Federal Practitioner

Some veterans who present to smaller facilities, such as rural hospitals, are transferred to larger facilities for diagnostic or therapeutic procedures. But that access also can mean hardship for rural veterans by taking them far from family and adding costs. Moreover, complex care coordination can cause “triage mismatch” when the patients are at their most vulnerable: “over-triage”—transferring patients unlikely to benefit and “under-triage”—failing to transfer those likely to benefit.  

Researchers from VA Iowa City Healthcare System and University of Iowa conducted a study to find out what proportion of VHA transfers were potentially avoidable. Their study included all veterans treated in any of 120 VHA emergency departments (EDs) and transferred to a VHA acute care hospital between January 2012 and December 2014.

Potentially avoidable transfers (PATs) were defined as transfers in which the patient was either discharged from the referral ED or admitted to the referral hospital for < 24 hours, without having an invasive procedure. The researchers chose that definition to identify patients whose transfer might have been avoided if real-time specialty telemedicine were available at the index hospital. (They caution that the definition was not intended to suggest that all PATs were inappropriate.)

Over 3 years, 18,852 patients were transferred. Of the total patients transferred, 36% were transferred from 1 VHA ED to another VHA facility. Of the VHA transfers, 8,639 (46%) were transferred to another VHA ED; the rest were transferred to another VHA facility inpatient unit. The median transfer distance was 81.5 miles. Rural residents were transferred 3 times as often as urban residents.

The good news is that PATs are rare. Only 0.8% of VHA ED visits resulted in transfer, and of those, only one-fourth were deemed potentially avoidable. And while rural veterans were more likely to be transferred, PATs were less prevalent among those transfers (20.8% vs 23.9% for urban veterans).

More than half of VHA transfers were for patients diagnosed with mental health, cardiac, and digestive conditions. The top ICD-9 diagnosis related to VHA ED transfer was suicidal ideation. The diagnostic procedures associated with most PATs were mental health (11% potentially avoidable) and cardiac (21% potentially avoidable).

Their research turned up some unexpected data: For example, smaller EDs did not have a higher prevalence of PATs, suggesting that ED size was not associated with transfer appropriateness. And the proportion of PATs was higher in hospitals with > 50% board-certified emergency physicians.

The researchers say their findings highlight important differences between the VHA health care and civilian health care systems, emphasizing that the resources available within the VHA health system “might be unique” and underlining the need for VHA-specific solutions to health care delivery challenges.

 The overall purpose of this study, the researchers say, was to identify areas where novel delivery of specialty care might reduce the need for some VHA transfers. Their analysis provides data for developing targeted intervention, such as ED-based telemedicine or “targeted remote care.”

Patients with mental health conditions—who made up more than one-third of all VHA-to-VHA interfacility transfers, higher than that reported in civilian hospitals—represent a “rich target population” for telehealth, the researchers suggest. They also note that because mental health providers are in critical shortage in most of the US, real-time telemedicine providing psychiatric resources could be an important and timely service.

Nearly half of medical directors of VHA EDs who responded to the VHA Healthcare Analysis and Information Group survey cited the transfer process as “overly burdensome,” and > 65% said administrative processes contribute to delay in transfer. Finding new ways to keep patients local could benefit providers as well.

Some veterans who present to smaller facilities, such as rural hospitals, are transferred to larger facilities for diagnostic or therapeutic procedures. But that access also can mean hardship for rural veterans by taking them far from family and adding costs. Moreover, complex care coordination can cause “triage mismatch” when the patients are at their most vulnerable: “over-triage”—transferring patients unlikely to benefit and “under-triage”—failing to transfer those likely to benefit.  

Researchers from VA Iowa City Healthcare System and University of Iowa conducted a study to find out what proportion of VHA transfers were potentially avoidable. Their study included all veterans treated in any of 120 VHA emergency departments (EDs) and transferred to a VHA acute care hospital between January 2012 and December 2014.

Potentially avoidable transfers (PATs) were defined as transfers in which the patient was either discharged from the referral ED or admitted to the referral hospital for < 24 hours, without having an invasive procedure. The researchers chose that definition to identify patients whose transfer might have been avoided if real-time specialty telemedicine were available at the index hospital. (They caution that the definition was not intended to suggest that all PATs were inappropriate.)

Over 3 years, 18,852 patients were transferred. Of the total patients transferred, 36% were transferred from 1 VHA ED to another VHA facility. Of the VHA transfers, 8,639 (46%) were transferred to another VHA ED; the rest were transferred to another VHA facility inpatient unit. The median transfer distance was 81.5 miles. Rural residents were transferred 3 times as often as urban residents.

The good news is that PATs are rare. Only 0.8% of VHA ED visits resulted in transfer, and of those, only one-fourth were deemed potentially avoidable. And while rural veterans were more likely to be transferred, PATs were less prevalent among those transfers (20.8% vs 23.9% for urban veterans).

More than half of VHA transfers were for patients diagnosed with mental health, cardiac, and digestive conditions. The top ICD-9 diagnosis related to VHA ED transfer was suicidal ideation. The diagnostic procedures associated with most PATs were mental health (11% potentially avoidable) and cardiac (21% potentially avoidable).

Their research turned up some unexpected data: For example, smaller EDs did not have a higher prevalence of PATs, suggesting that ED size was not associated with transfer appropriateness. And the proportion of PATs was higher in hospitals with > 50% board-certified emergency physicians.

The researchers say their findings highlight important differences between the VHA health care and civilian health care systems, emphasizing that the resources available within the VHA health system “might be unique” and underlining the need for VHA-specific solutions to health care delivery challenges.

 The overall purpose of this study, the researchers say, was to identify areas where novel delivery of specialty care might reduce the need for some VHA transfers. Their analysis provides data for developing targeted intervention, such as ED-based telemedicine or “targeted remote care.”

Patients with mental health conditions—who made up more than one-third of all VHA-to-VHA interfacility transfers, higher than that reported in civilian hospitals—represent a “rich target population” for telehealth, the researchers suggest. They also note that because mental health providers are in critical shortage in most of the US, real-time telemedicine providing psychiatric resources could be an important and timely service.

Nearly half of medical directors of VHA EDs who responded to the VHA Healthcare Analysis and Information Group survey cited the transfer process as “overly burdensome,” and > 65% said administrative processes contribute to delay in transfer. Finding new ways to keep patients local could benefit providers as well.

Some veterans who present to smaller facilities, such as rural hospitals, are transferred to larger facilities for diagnostic or therapeutic procedures. But that access also can mean hardship for rural veterans by taking them far from family and adding costs. Moreover, complex care coordination can cause “triage mismatch” when the patients are at their most vulnerable: “over-triage”—transferring patients unlikely to benefit and “under-triage”—failing to transfer those likely to benefit.  

Researchers from VA Iowa City Healthcare System and University of Iowa conducted a study to find out what proportion of VHA transfers were potentially avoidable. Their study included all veterans treated in any of 120 VHA emergency departments (EDs) and transferred to a VHA acute care hospital between January 2012 and December 2014.

Potentially avoidable transfers (PATs) were defined as transfers in which the patient was either discharged from the referral ED or admitted to the referral hospital for < 24 hours, without having an invasive procedure. The researchers chose that definition to identify patients whose transfer might have been avoided if real-time specialty telemedicine were available at the index hospital. (They caution that the definition was not intended to suggest that all PATs were inappropriate.)

Over 3 years, 18,852 patients were transferred. Of the total patients transferred, 36% were transferred from 1 VHA ED to another VHA facility. Of the VHA transfers, 8,639 (46%) were transferred to another VHA ED; the rest were transferred to another VHA facility inpatient unit. The median transfer distance was 81.5 miles. Rural residents were transferred 3 times as often as urban residents.

The good news is that PATs are rare. Only 0.8% of VHA ED visits resulted in transfer, and of those, only one-fourth were deemed potentially avoidable. And while rural veterans were more likely to be transferred, PATs were less prevalent among those transfers (20.8% vs 23.9% for urban veterans).

More than half of VHA transfers were for patients diagnosed with mental health, cardiac, and digestive conditions. The top ICD-9 diagnosis related to VHA ED transfer was suicidal ideation. The diagnostic procedures associated with most PATs were mental health (11% potentially avoidable) and cardiac (21% potentially avoidable).

Their research turned up some unexpected data: For example, smaller EDs did not have a higher prevalence of PATs, suggesting that ED size was not associated with transfer appropriateness. And the proportion of PATs was higher in hospitals with > 50% board-certified emergency physicians.

The researchers say their findings highlight important differences between the VHA health care and civilian health care systems, emphasizing that the resources available within the VHA health system “might be unique” and underlining the need for VHA-specific solutions to health care delivery challenges.

 The overall purpose of this study, the researchers say, was to identify areas where novel delivery of specialty care might reduce the need for some VHA transfers. Their analysis provides data for developing targeted intervention, such as ED-based telemedicine or “targeted remote care.”

Patients with mental health conditions—who made up more than one-third of all VHA-to-VHA interfacility transfers, higher than that reported in civilian hospitals—represent a “rich target population” for telehealth, the researchers suggest. They also note that because mental health providers are in critical shortage in most of the US, real-time telemedicine providing psychiatric resources could be an important and timely service.

Nearly half of medical directors of VHA EDs who responded to the VHA Healthcare Analysis and Information Group survey cited the transfer process as “overly burdensome,” and > 65% said administrative processes contribute to delay in transfer. Finding new ways to keep patients local could benefit providers as well.

MAUI, HAWAII – The use of interleukin inhibitors for treatment of rheumatologic diseases doubles a patient’s risk of serious infections, according to a comprehensive systematic review and meta-analysis of 74 randomized, placebo-controlled trials presented by Jawad Bilal, MBBS, at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

The meta-analysis, which incorporated 29,214 patients with a variety of rheumatic diseases, demonstrated that patients receiving interleukin (IL) inhibitors had a 1.97-fold increased risk of serious infections, a finding accompanied by a high degree of statistical certainty. The number-needed-to-harm was 67 patients treated for a median of 24 weeks in order to generate one additional serious infection.

“That number-needed-to-harm is a significant finding because having a serious infection means by definition you’re getting admitted to the hospital and receiving IV antibiotics,” Dr. Bilal observed in an interview.

The meta-analysis also found that IL inhibition was associated with a 2.35-fold increased risk of opportunistic infections and a 1.52-fold higher risk of developing cancer, both findings with statistical significance (P =.03) but only moderate certainty because fewer of those events were captured in the trials compared to the numbers of serious infections, explained Dr. Bilal of the University of Arizona, Tucson.

For opportunistic infections, the number-needed-to-harm was 250 patients treated with an IL inhibitor for a median of 54 weeks in order to result in one additional opportunistic infection. For cancer, the number-needed-to-harm was 250 for a median of 24 weeks.

Dr. Bilal noted that while the IL inhibitors are drugs of established efficacy in rheumatologic diseases, their safety has not previously undergone anything approaching the comprehensive scrutiny carried out in this meta-analysis. The meta-analysis, which included all published placebo-controlled randomized trials and their extension studies, employed rigorous methodology in accord with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement and the GRADE approach to data analysis. Studies of IL inhibitors in patients with dermatologic and GI diseases were excluded from the meta-analysis.

He offered a caveat regarding the cancer risk findings: “Our analysis showed that the cancer risk is increased, but the results are not conclusive because we only had a few years of data. With cancer, you really need at least 8-10 years of data. So the real-world experience with the interleukin inhibitors in the large registries is what’s going to tell if the cancer risk is really increased or not. In the meantime, we all have to be cautious.”

The number of serious infections collected in the meta-analysis afforded sufficient statistical power for the investigators to break down differential risks based on individual drugs and indications. Among the drugs associated with significantly increased risk of serious infections were anakinra, with an odds ratio of 2.67, compared with placebo; secukinumab with an OR of 2.43; and tocilizumab with an OR or 1.76. Ustekinumab and ixekizumab were associated with 2.57- and 3.89-fold increased risks, respectively, but the number of rheumatology patients treated with those two biologics wasn’t large enough for those findings to achieve statistical significance.

Rheumatoid arthritis patients who received an IL inhibitor rather than placebo had a 1.98-fold increased risk of serious infection, while those with psoriatic arthritis had a 2.21-fold increased risk. Patients treated for SLE had a 6.44-fold increased risk, and those with juvenile idiopathic arthritis had a 5.37-fold higher risk, but the margins for error were such that those results weren’t statistically significant.

“I think this study is going to help clinicians and patients when they’re trying to weigh the risks and benefits of IL inhibitors, especially if they already have risk factors, like a recent history of serious infection or a history of cancer or of opportunistic infection,” Dr. Bilal commented.

A study limitation was that he and his coinvestigators had to lump together the various IL inhibitors in order to gain statistical power, even though the drugs work differently, he noted.

Dr. Bilal reported having no financial conflicts regarding his study, the full details of which have been published (JAMA Netw Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.13102).

[email protected]

MAUI, HAWAII – The use of interleukin inhibitors for treatment of rheumatologic diseases doubles a patient’s risk of serious infections, according to a comprehensive systematic review and meta-analysis of 74 randomized, placebo-controlled trials presented by Jawad Bilal, MBBS, at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

The meta-analysis, which incorporated 29,214 patients with a variety of rheumatic diseases, demonstrated that patients receiving interleukin (IL) inhibitors had a 1.97-fold increased risk of serious infections, a finding accompanied by a high degree of statistical certainty. The number-needed-to-harm was 67 patients treated for a median of 24 weeks in order to generate one additional serious infection.

“That number-needed-to-harm is a significant finding because having a serious infection means by definition you’re getting admitted to the hospital and receiving IV antibiotics,” Dr. Bilal observed in an interview.

The meta-analysis also found that IL inhibition was associated with a 2.35-fold increased risk of opportunistic infections and a 1.52-fold higher risk of developing cancer, both findings with statistical significance (P =.03) but only moderate certainty because fewer of those events were captured in the trials compared to the numbers of serious infections, explained Dr. Bilal of the University of Arizona, Tucson.

For opportunistic infections, the number-needed-to-harm was 250 patients treated with an IL inhibitor for a median of 54 weeks in order to result in one additional opportunistic infection. For cancer, the number-needed-to-harm was 250 for a median of 24 weeks.

Dr. Bilal noted that while the IL inhibitors are drugs of established efficacy in rheumatologic diseases, their safety has not previously undergone anything approaching the comprehensive scrutiny carried out in this meta-analysis. The meta-analysis, which included all published placebo-controlled randomized trials and their extension studies, employed rigorous methodology in accord with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement and the GRADE approach to data analysis. Studies of IL inhibitors in patients with dermatologic and GI diseases were excluded from the meta-analysis.

He offered a caveat regarding the cancer risk findings: “Our analysis showed that the cancer risk is increased, but the results are not conclusive because we only had a few years of data. With cancer, you really need at least 8-10 years of data. So the real-world experience with the interleukin inhibitors in the large registries is what’s going to tell if the cancer risk is really increased or not. In the meantime, we all have to be cautious.”

The number of serious infections collected in the meta-analysis afforded sufficient statistical power for the investigators to break down differential risks based on individual drugs and indications. Among the drugs associated with significantly increased risk of serious infections were anakinra, with an odds ratio of 2.67, compared with placebo; secukinumab with an OR of 2.43; and tocilizumab with an OR or 1.76. Ustekinumab and ixekizumab were associated with 2.57- and 3.89-fold increased risks, respectively, but the number of rheumatology patients treated with those two biologics wasn’t large enough for those findings to achieve statistical significance.

Rheumatoid arthritis patients who received an IL inhibitor rather than placebo had a 1.98-fold increased risk of serious infection, while those with psoriatic arthritis had a 2.21-fold increased risk. Patients treated for SLE had a 6.44-fold increased risk, and those with juvenile idiopathic arthritis had a 5.37-fold higher risk, but the margins for error were such that those results weren’t statistically significant.

“I think this study is going to help clinicians and patients when they’re trying to weigh the risks and benefits of IL inhibitors, especially if they already have risk factors, like a recent history of serious infection or a history of cancer or of opportunistic infection,” Dr. Bilal commented.

A study limitation was that he and his coinvestigators had to lump together the various IL inhibitors in order to gain statistical power, even though the drugs work differently, he noted.

Dr. Bilal reported having no financial conflicts regarding his study, the full details of which have been published (JAMA Netw Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.13102).

[email protected]

MAUI, HAWAII – The use of interleukin inhibitors for treatment of rheumatologic diseases doubles a patient’s risk of serious infections, according to a comprehensive systematic review and meta-analysis of 74 randomized, placebo-controlled trials presented by Jawad Bilal, MBBS, at the 2020 Rheumatology Winter Clinical Symposium.

Bruce Jancin/MDedge News

The meta-analysis, which incorporated 29,214 patients with a variety of rheumatic diseases, demonstrated that patients receiving interleukin (IL) inhibitors had a 1.97-fold increased risk of serious infections, a finding accompanied by a high degree of statistical certainty. The number-needed-to-harm was 67 patients treated for a median of 24 weeks in order to generate one additional serious infection.

“That number-needed-to-harm is a significant finding because having a serious infection means by definition you’re getting admitted to the hospital and receiving IV antibiotics,” Dr. Bilal observed in an interview.

The meta-analysis also found that IL inhibition was associated with a 2.35-fold increased risk of opportunistic infections and a 1.52-fold higher risk of developing cancer, both findings with statistical significance (P =.03) but only moderate certainty because fewer of those events were captured in the trials compared to the numbers of serious infections, explained Dr. Bilal of the University of Arizona, Tucson.

For opportunistic infections, the number-needed-to-harm was 250 patients treated with an IL inhibitor for a median of 54 weeks in order to result in one additional opportunistic infection. For cancer, the number-needed-to-harm was 250 for a median of 24 weeks.

Dr. Bilal noted that while the IL inhibitors are drugs of established efficacy in rheumatologic diseases, their safety has not previously undergone anything approaching the comprehensive scrutiny carried out in this meta-analysis. The meta-analysis, which included all published placebo-controlled randomized trials and their extension studies, employed rigorous methodology in accord with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) statement and the GRADE approach to data analysis. Studies of IL inhibitors in patients with dermatologic and GI diseases were excluded from the meta-analysis.

He offered a caveat regarding the cancer risk findings: “Our analysis showed that the cancer risk is increased, but the results are not conclusive because we only had a few years of data. With cancer, you really need at least 8-10 years of data. So the real-world experience with the interleukin inhibitors in the large registries is what’s going to tell if the cancer risk is really increased or not. In the meantime, we all have to be cautious.”

The number of serious infections collected in the meta-analysis afforded sufficient statistical power for the investigators to break down differential risks based on individual drugs and indications. Among the drugs associated with significantly increased risk of serious infections were anakinra, with an odds ratio of 2.67, compared with placebo; secukinumab with an OR of 2.43; and tocilizumab with an OR or 1.76. Ustekinumab and ixekizumab were associated with 2.57- and 3.89-fold increased risks, respectively, but the number of rheumatology patients treated with those two biologics wasn’t large enough for those findings to achieve statistical significance.

Rheumatoid arthritis patients who received an IL inhibitor rather than placebo had a 1.98-fold increased risk of serious infection, while those with psoriatic arthritis had a 2.21-fold increased risk. Patients treated for SLE had a 6.44-fold increased risk, and those with juvenile idiopathic arthritis had a 5.37-fold higher risk, but the margins for error were such that those results weren’t statistically significant.

“I think this study is going to help clinicians and patients when they’re trying to weigh the risks and benefits of IL inhibitors, especially if they already have risk factors, like a recent history of serious infection or a history of cancer or of opportunistic infection,” Dr. Bilal commented.

A study limitation was that he and his coinvestigators had to lump together the various IL inhibitors in order to gain statistical power, even though the drugs work differently, he noted.

Dr. Bilal reported having no financial conflicts regarding his study, the full details of which have been published (JAMA Netw Open. 2019 Oct 2. doi: 10.1001/jamanetworkopen.2019.13102).

[email protected]

Glucocorticoid use is associated with greater mortality and cardiovascular risk in RA patients, and the associated risk is greater still in patients with RA and comorbid diabetes. The findings come from a new retrospective analysis derived from U.K. primary care records.

Although patients with diabetes actually had a lower relative risk for mortality than the nondiabetes cohort, they had a greater mortality difference because of a greater baseline risk. Ultimately, glucocorticoid (GC) use was associated with an additional 44.9 deaths per 1,000 person-years in the diabetes group, compared with 34.4 per 1,000 person-years in the RA-only group.

The study, led by Ruth Costello and William Dixon, MBBS, PhD of the University of Manchester (England), was published in BMC Rheumatology.

The findings aren’t particularly surprising, given that steroid use and diabetes have associated cardiovascular risks, and physicians generally try to reduce or eliminate their use. “There’s a group [of physicians] saying that we don’t need to use steroids at all in rheumatoid arthritis, except maybe for [a] short time at diagnosis to bridge to other therapies, or during flares,” Gordon Starkebaum, MD, professor emeritus of rheumatology at the University of Washington, Seattle, said in an interview. He recounted a session at last year’s annual meeting of the American College of Rheumatology that advocated for only injectable steroid use during flare-ups. “That was provocative,” Dr. Starkebaum said.

“It’s a retrospective study, so it has some limitations, but it provides good insight, and some substantiation to what we already think,” added Brett Smith, DO, a rheumatologist practicing in Knoxville, Tenn.

Dr. Smith suggested that the study further underscores the need to follow treat-to-target protocols in RA. He emphasized that lifetime exposure to steroids is likely the greatest concern, and that steady accumulating doses are a sign of trouble. “If you need that much steroids, you need to go up on your medication – your methotrexate, or sulfasalazine, or your biologic,” said Dr. Smith. “At least 50% of people will need a biologic to [achieve] disease control, and if you get them on it, they’re going to have better disease control, compliance is typically better, and they’re going to have less steroid exposure.”

Dr. Smith also noted that comorbid diabetes shouldn’t affect treat-to-target strategies. In fact, in such patients “you should probably be following it more tightly to reduce the cardiovascular outcomes,” he said.

The retrospective analysis included 9,085 patients with RA and with or without type 2 diabetes, with a mean follow-up of 5.2 years. They were recruited to the study between 1998 and 2011. Among patients with comorbid diabetes, those exposed to GC had a mortality of 67.4 per 1,000 person-years, compared with 22.5 among those not exposed to GC. Among those with RA alone, mortality was 44.6 versus 10.2 with and without GC exposure, respectively. Those with diabetes had a lower risk ratio for mortality (2.99 vs. 4.37), but a higher mortality difference (44.9 vs. 34.4 per 1,000 person-years).

“The increased absolute hazard for all-cause mortality indicates the greater public health impact of people with RA using GCs if they have [diabetes],” the researchers wrote. “Rheumatologists should consider [diabetes] status when prescribing GCs to patients with RA given this potential impact of GC therapy on glucose control and mortality.”

The study was limited by a lack of information on GC dose and cumulative exposure. Given its retrospective nature, the study could have been affected by confounding by indication, as well as unknown confounders.

The study was funded by the Centre for Epidemiology Versus Arthritis and the National Institute for Health Research Biomedical Research Centre. Dr. Starkebaum has no relevant financial disclosures. Dr. Smith is on the speaker’s bureau for AbbVie and serves on the company’s advisory board. He is also on the advisory boards of Regeneron and Sanofi Genzyme.

SOURCE: Costello R et al. BMC Rheumatol. 2020 Feb 19. doi: 10.1186/s41927-019-0105-4.

Glucocorticoid use is associated with greater mortality and cardiovascular risk in RA patients, and the associated risk is greater still in patients with RA and comorbid diabetes. The findings come from a new retrospective analysis derived from U.K. primary care records.

Although patients with diabetes actually had a lower relative risk for mortality than the nondiabetes cohort, they had a greater mortality difference because of a greater baseline risk. Ultimately, glucocorticoid (GC) use was associated with an additional 44.9 deaths per 1,000 person-years in the diabetes group, compared with 34.4 per 1,000 person-years in the RA-only group.

The study, led by Ruth Costello and William Dixon, MBBS, PhD of the University of Manchester (England), was published in BMC Rheumatology.

The findings aren’t particularly surprising, given that steroid use and diabetes have associated cardiovascular risks, and physicians generally try to reduce or eliminate their use. “There’s a group [of physicians] saying that we don’t need to use steroids at all in rheumatoid arthritis, except maybe for [a] short time at diagnosis to bridge to other therapies, or during flares,” Gordon Starkebaum, MD, professor emeritus of rheumatology at the University of Washington, Seattle, said in an interview. He recounted a session at last year’s annual meeting of the American College of Rheumatology that advocated for only injectable steroid use during flare-ups. “That was provocative,” Dr. Starkebaum said.

“It’s a retrospective study, so it has some limitations, but it provides good insight, and some substantiation to what we already think,” added Brett Smith, DO, a rheumatologist practicing in Knoxville, Tenn.

Dr. Smith suggested that the study further underscores the need to follow treat-to-target protocols in RA. He emphasized that lifetime exposure to steroids is likely the greatest concern, and that steady accumulating doses are a sign of trouble. “If you need that much steroids, you need to go up on your medication – your methotrexate, or sulfasalazine, or your biologic,” said Dr. Smith. “At least 50% of people will need a biologic to [achieve] disease control, and if you get them on it, they’re going to have better disease control, compliance is typically better, and they’re going to have less steroid exposure.”

Dr. Smith also noted that comorbid diabetes shouldn’t affect treat-to-target strategies. In fact, in such patients “you should probably be following it more tightly to reduce the cardiovascular outcomes,” he said.

The retrospective analysis included 9,085 patients with RA and with or without type 2 diabetes, with a mean follow-up of 5.2 years. They were recruited to the study between 1998 and 2011. Among patients with comorbid diabetes, those exposed to GC had a mortality of 67.4 per 1,000 person-years, compared with 22.5 among those not exposed to GC. Among those with RA alone, mortality was 44.6 versus 10.2 with and without GC exposure, respectively. Those with diabetes had a lower risk ratio for mortality (2.99 vs. 4.37), but a higher mortality difference (44.9 vs. 34.4 per 1,000 person-years).

“The increased absolute hazard for all-cause mortality indicates the greater public health impact of people with RA using GCs if they have [diabetes],” the researchers wrote. “Rheumatologists should consider [diabetes] status when prescribing GCs to patients with RA given this potential impact of GC therapy on glucose control and mortality.”

The study was limited by a lack of information on GC dose and cumulative exposure. Given its retrospective nature, the study could have been affected by confounding by indication, as well as unknown confounders.

The study was funded by the Centre for Epidemiology Versus Arthritis and the National Institute for Health Research Biomedical Research Centre. Dr. Starkebaum has no relevant financial disclosures. Dr. Smith is on the speaker’s bureau for AbbVie and serves on the company’s advisory board. He is also on the advisory boards of Regeneron and Sanofi Genzyme.

SOURCE: Costello R et al. BMC Rheumatol. 2020 Feb 19. doi: 10.1186/s41927-019-0105-4.

Glucocorticoid use is associated with greater mortality and cardiovascular risk in RA patients, and the associated risk is greater still in patients with RA and comorbid diabetes. The findings come from a new retrospective analysis derived from U.K. primary care records.

Although patients with diabetes actually had a lower relative risk for mortality than the nondiabetes cohort, they had a greater mortality difference because of a greater baseline risk. Ultimately, glucocorticoid (GC) use was associated with an additional 44.9 deaths per 1,000 person-years in the diabetes group, compared with 34.4 per 1,000 person-years in the RA-only group.

The study, led by Ruth Costello and William Dixon, MBBS, PhD of the University of Manchester (England), was published in BMC Rheumatology.

The findings aren’t particularly surprising, given that steroid use and diabetes have associated cardiovascular risks, and physicians generally try to reduce or eliminate their use. “There’s a group [of physicians] saying that we don’t need to use steroids at all in rheumatoid arthritis, except maybe for [a] short time at diagnosis to bridge to other therapies, or during flares,” Gordon Starkebaum, MD, professor emeritus of rheumatology at the University of Washington, Seattle, said in an interview. He recounted a session at last year’s annual meeting of the American College of Rheumatology that advocated for only injectable steroid use during flare-ups. “That was provocative,” Dr. Starkebaum said.

“It’s a retrospective study, so it has some limitations, but it provides good insight, and some substantiation to what we already think,” added Brett Smith, DO, a rheumatologist practicing in Knoxville, Tenn.

Dr. Smith suggested that the study further underscores the need to follow treat-to-target protocols in RA. He emphasized that lifetime exposure to steroids is likely the greatest concern, and that steady accumulating doses are a sign of trouble. “If you need that much steroids, you need to go up on your medication – your methotrexate, or sulfasalazine, or your biologic,” said Dr. Smith. “At least 50% of people will need a biologic to [achieve] disease control, and if you get them on it, they’re going to have better disease control, compliance is typically better, and they’re going to have less steroid exposure.”

Dr. Smith also noted that comorbid diabetes shouldn’t affect treat-to-target strategies. In fact, in such patients “you should probably be following it more tightly to reduce the cardiovascular outcomes,” he said.

The retrospective analysis included 9,085 patients with RA and with or without type 2 diabetes, with a mean follow-up of 5.2 years. They were recruited to the study between 1998 and 2011. Among patients with comorbid diabetes, those exposed to GC had a mortality of 67.4 per 1,000 person-years, compared with 22.5 among those not exposed to GC. Among those with RA alone, mortality was 44.6 versus 10.2 with and without GC exposure, respectively. Those with diabetes had a lower risk ratio for mortality (2.99 vs. 4.37), but a higher mortality difference (44.9 vs. 34.4 per 1,000 person-years).

“The increased absolute hazard for all-cause mortality indicates the greater public health impact of people with RA using GCs if they have [diabetes],” the researchers wrote. “Rheumatologists should consider [diabetes] status when prescribing GCs to patients with RA given this potential impact of GC therapy on glucose control and mortality.”

The study was limited by a lack of information on GC dose and cumulative exposure. Given its retrospective nature, the study could have been affected by confounding by indication, as well as unknown confounders.

The study was funded by the Centre for Epidemiology Versus Arthritis and the National Institute for Health Research Biomedical Research Centre. Dr. Starkebaum has no relevant financial disclosures. Dr. Smith is on the speaker’s bureau for AbbVie and serves on the company’s advisory board. He is also on the advisory boards of Regeneron and Sanofi Genzyme.

SOURCE: Costello R et al. BMC Rheumatol. 2020 Feb 19. doi: 10.1186/s41927-019-0105-4.

Physicians in internal medicine struggle to find happiness both in and outside the workplace, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

Only 22% of internists reported that they were very happy at work, with only neurologists reporting a worse at-work happiness rate, according to the Medscape report.

The news wasn’t much better when it came to happiness outside the office, as only 48% of internists reported they were very happy. Once again, neurologists had the lowest happiness rate outside the office, at 44%.

The rate of burnout among internists, at 43%, was similar to that of physicians overall at 41%; 14% of internists reported that they were both burned out and depressed. The most common contributing factors to burnout for internists were having too many bureaucratic tasks (62%), receiving a lack of respect from colleagues (34%), and spending too many hours at work (33%).

Internists dealt with burnout by isolating themselves from others (47%), talking with family/friends (45%), and exercising (41%). In addition, only 41% of internists took 3-4 weeks’ vacation, less than the 44% for physicians overall, and 43% took less than 3 weeks of vacation.

About 14% of internists said that they’d contemplated suicide, and 1% reported that they’d attempted it; 80% said they’d never thought about suicide. Only 16% said that they were seeking or planning to seek professional help for symptoms of burnout or depression, and 64% said they weren’t planning on seeking help and had never done so in the past.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

[email protected]

Physicians in internal medicine struggle to find happiness both in and outside the workplace, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

Only 22% of internists reported that they were very happy at work, with only neurologists reporting a worse at-work happiness rate, according to the Medscape report.

The news wasn’t much better when it came to happiness outside the office, as only 48% of internists reported they were very happy. Once again, neurologists had the lowest happiness rate outside the office, at 44%.

The rate of burnout among internists, at 43%, was similar to that of physicians overall at 41%; 14% of internists reported that they were both burned out and depressed. The most common contributing factors to burnout for internists were having too many bureaucratic tasks (62%), receiving a lack of respect from colleagues (34%), and spending too many hours at work (33%).

Internists dealt with burnout by isolating themselves from others (47%), talking with family/friends (45%), and exercising (41%). In addition, only 41% of internists took 3-4 weeks’ vacation, less than the 44% for physicians overall, and 43% took less than 3 weeks of vacation.

About 14% of internists said that they’d contemplated suicide, and 1% reported that they’d attempted it; 80% said they’d never thought about suicide. Only 16% said that they were seeking or planning to seek professional help for symptoms of burnout or depression, and 64% said they weren’t planning on seeking help and had never done so in the past.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

[email protected]

Physicians in internal medicine struggle to find happiness both in and outside the workplace, according to Medscape’s 2020 Lifestyle, Happiness, and Burnout Report.

Only 22% of internists reported that they were very happy at work, with only neurologists reporting a worse at-work happiness rate, according to the Medscape report.

The news wasn’t much better when it came to happiness outside the office, as only 48% of internists reported they were very happy. Once again, neurologists had the lowest happiness rate outside the office, at 44%.

The rate of burnout among internists, at 43%, was similar to that of physicians overall at 41%; 14% of internists reported that they were both burned out and depressed. The most common contributing factors to burnout for internists were having too many bureaucratic tasks (62%), receiving a lack of respect from colleagues (34%), and spending too many hours at work (33%).

Internists dealt with burnout by isolating themselves from others (47%), talking with family/friends (45%), and exercising (41%). In addition, only 41% of internists took 3-4 weeks’ vacation, less than the 44% for physicians overall, and 43% took less than 3 weeks of vacation.

About 14% of internists said that they’d contemplated suicide, and 1% reported that they’d attempted it; 80% said they’d never thought about suicide. Only 16% said that they were seeking or planning to seek professional help for symptoms of burnout or depression, and 64% said they weren’t planning on seeking help and had never done so in the past.

The Medscape survey was conducted from June 25 to Sept. 19, 2019, and involved 15,181 physicians.

[email protected]

Porphyria cutanea tarda (PCT) is the most common type of porphyria. The accumulation of porphyrin in various organ systems results from a deficiency of uroporphyrinogen decarboxylase (UROD).^1-3 Chronic hepatitis C virus (HCV) causes a hepatic decrease in hepcidin production, resulting in increased iron absorption. Iron loading and increased oxidative stress in the liver leads to nonporphyrin inhibition of UROD production and to oxidation of porphyrinogens to porphyrins.⁴ This in turn leads to accumulation of uroporphyrins and carboxylated metabolites that can be detected in urine.⁴

Signs of PCT include blisters, vesicles, and possibly milia developing on sun-exposed areas of the skin, such as the face, forearms, and dorsal hands.⁴ Case reports have demonstrated a resolution of PCT in patients with chronic HCV with treatment with direct-acting antivirals (DAAs), such as ledipasvir/sofosbuvir.^1,3 However, here we present 2 cases of patients who developed blistering diseases during treatment of chronic HCV with ledipasvir/sofosbuvir. Neither demonstrated complete resolution of symptoms during the treatment regimen.

Cases

Patient 1

A 63-year-old white male with a history of chronic HCV (genotype 1a), bipolar disorder, hyperlipidemia, tobacco dependence, and cirrhosis (F4 by elastography) presented with minimally to moderately painful blisters on his bilateral dorsal hands that had developed around weeks 8 to 9 of treatment with ledipasvir/sofosbuvir. The patient reported that no new blisters had appeared following completion of 12 weeks of treatment and that his current blisters were in various stages of healing. He reported alcohol use of 1 to 2 twelve-ounce beers daily and no history of dioxin exposure. His medications included doxepin, hydralazine, hydrochlorothiazide, quetiapine, folic acid, and thiamine. His hepatitis C viral load was 440,000 IU/mL prior to treatment. Tests for hepatitis B surface antigen and HIV antibodies were negative. His iron level was 135 µg/dL, total iron-binding capacity (TIBC) was 323 µg/dL, and ferritin was 299.0 ng/mL. His HFEgene was negative for mutations. Following 4 weeks of treatment with ledipasvir/sofosbuvir, a hepatitis C viral load was not detected.

A physical examination on presentation revealed erosions with overlying hemorrhagic crusts on the bilateral dorsal hands (Figure). 

At the 4-month follow-up, the patient reported no new blister formations. A physical examination revealed well-healed scars and several clustered milia on bilateral dorsal hands with no active vesicles or bullae noted.

Patient 2

An African American male aged 63 years presented with a 1-month history of moderately painful blisters on his bilateral dorsal hands during treatment of chronic HCV (genotype 1a) with ledipasvir/sofosbuvir. His medical history included gout, tobacco and alcohol addiction, osteoarthritis, and hepatic fibrosis (F3 by elastography). The patient’s medications included allopurinol, lisinopril, and hydrochlorothiazide. He reported no history of dioxin exposure. On the day of presentation, he was on week 9 of the 12-week treatment ledipasvir/sofosbuvir regimen. Laboratory results included an initial HCV viral load of 1,618,605 IU/mL. Tests for hepatitis B surface antigen and HIV antibodies were negative. His iron was 191 µg/dL, TIBC 388 µg/dL, and ferritin 459.0 ng/mL. After 4 weeks of treatment, the patient’s hepatitis C viral load was undetectable.

A physical examination revealed several resolving erosions to his bilateral dorsal hands, some of which had overlying crusting along with one small hemorrhagic vesicle on the right dorsal hand. A punch biopsy of the hemorrhagic vesicle was performed and demonstrated a cell-poor subepidermal blister with festooning of the dermal papilla. A direct immunofluorescence study showed immunoglobulin (Ig) G fluorescence along the dermal-epidermal junction and within vessel walls in the superficial dermis. Weak IgM and C3 fluorescence also was noted within vessel walls in the superficial dermis. All of the patient findings and history were consistent with PCT, although pseudo-PCT also was a consideration. A 24-hour urine sample yielded negative results for porphobilinogen. Urine porphyrin test results were not available, leading to a presumptive histological diagnosis of PCT.

The patient completed 11 of the prescribed 12 weeks of ledipasvir/sofosbuvir. The blisters resolved shortly thereafter.

Discussion

PCT has a well-established association with chronic HCV infection.⁴ We present 2 cases of a blistering disease clinically and histologically compatible with PCT that developed in patients only after initiation of treatment for chronic HCV with ledipasvir/sofosbuvir. One case was confirmed as PCT on the basis of compatible histopathologic findings and a urine porphyrin assay that showed elevated levels of uroporphyrins and carboxylated metabolites. The second case was clinically and histologically suggestive of PCT but not confirmed by urine porphyrin testing. In both patients, after 8 to 9 weeks of a 12-week course of antiviral therapy, the blistering lesions were noted but appeared to be resolving, and no new lesions were noted after discontinuation of therapy. It appeared that the antiviral treatment temporally triggered the initiation of the blistering skin disease, and as the chronic HCV infection cleared after treatment, the blistering lesions also began to resolve.

Mechanistically, it is known that the virally-induced hepatic damage leads to inhibition of uroporphyrinogen decarboxylase, and the subsequent oxidation of porphyrinogens to porphyrins. Cofactors such as HIV infection also may contribute to development of PCT.⁵

De novo PCT has been documented during therapy using interferon and ribavirin.⁶ The hemolytic anemia and increased hepatic iron were implicated as potential etiologies.⁶ Patients with HCV and PCT treated with the newer direct-acting antiviral therapies have been described to have experienced improvement in PCT symptoms.³

Although there were rare reports of deterioration in renal and liver function,⁷ reactivation of HBV infection,⁸ and Stevens-Johnson syndrome⁹ with antiviral therapy, these complications were not observed in these patients. Both patients also had successful resolution of HCV infection, and by completion of the antiviral therapy, the blistering also resolved.

Conclusion

PCT is an extrahepatic manifestation of HCV infection. Health care providers should be aware of the association of chronic HCV infection with PCT. The findings of PCT should not result in the delay or discontinuation of antiviral therapy.

Porphyria cutanea tarda (PCT) is the most common type of porphyria. The accumulation of porphyrin in various organ systems results from a deficiency of uroporphyrinogen decarboxylase (UROD).^1-3 Chronic hepatitis C virus (HCV) causes a hepatic decrease in hepcidin production, resulting in increased iron absorption. Iron loading and increased oxidative stress in the liver leads to nonporphyrin inhibition of UROD production and to oxidation of porphyrinogens to porphyrins.⁴ This in turn leads to accumulation of uroporphyrins and carboxylated metabolites that can be detected in urine.⁴

Signs of PCT include blisters, vesicles, and possibly milia developing on sun-exposed areas of the skin, such as the face, forearms, and dorsal hands.⁴ Case reports have demonstrated a resolution of PCT in patients with chronic HCV with treatment with direct-acting antivirals (DAAs), such as ledipasvir/sofosbuvir.^1,3 However, here we present 2 cases of patients who developed blistering diseases during treatment of chronic HCV with ledipasvir/sofosbuvir. Neither demonstrated complete resolution of symptoms during the treatment regimen.

Cases

Patient 1

A 63-year-old white male with a history of chronic HCV (genotype 1a), bipolar disorder, hyperlipidemia, tobacco dependence, and cirrhosis (F4 by elastography) presented with minimally to moderately painful blisters on his bilateral dorsal hands that had developed around weeks 8 to 9 of treatment with ledipasvir/sofosbuvir. The patient reported that no new blisters had appeared following completion of 12 weeks of treatment and that his current blisters were in various stages of healing. He reported alcohol use of 1 to 2 twelve-ounce beers daily and no history of dioxin exposure. His medications included doxepin, hydralazine, hydrochlorothiazide, quetiapine, folic acid, and thiamine. His hepatitis C viral load was 440,000 IU/mL prior to treatment. Tests for hepatitis B surface antigen and HIV antibodies were negative. His iron level was 135 µg/dL, total iron-binding capacity (TIBC) was 323 µg/dL, and ferritin was 299.0 ng/mL. His HFEgene was negative for mutations. Following 4 weeks of treatment with ledipasvir/sofosbuvir, a hepatitis C viral load was not detected.

A physical examination on presentation revealed erosions with overlying hemorrhagic crusts on the bilateral dorsal hands (Figure). 

At the 4-month follow-up, the patient reported no new blister formations. A physical examination revealed well-healed scars and several clustered milia on bilateral dorsal hands with no active vesicles or bullae noted.

Patient 2

An African American male aged 63 years presented with a 1-month history of moderately painful blisters on his bilateral dorsal hands during treatment of chronic HCV (genotype 1a) with ledipasvir/sofosbuvir. His medical history included gout, tobacco and alcohol addiction, osteoarthritis, and hepatic fibrosis (F3 by elastography). The patient’s medications included allopurinol, lisinopril, and hydrochlorothiazide. He reported no history of dioxin exposure. On the day of presentation, he was on week 9 of the 12-week treatment ledipasvir/sofosbuvir regimen. Laboratory results included an initial HCV viral load of 1,618,605 IU/mL. Tests for hepatitis B surface antigen and HIV antibodies were negative. His iron was 191 µg/dL, TIBC 388 µg/dL, and ferritin 459.0 ng/mL. After 4 weeks of treatment, the patient’s hepatitis C viral load was undetectable.

A physical examination revealed several resolving erosions to his bilateral dorsal hands, some of which had overlying crusting along with one small hemorrhagic vesicle on the right dorsal hand. A punch biopsy of the hemorrhagic vesicle was performed and demonstrated a cell-poor subepidermal blister with festooning of the dermal papilla. A direct immunofluorescence study showed immunoglobulin (Ig) G fluorescence along the dermal-epidermal junction and within vessel walls in the superficial dermis. Weak IgM and C3 fluorescence also was noted within vessel walls in the superficial dermis. All of the patient findings and history were consistent with PCT, although pseudo-PCT also was a consideration. A 24-hour urine sample yielded negative results for porphobilinogen. Urine porphyrin test results were not available, leading to a presumptive histological diagnosis of PCT.

The patient completed 11 of the prescribed 12 weeks of ledipasvir/sofosbuvir. The blisters resolved shortly thereafter.

Discussion

PCT has a well-established association with chronic HCV infection.⁴ We present 2 cases of a blistering disease clinically and histologically compatible with PCT that developed in patients only after initiation of treatment for chronic HCV with ledipasvir/sofosbuvir. One case was confirmed as PCT on the basis of compatible histopathologic findings and a urine porphyrin assay that showed elevated levels of uroporphyrins and carboxylated metabolites. The second case was clinically and histologically suggestive of PCT but not confirmed by urine porphyrin testing. In both patients, after 8 to 9 weeks of a 12-week course of antiviral therapy, the blistering lesions were noted but appeared to be resolving, and no new lesions were noted after discontinuation of therapy. It appeared that the antiviral treatment temporally triggered the initiation of the blistering skin disease, and as the chronic HCV infection cleared after treatment, the blistering lesions also began to resolve.

Mechanistically, it is known that the virally-induced hepatic damage leads to inhibition of uroporphyrinogen decarboxylase, and the subsequent oxidation of porphyrinogens to porphyrins. Cofactors such as HIV infection also may contribute to development of PCT.⁵

De novo PCT has been documented during therapy using interferon and ribavirin.⁶ The hemolytic anemia and increased hepatic iron were implicated as potential etiologies.⁶ Patients with HCV and PCT treated with the newer direct-acting antiviral therapies have been described to have experienced improvement in PCT symptoms.³

Although there were rare reports of deterioration in renal and liver function,⁷ reactivation of HBV infection,⁸ and Stevens-Johnson syndrome⁹ with antiviral therapy, these complications were not observed in these patients. Both patients also had successful resolution of HCV infection, and by completion of the antiviral therapy, the blistering also resolved.

Conclusion

PCT is an extrahepatic manifestation of HCV infection. Health care providers should be aware of the association of chronic HCV infection with PCT. The findings of PCT should not result in the delay or discontinuation of antiviral therapy.

Porphyria cutanea tarda (PCT) is the most common type of porphyria. The accumulation of porphyrin in various organ systems results from a deficiency of uroporphyrinogen decarboxylase (UROD).^1-3 Chronic hepatitis C virus (HCV) causes a hepatic decrease in hepcidin production, resulting in increased iron absorption. Iron loading and increased oxidative stress in the liver leads to nonporphyrin inhibition of UROD production and to oxidation of porphyrinogens to porphyrins.⁴ This in turn leads to accumulation of uroporphyrins and carboxylated metabolites that can be detected in urine.⁴

Signs of PCT include blisters, vesicles, and possibly milia developing on sun-exposed areas of the skin, such as the face, forearms, and dorsal hands.⁴ Case reports have demonstrated a resolution of PCT in patients with chronic HCV with treatment with direct-acting antivirals (DAAs), such as ledipasvir/sofosbuvir.^1,3 However, here we present 2 cases of patients who developed blistering diseases during treatment of chronic HCV with ledipasvir/sofosbuvir. Neither demonstrated complete resolution of symptoms during the treatment regimen.

Cases

Patient 1

A 63-year-old white male with a history of chronic HCV (genotype 1a), bipolar disorder, hyperlipidemia, tobacco dependence, and cirrhosis (F4 by elastography) presented with minimally to moderately painful blisters on his bilateral dorsal hands that had developed around weeks 8 to 9 of treatment with ledipasvir/sofosbuvir. The patient reported that no new blisters had appeared following completion of 12 weeks of treatment and that his current blisters were in various stages of healing. He reported alcohol use of 1 to 2 twelve-ounce beers daily and no history of dioxin exposure. His medications included doxepin, hydralazine, hydrochlorothiazide, quetiapine, folic acid, and thiamine. His hepatitis C viral load was 440,000 IU/mL prior to treatment. Tests for hepatitis B surface antigen and HIV antibodies were negative. His iron level was 135 µg/dL, total iron-binding capacity (TIBC) was 323 µg/dL, and ferritin was 299.0 ng/mL. His HFEgene was negative for mutations. Following 4 weeks of treatment with ledipasvir/sofosbuvir, a hepatitis C viral load was not detected.

A physical examination on presentation revealed erosions with overlying hemorrhagic crusts on the bilateral dorsal hands (Figure). 

At the 4-month follow-up, the patient reported no new blister formations. A physical examination revealed well-healed scars and several clustered milia on bilateral dorsal hands with no active vesicles or bullae noted.

Patient 2

An African American male aged 63 years presented with a 1-month history of moderately painful blisters on his bilateral dorsal hands during treatment of chronic HCV (genotype 1a) with ledipasvir/sofosbuvir. His medical history included gout, tobacco and alcohol addiction, osteoarthritis, and hepatic fibrosis (F3 by elastography). The patient’s medications included allopurinol, lisinopril, and hydrochlorothiazide. He reported no history of dioxin exposure. On the day of presentation, he was on week 9 of the 12-week treatment ledipasvir/sofosbuvir regimen. Laboratory results included an initial HCV viral load of 1,618,605 IU/mL. Tests for hepatitis B surface antigen and HIV antibodies were negative. His iron was 191 µg/dL, TIBC 388 µg/dL, and ferritin 459.0 ng/mL. After 4 weeks of treatment, the patient’s hepatitis C viral load was undetectable.

A physical examination revealed several resolving erosions to his bilateral dorsal hands, some of which had overlying crusting along with one small hemorrhagic vesicle on the right dorsal hand. A punch biopsy of the hemorrhagic vesicle was performed and demonstrated a cell-poor subepidermal blister with festooning of the dermal papilla. A direct immunofluorescence study showed immunoglobulin (Ig) G fluorescence along the dermal-epidermal junction and within vessel walls in the superficial dermis. Weak IgM and C3 fluorescence also was noted within vessel walls in the superficial dermis. All of the patient findings and history were consistent with PCT, although pseudo-PCT also was a consideration. A 24-hour urine sample yielded negative results for porphobilinogen. Urine porphyrin test results were not available, leading to a presumptive histological diagnosis of PCT.

The patient completed 11 of the prescribed 12 weeks of ledipasvir/sofosbuvir. The blisters resolved shortly thereafter.

Discussion

PCT has a well-established association with chronic HCV infection.⁴ We present 2 cases of a blistering disease clinically and histologically compatible with PCT that developed in patients only after initiation of treatment for chronic HCV with ledipasvir/sofosbuvir. One case was confirmed as PCT on the basis of compatible histopathologic findings and a urine porphyrin assay that showed elevated levels of uroporphyrins and carboxylated metabolites. The second case was clinically and histologically suggestive of PCT but not confirmed by urine porphyrin testing. In both patients, after 8 to 9 weeks of a 12-week course of antiviral therapy, the blistering lesions were noted but appeared to be resolving, and no new lesions were noted after discontinuation of therapy. It appeared that the antiviral treatment temporally triggered the initiation of the blistering skin disease, and as the chronic HCV infection cleared after treatment, the blistering lesions also began to resolve.

Mechanistically, it is known that the virally-induced hepatic damage leads to inhibition of uroporphyrinogen decarboxylase, and the subsequent oxidation of porphyrinogens to porphyrins. Cofactors such as HIV infection also may contribute to development of PCT.⁵

De novo PCT has been documented during therapy using interferon and ribavirin.⁶ The hemolytic anemia and increased hepatic iron were implicated as potential etiologies.⁶ Patients with HCV and PCT treated with the newer direct-acting antiviral therapies have been described to have experienced improvement in PCT symptoms.³

Although there were rare reports of deterioration in renal and liver function,⁷ reactivation of HBV infection,⁸ and Stevens-Johnson syndrome⁹ with antiviral therapy, these complications were not observed in these patients. Both patients also had successful resolution of HCV infection, and by completion of the antiviral therapy, the blistering also resolved.

Conclusion

PCT is an extrahepatic manifestation of HCV infection. Health care providers should be aware of the association of chronic HCV infection with PCT. The findings of PCT should not result in the delay or discontinuation of antiviral therapy.

Sepsis is a major public health concern: 10% of patients with sepsis die, and mortality quadruples with progression to septic shock.¹ Systemic inflammatory response syndrome (SIRS) criteria, originally published in 1992, are commonly used to detect sepsis, but as early as 2001, these criteria were recognized as lacking specificity.² Nonetheless, the use of SIRS criteria has persisted in practice. Sepsis was redefined in Sepsis-3 (2016) to guide earlier and more appropriate identification and treatment, which has been shown to greatly improve patient outcomes.^1,3 Key recommendations in Sepsis 3 included eliminating SIRS criteria, defining organ dysfunction by the Sequential Organ Failure Assessment (SOFA) score, and introducing the quick SOFA (qSOFA) score.¹

The qSOFA combines 3 clinical variables to provide a rapid, simple bedside score that measures the likelihood of poor outcomes, such as admission to an intensive care unit (ICU) or mortality in adults with suspected infection.^1,3 The qSOFA score is intended to aid healthcare professionals in more timely stratification of those patients who need escalated care to prevent deterioration.¹ The assessment also has been explored as a screening tool for sepsis in clinical practice; however, limited data exists concerning the comparative utility of qSOFA and SIRS in this capacity, and study results are inconsistent.^4-6

The most important attribute of a screening tool is high sensitivity, but high specificity also is desired. The qSOFA could supplant SIRS as a screening tool for sepsis if it maintained similarly high sensitivity but achieved superior specificity. Therefore, our primary objective for this study was to determine the effectiveness of qSOFA as a screening assessment for sepsis in the setting of a general inpatient medicine service by contrasting the sensitivity and specificity of qSOFA with SIRS in predicting sepsis, using a retrospective chart review design.

Methods

Administrative data from the Department of Veterans Affairs (VA) Corporate Data Warehouse were accessed via the VA Informatics and Computing Infrastructure (VINCI) and used to identify VA inpatient admissions and obtain the laboratory and vital sign data necessary to calculate SIRS, qSOFA, and SOFA scores. The data were supplemented by manual review of VA health records to obtain information that was not readily available in administrative records, including septic shock outcomes and laboratory and vital sign data obtained in the ICU. This study was approved by the institutional review board at the University of Iowa and the research and development committee at the Iowa City VA Medical Center (ICVAMC).

Patients

The study population included veterans admitted to the nonsurgical medicine unit at ICVAMC between August 1, 2014 and August 1, 2016 who were transferred to an ICU after admission; direct ICU admissions were not included as the qSOFA has been shown in studies to be more beneficial and offer better predictive validity outside the ICU. Excluding these direct admissions prevented any potential skewing of the data. To control for possible selection bias, veterans also were excluded if they transferred from another facility, were admitted under observation status, or if they had been admitted within the prior 30 days. These patients may have been more critically ill than those who presented directly to our facility and any prior treatment could affect the clinical status of the patient and assessment for sepsis at the time of presentation to the VA. Veterans were further required to have evidence of suspected infection based on manual review of the health record, which was determined by receipt of an antibiotic relevant to the empiric treatment of sepsis within 48 hours of admission.

Sepsis and Septic Shock Assessment Tools

As outlined in the Sepsis-3 guidelines, sepsis was defined as suspected or confirmed infection with an acute change in the SOFA score of ≥ 2 points, which is assumed to be 0 in those not known to have preexisting dysfunction.¹ The SOFA score includes variables from the respiratory, coagulation, hepatic, cardiovascular, renal, and central nervous systems.¹ Septic shock was defined as vasopressor administration and a serum lactic acid level > 2 mmol/L occurring up to 24 hours apart and within 3 days of the first antibiotic dose administered.

The SIRS assessment includes 4 clinical variables (temperature, heart rate, respiratory rate, and white blood cell count) while qSOFA is comprised of 3 variables (respiratory rate, systolic blood pressure, and altered mental status).¹ With both assessments, a score ≥ 2 is considered positive, which indicates increased risk for sepsis in patients with suspected infection.¹ In keeping with existing studies, qSOFA and SIRS assessments were scored using maximum values found within 48 hours before and 24 hours after the first administered antibiotic dose.³

Outcomes

The primary outcome variable was the presence of sepsis in adults with evidence of infection within 48 hours of admission. Secondary outcome measures included 30-day mortality and septic shock.

Performance between the SIRS and qSOFA assessments was contrasted using sensitivity, specificity, and positive and negative predictive value measurements. Associations of qSOFA and SIRS with septic shock and 30-day mortality were evaluated using a 2-tailed Fisher’s exact test with a threshold of α = 0.05 to determine statistical significance.

Results

The study sample of 481 veterans had a mean age of 67.4 years, 94% were male, and 91.1% were white (Table 1). 

Scores for qSOFA, but not SIRS, were significantly associated with septic shock (Fisher’s exact test; qSOFA: P = .009; SIRS: P = .58) (Table 3). 

Discussion

High sensitivity is critical for a sepsis screening tool. To be clinically useful, it has been suggested that biomarkers predicting poor outcomes for sepsis should have a sensitivity of > 80%.⁴ Although qSOFA demonstrated greater specificity than SIRS in our study (83.6% vs 25.7%), qSOFA showed lower sensitivity (44.7% vs 80.0%), which resulted in a greater potential for false negatives; 55.3% of those with sepsis would go undetected. Therefore, our study does not support qSOFA as a better screening assessment than SIRS for sepsis in the veteran population.

Most studies concur with our findings of low sensitivity and high specificity of qSOFA. In a systematic review and meta-analysis, Serafim and colleagues identified 10 studies published after Sepsis-3 that reported sensitivity or specificity of qSOFA and SIRS for sepsis diagnosis.⁵ Seven of the 10 studies reported sensitivities and favored SIRS in the diagnosis of sepsis (Relative risk: 1.32; 95% CI: 0.40-2.24; P < .0001; I² = 100%). The authors noted that substantial heterogeneity among studies, including differences in study design, sample size, and criteria for determination of infection, was an important limitation. In addition, most studies that contrast qSOFA and SIRS center on prognostic value in predicting mortality, rather than as a screening test for a diagnosis of sepsis.

We concluded SIRS was more sensitive and thus superior to qSOFA when used as a screening tool for sepsis but conceded that more prospective and homogenous investigations were necessary. To our knowledge, only 1 published study has deviated from this conclusion and reported comparable sensitivity between SIRS (92%) and qSOFA (90%).⁶ Our study adds to existing literature as it is the first conducted in a veteran population. Additionally, we performed our investigation in a general medicine population with methods similar to existing literature, including the key study validating clinical criteria for sepsis by Seymour and colleagues.³

Limitations

This study is not without limitations, including potential misclassification of cases if essential data points were not available during data collection via health record review or the data points were not representative of a true change from baseline (eg, the Glasgow Coma Scale score for altered mental status in the qSOFA or the SOFA score for organ dysfunction). Generalizability of the results also may be limited due to our retrospective, single-center design and characteristics typical of a veteran population (eg, older, white males). Additionally, many veterans were excluded from the study if they transferred from another facility. These veterans may have been more critically ill than those who presented directly to our facility, which possibly introduced selection bias.

Conclusion

Our findings do not support use of the qSOFA as a suitable replacement for SIRS as a sepsis screening tool among patients with suspected infection in the general medicine inpatient setting. The clinical concern with SIRS is that unfavorable specificity leads to unnecessary antibiotic exposure among patients who are falsely positive. While qSOFA has demonstrated higher specificity, its use would cause many sepsis cases to go undetected due to the technique’s low sensitivity. Frequent false negative qSOFA results could thus serve to impede, rather than enhance, early recognition and intervention for sepsis.

The ideal sepsis screening tool is rapid and possesses high sensitivity and specificity to promptly identify and manage sepsis and avert unfavorable outcomes such as septic shock and death. While the SIRS criteria do not satisfy these ideal features, its measurement characteristics are more suitable for the application of sepsis screening than the qSOFA and should thus remain the standard tool in this setting. Future prospectively designed studies with more uniform methodologies are necessary to ascertain the most effective approach to identify sepsis for which novel screening approaches with more clinically suitable measurement properties are greatly needed.

Acknowledgements
This research was supported by the Iowa City VA Health Care System, Department of Pharmacy Services. Additional support was provided by the Health Services Research and Development Service, Department of Veterans Affairs.

Sepsis is a major public health concern: 10% of patients with sepsis die, and mortality quadruples with progression to septic shock.¹ Systemic inflammatory response syndrome (SIRS) criteria, originally published in 1992, are commonly used to detect sepsis, but as early as 2001, these criteria were recognized as lacking specificity.² Nonetheless, the use of SIRS criteria has persisted in practice. Sepsis was redefined in Sepsis-3 (2016) to guide earlier and more appropriate identification and treatment, which has been shown to greatly improve patient outcomes.^1,3 Key recommendations in Sepsis 3 included eliminating SIRS criteria, defining organ dysfunction by the Sequential Organ Failure Assessment (SOFA) score, and introducing the quick SOFA (qSOFA) score.¹

The qSOFA combines 3 clinical variables to provide a rapid, simple bedside score that measures the likelihood of poor outcomes, such as admission to an intensive care unit (ICU) or mortality in adults with suspected infection.^1,3 The qSOFA score is intended to aid healthcare professionals in more timely stratification of those patients who need escalated care to prevent deterioration.¹ The assessment also has been explored as a screening tool for sepsis in clinical practice; however, limited data exists concerning the comparative utility of qSOFA and SIRS in this capacity, and study results are inconsistent.^4-6

The most important attribute of a screening tool is high sensitivity, but high specificity also is desired. The qSOFA could supplant SIRS as a screening tool for sepsis if it maintained similarly high sensitivity but achieved superior specificity. Therefore, our primary objective for this study was to determine the effectiveness of qSOFA as a screening assessment for sepsis in the setting of a general inpatient medicine service by contrasting the sensitivity and specificity of qSOFA with SIRS in predicting sepsis, using a retrospective chart review design.

Methods

Administrative data from the Department of Veterans Affairs (VA) Corporate Data Warehouse were accessed via the VA Informatics and Computing Infrastructure (VINCI) and used to identify VA inpatient admissions and obtain the laboratory and vital sign data necessary to calculate SIRS, qSOFA, and SOFA scores. The data were supplemented by manual review of VA health records to obtain information that was not readily available in administrative records, including septic shock outcomes and laboratory and vital sign data obtained in the ICU. This study was approved by the institutional review board at the University of Iowa and the research and development committee at the Iowa City VA Medical Center (ICVAMC).

Patients

The study population included veterans admitted to the nonsurgical medicine unit at ICVAMC between August 1, 2014 and August 1, 2016 who were transferred to an ICU after admission; direct ICU admissions were not included as the qSOFA has been shown in studies to be more beneficial and offer better predictive validity outside the ICU. Excluding these direct admissions prevented any potential skewing of the data. To control for possible selection bias, veterans also were excluded if they transferred from another facility, were admitted under observation status, or if they had been admitted within the prior 30 days. These patients may have been more critically ill than those who presented directly to our facility and any prior treatment could affect the clinical status of the patient and assessment for sepsis at the time of presentation to the VA. Veterans were further required to have evidence of suspected infection based on manual review of the health record, which was determined by receipt of an antibiotic relevant to the empiric treatment of sepsis within 48 hours of admission.

Sepsis and Septic Shock Assessment Tools

As outlined in the Sepsis-3 guidelines, sepsis was defined as suspected or confirmed infection with an acute change in the SOFA score of ≥ 2 points, which is assumed to be 0 in those not known to have preexisting dysfunction.¹ The SOFA score includes variables from the respiratory, coagulation, hepatic, cardiovascular, renal, and central nervous systems.¹ Septic shock was defined as vasopressor administration and a serum lactic acid level > 2 mmol/L occurring up to 24 hours apart and within 3 days of the first antibiotic dose administered.

The SIRS assessment includes 4 clinical variables (temperature, heart rate, respiratory rate, and white blood cell count) while qSOFA is comprised of 3 variables (respiratory rate, systolic blood pressure, and altered mental status).¹ With both assessments, a score ≥ 2 is considered positive, which indicates increased risk for sepsis in patients with suspected infection.¹ In keeping with existing studies, qSOFA and SIRS assessments were scored using maximum values found within 48 hours before and 24 hours after the first administered antibiotic dose.³

Outcomes

The primary outcome variable was the presence of sepsis in adults with evidence of infection within 48 hours of admission. Secondary outcome measures included 30-day mortality and septic shock.

Performance between the SIRS and qSOFA assessments was contrasted using sensitivity, specificity, and positive and negative predictive value measurements. Associations of qSOFA and SIRS with septic shock and 30-day mortality were evaluated using a 2-tailed Fisher’s exact test with a threshold of α = 0.05 to determine statistical significance.

Results

The study sample of 481 veterans had a mean age of 67.4 years, 94% were male, and 91.1% were white (Table 1). 

Scores for qSOFA, but not SIRS, were significantly associated with septic shock (Fisher’s exact test; qSOFA: P = .009; SIRS: P = .58) (Table 3). 

Discussion

High sensitivity is critical for a sepsis screening tool. To be clinically useful, it has been suggested that biomarkers predicting poor outcomes for sepsis should have a sensitivity of > 80%.⁴ Although qSOFA demonstrated greater specificity than SIRS in our study (83.6% vs 25.7%), qSOFA showed lower sensitivity (44.7% vs 80.0%), which resulted in a greater potential for false negatives; 55.3% of those with sepsis would go undetected. Therefore, our study does not support qSOFA as a better screening assessment than SIRS for sepsis in the veteran population.

Most studies concur with our findings of low sensitivity and high specificity of qSOFA. In a systematic review and meta-analysis, Serafim and colleagues identified 10 studies published after Sepsis-3 that reported sensitivity or specificity of qSOFA and SIRS for sepsis diagnosis.⁵ Seven of the 10 studies reported sensitivities and favored SIRS in the diagnosis of sepsis (Relative risk: 1.32; 95% CI: 0.40-2.24; P < .0001; I² = 100%). The authors noted that substantial heterogeneity among studies, including differences in study design, sample size, and criteria for determination of infection, was an important limitation. In addition, most studies that contrast qSOFA and SIRS center on prognostic value in predicting mortality, rather than as a screening test for a diagnosis of sepsis.

We concluded SIRS was more sensitive and thus superior to qSOFA when used as a screening tool for sepsis but conceded that more prospective and homogenous investigations were necessary. To our knowledge, only 1 published study has deviated from this conclusion and reported comparable sensitivity between SIRS (92%) and qSOFA (90%).⁶ Our study adds to existing literature as it is the first conducted in a veteran population. Additionally, we performed our investigation in a general medicine population with methods similar to existing literature, including the key study validating clinical criteria for sepsis by Seymour and colleagues.³

Limitations

This study is not without limitations, including potential misclassification of cases if essential data points were not available during data collection via health record review or the data points were not representative of a true change from baseline (eg, the Glasgow Coma Scale score for altered mental status in the qSOFA or the SOFA score for organ dysfunction). Generalizability of the results also may be limited due to our retrospective, single-center design and characteristics typical of a veteran population (eg, older, white males). Additionally, many veterans were excluded from the study if they transferred from another facility. These veterans may have been more critically ill than those who presented directly to our facility, which possibly introduced selection bias.

Conclusion

Our findings do not support use of the qSOFA as a suitable replacement for SIRS as a sepsis screening tool among patients with suspected infection in the general medicine inpatient setting. The clinical concern with SIRS is that unfavorable specificity leads to unnecessary antibiotic exposure among patients who are falsely positive. While qSOFA has demonstrated higher specificity, its use would cause many sepsis cases to go undetected due to the technique’s low sensitivity. Frequent false negative qSOFA results could thus serve to impede, rather than enhance, early recognition and intervention for sepsis.

The ideal sepsis screening tool is rapid and possesses high sensitivity and specificity to promptly identify and manage sepsis and avert unfavorable outcomes such as septic shock and death. While the SIRS criteria do not satisfy these ideal features, its measurement characteristics are more suitable for the application of sepsis screening than the qSOFA and should thus remain the standard tool in this setting. Future prospectively designed studies with more uniform methodologies are necessary to ascertain the most effective approach to identify sepsis for which novel screening approaches with more clinically suitable measurement properties are greatly needed.

Acknowledgements
This research was supported by the Iowa City VA Health Care System, Department of Pharmacy Services. Additional support was provided by the Health Services Research and Development Service, Department of Veterans Affairs.

Sepsis is a major public health concern: 10% of patients with sepsis die, and mortality quadruples with progression to septic shock.¹ Systemic inflammatory response syndrome (SIRS) criteria, originally published in 1992, are commonly used to detect sepsis, but as early as 2001, these criteria were recognized as lacking specificity.² Nonetheless, the use of SIRS criteria has persisted in practice. Sepsis was redefined in Sepsis-3 (2016) to guide earlier and more appropriate identification and treatment, which has been shown to greatly improve patient outcomes.^1,3 Key recommendations in Sepsis 3 included eliminating SIRS criteria, defining organ dysfunction by the Sequential Organ Failure Assessment (SOFA) score, and introducing the quick SOFA (qSOFA) score.¹

The qSOFA combines 3 clinical variables to provide a rapid, simple bedside score that measures the likelihood of poor outcomes, such as admission to an intensive care unit (ICU) or mortality in adults with suspected infection.^1,3 The qSOFA score is intended to aid healthcare professionals in more timely stratification of those patients who need escalated care to prevent deterioration.¹ The assessment also has been explored as a screening tool for sepsis in clinical practice; however, limited data exists concerning the comparative utility of qSOFA and SIRS in this capacity, and study results are inconsistent.^4-6

The most important attribute of a screening tool is high sensitivity, but high specificity also is desired. The qSOFA could supplant SIRS as a screening tool for sepsis if it maintained similarly high sensitivity but achieved superior specificity. Therefore, our primary objective for this study was to determine the effectiveness of qSOFA as a screening assessment for sepsis in the setting of a general inpatient medicine service by contrasting the sensitivity and specificity of qSOFA with SIRS in predicting sepsis, using a retrospective chart review design.

Methods

Administrative data from the Department of Veterans Affairs (VA) Corporate Data Warehouse were accessed via the VA Informatics and Computing Infrastructure (VINCI) and used to identify VA inpatient admissions and obtain the laboratory and vital sign data necessary to calculate SIRS, qSOFA, and SOFA scores. The data were supplemented by manual review of VA health records to obtain information that was not readily available in administrative records, including septic shock outcomes and laboratory and vital sign data obtained in the ICU. This study was approved by the institutional review board at the University of Iowa and the research and development committee at the Iowa City VA Medical Center (ICVAMC).

Patients

The study population included veterans admitted to the nonsurgical medicine unit at ICVAMC between August 1, 2014 and August 1, 2016 who were transferred to an ICU after admission; direct ICU admissions were not included as the qSOFA has been shown in studies to be more beneficial and offer better predictive validity outside the ICU. Excluding these direct admissions prevented any potential skewing of the data. To control for possible selection bias, veterans also were excluded if they transferred from another facility, were admitted under observation status, or if they had been admitted within the prior 30 days. These patients may have been more critically ill than those who presented directly to our facility and any prior treatment could affect the clinical status of the patient and assessment for sepsis at the time of presentation to the VA. Veterans were further required to have evidence of suspected infection based on manual review of the health record, which was determined by receipt of an antibiotic relevant to the empiric treatment of sepsis within 48 hours of admission.

Sepsis and Septic Shock Assessment Tools

As outlined in the Sepsis-3 guidelines, sepsis was defined as suspected or confirmed infection with an acute change in the SOFA score of ≥ 2 points, which is assumed to be 0 in those not known to have preexisting dysfunction.¹ The SOFA score includes variables from the respiratory, coagulation, hepatic, cardiovascular, renal, and central nervous systems.¹ Septic shock was defined as vasopressor administration and a serum lactic acid level > 2 mmol/L occurring up to 24 hours apart and within 3 days of the first antibiotic dose administered.

The SIRS assessment includes 4 clinical variables (temperature, heart rate, respiratory rate, and white blood cell count) while qSOFA is comprised of 3 variables (respiratory rate, systolic blood pressure, and altered mental status).¹ With both assessments, a score ≥ 2 is considered positive, which indicates increased risk for sepsis in patients with suspected infection.¹ In keeping with existing studies, qSOFA and SIRS assessments were scored using maximum values found within 48 hours before and 24 hours after the first administered antibiotic dose.³

Outcomes

The primary outcome variable was the presence of sepsis in adults with evidence of infection within 48 hours of admission. Secondary outcome measures included 30-day mortality and septic shock.

Performance between the SIRS and qSOFA assessments was contrasted using sensitivity, specificity, and positive and negative predictive value measurements. Associations of qSOFA and SIRS with septic shock and 30-day mortality were evaluated using a 2-tailed Fisher’s exact test with a threshold of α = 0.05 to determine statistical significance.

Results

The study sample of 481 veterans had a mean age of 67.4 years, 94% were male, and 91.1% were white (Table 1). 

Scores for qSOFA, but not SIRS, were significantly associated with septic shock (Fisher’s exact test; qSOFA: P = .009; SIRS: P = .58) (Table 3). 

Discussion

High sensitivity is critical for a sepsis screening tool. To be clinically useful, it has been suggested that biomarkers predicting poor outcomes for sepsis should have a sensitivity of > 80%.⁴ Although qSOFA demonstrated greater specificity than SIRS in our study (83.6% vs 25.7%), qSOFA showed lower sensitivity (44.7% vs 80.0%), which resulted in a greater potential for false negatives; 55.3% of those with sepsis would go undetected. Therefore, our study does not support qSOFA as a better screening assessment than SIRS for sepsis in the veteran population.

Most studies concur with our findings of low sensitivity and high specificity of qSOFA. In a systematic review and meta-analysis, Serafim and colleagues identified 10 studies published after Sepsis-3 that reported sensitivity or specificity of qSOFA and SIRS for sepsis diagnosis.⁵ Seven of the 10 studies reported sensitivities and favored SIRS in the diagnosis of sepsis (Relative risk: 1.32; 95% CI: 0.40-2.24; P < .0001; I² = 100%). The authors noted that substantial heterogeneity among studies, including differences in study design, sample size, and criteria for determination of infection, was an important limitation. In addition, most studies that contrast qSOFA and SIRS center on prognostic value in predicting mortality, rather than as a screening test for a diagnosis of sepsis.

We concluded SIRS was more sensitive and thus superior to qSOFA when used as a screening tool for sepsis but conceded that more prospective and homogenous investigations were necessary. To our knowledge, only 1 published study has deviated from this conclusion and reported comparable sensitivity between SIRS (92%) and qSOFA (90%).⁶ Our study adds to existing literature as it is the first conducted in a veteran population. Additionally, we performed our investigation in a general medicine population with methods similar to existing literature, including the key study validating clinical criteria for sepsis by Seymour and colleagues.³

Limitations

This study is not without limitations, including potential misclassification of cases if essential data points were not available during data collection via health record review or the data points were not representative of a true change from baseline (eg, the Glasgow Coma Scale score for altered mental status in the qSOFA or the SOFA score for organ dysfunction). Generalizability of the results also may be limited due to our retrospective, single-center design and characteristics typical of a veteran population (eg, older, white males). Additionally, many veterans were excluded from the study if they transferred from another facility. These veterans may have been more critically ill than those who presented directly to our facility, which possibly introduced selection bias.

Conclusion

Our findings do not support use of the qSOFA as a suitable replacement for SIRS as a sepsis screening tool among patients with suspected infection in the general medicine inpatient setting. The clinical concern with SIRS is that unfavorable specificity leads to unnecessary antibiotic exposure among patients who are falsely positive. While qSOFA has demonstrated higher specificity, its use would cause many sepsis cases to go undetected due to the technique’s low sensitivity. Frequent false negative qSOFA results could thus serve to impede, rather than enhance, early recognition and intervention for sepsis.

The ideal sepsis screening tool is rapid and possesses high sensitivity and specificity to promptly identify and manage sepsis and avert unfavorable outcomes such as septic shock and death. While the SIRS criteria do not satisfy these ideal features, its measurement characteristics are more suitable for the application of sepsis screening than the qSOFA and should thus remain the standard tool in this setting. Future prospectively designed studies with more uniform methodologies are necessary to ascertain the most effective approach to identify sepsis for which novel screening approaches with more clinically suitable measurement properties are greatly needed.

Acknowledgements
This research was supported by the Iowa City VA Health Care System, Department of Pharmacy Services. Additional support was provided by the Health Services Research and Development Service, Department of Veterans Affairs.

The first death in the United States from the novel coronavirus (COVID-19) was a Washington state man in his 50s who had underlying health conditions, state health officials announced on Feb 29. At the same time, officials there are investigating a possible COVID-19 outbreak at a long-term care facility.

Washington state officials reported two other presumptive positive cases of COVID-19, both of whom are associated with LifeCare of Kirkland, Washington. One is a woman in her 70s who is a resident at the facility and the other is a woman in her 40s who is a health care worker at the facility.

Additionally, many residents and staff members at the facility have reported respiratory symptoms, according to Jeff Duchin, MD, health officer for public health in Seattle and King County. Among the more than 100 residents at the facility, 27 have respiratory symptoms; while among the 180 staff members, 25 have reported symptoms.

Overall, these reports bring the total number of U.S. COVID-19 cases detected by the public health system to 22, though that number is expected to climb as these investigations continue.

The general risk to the American public is still low, including residents in long-term care facilities, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during the Feb. 29 press briefing. Older people are are higher risk, however, and long-term care facilities should emphasize handwashing and the early identification of individuals with symptoms.

Dr. Duchin added that health care workers who are sick should stay home and that visitors should be screened for symptoms, the same advice offered to limit the spread of influenza at long-term care facilities.

Whitehouse.gov

The CDC briefing comes after President Trump held his own press conference at the White House where he identified the person who had died as being a woman in her 50s who was medically at risk.

During that press conference, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said that the current pattern of disease with COVID-19 suggests that 75%-80% of patients will have mild illness and recover, while 15%-20% will require advanced medical care.

For the most part, the more serious cases will occur in those who are elderly or have underlying medical conditions. There is “no indication” that individuals who recover from the virus are becoming re-infected, Dr. Fauci said.

The administration also announced a series of actions aimed at slowing the spread of the virus and responding to it. On March 2, President Trump will meet with leaders in the pharmaceutical industry at the White House to discuss vaccine development. The administration is also working to ensure an adequate supply of face masks. Vice President Mike Pence said there are currently more than 40 million masks available, but that the administration has received promises of 35 million more masks per month from manufacturers. Access to masks will be prioritized for high-risk health care workers, Vice President Pence said. “The average American does not need to go out and buy a mask,” he added.

Additionally, Vice President Pence announced new travel restrictions with Iran that would bar entry to the United States for any foreign national who visited Iran in the last 14 days. The federal government is also advising Americans not to travel to the regions in Italy and South Korea that have been most affected by COVID-19. The government is also working with officials in Italy and South Korea to conduct medical screening of anyone coming into the United States from those countries.

[email protected]

The first death in the United States from the novel coronavirus (COVID-19) was a Washington state man in his 50s who had underlying health conditions, state health officials announced on Feb 29. At the same time, officials there are investigating a possible COVID-19 outbreak at a long-term care facility.

Washington state officials reported two other presumptive positive cases of COVID-19, both of whom are associated with LifeCare of Kirkland, Washington. One is a woman in her 70s who is a resident at the facility and the other is a woman in her 40s who is a health care worker at the facility.

Additionally, many residents and staff members at the facility have reported respiratory symptoms, according to Jeff Duchin, MD, health officer for public health in Seattle and King County. Among the more than 100 residents at the facility, 27 have respiratory symptoms; while among the 180 staff members, 25 have reported symptoms.

Overall, these reports bring the total number of U.S. COVID-19 cases detected by the public health system to 22, though that number is expected to climb as these investigations continue.

The general risk to the American public is still low, including residents in long-term care facilities, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during the Feb. 29 press briefing. Older people are are higher risk, however, and long-term care facilities should emphasize handwashing and the early identification of individuals with symptoms.

Dr. Duchin added that health care workers who are sick should stay home and that visitors should be screened for symptoms, the same advice offered to limit the spread of influenza at long-term care facilities.

Whitehouse.gov

The CDC briefing comes after President Trump held his own press conference at the White House where he identified the person who had died as being a woman in her 50s who was medically at risk.

During that press conference, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said that the current pattern of disease with COVID-19 suggests that 75%-80% of patients will have mild illness and recover, while 15%-20% will require advanced medical care.

For the most part, the more serious cases will occur in those who are elderly or have underlying medical conditions. There is “no indication” that individuals who recover from the virus are becoming re-infected, Dr. Fauci said.

The administration also announced a series of actions aimed at slowing the spread of the virus and responding to it. On March 2, President Trump will meet with leaders in the pharmaceutical industry at the White House to discuss vaccine development. The administration is also working to ensure an adequate supply of face masks. Vice President Mike Pence said there are currently more than 40 million masks available, but that the administration has received promises of 35 million more masks per month from manufacturers. Access to masks will be prioritized for high-risk health care workers, Vice President Pence said. “The average American does not need to go out and buy a mask,” he added.

Additionally, Vice President Pence announced new travel restrictions with Iran that would bar entry to the United States for any foreign national who visited Iran in the last 14 days. The federal government is also advising Americans not to travel to the regions in Italy and South Korea that have been most affected by COVID-19. The government is also working with officials in Italy and South Korea to conduct medical screening of anyone coming into the United States from those countries.

[email protected]

The first death in the United States from the novel coronavirus (COVID-19) was a Washington state man in his 50s who had underlying health conditions, state health officials announced on Feb 29. At the same time, officials there are investigating a possible COVID-19 outbreak at a long-term care facility.

Washington state officials reported two other presumptive positive cases of COVID-19, both of whom are associated with LifeCare of Kirkland, Washington. One is a woman in her 70s who is a resident at the facility and the other is a woman in her 40s who is a health care worker at the facility.

Additionally, many residents and staff members at the facility have reported respiratory symptoms, according to Jeff Duchin, MD, health officer for public health in Seattle and King County. Among the more than 100 residents at the facility, 27 have respiratory symptoms; while among the 180 staff members, 25 have reported symptoms.

Overall, these reports bring the total number of U.S. COVID-19 cases detected by the public health system to 22, though that number is expected to climb as these investigations continue.

The general risk to the American public is still low, including residents in long-term care facilities, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention, said during the Feb. 29 press briefing. Older people are are higher risk, however, and long-term care facilities should emphasize handwashing and the early identification of individuals with symptoms.

Dr. Duchin added that health care workers who are sick should stay home and that visitors should be screened for symptoms, the same advice offered to limit the spread of influenza at long-term care facilities.

Whitehouse.gov

The CDC briefing comes after President Trump held his own press conference at the White House where he identified the person who had died as being a woman in her 50s who was medically at risk.

During that press conference, Anthony S. Fauci, MD, director of the National Institute of Allergy and Infectious Diseases, said that the current pattern of disease with COVID-19 suggests that 75%-80% of patients will have mild illness and recover, while 15%-20% will require advanced medical care.

For the most part, the more serious cases will occur in those who are elderly or have underlying medical conditions. There is “no indication” that individuals who recover from the virus are becoming re-infected, Dr. Fauci said.

The administration also announced a series of actions aimed at slowing the spread of the virus and responding to it. On March 2, President Trump will meet with leaders in the pharmaceutical industry at the White House to discuss vaccine development. The administration is also working to ensure an adequate supply of face masks. Vice President Mike Pence said there are currently more than 40 million masks available, but that the administration has received promises of 35 million more masks per month from manufacturers. Access to masks will be prioritized for high-risk health care workers, Vice President Pence said. “The average American does not need to go out and buy a mask,” he added.

Additionally, Vice President Pence announced new travel restrictions with Iran that would bar entry to the United States for any foreign national who visited Iran in the last 14 days. The federal government is also advising Americans not to travel to the regions in Italy and South Korea that have been most affected by COVID-19. The government is also working with officials in Italy and South Korea to conduct medical screening of anyone coming into the United States from those countries.

[email protected]

WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.

More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.

To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.

The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.

Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.

The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.

“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”

The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.

The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.

Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.

[email protected]

SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.

WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.

More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.

To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.

The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.

Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.

The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.

“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”

The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.

The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.

Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.

[email protected]

SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.

WEST PALM BEACH, FLA. – Among patients with relapsing-remitting multiple sclerosis (MS), depression increases the likelihood of having worse neurologic function one year later, according to a study presented at ACTRIMS Forum 2020. Patients’ subjective descriptions of disease activity did not significantly change during that time, which “suggests that depression is not merely a reactive phenomenon, but rather an independent contributor to clinical worsening in the long term,” said Jenny Feng, MD, a neuroimmunology fellow at the Mellen Center for MS Treatment and Research at the Cleveland Clinic.

The researchers hypothesize that depression’s influence on psychomotor function may contribute to clinical worsening in MS.

More than half of patients with MS have depression, and there is a higher prevalence of depression in relapsing-remitting MS than in progressive disease. “Depression is associated with systemic inflammation,” Dr. Feng said at the meeting held by the Americas Committee for Treatment and Research in Multiple Sclerosis. “We know that depressed individuals tend to have slower walking speeds, slower processing speeds, and worse quality of life measures.” But neurologists do not know whether patients feel depressed because the disease is getting worse, or whether depression is an independent contributing factor to MS, Dr. Feng said.

To examine whether depression affects neurologic performance and disease activity in patients with MS, Dr. Feng and colleagues analyzed real-world data from about 2,400 patients in MS PATHS (Multiple Sclerosis Partners Advancing Technology and Health Solutions), a network of centers in the United States and Europe. The researchers assessed the longitudinal relationship between depression, measures of neurologic function, and MRI metrics.

The researchers included patients with relapsing-remitting MS who had clinical and imaging data available at baseline and about 1 year later. Patients completed tests of manual dexterity, walking speed, and processing speed that are based on the Multiple Sclerosis Functional Composite. A worsening of 20% on any measure is considered clinically significant.

Patients had a mean age of about 45 years and mean disease duration of about 14 years. Patients with a T score greater than 45 on the Neuro-QoL depression questionnaire were classified as having depression, and approximately half of the population had depression. Patients with depression were more likely to have an employment status of disabled and to receive infusion medications.

The investigators used propensity score analysis to adjust for baseline differences between patients with and without depression and evaluated the effect of depression on year 1 outcome measures using logistic regression for categorical variables and linear regression for continuous variables.

“After propensity weighting for baseline covariates including neuroperformance scores, individuals with depression continued to worsen,” Dr. Feng said. Patients with depression were more likely to have a 20% worsening in at least one measure of neurologic performance at year 1 (odds ratio, 1.31). “There was a trend for increased odds of interval relapses, increased T2 lesion burden, and contrast-enhancing lesions at year 1” in patients with depression, but the results were not statistically significant. “Despite worsening neuroperformance at year 1 in individuals with baseline depression, their [patient-reported outcomes] at year 1 were not significantly worse.”

The researcher lacked information about the date of depression onset and medication compliance, Dr. Feng said. In addition, propensity weighting does not account for potential bias due to missing data.

The findings support the existing practice of actively screening for and treating depression in patients with MS, Dr. Feng said.

Dr. Feng had no disclosures. Coauthors have consulted for and received research support from pharmaceutical companies. MS PATHS is supported by Biogen.

[email protected]

SOURCE: Feng JJ et al. ACTRIMS Forum 2020. Abstract P226.

In a telebriefing on the COVID-19 outbreak, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention announced that the agency has updated the definition of “Person Under Investigation,” or PUI, for the disease.

The definition has been revised “to meet the needs of this rapidly evolving situation,” she said. The new PUI definition includes travel to more geographic areas to reflect this past week’s marked uptick in coronavirus activity in Italy and Iran. In addition to these countries and China, recent travel to Japan or South Korea also constitutes an epidemiologic risk factor which, in conjunction with clinical features, warrant an individual being classified as a PUI. These five countries each now have widespread person-to-person transmission of the virus.

Dr. Messonnier left open the possibility that the PUI definition would continue to evolve if such transmission within communities becomes more common. Asked whether the small number of U.S. cases thus might be an artifact of low test volumes, she said, “We aggressively controlled our borders to slow the spread. This was an intentional U.S. strategy. The CDC has always had the capacity to test rapidly from the time the sequence was available. ...We have been testing aggressively.”

The original PUI definition, she explained, emphasized individuals with fever, cough, or trouble breathing who had traveled recently from areas with COVID-19 activity, in particular China’s Hubei province. “We have been most focused on symptomatic people who are closely linked to, or who had, travel history, but our criteria also allow for clinical discretion,” she said. “There is no substitute for an astute clinician on the front lines of patient care.”

The first COVID-19 case from person-to-person spread was reported on Feb. 27. “At this time, we don’t know how or where this person became infected,” said Dr. Messonnier, although investigations are still underway. She responded to a question about whether the CDC delayed allowing COVID-19 testing for the patient for several days, as was reported in some media accounts. “According to CDC records, the first call we got was Feb. 23,” when public health officials in California reported a severely ill person with no travel abroad and no known contacts with individuals that would trigger suspicions for coronavirus. The CDC recommended COVID-19 testing on that day, she said.

Dr. Messonnier declined to answer questions about a whistleblower report alleging improper training and inadequate protective measures for Department of Health & Human Services workers at the quarantine center at Travis Air Force Base, Calif.

Dr. Messonnier said that the CDC has been working closely with the Food and Drug Administration to address problems with the COVID-19 test kits that were unusable because of a large number of indeterminate results. The two agencies together have determined that of the three reactions that were initially deemed necessary for a definitive COVID-19 diagnosis, just two are sufficient, so new kits that omit the problematic chemical are being manufactured and distributed.

These new kits are rapidly being made available; the goal, said Dr. Messonnier, is to have to state and local public health departments equipped with test kits by about March 7.

As local tests become available, the most updated information will be coming from state and local public health departments, she stressed, adding that the CDC would continue to update case counts on Monday, Wednesday, and Friday of each week. Procedures are being developed for the management of patients presumed to have COVID-19, where local health departments see positive tests but the mandatory CDC confirmatory test hasn’t been completed.

While new cases emerge across Europe and Asia, China’s earlier COVID-19 explosion seems to be slowing. “It’s really good news that the case counts in China are decreasing,” both for the well-being of that country’s citizens, and as a sign of the disease’s potential global effects, said Dr. Messonnier. She added that epidemiologists and mathematical modelers are parsing case fatality rates as well.

She advised health care providers and public health officials to keep abreast of changes in CDC guidance by checking frequently at https://www.cdc.gov/coronavirus/2019-ncov/index.html.

[email protected]

In a telebriefing on the COVID-19 outbreak, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention announced that the agency has updated the definition of “Person Under Investigation,” or PUI, for the disease.

The definition has been revised “to meet the needs of this rapidly evolving situation,” she said. The new PUI definition includes travel to more geographic areas to reflect this past week’s marked uptick in coronavirus activity in Italy and Iran. In addition to these countries and China, recent travel to Japan or South Korea also constitutes an epidemiologic risk factor which, in conjunction with clinical features, warrant an individual being classified as a PUI. These five countries each now have widespread person-to-person transmission of the virus.

Dr. Messonnier left open the possibility that the PUI definition would continue to evolve if such transmission within communities becomes more common. Asked whether the small number of U.S. cases thus might be an artifact of low test volumes, she said, “We aggressively controlled our borders to slow the spread. This was an intentional U.S. strategy. The CDC has always had the capacity to test rapidly from the time the sequence was available. ...We have been testing aggressively.”

The original PUI definition, she explained, emphasized individuals with fever, cough, or trouble breathing who had traveled recently from areas with COVID-19 activity, in particular China’s Hubei province. “We have been most focused on symptomatic people who are closely linked to, or who had, travel history, but our criteria also allow for clinical discretion,” she said. “There is no substitute for an astute clinician on the front lines of patient care.”

The first COVID-19 case from person-to-person spread was reported on Feb. 27. “At this time, we don’t know how or where this person became infected,” said Dr. Messonnier, although investigations are still underway. She responded to a question about whether the CDC delayed allowing COVID-19 testing for the patient for several days, as was reported in some media accounts. “According to CDC records, the first call we got was Feb. 23,” when public health officials in California reported a severely ill person with no travel abroad and no known contacts with individuals that would trigger suspicions for coronavirus. The CDC recommended COVID-19 testing on that day, she said.

Dr. Messonnier declined to answer questions about a whistleblower report alleging improper training and inadequate protective measures for Department of Health & Human Services workers at the quarantine center at Travis Air Force Base, Calif.

Dr. Messonnier said that the CDC has been working closely with the Food and Drug Administration to address problems with the COVID-19 test kits that were unusable because of a large number of indeterminate results. The two agencies together have determined that of the three reactions that were initially deemed necessary for a definitive COVID-19 diagnosis, just two are sufficient, so new kits that omit the problematic chemical are being manufactured and distributed.

These new kits are rapidly being made available; the goal, said Dr. Messonnier, is to have to state and local public health departments equipped with test kits by about March 7.

As local tests become available, the most updated information will be coming from state and local public health departments, she stressed, adding that the CDC would continue to update case counts on Monday, Wednesday, and Friday of each week. Procedures are being developed for the management of patients presumed to have COVID-19, where local health departments see positive tests but the mandatory CDC confirmatory test hasn’t been completed.

While new cases emerge across Europe and Asia, China’s earlier COVID-19 explosion seems to be slowing. “It’s really good news that the case counts in China are decreasing,” both for the well-being of that country’s citizens, and as a sign of the disease’s potential global effects, said Dr. Messonnier. She added that epidemiologists and mathematical modelers are parsing case fatality rates as well.

She advised health care providers and public health officials to keep abreast of changes in CDC guidance by checking frequently at https://www.cdc.gov/coronavirus/2019-ncov/index.html.

[email protected]

In a telebriefing on the COVID-19 outbreak, Nancy Messonnier, MD, director of the National Center for Immunization and Respiratory Diseases at the Centers for Disease Control and Prevention announced that the agency has updated the definition of “Person Under Investigation,” or PUI, for the disease.

The definition has been revised “to meet the needs of this rapidly evolving situation,” she said. The new PUI definition includes travel to more geographic areas to reflect this past week’s marked uptick in coronavirus activity in Italy and Iran. In addition to these countries and China, recent travel to Japan or South Korea also constitutes an epidemiologic risk factor which, in conjunction with clinical features, warrant an individual being classified as a PUI. These five countries each now have widespread person-to-person transmission of the virus.

Dr. Messonnier left open the possibility that the PUI definition would continue to evolve if such transmission within communities becomes more common. Asked whether the small number of U.S. cases thus might be an artifact of low test volumes, she said, “We aggressively controlled our borders to slow the spread. This was an intentional U.S. strategy. The CDC has always had the capacity to test rapidly from the time the sequence was available. ...We have been testing aggressively.”

The original PUI definition, she explained, emphasized individuals with fever, cough, or trouble breathing who had traveled recently from areas with COVID-19 activity, in particular China’s Hubei province. “We have been most focused on symptomatic people who are closely linked to, or who had, travel history, but our criteria also allow for clinical discretion,” she said. “There is no substitute for an astute clinician on the front lines of patient care.”

The first COVID-19 case from person-to-person spread was reported on Feb. 27. “At this time, we don’t know how or where this person became infected,” said Dr. Messonnier, although investigations are still underway. She responded to a question about whether the CDC delayed allowing COVID-19 testing for the patient for several days, as was reported in some media accounts. “According to CDC records, the first call we got was Feb. 23,” when public health officials in California reported a severely ill person with no travel abroad and no known contacts with individuals that would trigger suspicions for coronavirus. The CDC recommended COVID-19 testing on that day, she said.

Dr. Messonnier declined to answer questions about a whistleblower report alleging improper training and inadequate protective measures for Department of Health & Human Services workers at the quarantine center at Travis Air Force Base, Calif.

Dr. Messonnier said that the CDC has been working closely with the Food and Drug Administration to address problems with the COVID-19 test kits that were unusable because of a large number of indeterminate results. The two agencies together have determined that of the three reactions that were initially deemed necessary for a definitive COVID-19 diagnosis, just two are sufficient, so new kits that omit the problematic chemical are being manufactured and distributed.

These new kits are rapidly being made available; the goal, said Dr. Messonnier, is to have to state and local public health departments equipped with test kits by about March 7.

As local tests become available, the most updated information will be coming from state and local public health departments, she stressed, adding that the CDC would continue to update case counts on Monday, Wednesday, and Friday of each week. Procedures are being developed for the management of patients presumed to have COVID-19, where local health departments see positive tests but the mandatory CDC confirmatory test hasn’t been completed.

While new cases emerge across Europe and Asia, China’s earlier COVID-19 explosion seems to be slowing. “It’s really good news that the case counts in China are decreasing,” both for the well-being of that country’s citizens, and as a sign of the disease’s potential global effects, said Dr. Messonnier. She added that epidemiologists and mathematical modelers are parsing case fatality rates as well.

She advised health care providers and public health officials to keep abreast of changes in CDC guidance by checking frequently at https://www.cdc.gov/coronavirus/2019-ncov/index.html.

[email protected]

The VA has released an updated list of locations outside of Vietnam where tactical herbicides have been used, tested, or stored by the US military. The list, which includes the “rainbow” herbicides (Agents Orange, Pink, Green, Purple, Blue, and White), comes from the DoD, after a “thorough review” of research, reports, and government publications in response to a November 2018 US Government Accountability Office (GAO) report.

The GAO made 6 recommendations, including that the DoD develop a process for updating the list, and that the DoD and the VA develop a process for coordinating the communication of the information. The DoD concurred with 4 recommendations.

The VA, responding to the GAO report, said it was “concerned that the report conflates the terms commercial herbicides with tactical herbicides, which are distinct from one another.” Certain testing and storage locations (eg, Kelly Air Force Base), it noted, are added to the list based on the presence of commercial herbicides or “mere components” of Agent Orange or other rainbow agents.

The distinction is important for veterans applying for disability benefits. The impetus for creating the list of testing and storage sites, the VA says, was to carry out the administration of providing disability benefits in accordance with the applicable Agent Orange statute and regulations. Exposure to tactical herbicides (herbicides intended for military operations in Vietnam) is required for the VA to grant benefits on a presumptive basis for Agent Orange conditions outside of Vietnam. Thus, the VA concludes in its response, unless the commercial herbicides were the “same composition, forms, and mixtures” as the estimated 20 million gallons of rainbow agents specifically produced for operations in Vietnam, the “discussion is misleading.”

The VA also did not concur with the recommendation that it take the lead on developing “clear and transparent criteria” for what constitutes a location to be included on the list.

The DoD and VA did agree with the recommendation that the DoD should be the lead agency for producing and updating the list, while the VA will be the lead agency in providing information to veterans. The list will be updated as verifiable information becomes available, said Defense Secretary Mark Esper.

The full list of locations is available at https://www.publichealth.va.gov/docs/agentorange/dod_herbicides_outside_vietnam.pdf.
The GAO report is available at https://www.gao.gov/assets/gao-19-24.pdf.