

A Crucial Period

Research shows that the most active period of neural development is in the first 1,000 days. During this time, structures and processes develop that influence behavior and provide a basis for later-developing structures, including auditory and visual systems, myelination, and brain circuits involved in social development.

The importance of macronutrients for development was highlighted in a study of rural Guatemalan children between 1969 and 1989. Children in some villages received a high-calorie, high-protein supplement, and some children received a low-calorie supplement without protein. Both supplements contained vitamins and minerals. Children who received the high-calorie, high-protein supplements before age 2 had higher test scores, better reading and vocabulary skills, and faster information processing, compared with children who received the low-calorie supplements.

Many populations lack access to high-quality macronutrient sources, however. In the United States in 2015, 16.6% of households (6.4 million) were food insecure (ie, their access to adequate food was limited by a lack of money or other resources). In households with incomes below 185% of the poverty line, 36.8% were food insecure, according to the Department of Agriculture.

Food insecurity extends to micronutrients such as vitamins and minerals like zinc; iron; choline; folate; iodine; vitamins A, D, B6, and B12; and long-chain polyunsaturated fatty acids. A lack of any of these micronutrients in early childhood can lead to neurodevelopmental issues later in life, the authors said. An important source of micronutrients is human milk, provided by breastfeeding. Studies have shown that infants who are fed human milk have improved cognitive performance, compared with infants who consume formula.

Government-sponsored programs exist that provide nutritional support to women, infants, and young children. The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is one of the most important programs, helping 53% of children under age 1, the authors said. The Supplemental Nutrition Assistance Program (SNAP) provides economic aid to buy food; it kept approximately 4.9 million children out of poverty in 2012, the authors said. SNAP Nutrition Education is intended to help people make healthy food choices with limited money.

10 Recommendations

The AAP policy statement includes the following 10 recommendations:

• Be knowledgeable about breastfeeding, and help breastfeeding mothers. The AAP recommends exclusive breastfeeding for the first six months and continued breastfeeding with the addition of food for at least the first year.
• Advocate at the local, state, and federal levels to preserve and strengthen programs focused on maternal, fetal, and neonatal nutrition.
• Be familiar with food sources that supply nutrients necessary for brain development, and make appropriate dietary recommendations. Know which nutrients are at risk in the breastfed infant after six months, such as zinc, iron, and vitamin D.
• Nutritional advice should convey that eating healthy is a positive choice, not just an avoidance of unhealthy foods.
• Existing assistance programs should aim to improve micro- and macronutrient offerings. For example, food pantries and soup kitchens can create food packages and meals that target the needs of pregnant women, breastfeeding women, and children up to age 2.
• Encourage parents to use programs that provide early childhood nutrition (eg, WIC), and advocate for the removal of barriers to enrolling or staying enrolled in these programs.
• Oppose changes in eligibility or financing structures that would adversely affect programs providing early childhood nutrition.
• Anticipate neurodevelopmental issues in children with early nutrient deficiency.
• Work with obstetricians and family physicians to encourage improvements in maternal diet and identify clinical situations that may limit the availability of crucial micronutrients to the fetus.
• Advocate to reduce hunger at the local, national, and global levels. The statement lists organizations focused on hunger, such as Feeding America, 1,000 Days, and Share Our Strength.

—Ian Lacy

Suggested Reading

Schwarzenberg SJ, Georgieff MK; Committee on Nutrition. Advocacy for improving nutrition in the first 1000 days to support childhood development and adult health. Pediatrics. 2018;141(2). pii: e20173716.

Nutrition during a child’s first 1,000 days—from conception to age 2—is pivotal for a child’s neurodevelopment and lifelong health, according to an American Academy of Pediatrics (AAP) policy statement.

“Healthy, normal neurodevelopment is a complex process involving cellular and structural changes in the brain that proceed in a specified sequence,” said Sara Jane Schwarzenberg, MD, and Michael K. Georgieff, MD, both of the University of Minnesota Masonic Children’s Hospital, Minneapolis, and the AAP Committee on Nutrition, in the statement. “Changes that are too rapid or too slow in one part of the brain may result in the failure of crucial pathway connections to other parts of the brain. Timing is crucial; once a particular developmental sequence fails, it may not be possible to retrieve all the lost function.”

The policy statement was published in the February issue of Pediatrics.

A Crucial Period

Research shows that the most active period of neural development is in the first 1,000 days. During this time, structures and processes develop that influence behavior and provide a basis for later-developing structures, including auditory and visual systems, myelination, and brain circuits involved in social development.

The importance of macronutrients for development was highlighted in a study of rural Guatemalan children between 1969 and 1989. Children in some villages received a high-calorie, high-protein supplement, and some children received a low-calorie supplement without protein. Both supplements contained vitamins and minerals. Children who received the high-calorie, high-protein supplements before age 2 had higher test scores, better reading and vocabulary skills, and faster information processing, compared with children who received the low-calorie supplements.

Many populations lack access to high-quality macronutrient sources, however. In the United States in 2015, 16.6% of households (6.4 million) were food insecure (ie, their access to adequate food was limited by a lack of money or other resources). In households with incomes below 185% of the poverty line, 36.8% were food insecure, according to the Department of Agriculture.

Food insecurity extends to micronutrients such as vitamins and minerals like zinc; iron; choline; folate; iodine; vitamins A, D, B6, and B12; and long-chain polyunsaturated fatty acids. A lack of any of these micronutrients in early childhood can lead to neurodevelopmental issues later in life, the authors said. An important source of micronutrients is human milk, provided by breastfeeding. Studies have shown that infants who are fed human milk have improved cognitive performance, compared with infants who consume formula.

Government-sponsored programs exist that provide nutritional support to women, infants, and young children. The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is one of the most important programs, helping 53% of children under age 1, the authors said. The Supplemental Nutrition Assistance Program (SNAP) provides economic aid to buy food; it kept approximately 4.9 million children out of poverty in 2012, the authors said. SNAP Nutrition Education is intended to help people make healthy food choices with limited money.

10 Recommendations

The AAP policy statement includes the following 10 recommendations:

• Be knowledgeable about breastfeeding, and help breastfeeding mothers. The AAP recommends exclusive breastfeeding for the first six months and continued breastfeeding with the addition of food for at least the first year.
• Advocate at the local, state, and federal levels to preserve and strengthen programs focused on maternal, fetal, and neonatal nutrition.
• Be familiar with food sources that supply nutrients necessary for brain development, and make appropriate dietary recommendations. Know which nutrients are at risk in the breastfed infant after six months, such as zinc, iron, and vitamin D.
• Nutritional advice should convey that eating healthy is a positive choice, not just an avoidance of unhealthy foods.
• Existing assistance programs should aim to improve micro- and macronutrient offerings. For example, food pantries and soup kitchens can create food packages and meals that target the needs of pregnant women, breastfeeding women, and children up to age 2.
• Encourage parents to use programs that provide early childhood nutrition (eg, WIC), and advocate for the removal of barriers to enrolling or staying enrolled in these programs.
• Oppose changes in eligibility or financing structures that would adversely affect programs providing early childhood nutrition.
• Anticipate neurodevelopmental issues in children with early nutrient deficiency.
• Work with obstetricians and family physicians to encourage improvements in maternal diet and identify clinical situations that may limit the availability of crucial micronutrients to the fetus.
• Advocate to reduce hunger at the local, national, and global levels. The statement lists organizations focused on hunger, such as Feeding America, 1,000 Days, and Share Our Strength.

—Ian Lacy

Suggested Reading

Schwarzenberg SJ, Georgieff MK; Committee on Nutrition. Advocacy for improving nutrition in the first 1000 days to support childhood development and adult health. Pediatrics. 2018;141(2). pii: e20173716.

SAN DIEGO – Be mindful of what lies below the skin.

That was the message of Joseph Merola, MD, during a session on “rheumatology for the dermatologist” at the annual meeting of the American Academy of Dermatology.

“The idea is really to start to try to get our dermatology colleagues thinking more systemically and outside of just the skin,” said Dr. Merola, a rheumatologist and dermatologist who is codirector of the center for skin and related musculoskeletal diseases at Brigham and Women’s Hospital, Boston.

“If we look at all the different manifestations of lupus that can present to a physician, the second most common is the skin manifestations in up to 30% of patients,” he noted.

He urged his colleagues to ask patients functional questions; for example, those pertaining to sicca symptoms; and how to parse out whether a patient’s joint pain is inflammatory or non-inflammatory.

In a video interview, Dr. Merola also discussed lab tests used to evaluate patients with lupus, the value of a simple urine test, and recent work on the development of the first international classification criteria set for discoid type skin lupus.

Vidyard Video

Dr. Merola had no relevant disclosures.

[email protected]

SAN DIEGO – Be mindful of what lies below the skin.

That was the message of Joseph Merola, MD, during a session on “rheumatology for the dermatologist” at the annual meeting of the American Academy of Dermatology.

“The idea is really to start to try to get our dermatology colleagues thinking more systemically and outside of just the skin,” said Dr. Merola, a rheumatologist and dermatologist who is codirector of the center for skin and related musculoskeletal diseases at Brigham and Women’s Hospital, Boston.

“If we look at all the different manifestations of lupus that can present to a physician, the second most common is the skin manifestations in up to 30% of patients,” he noted.

He urged his colleagues to ask patients functional questions; for example, those pertaining to sicca symptoms; and how to parse out whether a patient’s joint pain is inflammatory or non-inflammatory.

In a video interview, Dr. Merola also discussed lab tests used to evaluate patients with lupus, the value of a simple urine test, and recent work on the development of the first international classification criteria set for discoid type skin lupus.

Vidyard Video

Dr. Merola had no relevant disclosures.

[email protected]

SAN DIEGO – Be mindful of what lies below the skin.

That was the message of Joseph Merola, MD, during a session on “rheumatology for the dermatologist” at the annual meeting of the American Academy of Dermatology.

“The idea is really to start to try to get our dermatology colleagues thinking more systemically and outside of just the skin,” said Dr. Merola, a rheumatologist and dermatologist who is codirector of the center for skin and related musculoskeletal diseases at Brigham and Women’s Hospital, Boston.

“If we look at all the different manifestations of lupus that can present to a physician, the second most common is the skin manifestations in up to 30% of patients,” he noted.

He urged his colleagues to ask patients functional questions; for example, those pertaining to sicca symptoms; and how to parse out whether a patient’s joint pain is inflammatory or non-inflammatory.

In a video interview, Dr. Merola also discussed lab tests used to evaluate patients with lupus, the value of a simple urine test, and recent work on the development of the first international classification criteria set for discoid type skin lupus.

Vidyard Video

Dr. Merola had no relevant disclosures.

[email protected]