LAS VEGAS—Through various programs, the BRAIN Initiative seeks to fund research in 2016 that could advance the field of neuromodulation, according to a lecture given at the 19th Annual Meeting of the North American Neuromodulation Society. These investigations could affect the treatment of epilepsy, headache, Parkinson’s disease, or other neurologic disorders.

The BRAIN Initiative has two main objectives, said Stephanie Fertig, MBA, Director of Small Business Programs at the National Institute of Neurological Disorders and Stroke. The first is to foster the development of new technologies for mapping connections in the brain and discovering patterns of neural activity. The second goal is to use these new technologies, as well as existing technologies, to further neurologists’ understanding of how the neural circuit affects the function of the healthy or diseased brain. The initiative, which President Obama introduced in 2013, is a collaboration between federal agencies, including the National Science Foundation and NIH, private foundations, universities, and industry. Information on the BRAIN Initiative can be found online at www.braininitiative.nih.gov.

Researchers Invited to Apply for Funding

Several of the BRAIN Initiative’s programs are intended to promote the identification, development, and optimization of new technologies and approaches for large-scale recording and modulation in the nervous system. The goal is to foster research that will add to scientific understanding of the dynamic signaling in the nervous system, said Ms. Fertig. One program seeks applications to study new and untested ideas for recording and modulating technology, including ideas in the initial stages of conceptualization. Other programs aim to further proof-of-concept testing for such technology, as well as to enable the optimization of the technology with feedback from the user community.

Another of the initiative’s programs is intended to fund nonclinical and clinical studies that will help advance invasive recording or stimulating devices that could, in turn, treat CNS disorders and improve understanding of the human brain. Researchers will receive support for the implementation of clinical prototype devices, nonclinical safety and efficacy testing, design verification and validation activities, and pursuit of regulatory approval for a small clinical study. The program will consider clinical studies of acute or short-term procedures that entail nonsignificant risk (as determined by an Institutional Review Board), as well as those that entail a significant risk and require an Investigational Device Exemption (IDE) from the FDA. The BRAIN Initiative provides two options for researchers interested in funding for invasive devices, said Ms. Fertig. “One is if you need to do some nonclinical work before you get your IDE and then move into the clinic. That’s the phase translational to clinical research track. Then there’s the direct-to-clinical research program,” which is appropriate for investigators who do not need to perform nonclinical work and are ready for a clinical study.

Public–Private Partnership Program

The BRAIN Initiative also created a Public–Private Partnership Program to facilitate collaboration between clinical investigators and manufacturers of invasive recording or stimulating devices. This program is intended to promote clinical research and foster partnerships between clinical researchers and the developers of “next-generation implantable stimulating–recording devices,” said Ms. Fertig. Data about the safety and utility of such devices can be costly to obtain, but the Public–Private Partnership Program will enable researchers to use existing manufacturers’ safety data. To date, six device manufacturers (ie, Medtronic, Boston Scientific, Blackrock, NeuroPace, NeuroNexus, and Second Sight) have signed a memorandum of understanding with NIH to provide support and information on materials (eg, devices and software). The information will guide investigators who want to pursue specific agreements with manufacturers for the submission of research proposals to NIH. Furthermore, NIH has created templates of collaborative research agreements and confidential disclosure agreements to quicken the legal and administrative process for establishing partnerships between manufacturers and academic research institutions.

Funding Supports Device-Related Research

The BRAIN Initiative already has funded various studies that could lead to new invasive treatments for various neurologic disorders. Leigh R. Hochberg, MD, PhD, Director of the Neurotechnology Trials Unit at Massachusetts General Hospital in Boston, and associates received NIH support for the development of the BrainGate device. Dr. Hochberg created BrainGate, a brain implant system, to allow patients with quadriplegia to control external devices such as prosthetic arms by thought alone. Dr. Hochberg’s BRAIN project is to develop BrainGate into a fully implanted medical treatment system without external components. The goal is to enable patients to use the device independently on an ongoing basis.

In addition, Gregory A. Worrell, MD, PhD, Professor of Neurology at Mayo Clinic in Rochester, Minnesota, and colleagues received funding to study wireless devices that measure brain activity, predict seizure onset, and deliver therapeutic stimulation to mitigate seizures. Dr. Worrell’s group initially plans to conduct a preclinical study to test one such device in dogs with epilepsy. If the device is successful, the group will perform a pilot clinical trial in patients with epilepsy.

Finally, Nicholas D. Schiff, MD, Jerold B. Katz Professor of Neurology and Neuroscience at Weill Cornell Medical College in New York, and colleagues received support for their efforts to develop device therapy for cognitive impairment associated with traumatic brain injury. They are focusing on a device that delivers deep brain stimulation to the thalamus, which they hypothesize may restore the disrupted circuit function that underlies the cognitive disability.

—Erik Greb

LAS VEGAS—Through various programs, the BRAIN Initiative seeks to fund research in 2016 that could advance the field of neuromodulation, according to a lecture given at the 19th Annual Meeting of the North American Neuromodulation Society. These investigations could affect the treatment of epilepsy, headache, Parkinson’s disease, or other neurologic disorders.

The BRAIN Initiative has two main objectives, said Stephanie Fertig, MBA, Director of Small Business Programs at the National Institute of Neurological Disorders and Stroke. The first is to foster the development of new technologies for mapping connections in the brain and discovering patterns of neural activity. The second goal is to use these new technologies, as well as existing technologies, to further neurologists’ understanding of how the neural circuit affects the function of the healthy or diseased brain. The initiative, which President Obama introduced in 2013, is a collaboration between federal agencies, including the National Science Foundation and NIH, private foundations, universities, and industry. Information on the BRAIN Initiative can be found online at www.braininitiative.nih.gov.

Researchers Invited to Apply for Funding

Several of the BRAIN Initiative’s programs are intended to promote the identification, development, and optimization of new technologies and approaches for large-scale recording and modulation in the nervous system. The goal is to foster research that will add to scientific understanding of the dynamic signaling in the nervous system, said Ms. Fertig. One program seeks applications to study new and untested ideas for recording and modulating technology, including ideas in the initial stages of conceptualization. Other programs aim to further proof-of-concept testing for such technology, as well as to enable the optimization of the technology with feedback from the user community.

Another of the initiative’s programs is intended to fund nonclinical and clinical studies that will help advance invasive recording or stimulating devices that could, in turn, treat CNS disorders and improve understanding of the human brain. Researchers will receive support for the implementation of clinical prototype devices, nonclinical safety and efficacy testing, design verification and validation activities, and pursuit of regulatory approval for a small clinical study. The program will consider clinical studies of acute or short-term procedures that entail nonsignificant risk (as determined by an Institutional Review Board), as well as those that entail a significant risk and require an Investigational Device Exemption (IDE) from the FDA. The BRAIN Initiative provides two options for researchers interested in funding for invasive devices, said Ms. Fertig. “One is if you need to do some nonclinical work before you get your IDE and then move into the clinic. That’s the phase translational to clinical research track. Then there’s the direct-to-clinical research program,” which is appropriate for investigators who do not need to perform nonclinical work and are ready for a clinical study.

Public–Private Partnership Program

The BRAIN Initiative also created a Public–Private Partnership Program to facilitate collaboration between clinical investigators and manufacturers of invasive recording or stimulating devices. This program is intended to promote clinical research and foster partnerships between clinical researchers and the developers of “next-generation implantable stimulating–recording devices,” said Ms. Fertig. Data about the safety and utility of such devices can be costly to obtain, but the Public–Private Partnership Program will enable researchers to use existing manufacturers’ safety data. To date, six device manufacturers (ie, Medtronic, Boston Scientific, Blackrock, NeuroPace, NeuroNexus, and Second Sight) have signed a memorandum of understanding with NIH to provide support and information on materials (eg, devices and software). The information will guide investigators who want to pursue specific agreements with manufacturers for the submission of research proposals to NIH. Furthermore, NIH has created templates of collaborative research agreements and confidential disclosure agreements to quicken the legal and administrative process for establishing partnerships between manufacturers and academic research institutions.

Funding Supports Device-Related Research

The BRAIN Initiative already has funded various studies that could lead to new invasive treatments for various neurologic disorders. Leigh R. Hochberg, MD, PhD, Director of the Neurotechnology Trials Unit at Massachusetts General Hospital in Boston, and associates received NIH support for the development of the BrainGate device. Dr. Hochberg created BrainGate, a brain implant system, to allow patients with quadriplegia to control external devices such as prosthetic arms by thought alone. Dr. Hochberg’s BRAIN project is to develop BrainGate into a fully implanted medical treatment system without external components. The goal is to enable patients to use the device independently on an ongoing basis.

In addition, Gregory A. Worrell, MD, PhD, Professor of Neurology at Mayo Clinic in Rochester, Minnesota, and colleagues received funding to study wireless devices that measure brain activity, predict seizure onset, and deliver therapeutic stimulation to mitigate seizures. Dr. Worrell’s group initially plans to conduct a preclinical study to test one such device in dogs with epilepsy. If the device is successful, the group will perform a pilot clinical trial in patients with epilepsy.

Finally, Nicholas D. Schiff, MD, Jerold B. Katz Professor of Neurology and Neuroscience at Weill Cornell Medical College in New York, and colleagues received support for their efforts to develop device therapy for cognitive impairment associated with traumatic brain injury. They are focusing on a device that delivers deep brain stimulation to the thalamus, which they hypothesize may restore the disrupted circuit function that underlies the cognitive disability.

—Erik Greb

LAS VEGAS—Through various programs, the BRAIN Initiative seeks to fund research in 2016 that could advance the field of neuromodulation, according to a lecture given at the 19th Annual Meeting of the North American Neuromodulation Society. These investigations could affect the treatment of epilepsy, headache, Parkinson’s disease, or other neurologic disorders.

The BRAIN Initiative has two main objectives, said Stephanie Fertig, MBA, Director of Small Business Programs at the National Institute of Neurological Disorders and Stroke. The first is to foster the development of new technologies for mapping connections in the brain and discovering patterns of neural activity. The second goal is to use these new technologies, as well as existing technologies, to further neurologists’ understanding of how the neural circuit affects the function of the healthy or diseased brain. The initiative, which President Obama introduced in 2013, is a collaboration between federal agencies, including the National Science Foundation and NIH, private foundations, universities, and industry. Information on the BRAIN Initiative can be found online at www.braininitiative.nih.gov.

Researchers Invited to Apply for Funding

Several of the BRAIN Initiative’s programs are intended to promote the identification, development, and optimization of new technologies and approaches for large-scale recording and modulation in the nervous system. The goal is to foster research that will add to scientific understanding of the dynamic signaling in the nervous system, said Ms. Fertig. One program seeks applications to study new and untested ideas for recording and modulating technology, including ideas in the initial stages of conceptualization. Other programs aim to further proof-of-concept testing for such technology, as well as to enable the optimization of the technology with feedback from the user community.

Another of the initiative’s programs is intended to fund nonclinical and clinical studies that will help advance invasive recording or stimulating devices that could, in turn, treat CNS disorders and improve understanding of the human brain. Researchers will receive support for the implementation of clinical prototype devices, nonclinical safety and efficacy testing, design verification and validation activities, and pursuit of regulatory approval for a small clinical study. The program will consider clinical studies of acute or short-term procedures that entail nonsignificant risk (as determined by an Institutional Review Board), as well as those that entail a significant risk and require an Investigational Device Exemption (IDE) from the FDA. The BRAIN Initiative provides two options for researchers interested in funding for invasive devices, said Ms. Fertig. “One is if you need to do some nonclinical work before you get your IDE and then move into the clinic. That’s the phase translational to clinical research track. Then there’s the direct-to-clinical research program,” which is appropriate for investigators who do not need to perform nonclinical work and are ready for a clinical study.

Public–Private Partnership Program

The BRAIN Initiative also created a Public–Private Partnership Program to facilitate collaboration between clinical investigators and manufacturers of invasive recording or stimulating devices. This program is intended to promote clinical research and foster partnerships between clinical researchers and the developers of “next-generation implantable stimulating–recording devices,” said Ms. Fertig. Data about the safety and utility of such devices can be costly to obtain, but the Public–Private Partnership Program will enable researchers to use existing manufacturers’ safety data. To date, six device manufacturers (ie, Medtronic, Boston Scientific, Blackrock, NeuroPace, NeuroNexus, and Second Sight) have signed a memorandum of understanding with NIH to provide support and information on materials (eg, devices and software). The information will guide investigators who want to pursue specific agreements with manufacturers for the submission of research proposals to NIH. Furthermore, NIH has created templates of collaborative research agreements and confidential disclosure agreements to quicken the legal and administrative process for establishing partnerships between manufacturers and academic research institutions.

Funding Supports Device-Related Research

The BRAIN Initiative already has funded various studies that could lead to new invasive treatments for various neurologic disorders. Leigh R. Hochberg, MD, PhD, Director of the Neurotechnology Trials Unit at Massachusetts General Hospital in Boston, and associates received NIH support for the development of the BrainGate device. Dr. Hochberg created BrainGate, a brain implant system, to allow patients with quadriplegia to control external devices such as prosthetic arms by thought alone. Dr. Hochberg’s BRAIN project is to develop BrainGate into a fully implanted medical treatment system without external components. The goal is to enable patients to use the device independently on an ongoing basis.

In addition, Gregory A. Worrell, MD, PhD, Professor of Neurology at Mayo Clinic in Rochester, Minnesota, and colleagues received funding to study wireless devices that measure brain activity, predict seizure onset, and deliver therapeutic stimulation to mitigate seizures. Dr. Worrell’s group initially plans to conduct a preclinical study to test one such device in dogs with epilepsy. If the device is successful, the group will perform a pilot clinical trial in patients with epilepsy.

Finally, Nicholas D. Schiff, MD, Jerold B. Katz Professor of Neurology and Neuroscience at Weill Cornell Medical College in New York, and colleagues received support for their efforts to develop device therapy for cognitive impairment associated with traumatic brain injury. They are focusing on a device that delivers deep brain stimulation to the thalamus, which they hypothesize may restore the disrupted circuit function that underlies the cognitive disability.

—Erik Greb

LOS ANGELES – For intraventricular hemorrhages of at least 20 mL, alteplase (Activase – Genentech) delivered directly into the clot by external ventricular drain almost doubles the odds of achieving a modified Rankin Score of 0-3 by 6 months.

More clot is removed – and patients with large intraventricular hemorrhages (IVHs) do better – with more vigorous alteplase dosing and when more than one drain is used.

The findings come from the Clot Lysis Evaluation of Accelerated Resolution (CLEAR III) trial, which randomized 249 IVH patients to 1 mg alteplase every 8 hours for up to 12 doses, and 251 to saline on the same schedule, delivered by external ventricular drain. The intervention didn’t make much difference with small hemorrhages.

In a video interview at the International Stroke Conference, investigator Dr. Issam Awad, a professor of surgery and neurology and director of neurovascular surgery at the University of Chicago, explained how to do the technique correctly for larger clots, and the expected benefits.

[email protected]

LOS ANGELES – For intraventricular hemorrhages of at least 20 mL, alteplase (Activase – Genentech) delivered directly into the clot by external ventricular drain almost doubles the odds of achieving a modified Rankin Score of 0-3 by 6 months.

More clot is removed – and patients with large intraventricular hemorrhages (IVHs) do better – with more vigorous alteplase dosing and when more than one drain is used.

The findings come from the Clot Lysis Evaluation of Accelerated Resolution (CLEAR III) trial, which randomized 249 IVH patients to 1 mg alteplase every 8 hours for up to 12 doses, and 251 to saline on the same schedule, delivered by external ventricular drain. The intervention didn’t make much difference with small hemorrhages.

In a video interview at the International Stroke Conference, investigator Dr. Issam Awad, a professor of surgery and neurology and director of neurovascular surgery at the University of Chicago, explained how to do the technique correctly for larger clots, and the expected benefits.

[email protected]

LOS ANGELES – For intraventricular hemorrhages of at least 20 mL, alteplase (Activase – Genentech) delivered directly into the clot by external ventricular drain almost doubles the odds of achieving a modified Rankin Score of 0-3 by 6 months.

More clot is removed – and patients with large intraventricular hemorrhages (IVHs) do better – with more vigorous alteplase dosing and when more than one drain is used.

The findings come from the Clot Lysis Evaluation of Accelerated Resolution (CLEAR III) trial, which randomized 249 IVH patients to 1 mg alteplase every 8 hours for up to 12 doses, and 251 to saline on the same schedule, delivered by external ventricular drain. The intervention didn’t make much difference with small hemorrhages.

In a video interview at the International Stroke Conference, investigator Dr. Issam Awad, a professor of surgery and neurology and director of neurovascular surgery at the University of Chicago, explained how to do the technique correctly for larger clots, and the expected benefits.

[email protected]

LOS ANGELES – The international normalized ratio fell to 1.2 or less within 3 hours among 18 of 27 (67%) patients who received four-factor prothrombin complex concentrate (octaplex [Octapharma]) for warfarin-related intracranial hemorrhages, but only 2 of 23 (9%) who received fresh frozen plasma, according to a randomized trial from Germany.

Hematoma expansion was reduced by 16.9 mL (P = .026) at 3 hours and 16.4 mL (P = .018) at 24 hours in the prothrombin complex concentrate (PCC) group.

All the patients presented within 12 hours of symptom onset with an INR of at least 2; they received fresh frozen plasma (FFP) or four-factor PCC within an hour of their cerebral CT. There were eight deaths in the FFP group, including five due to hematoma expansion. The five deaths in the PCC group occurred after day 5, and one was thought to be because of hematoma expansion. Patients were 76 years old, on average, and the majority were men; both groups received vitamin K.

The findings make a case for PCC at a time when it’s unclear how best to handle warfarin-related intracranial bleeds, and whether the extra cost of PCC is worth it. Investigator Dr. Thorsten Steiner, a professor of neurology at the University of Heidelberg (Germany), addressed the relevant issues, including PCC safety, in a video interview at the International Stroke Conference sponsored by the American Heart Association. The investigator-initiated trial was funded by Octapharma, and Dr. Steiner reported receiving a research grant from the company.

[email protected]

LOS ANGELES – The international normalized ratio fell to 1.2 or less within 3 hours among 18 of 27 (67%) patients who received four-factor prothrombin complex concentrate (octaplex [Octapharma]) for warfarin-related intracranial hemorrhages, but only 2 of 23 (9%) who received fresh frozen plasma, according to a randomized trial from Germany.

Hematoma expansion was reduced by 16.9 mL (P = .026) at 3 hours and 16.4 mL (P = .018) at 24 hours in the prothrombin complex concentrate (PCC) group.

All the patients presented within 12 hours of symptom onset with an INR of at least 2; they received fresh frozen plasma (FFP) or four-factor PCC within an hour of their cerebral CT. There were eight deaths in the FFP group, including five due to hematoma expansion. The five deaths in the PCC group occurred after day 5, and one was thought to be because of hematoma expansion. Patients were 76 years old, on average, and the majority were men; both groups received vitamin K.

The findings make a case for PCC at a time when it’s unclear how best to handle warfarin-related intracranial bleeds, and whether the extra cost of PCC is worth it. Investigator Dr. Thorsten Steiner, a professor of neurology at the University of Heidelberg (Germany), addressed the relevant issues, including PCC safety, in a video interview at the International Stroke Conference sponsored by the American Heart Association. The investigator-initiated trial was funded by Octapharma, and Dr. Steiner reported receiving a research grant from the company.

[email protected]

LOS ANGELES – The international normalized ratio fell to 1.2 or less within 3 hours among 18 of 27 (67%) patients who received four-factor prothrombin complex concentrate (octaplex [Octapharma]) for warfarin-related intracranial hemorrhages, but only 2 of 23 (9%) who received fresh frozen plasma, according to a randomized trial from Germany.

Hematoma expansion was reduced by 16.9 mL (P = .026) at 3 hours and 16.4 mL (P = .018) at 24 hours in the prothrombin complex concentrate (PCC) group.

All the patients presented within 12 hours of symptom onset with an INR of at least 2; they received fresh frozen plasma (FFP) or four-factor PCC within an hour of their cerebral CT. There were eight deaths in the FFP group, including five due to hematoma expansion. The five deaths in the PCC group occurred after day 5, and one was thought to be because of hematoma expansion. Patients were 76 years old, on average, and the majority were men; both groups received vitamin K.

The findings make a case for PCC at a time when it’s unclear how best to handle warfarin-related intracranial bleeds, and whether the extra cost of PCC is worth it. Investigator Dr. Thorsten Steiner, a professor of neurology at the University of Heidelberg (Germany), addressed the relevant issues, including PCC safety, in a video interview at the International Stroke Conference sponsored by the American Heart Association. The investigator-initiated trial was funded by Octapharma, and Dr. Steiner reported receiving a research grant from the company.

[email protected]

Patients with multiple sclerosis (MS) who receive natalizumab may have as much as a 10-fold greater risk of seroconversion to John Cunningham virus (JCV)-positive status, according to a study published online January 27 in Neurology Neuroimmunology & Neuroinflammation.

“An increase in the levels of anti-JCV antibodies could signify an increased risk of progressive multifocal leukoencephalopathy (PML),” said the study’s senior author, Heinz Wiendl, MD, Professor of Neurology at the University of Münster in Germany.

Dr. Wiendl and colleagues performed a longitudinal analysis of 525 German patients with MS and 711 French patients with MS, all of whom were treated with natalizumab, to assess whether the therapy influenced JCV seroconversion or JCV index value (ie, the level of anti-JCV antibody titers). An independent contractor processed and analyzed sera samples with the second-generation enzyme-linked immunosorbent assay kit STRATIFY JCV DxSelect.

Seroconversion and Increasing Index Value

Of the 525 German patients, 296 (56.4%) were JCV-negative throughout the observation period, and 171 were JCV-positive (32.6%). Forty-three patients changed from being JCV-negative to JCV-positive (8.2%), and 15 patients changed from being JCV-positive to JCV-negative (2.9%). When the authors used JCV serostatus to determine seroconversion, the longitudinal assessment started out with 339 initially JCV-negative patients. The serostatus of 43 of these initially JCV-negative patients changed to JCV-positive, which is a rate of 12.7% in 14.8 months (10.3% per year).

Of the 711 French patients, 243 initially were JCV-negative. The serostatus of 20 (8.2%) of these latter patients changed to JCV-positive in their first year of treatment, and 21 (8.6%) of the patients became JCV-positive in their second year of treatment. In all, the serostatus of 41 of 243 patients (16.9%) changed to JCV-positive in the first two years of natalizumab treatment (8.5% per year).

In addition, JCV index values changed in 525 patients during the observation period. The proportion of patients with an index value less than 0.4 was reduced by 20 patients (ie, from 65.1% to 61.3%), and the group of patients with low risk (ie, values between 0.4 and 0.9) was reduced by one patient to 7.8%. The patient groups with medium (ie, 0.9–1.5) and high risk (ie, greater than 1.5) increased by seven patients from 4.6% to 5.9% and by 14 patients from 22.3% to 25%, respectively.Furthermore, 161 of 201 JCV-positive patients (80%) had stable JCV index values over time. The remaining 40 patients (20%) had fluctuations of more than 30% in 14.8 months. Six of these patients (3%) had decreasing index values, and 34 (17%) had increasing index values (mean, 200.8%). Overall, the index value of all JCV-positive patients increased by an average of 15.9% in 14.8 months (12.9% per year).

Increased Index May Not Indicate Imminent PML

The high rate of seroconversion that the investigators observed “clearly supports the facilitation by treatment with natalizumab,” said Dr. Wiendl. “Our observed seroconversion of 8% to 10% per year and the rise in seroprevalence of 5% to 6% in 15 to 24 months is at least eight to 10 times as much as would be expected by age.” The study results imply that not every patient with MS is susceptible to JCV seroconversion by treatment, but natalizumab might facilitate seroconversion in patients who are susceptible.

No research has examined the influence of other MS treatments on JCV index values, and the investigators thus cannot be certain that natalizumab treatment caused the increase in index values observed in the study. But because there was no correlation between age and index value in JCV-positive patients, it is valid to speculate that natalizumab treatment induces rising JCV index values.

“If the hypothesis that treatment with natalizumab is associated with enhanced JCV seroconversion and higher index values is proven, it would also be important to determine whether cessation of natalizumab therapy (or perhaps prolonged infusion intervals) could lead to lower JCV index values as well,” Dr. Wiendl continued. The association “does not diminish [natalizumab’s] clinical efficacy, but calls for more elaborate strategies for PML risk stratification according to current scientific developments, also regarding patients with prior use of immunosuppressants, where the JCV index is not helpful.

“It is important that people with MS taking natalizumab speak with their doctor before making any changes to their treatment,” Dr. Wiendl added. “Still, this study shows anti-JCV antibodies may serve as a useful biomarker…. The results of this study underscore the need for frequent monitoring of anti-JCV antibodies in people who are being treated with natalizumab for MS.”

JCV serology, however, should not be the only PML risk biomarker to stratify patients treated with natalizumab, said Dr. Wiendl. Neurologists should explore and potentially apply additional biomarkers such as CD62L in peripheral blood or IgM bands in CSF. Together, all of these biomarkers may provide more accurate information about patients’ PML risk and help reduce the incidence of PML.

The investigators’ data extend earlier paired, longitudinal studies in various countries of patients treated with natalizumab who had similarly high rates of conversion and a rise in titers, said Adil Javed, MD, PhD, Associate Professor of Neurology, and Anthony T. Reder, MD, Professor of Neurology, both at the University of Chicago, in an accompanying editorial. Although the JCV index appears to be a valid serum marker of risk for PML, “risk is relative,” they said. “Despite a higher JCV replication state, an increase in JCV-antibody index does not necessarily mean that PML infection is imminent…. Schwab et al extend growing observations that JCV-antibody index values need to be monitored and that seroconversion or rising JCV-antibody titers alter the risk of PML in patients treated with natalizumab.”

—Erik Greb

Patients with multiple sclerosis (MS) who receive natalizumab may have as much as a 10-fold greater risk of seroconversion to John Cunningham virus (JCV)-positive status, according to a study published online January 27 in Neurology Neuroimmunology & Neuroinflammation.

“An increase in the levels of anti-JCV antibodies could signify an increased risk of progressive multifocal leukoencephalopathy (PML),” said the study’s senior author, Heinz Wiendl, MD, Professor of Neurology at the University of Münster in Germany.

Dr. Wiendl and colleagues performed a longitudinal analysis of 525 German patients with MS and 711 French patients with MS, all of whom were treated with natalizumab, to assess whether the therapy influenced JCV seroconversion or JCV index value (ie, the level of anti-JCV antibody titers). An independent contractor processed and analyzed sera samples with the second-generation enzyme-linked immunosorbent assay kit STRATIFY JCV DxSelect.

Seroconversion and Increasing Index Value

Of the 525 German patients, 296 (56.4%) were JCV-negative throughout the observation period, and 171 were JCV-positive (32.6%). Forty-three patients changed from being JCV-negative to JCV-positive (8.2%), and 15 patients changed from being JCV-positive to JCV-negative (2.9%). When the authors used JCV serostatus to determine seroconversion, the longitudinal assessment started out with 339 initially JCV-negative patients. The serostatus of 43 of these initially JCV-negative patients changed to JCV-positive, which is a rate of 12.7% in 14.8 months (10.3% per year).

Of the 711 French patients, 243 initially were JCV-negative. The serostatus of 20 (8.2%) of these latter patients changed to JCV-positive in their first year of treatment, and 21 (8.6%) of the patients became JCV-positive in their second year of treatment. In all, the serostatus of 41 of 243 patients (16.9%) changed to JCV-positive in the first two years of natalizumab treatment (8.5% per year).

In addition, JCV index values changed in 525 patients during the observation period. The proportion of patients with an index value less than 0.4 was reduced by 20 patients (ie, from 65.1% to 61.3%), and the group of patients with low risk (ie, values between 0.4 and 0.9) was reduced by one patient to 7.8%. The patient groups with medium (ie, 0.9–1.5) and high risk (ie, greater than 1.5) increased by seven patients from 4.6% to 5.9% and by 14 patients from 22.3% to 25%, respectively.Furthermore, 161 of 201 JCV-positive patients (80%) had stable JCV index values over time. The remaining 40 patients (20%) had fluctuations of more than 30% in 14.8 months. Six of these patients (3%) had decreasing index values, and 34 (17%) had increasing index values (mean, 200.8%). Overall, the index value of all JCV-positive patients increased by an average of 15.9% in 14.8 months (12.9% per year).

Increased Index May Not Indicate Imminent PML

The high rate of seroconversion that the investigators observed “clearly supports the facilitation by treatment with natalizumab,” said Dr. Wiendl. “Our observed seroconversion of 8% to 10% per year and the rise in seroprevalence of 5% to 6% in 15 to 24 months is at least eight to 10 times as much as would be expected by age.” The study results imply that not every patient with MS is susceptible to JCV seroconversion by treatment, but natalizumab might facilitate seroconversion in patients who are susceptible.

No research has examined the influence of other MS treatments on JCV index values, and the investigators thus cannot be certain that natalizumab treatment caused the increase in index values observed in the study. But because there was no correlation between age and index value in JCV-positive patients, it is valid to speculate that natalizumab treatment induces rising JCV index values.

“If the hypothesis that treatment with natalizumab is associated with enhanced JCV seroconversion and higher index values is proven, it would also be important to determine whether cessation of natalizumab therapy (or perhaps prolonged infusion intervals) could lead to lower JCV index values as well,” Dr. Wiendl continued. The association “does not diminish [natalizumab’s] clinical efficacy, but calls for more elaborate strategies for PML risk stratification according to current scientific developments, also regarding patients with prior use of immunosuppressants, where the JCV index is not helpful.

“It is important that people with MS taking natalizumab speak with their doctor before making any changes to their treatment,” Dr. Wiendl added. “Still, this study shows anti-JCV antibodies may serve as a useful biomarker…. The results of this study underscore the need for frequent monitoring of anti-JCV antibodies in people who are being treated with natalizumab for MS.”

JCV serology, however, should not be the only PML risk biomarker to stratify patients treated with natalizumab, said Dr. Wiendl. Neurologists should explore and potentially apply additional biomarkers such as CD62L in peripheral blood or IgM bands in CSF. Together, all of these biomarkers may provide more accurate information about patients’ PML risk and help reduce the incidence of PML.

The investigators’ data extend earlier paired, longitudinal studies in various countries of patients treated with natalizumab who had similarly high rates of conversion and a rise in titers, said Adil Javed, MD, PhD, Associate Professor of Neurology, and Anthony T. Reder, MD, Professor of Neurology, both at the University of Chicago, in an accompanying editorial. Although the JCV index appears to be a valid serum marker of risk for PML, “risk is relative,” they said. “Despite a higher JCV replication state, an increase in JCV-antibody index does not necessarily mean that PML infection is imminent…. Schwab et al extend growing observations that JCV-antibody index values need to be monitored and that seroconversion or rising JCV-antibody titers alter the risk of PML in patients treated with natalizumab.”

—Erik Greb

Patients with multiple sclerosis (MS) who receive natalizumab may have as much as a 10-fold greater risk of seroconversion to John Cunningham virus (JCV)-positive status, according to a study published online January 27 in Neurology Neuroimmunology & Neuroinflammation.

“An increase in the levels of anti-JCV antibodies could signify an increased risk of progressive multifocal leukoencephalopathy (PML),” said the study’s senior author, Heinz Wiendl, MD, Professor of Neurology at the University of Münster in Germany.

Dr. Wiendl and colleagues performed a longitudinal analysis of 525 German patients with MS and 711 French patients with MS, all of whom were treated with natalizumab, to assess whether the therapy influenced JCV seroconversion or JCV index value (ie, the level of anti-JCV antibody titers). An independent contractor processed and analyzed sera samples with the second-generation enzyme-linked immunosorbent assay kit STRATIFY JCV DxSelect.

Seroconversion and Increasing Index Value

Of the 525 German patients, 296 (56.4%) were JCV-negative throughout the observation period, and 171 were JCV-positive (32.6%). Forty-three patients changed from being JCV-negative to JCV-positive (8.2%), and 15 patients changed from being JCV-positive to JCV-negative (2.9%). When the authors used JCV serostatus to determine seroconversion, the longitudinal assessment started out with 339 initially JCV-negative patients. The serostatus of 43 of these initially JCV-negative patients changed to JCV-positive, which is a rate of 12.7% in 14.8 months (10.3% per year).

Of the 711 French patients, 243 initially were JCV-negative. The serostatus of 20 (8.2%) of these latter patients changed to JCV-positive in their first year of treatment, and 21 (8.6%) of the patients became JCV-positive in their second year of treatment. In all, the serostatus of 41 of 243 patients (16.9%) changed to JCV-positive in the first two years of natalizumab treatment (8.5% per year).

In addition, JCV index values changed in 525 patients during the observation period. The proportion of patients with an index value less than 0.4 was reduced by 20 patients (ie, from 65.1% to 61.3%), and the group of patients with low risk (ie, values between 0.4 and 0.9) was reduced by one patient to 7.8%. The patient groups with medium (ie, 0.9–1.5) and high risk (ie, greater than 1.5) increased by seven patients from 4.6% to 5.9% and by 14 patients from 22.3% to 25%, respectively.Furthermore, 161 of 201 JCV-positive patients (80%) had stable JCV index values over time. The remaining 40 patients (20%) had fluctuations of more than 30% in 14.8 months. Six of these patients (3%) had decreasing index values, and 34 (17%) had increasing index values (mean, 200.8%). Overall, the index value of all JCV-positive patients increased by an average of 15.9% in 14.8 months (12.9% per year).

Increased Index May Not Indicate Imminent PML

The high rate of seroconversion that the investigators observed “clearly supports the facilitation by treatment with natalizumab,” said Dr. Wiendl. “Our observed seroconversion of 8% to 10% per year and the rise in seroprevalence of 5% to 6% in 15 to 24 months is at least eight to 10 times as much as would be expected by age.” The study results imply that not every patient with MS is susceptible to JCV seroconversion by treatment, but natalizumab might facilitate seroconversion in patients who are susceptible.

No research has examined the influence of other MS treatments on JCV index values, and the investigators thus cannot be certain that natalizumab treatment caused the increase in index values observed in the study. But because there was no correlation between age and index value in JCV-positive patients, it is valid to speculate that natalizumab treatment induces rising JCV index values.

“If the hypothesis that treatment with natalizumab is associated with enhanced JCV seroconversion and higher index values is proven, it would also be important to determine whether cessation of natalizumab therapy (or perhaps prolonged infusion intervals) could lead to lower JCV index values as well,” Dr. Wiendl continued. The association “does not diminish [natalizumab’s] clinical efficacy, but calls for more elaborate strategies for PML risk stratification according to current scientific developments, also regarding patients with prior use of immunosuppressants, where the JCV index is not helpful.

“It is important that people with MS taking natalizumab speak with their doctor before making any changes to their treatment,” Dr. Wiendl added. “Still, this study shows anti-JCV antibodies may serve as a useful biomarker…. The results of this study underscore the need for frequent monitoring of anti-JCV antibodies in people who are being treated with natalizumab for MS.”

JCV serology, however, should not be the only PML risk biomarker to stratify patients treated with natalizumab, said Dr. Wiendl. Neurologists should explore and potentially apply additional biomarkers such as CD62L in peripheral blood or IgM bands in CSF. Together, all of these biomarkers may provide more accurate information about patients’ PML risk and help reduce the incidence of PML.

The investigators’ data extend earlier paired, longitudinal studies in various countries of patients treated with natalizumab who had similarly high rates of conversion and a rise in titers, said Adil Javed, MD, PhD, Associate Professor of Neurology, and Anthony T. Reder, MD, Professor of Neurology, both at the University of Chicago, in an accompanying editorial. Although the JCV index appears to be a valid serum marker of risk for PML, “risk is relative,” they said. “Despite a higher JCV replication state, an increase in JCV-antibody index does not necessarily mean that PML infection is imminent…. Schwab et al extend growing observations that JCV-antibody index values need to be monitored and that seroconversion or rising JCV-antibody titers alter the risk of PML in patients treated with natalizumab.”

—Erik Greb

Code 99291 is used for critical care, evaluation, and management of the critically ill or critically injured patient, first 30–74 minutes.1 It is to be reported only once per day per physician or group member of the same specialty.

Code 99292 is for critical care, evaluation, and management of the critically ill or critically injured patient, each additional 30 minutes. It is to be listed separately in addition to the code for primary service.1 Code 99292 is categorized as an add-on code. It must be reported on the same invoice as its primary code, 99291. Multiple units of code 99292 can be reported per day per physician/group.

Despite the increased resources and references for critical care billing, critical care reporting issues persist. Medicare data analysis continues to identify 99291 as high risk for claim payment errors, perpetuating prepayment claim edits for outlier utilization and location discrepancies (i.e., settings other than inpatient hospital, outpatient hospital, or the emergency department). 2,3,4

Bolster your documentation with these three key elements.

Critical Illness, Injury Management

Current Procedural Terminology (CPT) and the Centers for Medicare & Medicaid Services (CMS) define “critical illness or injury” as a condition that acutely impairs one or more vital organ systems such that there is a high probability of imminent or life-threatening deterioration in the patient’s condition (e.g., central nervous system failure; circulatory failure; shock; renal, hepatic, metabolic, and/or respiratory failure).5

Hospitalists providing care to the critically ill patient must perform highly complex decision making and interventions of high intensity that are required to prevent the patient’s inevitable decline. CMS further elaborates that “the patient shall be critically ill or injured at the time of the physician’s visit.”6 This is to ensure that hospitalists and other specialists support the medical necessity of the service and do not continue to report critical care codes on days after the patient has become stable and improved.

Consider the following scenarios:

CMS examples of patients whose medical condition may warrant critical care services (99291, 99292):6

• An 81-year-old male patient is admitted to the ICU following abdominal aortic aneurysm resection. Two days after surgery, he requires fluids and pressors to maintain adequate perfusion and arterial pressures. He remains ventilator dependent.
• A 67-year-old female patient is three days post mitral valve repair. She develops petechiae, hypotension, and hypoxia requiring respiratory and circulatory support.
• A 70-year-old admitted for right lower lobe pneumococcal pneumonia with a history of COPD becomes hypoxic and hypotensive two days after admission.
• A 68-year-old admitted for an acute anterior wall myocardial infarction continues to have symptomatic ventricular tachycardia that is marginally responsive to antiarrhythmic therapy.

CMS examples of patients who may not satisfy Medicare medical necessity criteria, or do not meet critical care criteria, or who do not have a critical care illness or injury and, therefore, are not eligible for critical care payment but may be reported using another appropriate hospital care code, such as subsequent hospital care codes (99231–99233), initial hospital care codes (99221–99223), or hospital consultation codes (99251–99255) when applicable:1,6

• Patients admitted to a critical care unit because no other hospital beds were available;
• Patients admitted to a critical care unit for close nursing observation and/or frequent monitoring of vital signs (e.g., drug toxicity or overdose);
• Patients admitted to a critical care unit because hospital rules require certain treatments (e.g., insulin infusions) to be administered in the critical care unit; and
• Patients receiving only care of a chronic illness in absence of care for a critical illness (e.g., daily management of a chronic ventilator patient, management of or care related to dialysis for end-stage renal disease). Services considered palliative in nature as this type of care do not meet the definition of critical care services.7

Concurrent Care

Critically ill patients often require the care of hospitalists and other specialists throughout the course of treatment. Payors are sensitive to the multiple hours billed by multiple providers for a single patient on a given day. Claim logic provides an automated response to only allow reimbursement for 99291 once per day when reported by physicians of the same group and specialty.8 Physicians of different specialties can separately report critical care hours as long as they are caring for a condition that meets the definition of critical care.

The CMS example of this: A dermatologist evaluates and treats a rash on an ICU patient who is maintained on a ventilator and nitroglycerine infusion that are being managed by an intensivist. The dermatologist should not report a service for critical care.6

Similarly for hospitalists, if an intensivist is taking care of the critical condition and there is nothing more for the hospitalist to add to the plan of care for the critical condition, critical care services may not be justified.

When different specialists are reporting critical care on the same day, it is imperative for the documentation to demonstrate that care is not duplicative of any other provider’s care (i.e., identify management of different conditions or revising elements of the plan). The care cannot overlap the same time period of any other physician reporting critical care services.

Calculating Time

Critical care time constitutes bedside time and time spent on the patient’s unit/floor where the physician is immediately available to the patient (see Table 1). Certain labs, diagnostic studies, and procedures are considered inherent to critical care services and are not reported separately on the claim form: cardiac output measurements (93561, 93562); chest X-rays (71010, 71015, 71020); pulse oximetry (94760, 94761, 94762); blood gases and interpretation of data stored in computers, such as ECGs, blood pressures, and hematologic data (99090); gastric intubation (43752, 43753); temporary transcutaneous pacing (92953); ventilation management (94002–94004, 94660, 94662); and vascular access procedures (36000, 36410, 36415, 36591, 36600).1

Instead, physician time associated with the performance and/or interpretation of these services is toward the cumulative critical care time of the day. Services or procedures that are considered separately billable (e.g., central line placement, intubation, CPR) cannot contribute to critical care time.

When separately billable procedures are performed by the same provider/specialty group on the same day as critical care, physicians should make a notation in the medical record indicating the non-overlapping service times (e.g., “central line insertion is not included as critical care time”). This may assist with securing reimbursement when the payor requests the documentation for each reported claim item.

Activities on the floor/unit that do not directly contribute to patient care or management (e.g., review of literature, teaching rounds) cannot be counted toward critical care time. Do not count time associated with indirect care provided outside of the patient’s unit/floor (e.g., reviewing data or calling the family from the office) toward critical care time.

Family discussions can be counted toward critical care time but must take place at bedside or on the patient’s unit/floor. The patient must participate in the discussion unless medically unable or clinically incompetent to participate. If unable to participate, a notation in the chart must delineate the patient’s inability to participate and the reason.

Credited time can only involve obtaining a medical history and/or discussing treatment options or limitation(s) of treatment. The conversation must bear directly on patient management.1,7 Do not count time associated with providing periodic condition updates to the family, answering questions about the patient’s condition that are unrelated to decision making, or counseling the family during their grief process. If the conversation must take place via phone, it may be counted toward critical care time if the physician is calling from the patient’s unit/floor and the conversation involves the same criterion identified for face-to-face family meetings.10

Physicians should keep track of their critical care time throughout the day. Since critical care time is a cumulative service, each entry should include the total time that critical care services were provided (e.g., 45 minutes).10 Some payors may still impose the notation of “start-and-stop time” per encounter (e.g., 2–2:50 a.m.).

Same-specialty physicians (i.e., two hospitalists from the same group practice) may require separate claims. The initial critical care hour (99291) must be met by a single physician. Medically necessary critical care time beyond the first hour (99292) may be met individually by the same physician or collectively with another physician from the same group. The physician performing the additional time, beyond the first hour, reports the appropriate units of 99292 (see Table 1) under the corresponding NPI.11

CMS has issued instructions for contractors to recognize this atypical reporting method. However, non-Medicare payors may not recognize this newer reporting method and maintain that the cumulative service (by the same-specialty physician in the same provider group) should be reported under one physician name. Be sure to query the payors for appropriate reporting methods. TH

References

1. Abraham M, Ahlman J, Boudreau A, Connelly J, Crosslin, R. Current Procedural Terminology 2015 Professional Edition. Chicago: American Medical Association Press; 2014. 23-25.
2. Widespread prepayment targeted review notification—CPT 99291. Cahaba website. Available at: www.cahabagba.com/news/widespread-prepayment-targeted-review-notification-part-b/. Accessed December 17, 2015.
3. Critical care CPT 99291 widespread prepayment targeted review results. Cahaba website. Available at: https://www.cahabagba.com/news/critical-care-cpt-99291-widespread-prepayment-targeted-review-results-2/. Accessed December 17, 2015.
4. Prepayment edit of evaluation and management (E/M) code 99291. First Coast Service Options, Inc. website. Available at: medicare.fcso.com/Publications_B/2013/251608.pdf. Accessed December 17, 2015.
5. Medicare claims processing manual: chapter 12, section 30.6.12A. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.
6. Medicare claims processing manual: chapter 12, section 30.6.12B. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.
7. Critical care fact sheet. CGS Administrators, LLC website. Available at: www.cgsmedicare.com/partb/mr/pdf/critical_care_fact_sheet.pdf. Accessed December 17, 2015.
8. Same day same service policy. United Healthcare website. Available at: www.unitedhealthcareonline.com/ccmcontent/ProviderII/UHC/en-US/Main%20Menu/Tools%20&%20Resources/Policies%20and%20Protocols/Medicare%20Advantage%20Reimbursement%20Policies/S/SameDaySameService.pdf. Accessed December 17, 2015.
9. Medicare claims processing manual: chapter 12, section 30.6.12G. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.
10. Medicare claims processing manual: chapter 12, section 30.6.12E. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.
11. Medicare claims processing manual: chapter 12, section 30.6.12I. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.

Code 99291 is used for critical care, evaluation, and management of the critically ill or critically injured patient, first 30–74 minutes.1 It is to be reported only once per day per physician or group member of the same specialty.

Code 99292 is for critical care, evaluation, and management of the critically ill or critically injured patient, each additional 30 minutes. It is to be listed separately in addition to the code for primary service.1 Code 99292 is categorized as an add-on code. It must be reported on the same invoice as its primary code, 99291. Multiple units of code 99292 can be reported per day per physician/group.

Despite the increased resources and references for critical care billing, critical care reporting issues persist. Medicare data analysis continues to identify 99291 as high risk for claim payment errors, perpetuating prepayment claim edits for outlier utilization and location discrepancies (i.e., settings other than inpatient hospital, outpatient hospital, or the emergency department). 2,3,4

Bolster your documentation with these three key elements.

Critical Illness, Injury Management

Current Procedural Terminology (CPT) and the Centers for Medicare & Medicaid Services (CMS) define “critical illness or injury” as a condition that acutely impairs one or more vital organ systems such that there is a high probability of imminent or life-threatening deterioration in the patient’s condition (e.g., central nervous system failure; circulatory failure; shock; renal, hepatic, metabolic, and/or respiratory failure).5

Hospitalists providing care to the critically ill patient must perform highly complex decision making and interventions of high intensity that are required to prevent the patient’s inevitable decline. CMS further elaborates that “the patient shall be critically ill or injured at the time of the physician’s visit.”6 This is to ensure that hospitalists and other specialists support the medical necessity of the service and do not continue to report critical care codes on days after the patient has become stable and improved.

Consider the following scenarios:

CMS examples of patients whose medical condition may warrant critical care services (99291, 99292):6

• An 81-year-old male patient is admitted to the ICU following abdominal aortic aneurysm resection. Two days after surgery, he requires fluids and pressors to maintain adequate perfusion and arterial pressures. He remains ventilator dependent.
• A 67-year-old female patient is three days post mitral valve repair. She develops petechiae, hypotension, and hypoxia requiring respiratory and circulatory support.
• A 70-year-old admitted for right lower lobe pneumococcal pneumonia with a history of COPD becomes hypoxic and hypotensive two days after admission.
• A 68-year-old admitted for an acute anterior wall myocardial infarction continues to have symptomatic ventricular tachycardia that is marginally responsive to antiarrhythmic therapy.

CMS examples of patients who may not satisfy Medicare medical necessity criteria, or do not meet critical care criteria, or who do not have a critical care illness or injury and, therefore, are not eligible for critical care payment but may be reported using another appropriate hospital care code, such as subsequent hospital care codes (99231–99233), initial hospital care codes (99221–99223), or hospital consultation codes (99251–99255) when applicable:1,6

• Patients admitted to a critical care unit because no other hospital beds were available;
• Patients admitted to a critical care unit for close nursing observation and/or frequent monitoring of vital signs (e.g., drug toxicity or overdose);
• Patients admitted to a critical care unit because hospital rules require certain treatments (e.g., insulin infusions) to be administered in the critical care unit; and
• Patients receiving only care of a chronic illness in absence of care for a critical illness (e.g., daily management of a chronic ventilator patient, management of or care related to dialysis for end-stage renal disease). Services considered palliative in nature as this type of care do not meet the definition of critical care services.7

Concurrent Care

Critically ill patients often require the care of hospitalists and other specialists throughout the course of treatment. Payors are sensitive to the multiple hours billed by multiple providers for a single patient on a given day. Claim logic provides an automated response to only allow reimbursement for 99291 once per day when reported by physicians of the same group and specialty.8 Physicians of different specialties can separately report critical care hours as long as they are caring for a condition that meets the definition of critical care.

The CMS example of this: A dermatologist evaluates and treats a rash on an ICU patient who is maintained on a ventilator and nitroglycerine infusion that are being managed by an intensivist. The dermatologist should not report a service for critical care.6

Similarly for hospitalists, if an intensivist is taking care of the critical condition and there is nothing more for the hospitalist to add to the plan of care for the critical condition, critical care services may not be justified.

When different specialists are reporting critical care on the same day, it is imperative for the documentation to demonstrate that care is not duplicative of any other provider’s care (i.e., identify management of different conditions or revising elements of the plan). The care cannot overlap the same time period of any other physician reporting critical care services.

Calculating Time

Critical care time constitutes bedside time and time spent on the patient’s unit/floor where the physician is immediately available to the patient (see Table 1). Certain labs, diagnostic studies, and procedures are considered inherent to critical care services and are not reported separately on the claim form: cardiac output measurements (93561, 93562); chest X-rays (71010, 71015, 71020); pulse oximetry (94760, 94761, 94762); blood gases and interpretation of data stored in computers, such as ECGs, blood pressures, and hematologic data (99090); gastric intubation (43752, 43753); temporary transcutaneous pacing (92953); ventilation management (94002–94004, 94660, 94662); and vascular access procedures (36000, 36410, 36415, 36591, 36600).1

Instead, physician time associated with the performance and/or interpretation of these services is toward the cumulative critical care time of the day. Services or procedures that are considered separately billable (e.g., central line placement, intubation, CPR) cannot contribute to critical care time.

When separately billable procedures are performed by the same provider/specialty group on the same day as critical care, physicians should make a notation in the medical record indicating the non-overlapping service times (e.g., “central line insertion is not included as critical care time”). This may assist with securing reimbursement when the payor requests the documentation for each reported claim item.

Activities on the floor/unit that do not directly contribute to patient care or management (e.g., review of literature, teaching rounds) cannot be counted toward critical care time. Do not count time associated with indirect care provided outside of the patient’s unit/floor (e.g., reviewing data or calling the family from the office) toward critical care time.

Family discussions can be counted toward critical care time but must take place at bedside or on the patient’s unit/floor. The patient must participate in the discussion unless medically unable or clinically incompetent to participate. If unable to participate, a notation in the chart must delineate the patient’s inability to participate and the reason.

Credited time can only involve obtaining a medical history and/or discussing treatment options or limitation(s) of treatment. The conversation must bear directly on patient management.1,7 Do not count time associated with providing periodic condition updates to the family, answering questions about the patient’s condition that are unrelated to decision making, or counseling the family during their grief process. If the conversation must take place via phone, it may be counted toward critical care time if the physician is calling from the patient’s unit/floor and the conversation involves the same criterion identified for face-to-face family meetings.10

Physicians should keep track of their critical care time throughout the day. Since critical care time is a cumulative service, each entry should include the total time that critical care services were provided (e.g., 45 minutes).10 Some payors may still impose the notation of “start-and-stop time” per encounter (e.g., 2–2:50 a.m.).

Same-specialty physicians (i.e., two hospitalists from the same group practice) may require separate claims. The initial critical care hour (99291) must be met by a single physician. Medically necessary critical care time beyond the first hour (99292) may be met individually by the same physician or collectively with another physician from the same group. The physician performing the additional time, beyond the first hour, reports the appropriate units of 99292 (see Table 1) under the corresponding NPI.11

CMS has issued instructions for contractors to recognize this atypical reporting method. However, non-Medicare payors may not recognize this newer reporting method and maintain that the cumulative service (by the same-specialty physician in the same provider group) should be reported under one physician name. Be sure to query the payors for appropriate reporting methods. TH

References

1. Abraham M, Ahlman J, Boudreau A, Connelly J, Crosslin, R. Current Procedural Terminology 2015 Professional Edition. Chicago: American Medical Association Press; 2014. 23-25.
2. Widespread prepayment targeted review notification—CPT 99291. Cahaba website. Available at: www.cahabagba.com/news/widespread-prepayment-targeted-review-notification-part-b/. Accessed December 17, 2015.
3. Critical care CPT 99291 widespread prepayment targeted review results. Cahaba website. Available at: https://www.cahabagba.com/news/critical-care-cpt-99291-widespread-prepayment-targeted-review-results-2/. Accessed December 17, 2015.
4. Prepayment edit of evaluation and management (E/M) code 99291. First Coast Service Options, Inc. website. Available at: medicare.fcso.com/Publications_B/2013/251608.pdf. Accessed December 17, 2015.
5. Medicare claims processing manual: chapter 12, section 30.6.12A. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.
6. Medicare claims processing manual: chapter 12, section 30.6.12B. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.
7. Critical care fact sheet. CGS Administrators, LLC website. Available at: www.cgsmedicare.com/partb/mr/pdf/critical_care_fact_sheet.pdf. Accessed December 17, 2015.
8. Same day same service policy. United Healthcare website. Available at: www.unitedhealthcareonline.com/ccmcontent/ProviderII/UHC/en-US/Main%20Menu/Tools%20&%20Resources/Policies%20and%20Protocols/Medicare%20Advantage%20Reimbursement%20Policies/S/SameDaySameService.pdf. Accessed December 17, 2015.
9. Medicare claims processing manual: chapter 12, section 30.6.12G. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.
10. Medicare claims processing manual: chapter 12, section 30.6.12E. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.
11. Medicare claims processing manual: chapter 12, section 30.6.12I. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.

Code 99291 is used for critical care, evaluation, and management of the critically ill or critically injured patient, first 30–74 minutes.1 It is to be reported only once per day per physician or group member of the same specialty.

Code 99292 is for critical care, evaluation, and management of the critically ill or critically injured patient, each additional 30 minutes. It is to be listed separately in addition to the code for primary service.1 Code 99292 is categorized as an add-on code. It must be reported on the same invoice as its primary code, 99291. Multiple units of code 99292 can be reported per day per physician/group.

Despite the increased resources and references for critical care billing, critical care reporting issues persist. Medicare data analysis continues to identify 99291 as high risk for claim payment errors, perpetuating prepayment claim edits for outlier utilization and location discrepancies (i.e., settings other than inpatient hospital, outpatient hospital, or the emergency department). 2,3,4

Bolster your documentation with these three key elements.

Critical Illness, Injury Management

Current Procedural Terminology (CPT) and the Centers for Medicare & Medicaid Services (CMS) define “critical illness or injury” as a condition that acutely impairs one or more vital organ systems such that there is a high probability of imminent or life-threatening deterioration in the patient’s condition (e.g., central nervous system failure; circulatory failure; shock; renal, hepatic, metabolic, and/or respiratory failure).5

Hospitalists providing care to the critically ill patient must perform highly complex decision making and interventions of high intensity that are required to prevent the patient’s inevitable decline. CMS further elaborates that “the patient shall be critically ill or injured at the time of the physician’s visit.”6 This is to ensure that hospitalists and other specialists support the medical necessity of the service and do not continue to report critical care codes on days after the patient has become stable and improved.

Consider the following scenarios:

CMS examples of patients whose medical condition may warrant critical care services (99291, 99292):6

• An 81-year-old male patient is admitted to the ICU following abdominal aortic aneurysm resection. Two days after surgery, he requires fluids and pressors to maintain adequate perfusion and arterial pressures. He remains ventilator dependent.
• A 67-year-old female patient is three days post mitral valve repair. She develops petechiae, hypotension, and hypoxia requiring respiratory and circulatory support.
• A 70-year-old admitted for right lower lobe pneumococcal pneumonia with a history of COPD becomes hypoxic and hypotensive two days after admission.
• A 68-year-old admitted for an acute anterior wall myocardial infarction continues to have symptomatic ventricular tachycardia that is marginally responsive to antiarrhythmic therapy.

CMS examples of patients who may not satisfy Medicare medical necessity criteria, or do not meet critical care criteria, or who do not have a critical care illness or injury and, therefore, are not eligible for critical care payment but may be reported using another appropriate hospital care code, such as subsequent hospital care codes (99231–99233), initial hospital care codes (99221–99223), or hospital consultation codes (99251–99255) when applicable:1,6

• Patients admitted to a critical care unit because no other hospital beds were available;
• Patients admitted to a critical care unit for close nursing observation and/or frequent monitoring of vital signs (e.g., drug toxicity or overdose);
• Patients admitted to a critical care unit because hospital rules require certain treatments (e.g., insulin infusions) to be administered in the critical care unit; and
• Patients receiving only care of a chronic illness in absence of care for a critical illness (e.g., daily management of a chronic ventilator patient, management of or care related to dialysis for end-stage renal disease). Services considered palliative in nature as this type of care do not meet the definition of critical care services.7

Concurrent Care

Critically ill patients often require the care of hospitalists and other specialists throughout the course of treatment. Payors are sensitive to the multiple hours billed by multiple providers for a single patient on a given day. Claim logic provides an automated response to only allow reimbursement for 99291 once per day when reported by physicians of the same group and specialty.8 Physicians of different specialties can separately report critical care hours as long as they are caring for a condition that meets the definition of critical care.

The CMS example of this: A dermatologist evaluates and treats a rash on an ICU patient who is maintained on a ventilator and nitroglycerine infusion that are being managed by an intensivist. The dermatologist should not report a service for critical care.6

Similarly for hospitalists, if an intensivist is taking care of the critical condition and there is nothing more for the hospitalist to add to the plan of care for the critical condition, critical care services may not be justified.

When different specialists are reporting critical care on the same day, it is imperative for the documentation to demonstrate that care is not duplicative of any other provider’s care (i.e., identify management of different conditions or revising elements of the plan). The care cannot overlap the same time period of any other physician reporting critical care services.

Calculating Time

Critical care time constitutes bedside time and time spent on the patient’s unit/floor where the physician is immediately available to the patient (see Table 1). Certain labs, diagnostic studies, and procedures are considered inherent to critical care services and are not reported separately on the claim form: cardiac output measurements (93561, 93562); chest X-rays (71010, 71015, 71020); pulse oximetry (94760, 94761, 94762); blood gases and interpretation of data stored in computers, such as ECGs, blood pressures, and hematologic data (99090); gastric intubation (43752, 43753); temporary transcutaneous pacing (92953); ventilation management (94002–94004, 94660, 94662); and vascular access procedures (36000, 36410, 36415, 36591, 36600).1

Instead, physician time associated with the performance and/or interpretation of these services is toward the cumulative critical care time of the day. Services or procedures that are considered separately billable (e.g., central line placement, intubation, CPR) cannot contribute to critical care time.

When separately billable procedures are performed by the same provider/specialty group on the same day as critical care, physicians should make a notation in the medical record indicating the non-overlapping service times (e.g., “central line insertion is not included as critical care time”). This may assist with securing reimbursement when the payor requests the documentation for each reported claim item.

Activities on the floor/unit that do not directly contribute to patient care or management (e.g., review of literature, teaching rounds) cannot be counted toward critical care time. Do not count time associated with indirect care provided outside of the patient’s unit/floor (e.g., reviewing data or calling the family from the office) toward critical care time.

Family discussions can be counted toward critical care time but must take place at bedside or on the patient’s unit/floor. The patient must participate in the discussion unless medically unable or clinically incompetent to participate. If unable to participate, a notation in the chart must delineate the patient’s inability to participate and the reason.

Credited time can only involve obtaining a medical history and/or discussing treatment options or limitation(s) of treatment. The conversation must bear directly on patient management.1,7 Do not count time associated with providing periodic condition updates to the family, answering questions about the patient’s condition that are unrelated to decision making, or counseling the family during their grief process. If the conversation must take place via phone, it may be counted toward critical care time if the physician is calling from the patient’s unit/floor and the conversation involves the same criterion identified for face-to-face family meetings.10

Physicians should keep track of their critical care time throughout the day. Since critical care time is a cumulative service, each entry should include the total time that critical care services were provided (e.g., 45 minutes).10 Some payors may still impose the notation of “start-and-stop time” per encounter (e.g., 2–2:50 a.m.).

Same-specialty physicians (i.e., two hospitalists from the same group practice) may require separate claims. The initial critical care hour (99291) must be met by a single physician. Medically necessary critical care time beyond the first hour (99292) may be met individually by the same physician or collectively with another physician from the same group. The physician performing the additional time, beyond the first hour, reports the appropriate units of 99292 (see Table 1) under the corresponding NPI.11

CMS has issued instructions for contractors to recognize this atypical reporting method. However, non-Medicare payors may not recognize this newer reporting method and maintain that the cumulative service (by the same-specialty physician in the same provider group) should be reported under one physician name. Be sure to query the payors for appropriate reporting methods. TH

References

1. Abraham M, Ahlman J, Boudreau A, Connelly J, Crosslin, R. Current Procedural Terminology 2015 Professional Edition. Chicago: American Medical Association Press; 2014. 23-25.
2. Widespread prepayment targeted review notification—CPT 99291. Cahaba website. Available at: www.cahabagba.com/news/widespread-prepayment-targeted-review-notification-part-b/. Accessed December 17, 2015.
3. Critical care CPT 99291 widespread prepayment targeted review results. Cahaba website. Available at: https://www.cahabagba.com/news/critical-care-cpt-99291-widespread-prepayment-targeted-review-results-2/. Accessed December 17, 2015.
4. Prepayment edit of evaluation and management (E/M) code 99291. First Coast Service Options, Inc. website. Available at: medicare.fcso.com/Publications_B/2013/251608.pdf. Accessed December 17, 2015.
5. Medicare claims processing manual: chapter 12, section 30.6.12A. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.
6. Medicare claims processing manual: chapter 12, section 30.6.12B. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.
7. Critical care fact sheet. CGS Administrators, LLC website. Available at: www.cgsmedicare.com/partb/mr/pdf/critical_care_fact_sheet.pdf. Accessed December 17, 2015.
8. Same day same service policy. United Healthcare website. Available at: www.unitedhealthcareonline.com/ccmcontent/ProviderII/UHC/en-US/Main%20Menu/Tools%20&%20Resources/Policies%20and%20Protocols/Medicare%20Advantage%20Reimbursement%20Policies/S/SameDaySameService.pdf. Accessed December 17, 2015.
9. Medicare claims processing manual: chapter 12, section 30.6.12G. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.
10. Medicare claims processing manual: chapter 12, section 30.6.12E. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.
11. Medicare claims processing manual: chapter 12, section 30.6.12I. Centers for Medicare & Medicaid Services website. Available at: www.cms.gov/Regulations-and-Guidance/Guidance/Manuals/downloads/clm104c12.pdf. Accessed December 17, 2015.

Pregnant woman

Photo by Nina Matthews

Researchers have found a potential correlation between pre-labor cesarean delivery (PLCD) and acute lymphoblastic leukemia (ALL).

The team analyzed data from 13 studies and found a 23% increase in the risk of ALL in children born by PLCD.

However, there was no link between PLCD and acute myeloid leukemia (AML), and there was no correlation between emergency cesareans and ALL or AML.

Erin Marcotte, PhD, of the University of Minnesota, and her colleagues reported these results in The Lancet Haematology.

The researchers analyzed data from the Childhood Leukemia International Consortium. They looked at 33,571 subjects overall, including 23,351 control subjects, 8780 cases of ALL, and 1332 cases of AML.

The analyses were controlled for a number of outside factors, including breastfeeding, parental education levels, and ethnicity.

“Our goal was to determine if there was an association between cesarean deliveries and ALL [and] to identify potential new targets for research into cancer prevention if there is a correlation,” Dr Marcotte said.

“While the link between overall cesarean delivery and childhood leukemia was not statistically significant, it was notable to find an association between pre-labor cesarean delivery and ALL.”

The data suggested AML was not associated with cesarean delivery. The odds ratios (ORs) were 0.99 for all cesarean deliveries, 0.83 for PLCD, and 1.05 for emergency cesarean delivery.

The ORs for ALL were 1.06 overall, 1.02 for emergency cesarean delivery, and 1.23 (P=0.018) for PLCD.

The reason for the increased risk of ALL with PLCD is not known. The researchers said several mechanisms may be at play, including the stress response in the fetus caused by labor and the colonization of microbiota a newborn experiences during a vaginal delivery that is missed during a cesarean birth.

“The most plausible explanation for the association between ALL and pre-labor cesarean delivery is in the cortisol, or stress-related, mechanism,” Dr Marcotte said. “Because ALL is not associated with all cesarean deliveries, it seems less likely the microbiota colonization is a significant factor in this phenomenon. We believe further investigation into this cortisol-mechanism link is warranted due to these findings.”

The researchers said the strength of association in these findings is comparable to other studies looking at cesarean delivery rates and other childhood outcomes, including Type I diabetes and asthma. They believe further investigation into this study’s findings is needed, utilizing more detailed and reliable delivery information.

“This association deserves a closer look to better determine what’s behind the link,” said Logan Spector, PhD, of the University of Minnesota.

“Cortisol exposure is plausible since similar compounds are used to treat ALL. We also know that some are born with cells that are on the path to becoming leukemia. Thus, our working hypothesis is that cortisol exposure at birth may eliminate these pre-leukemic cells.”

Pregnant woman

Photo by Nina Matthews

Researchers have found a potential correlation between pre-labor cesarean delivery (PLCD) and acute lymphoblastic leukemia (ALL).

The team analyzed data from 13 studies and found a 23% increase in the risk of ALL in children born by PLCD.

However, there was no link between PLCD and acute myeloid leukemia (AML), and there was no correlation between emergency cesareans and ALL or AML.

Erin Marcotte, PhD, of the University of Minnesota, and her colleagues reported these results in The Lancet Haematology.

The researchers analyzed data from the Childhood Leukemia International Consortium. They looked at 33,571 subjects overall, including 23,351 control subjects, 8780 cases of ALL, and 1332 cases of AML.

The analyses were controlled for a number of outside factors, including breastfeeding, parental education levels, and ethnicity.

“Our goal was to determine if there was an association between cesarean deliveries and ALL [and] to identify potential new targets for research into cancer prevention if there is a correlation,” Dr Marcotte said.

“While the link between overall cesarean delivery and childhood leukemia was not statistically significant, it was notable to find an association between pre-labor cesarean delivery and ALL.”

The data suggested AML was not associated with cesarean delivery. The odds ratios (ORs) were 0.99 for all cesarean deliveries, 0.83 for PLCD, and 1.05 for emergency cesarean delivery.

The ORs for ALL were 1.06 overall, 1.02 for emergency cesarean delivery, and 1.23 (P=0.018) for PLCD.

The reason for the increased risk of ALL with PLCD is not known. The researchers said several mechanisms may be at play, including the stress response in the fetus caused by labor and the colonization of microbiota a newborn experiences during a vaginal delivery that is missed during a cesarean birth.

“The most plausible explanation for the association between ALL and pre-labor cesarean delivery is in the cortisol, or stress-related, mechanism,” Dr Marcotte said. “Because ALL is not associated with all cesarean deliveries, it seems less likely the microbiota colonization is a significant factor in this phenomenon. We believe further investigation into this cortisol-mechanism link is warranted due to these findings.”

The researchers said the strength of association in these findings is comparable to other studies looking at cesarean delivery rates and other childhood outcomes, including Type I diabetes and asthma. They believe further investigation into this study’s findings is needed, utilizing more detailed and reliable delivery information.

“This association deserves a closer look to better determine what’s behind the link,” said Logan Spector, PhD, of the University of Minnesota.

“Cortisol exposure is plausible since similar compounds are used to treat ALL. We also know that some are born with cells that are on the path to becoming leukemia. Thus, our working hypothesis is that cortisol exposure at birth may eliminate these pre-leukemic cells.”

Pregnant woman

Photo by Nina Matthews

Researchers have found a potential correlation between pre-labor cesarean delivery (PLCD) and acute lymphoblastic leukemia (ALL).

The team analyzed data from 13 studies and found a 23% increase in the risk of ALL in children born by PLCD.

However, there was no link between PLCD and acute myeloid leukemia (AML), and there was no correlation between emergency cesareans and ALL or AML.

Erin Marcotte, PhD, of the University of Minnesota, and her colleagues reported these results in The Lancet Haematology.

The researchers analyzed data from the Childhood Leukemia International Consortium. They looked at 33,571 subjects overall, including 23,351 control subjects, 8780 cases of ALL, and 1332 cases of AML.

The analyses were controlled for a number of outside factors, including breastfeeding, parental education levels, and ethnicity.

“Our goal was to determine if there was an association between cesarean deliveries and ALL [and] to identify potential new targets for research into cancer prevention if there is a correlation,” Dr Marcotte said.

“While the link between overall cesarean delivery and childhood leukemia was not statistically significant, it was notable to find an association between pre-labor cesarean delivery and ALL.”

The data suggested AML was not associated with cesarean delivery. The odds ratios (ORs) were 0.99 for all cesarean deliveries, 0.83 for PLCD, and 1.05 for emergency cesarean delivery.

The ORs for ALL were 1.06 overall, 1.02 for emergency cesarean delivery, and 1.23 (P=0.018) for PLCD.

The reason for the increased risk of ALL with PLCD is not known. The researchers said several mechanisms may be at play, including the stress response in the fetus caused by labor and the colonization of microbiota a newborn experiences during a vaginal delivery that is missed during a cesarean birth.

“The most plausible explanation for the association between ALL and pre-labor cesarean delivery is in the cortisol, or stress-related, mechanism,” Dr Marcotte said. “Because ALL is not associated with all cesarean deliveries, it seems less likely the microbiota colonization is a significant factor in this phenomenon. We believe further investigation into this cortisol-mechanism link is warranted due to these findings.”

The researchers said the strength of association in these findings is comparable to other studies looking at cesarean delivery rates and other childhood outcomes, including Type I diabetes and asthma. They believe further investigation into this study’s findings is needed, utilizing more detailed and reliable delivery information.

“This association deserves a closer look to better determine what’s behind the link,” said Logan Spector, PhD, of the University of Minnesota.

“Cortisol exposure is plausible since similar compounds are used to treat ALL. We also know that some are born with cells that are on the path to becoming leukemia. Thus, our working hypothesis is that cortisol exposure at birth may eliminate these pre-leukemic cells.”

Blood samples

Photo by Jeremy L. Grisham

The US Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for a laboratory test used to detect the Zika virus.

The test, which was developed by the Centers for Disease Control and Prevention (CDC), is called the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).

It will be distributed to certain laboratories in the US and abroad over the next 2 weeks.

The test will not be available in US hospitals or other primary care settings.

The Zika MAC-ELISA test can detect human immunoglobulin M (IgM) antibodies to the Zika virus. These antibodies appear in the blood of an infected person 4 to 5 days after the start of the illness, and they remain in the blood for about 12 weeks.

The Zika MAC-ELISA test is intended for use in sera or cerebrospinal fluid when submitted with a patient-matched serum sample from individuals meeting CDC Zika clinical and epidemiological criteria for testing. This includes people with a history of symptoms associated with Zika and/or people who have recently traveled to an area that has active Zika transmission.

Results of Zika MAC-ELISA tests require careful interpretation. The test can give false-positive results when someone has been infected with a virus closely related to Zika (such as dengue virus).

When positive or inconclusive results occur, additional testing (plaque reduction neutralization test) to confirm the presence of antibodies to Zika virus will be performed by the CDC or a CDC-authorized laboratory.

Moreover, a negative test result does not necessarily mean a person has not been infected with Zika virus. If a sample is collected just after a person becomes ill, there may not be enough IgM antibodies for the test to measure, resulting in a false-negative.

Similarly, if the sample was collected more than 12 weeks after illness, it is possible that the body has successfully fought the virus and IgM antibody levels have dropped below the detectable limit.

The CDC will begin distributing the Zika MAC-ELISA test over the next 2 weeks to qualified laboratories in the Laboratory Response Network, an integrated network of domestic and international laboratories that can respond to public health emergencies.

About the EUA

An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency. The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

As there are no commercially available diagnostic tests approved by the FDA for the detection of Zika virus infection, the agency decided an EUA was crucial to ensure timely access to a diagnostic tool.

The FDA issued the EUA for the Zika MAC-ELISA test based on data submitted by the CDC and on the US Secretary of Health and Human Services’ declaration that circumstances exist to justify the emergency use of in vitro diagnostic tests for the detection of Zika virus and Zika virus infection. This EUA will end when the Secretary’s declaration ends, unless the FDA revokes it sooner.

Blood samples

Photo by Jeremy L. Grisham

The US Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for a laboratory test used to detect the Zika virus.

The test, which was developed by the Centers for Disease Control and Prevention (CDC), is called the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).

It will be distributed to certain laboratories in the US and abroad over the next 2 weeks.

The test will not be available in US hospitals or other primary care settings.

The Zika MAC-ELISA test can detect human immunoglobulin M (IgM) antibodies to the Zika virus. These antibodies appear in the blood of an infected person 4 to 5 days after the start of the illness, and they remain in the blood for about 12 weeks.

The Zika MAC-ELISA test is intended for use in sera or cerebrospinal fluid when submitted with a patient-matched serum sample from individuals meeting CDC Zika clinical and epidemiological criteria for testing. This includes people with a history of symptoms associated with Zika and/or people who have recently traveled to an area that has active Zika transmission.

Results of Zika MAC-ELISA tests require careful interpretation. The test can give false-positive results when someone has been infected with a virus closely related to Zika (such as dengue virus).

When positive or inconclusive results occur, additional testing (plaque reduction neutralization test) to confirm the presence of antibodies to Zika virus will be performed by the CDC or a CDC-authorized laboratory.

Moreover, a negative test result does not necessarily mean a person has not been infected with Zika virus. If a sample is collected just after a person becomes ill, there may not be enough IgM antibodies for the test to measure, resulting in a false-negative.

Similarly, if the sample was collected more than 12 weeks after illness, it is possible that the body has successfully fought the virus and IgM antibody levels have dropped below the detectable limit.

The CDC will begin distributing the Zika MAC-ELISA test over the next 2 weeks to qualified laboratories in the Laboratory Response Network, an integrated network of domestic and international laboratories that can respond to public health emergencies.

About the EUA

An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency. The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

As there are no commercially available diagnostic tests approved by the FDA for the detection of Zika virus infection, the agency decided an EUA was crucial to ensure timely access to a diagnostic tool.

The FDA issued the EUA for the Zika MAC-ELISA test based on data submitted by the CDC and on the US Secretary of Health and Human Services’ declaration that circumstances exist to justify the emergency use of in vitro diagnostic tests for the detection of Zika virus and Zika virus infection. This EUA will end when the Secretary’s declaration ends, unless the FDA revokes it sooner.

Blood samples

Photo by Jeremy L. Grisham

The US Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for a laboratory test used to detect the Zika virus.

The test, which was developed by the Centers for Disease Control and Prevention (CDC), is called the Zika IgM Antibody Capture Enzyme-Linked Immunosorbent Assay (Zika MAC-ELISA).

It will be distributed to certain laboratories in the US and abroad over the next 2 weeks.

The test will not be available in US hospitals or other primary care settings.

The Zika MAC-ELISA test can detect human immunoglobulin M (IgM) antibodies to the Zika virus. These antibodies appear in the blood of an infected person 4 to 5 days after the start of the illness, and they remain in the blood for about 12 weeks.

The Zika MAC-ELISA test is intended for use in sera or cerebrospinal fluid when submitted with a patient-matched serum sample from individuals meeting CDC Zika clinical and epidemiological criteria for testing. This includes people with a history of symptoms associated with Zika and/or people who have recently traveled to an area that has active Zika transmission.

Results of Zika MAC-ELISA tests require careful interpretation. The test can give false-positive results when someone has been infected with a virus closely related to Zika (such as dengue virus).

When positive or inconclusive results occur, additional testing (plaque reduction neutralization test) to confirm the presence of antibodies to Zika virus will be performed by the CDC or a CDC-authorized laboratory.

Moreover, a negative test result does not necessarily mean a person has not been infected with Zika virus. If a sample is collected just after a person becomes ill, there may not be enough IgM antibodies for the test to measure, resulting in a false-negative.

Similarly, if the sample was collected more than 12 weeks after illness, it is possible that the body has successfully fought the virus and IgM antibody levels have dropped below the detectable limit.

The CDC will begin distributing the Zika MAC-ELISA test over the next 2 weeks to qualified laboratories in the Laboratory Response Network, an integrated network of domestic and international laboratories that can respond to public health emergencies.

About the EUA

An EUA allows the use of unapproved medical products or unapproved uses of approved medical products in an emergency. The products must be used to diagnose, treat, or prevent serious or life-threatening conditions caused by chemical, biological, radiological, or nuclear threat agents, when there are no adequate alternatives.

As there are no commercially available diagnostic tests approved by the FDA for the detection of Zika virus infection, the agency decided an EUA was crucial to ensure timely access to a diagnostic tool.

The FDA issued the EUA for the Zika MAC-ELISA test based on data submitted by the CDC and on the US Secretary of Health and Human Services’ declaration that circumstances exist to justify the emergency use of in vitro diagnostic tests for the detection of Zika virus and Zika virus infection. This EUA will end when the Secretary’s declaration ends, unless the FDA revokes it sooner.