Mixed Topics

SNOWMASS, COLO. – The tragic opioid epidemic has “one small bright spot”: an expanding pool of eligible donor hearts for transplantation, Akshay S. Desai, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

For decades, the annual volume of heart transplantations performed in the U.S. was static because of the huge mismatch between donor organ supply and demand. But heart transplant volume has increased steadily in the last few years – a result of the opioid epidemic.

Data from the U.S. Organ Procurement and Transplantation Network show that the proportion of donor hearts obtained from individuals who died from drug intoxication climbed from a mere 1.5% in 1999 to 17.6% in 2017, the most recent year for which data are available. Meanwhile, the size of the heart transplant waiting list, which rose year after year in 2009-2015, has since declined (N Engl J Med. 2019 Feb 7;380[6]:597-9).

“What’s amazing is that, even though these patients might have historically been considered high risk in general, the organs recovered from these patients – and particularly the hearts – don’t seem to be any worse in terms of allograft survival than the organs recovered from patients who died from other causes, which are the traditional sources, like blunt head trauma, gunshot wounds, or stroke, that lead to brain death. In general, these organs are useful and do quite well,” according to Dr. Desai, medical director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital, Boston.

He highlighted several other recent developments in the field of cardiac transplantation that promise to further expand the donor heart pool, including acceptance of hepatitis C–infected donors and organ donation after circulatory rather than brain death. Dr. Desai also drew attention to the unintended perverse consequences of a recent redesign of the U.S. donor heart allocation system and discussed the impressive improvement in clinical outcomes with mechanical circulatory support. He noted that, while relatively few cardiologists practice in the highly specialized centers where heart transplants take place, virtually all cardiologists are affected by advances in heart transplantation since hundreds of thousands of the estimated 7 million Americans with heart failure have advanced disease.

Heart transplantation, he emphasized, is becoming increasingly complex. Recipients are on average older, sicker, and have more comorbidities than in times past. As a result, there is greater need for dual organ transplants: heart/lung, heart/liver, or heart/kidney. Plus, more patients come to transplantation after prior cardiac surgery for implantation of a ventricular assist device, so sensitization to blood products is a growing issue. And, of course, the pool of transplant candidates has expanded.

“We’re now forced to take patients previously considered to have contraindications to transplant; for example, diabetes was a contraindication to transplant in the early years, but now it’s the rule in 35%-40% of our patients who present with advanced heart failure,” the cardiologist noted.
 

Transplants from HCV-infected donors to uninfected recipients

Hearts and lungs from donors with hepatitis C viremia were traditionally deemed unsuitable for transplant. That’s all changed in the current era of highly effective direct-acting antiviral agents for the treatment of HCV infection.

In the DONATE HCV trial, Dr. Desai’s colleagues at Brigham and Women’s Hospital showed that giving HCV-uninfected recipients of hearts or lungs from HCV-viremic donors a shortened 4-week course of treatment with sofosbuvir-velpatasvir (Epclusa) beginning within a few hours after transplantation uniformly blocked viral replication. Six months after transplantation, none of the study participants had a detectable HCV viral load, and all had excellent graft function (N Engl J Med. 2019 Apr 25;380[17]:1606-17).

“This is effective prevention of HCV infection by aggressive upfront therapy,” Dr. Desai explained. “We can now take organs from HCV-viremic patients and use them in solid organ transplantation. This has led to a skyrocketing increase in donors with HCV infection, and those donations have helped us clear the waiting list.”
 

Donation after circulatory death

Australian transplant physicians have pioneered the use of donor hearts obtained after circulatory death in individuals with devastating neurologic injury who didn’t quite meet the criteria for brain death, which is the traditional prerequisite. In the new scenario, withdrawal of life-supporting therapy is followed by circulatory death, then the donor heart is procured and preserved via extracorporeal perfusion until transplantation.

The Australians report excellent outcomes, with rates of overall survival and rejection episodes similar to outcomes from brain-dead donors (J Am Coll Cardiol. 2019 Apr 2;73[12]:1447-59). The first U.S. heart transplant involving donation after circulatory death took place at Duke University in Durham, North Carolina. A multicenter U.S. clinical trial of this practice is underway.

If the results are positive and the practice of donation after circulatory death becomes widely implemented, the U.S. heart donor pool could increase by 30%.
 

Recent overhaul of donor heart allocation system may have backfired

The U.S. donor heart allocation system was redesigned in the fall of 2018 in an effort to reduce waiting times. One of the biggest changes involved breaking down the category with the highest urgency status into three new subcategories based upon sickness. Now, the highest-urgency category is for patients in cardiogenic shock who are supported by extracorporeal membrane oxygenation (ECMO) or other temporary mechanical circulatory support devices.

But an analysis of United Network for Organ Sharing (UNOS) data suggests this change has unintended adverse consequences for clinical outcomes.

Indeed, the investigators reported that the use of ECMO support is fourfold greater in the new system, the use of durable left ventricular assist devices (LVADs) as a bridge to transplant is down, and outcomes are worse. The 180-day rate of freedom from death or retransplantation was 77.9%, down significantly from 93.4% in the former system. In a multivariate analysis, patients transplanted in the new system had an adjusted 2.1-fold increased risk of death or retransplantation (J Heart Lung Transplant. 2020 Jan;39[1]:1-4).

“When you create a new listing system, you create new incentives, and people start to manage patients differently,” Dr. Desai observed. “Increasingly now, the path direct to transplant is through temporary mechanical circulatory support rather than durable mechanical circulatory support. Is that a good idea? We don’t know, but if you look at the best data, those on ECMO or percutaneous VADs have the worst outcomes. So the question of whether we should take the sickest of sick patients directly to transplant as a standard strategy has come under scrutiny.”
 

Improved durable LVAD technology brings impressive clinical outcomes

Results of the landmark MOMENTUM 3 randomized trial showed that 2-year clinical outcomes with the magnetically levitated centrifugal-flow HeartMate 3 LVAD now rival those of percutaneous mitral valve repair using the MitraClip device. Two-year all-cause mortality in the LVAD recipients was 22% versus 29.1% with the MitraClip in the COAPT trial and 34.9% in the MITRA-FR trial. The HeartMate 3 reduces the hemocompatibility issues that plagued earlier-generation durable LVADs, with resultant lower rates of pump thrombosis, stroke, and GI bleeding. Indeed, the outcomes in MOMENTUM 3 were so good – and so similar – with the HeartMate 3, regardless of whether the intended treatment goal was as a bridge to transplant or as lifelong destination therapy, that the investigators have recently proposed doing away with those distinctions.

“It is possible that use of arbitrary categorizations based on current or future transplant eligibility should be clinically abandoned in favor of a single preimplant strategy: to extend the survival and improve the quality of life of patients with medically refractory heart failure,” according to the investigators (JAMA Cardiol. 2020 Jan 15. doi: 10.1001/jamacardio.2019.5323).

The next step forward in LVAD technology is already on the horizon: a fully implantable device that eliminates the transcutaneous drive-line for the power supply, which is prone to infection and diminishes overall quality of life. This investigational device utilizes wireless coplanar energy transfer, with a coil ring placed around the lung and fixed to the chest wall. The implanted battery provides more than 6 hours of power without a recharge (J Heart Lung Transplant. 2019 Apr;38[4]:339-43).

“The first LVAD patient has gone swimming in Kazakhstan,” according to Dr. Desai.

Myocardial recovery in LVAD recipients remains elusive

The initial hope for LVADs was that they would not only be able to serve as a bridge to transplantation or as lifetime therapy, but that the prolonged unloading of the ventricle would enable potent medical therapy to rescue myocardial function so that the device could eventually be explanted. That does happen, but only rarely. In a large registry study, myocardial recovery occurred in only about 1% of patients on mechanical circulatory support. Attempts to enhance the process by add-on stem cell therapy have thus far been ineffective.

“For the moment, recovery is still a hope, not a reality,” the cardiologist said.

He reported serving as a consultant to more than a dozen pharmaceutical or medical device companies and receiving research grants from Alnylam, AstraZeneca, Bayer Healthcare, MyoKardia, and Novartis.

[email protected]
 

SNOWMASS, COLO. – The tragic opioid epidemic has “one small bright spot”: an expanding pool of eligible donor hearts for transplantation, Akshay S. Desai, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

For decades, the annual volume of heart transplantations performed in the U.S. was static because of the huge mismatch between donor organ supply and demand. But heart transplant volume has increased steadily in the last few years – a result of the opioid epidemic.

Data from the U.S. Organ Procurement and Transplantation Network show that the proportion of donor hearts obtained from individuals who died from drug intoxication climbed from a mere 1.5% in 1999 to 17.6% in 2017, the most recent year for which data are available. Meanwhile, the size of the heart transplant waiting list, which rose year after year in 2009-2015, has since declined (N Engl J Med. 2019 Feb 7;380[6]:597-9).

“What’s amazing is that, even though these patients might have historically been considered high risk in general, the organs recovered from these patients – and particularly the hearts – don’t seem to be any worse in terms of allograft survival than the organs recovered from patients who died from other causes, which are the traditional sources, like blunt head trauma, gunshot wounds, or stroke, that lead to brain death. In general, these organs are useful and do quite well,” according to Dr. Desai, medical director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital, Boston.

He highlighted several other recent developments in the field of cardiac transplantation that promise to further expand the donor heart pool, including acceptance of hepatitis C–infected donors and organ donation after circulatory rather than brain death. Dr. Desai also drew attention to the unintended perverse consequences of a recent redesign of the U.S. donor heart allocation system and discussed the impressive improvement in clinical outcomes with mechanical circulatory support. He noted that, while relatively few cardiologists practice in the highly specialized centers where heart transplants take place, virtually all cardiologists are affected by advances in heart transplantation since hundreds of thousands of the estimated 7 million Americans with heart failure have advanced disease.

Heart transplantation, he emphasized, is becoming increasingly complex. Recipients are on average older, sicker, and have more comorbidities than in times past. As a result, there is greater need for dual organ transplants: heart/lung, heart/liver, or heart/kidney. Plus, more patients come to transplantation after prior cardiac surgery for implantation of a ventricular assist device, so sensitization to blood products is a growing issue. And, of course, the pool of transplant candidates has expanded.

“We’re now forced to take patients previously considered to have contraindications to transplant; for example, diabetes was a contraindication to transplant in the early years, but now it’s the rule in 35%-40% of our patients who present with advanced heart failure,” the cardiologist noted.
 

Transplants from HCV-infected donors to uninfected recipients

Hearts and lungs from donors with hepatitis C viremia were traditionally deemed unsuitable for transplant. That’s all changed in the current era of highly effective direct-acting antiviral agents for the treatment of HCV infection.

In the DONATE HCV trial, Dr. Desai’s colleagues at Brigham and Women’s Hospital showed that giving HCV-uninfected recipients of hearts or lungs from HCV-viremic donors a shortened 4-week course of treatment with sofosbuvir-velpatasvir (Epclusa) beginning within a few hours after transplantation uniformly blocked viral replication. Six months after transplantation, none of the study participants had a detectable HCV viral load, and all had excellent graft function (N Engl J Med. 2019 Apr 25;380[17]:1606-17).

“This is effective prevention of HCV infection by aggressive upfront therapy,” Dr. Desai explained. “We can now take organs from HCV-viremic patients and use them in solid organ transplantation. This has led to a skyrocketing increase in donors with HCV infection, and those donations have helped us clear the waiting list.”
 

Donation after circulatory death

Australian transplant physicians have pioneered the use of donor hearts obtained after circulatory death in individuals with devastating neurologic injury who didn’t quite meet the criteria for brain death, which is the traditional prerequisite. In the new scenario, withdrawal of life-supporting therapy is followed by circulatory death, then the donor heart is procured and preserved via extracorporeal perfusion until transplantation.

The Australians report excellent outcomes, with rates of overall survival and rejection episodes similar to outcomes from brain-dead donors (J Am Coll Cardiol. 2019 Apr 2;73[12]:1447-59). The first U.S. heart transplant involving donation after circulatory death took place at Duke University in Durham, North Carolina. A multicenter U.S. clinical trial of this practice is underway.

If the results are positive and the practice of donation after circulatory death becomes widely implemented, the U.S. heart donor pool could increase by 30%.
 

Recent overhaul of donor heart allocation system may have backfired

The U.S. donor heart allocation system was redesigned in the fall of 2018 in an effort to reduce waiting times. One of the biggest changes involved breaking down the category with the highest urgency status into three new subcategories based upon sickness. Now, the highest-urgency category is for patients in cardiogenic shock who are supported by extracorporeal membrane oxygenation (ECMO) or other temporary mechanical circulatory support devices.

But an analysis of United Network for Organ Sharing (UNOS) data suggests this change has unintended adverse consequences for clinical outcomes.

Indeed, the investigators reported that the use of ECMO support is fourfold greater in the new system, the use of durable left ventricular assist devices (LVADs) as a bridge to transplant is down, and outcomes are worse. The 180-day rate of freedom from death or retransplantation was 77.9%, down significantly from 93.4% in the former system. In a multivariate analysis, patients transplanted in the new system had an adjusted 2.1-fold increased risk of death or retransplantation (J Heart Lung Transplant. 2020 Jan;39[1]:1-4).

“When you create a new listing system, you create new incentives, and people start to manage patients differently,” Dr. Desai observed. “Increasingly now, the path direct to transplant is through temporary mechanical circulatory support rather than durable mechanical circulatory support. Is that a good idea? We don’t know, but if you look at the best data, those on ECMO or percutaneous VADs have the worst outcomes. So the question of whether we should take the sickest of sick patients directly to transplant as a standard strategy has come under scrutiny.”
 

Improved durable LVAD technology brings impressive clinical outcomes

Results of the landmark MOMENTUM 3 randomized trial showed that 2-year clinical outcomes with the magnetically levitated centrifugal-flow HeartMate 3 LVAD now rival those of percutaneous mitral valve repair using the MitraClip device. Two-year all-cause mortality in the LVAD recipients was 22% versus 29.1% with the MitraClip in the COAPT trial and 34.9% in the MITRA-FR trial. The HeartMate 3 reduces the hemocompatibility issues that plagued earlier-generation durable LVADs, with resultant lower rates of pump thrombosis, stroke, and GI bleeding. Indeed, the outcomes in MOMENTUM 3 were so good – and so similar – with the HeartMate 3, regardless of whether the intended treatment goal was as a bridge to transplant or as lifelong destination therapy, that the investigators have recently proposed doing away with those distinctions.

“It is possible that use of arbitrary categorizations based on current or future transplant eligibility should be clinically abandoned in favor of a single preimplant strategy: to extend the survival and improve the quality of life of patients with medically refractory heart failure,” according to the investigators (JAMA Cardiol. 2020 Jan 15. doi: 10.1001/jamacardio.2019.5323).

The next step forward in LVAD technology is already on the horizon: a fully implantable device that eliminates the transcutaneous drive-line for the power supply, which is prone to infection and diminishes overall quality of life. This investigational device utilizes wireless coplanar energy transfer, with a coil ring placed around the lung and fixed to the chest wall. The implanted battery provides more than 6 hours of power without a recharge (J Heart Lung Transplant. 2019 Apr;38[4]:339-43).

“The first LVAD patient has gone swimming in Kazakhstan,” according to Dr. Desai.

Myocardial recovery in LVAD recipients remains elusive

The initial hope for LVADs was that they would not only be able to serve as a bridge to transplantation or as lifetime therapy, but that the prolonged unloading of the ventricle would enable potent medical therapy to rescue myocardial function so that the device could eventually be explanted. That does happen, but only rarely. In a large registry study, myocardial recovery occurred in only about 1% of patients on mechanical circulatory support. Attempts to enhance the process by add-on stem cell therapy have thus far been ineffective.

“For the moment, recovery is still a hope, not a reality,” the cardiologist said.

He reported serving as a consultant to more than a dozen pharmaceutical or medical device companies and receiving research grants from Alnylam, AstraZeneca, Bayer Healthcare, MyoKardia, and Novartis.

[email protected]
 

SNOWMASS, COLO. – The tragic opioid epidemic has “one small bright spot”: an expanding pool of eligible donor hearts for transplantation, Akshay S. Desai, MD, said at the annual Cardiovascular Conference at Snowmass sponsored by the American College of Cardiology.

Bruce Jancin/MDedge News

For decades, the annual volume of heart transplantations performed in the U.S. was static because of the huge mismatch between donor organ supply and demand. But heart transplant volume has increased steadily in the last few years – a result of the opioid epidemic.

Data from the U.S. Organ Procurement and Transplantation Network show that the proportion of donor hearts obtained from individuals who died from drug intoxication climbed from a mere 1.5% in 1999 to 17.6% in 2017, the most recent year for which data are available. Meanwhile, the size of the heart transplant waiting list, which rose year after year in 2009-2015, has since declined (N Engl J Med. 2019 Feb 7;380[6]:597-9).

“What’s amazing is that, even though these patients might have historically been considered high risk in general, the organs recovered from these patients – and particularly the hearts – don’t seem to be any worse in terms of allograft survival than the organs recovered from patients who died from other causes, which are the traditional sources, like blunt head trauma, gunshot wounds, or stroke, that lead to brain death. In general, these organs are useful and do quite well,” according to Dr. Desai, medical director of the cardiomyopathy and heart failure program at Brigham and Women’s Hospital, Boston.

He highlighted several other recent developments in the field of cardiac transplantation that promise to further expand the donor heart pool, including acceptance of hepatitis C–infected donors and organ donation after circulatory rather than brain death. Dr. Desai also drew attention to the unintended perverse consequences of a recent redesign of the U.S. donor heart allocation system and discussed the impressive improvement in clinical outcomes with mechanical circulatory support. He noted that, while relatively few cardiologists practice in the highly specialized centers where heart transplants take place, virtually all cardiologists are affected by advances in heart transplantation since hundreds of thousands of the estimated 7 million Americans with heart failure have advanced disease.

Heart transplantation, he emphasized, is becoming increasingly complex. Recipients are on average older, sicker, and have more comorbidities than in times past. As a result, there is greater need for dual organ transplants: heart/lung, heart/liver, or heart/kidney. Plus, more patients come to transplantation after prior cardiac surgery for implantation of a ventricular assist device, so sensitization to blood products is a growing issue. And, of course, the pool of transplant candidates has expanded.

“We’re now forced to take patients previously considered to have contraindications to transplant; for example, diabetes was a contraindication to transplant in the early years, but now it’s the rule in 35%-40% of our patients who present with advanced heart failure,” the cardiologist noted.
 

Transplants from HCV-infected donors to uninfected recipients

Hearts and lungs from donors with hepatitis C viremia were traditionally deemed unsuitable for transplant. That’s all changed in the current era of highly effective direct-acting antiviral agents for the treatment of HCV infection.

In the DONATE HCV trial, Dr. Desai’s colleagues at Brigham and Women’s Hospital showed that giving HCV-uninfected recipients of hearts or lungs from HCV-viremic donors a shortened 4-week course of treatment with sofosbuvir-velpatasvir (Epclusa) beginning within a few hours after transplantation uniformly blocked viral replication. Six months after transplantation, none of the study participants had a detectable HCV viral load, and all had excellent graft function (N Engl J Med. 2019 Apr 25;380[17]:1606-17).

“This is effective prevention of HCV infection by aggressive upfront therapy,” Dr. Desai explained. “We can now take organs from HCV-viremic patients and use them in solid organ transplantation. This has led to a skyrocketing increase in donors with HCV infection, and those donations have helped us clear the waiting list.”
 

Donation after circulatory death

Australian transplant physicians have pioneered the use of donor hearts obtained after circulatory death in individuals with devastating neurologic injury who didn’t quite meet the criteria for brain death, which is the traditional prerequisite. In the new scenario, withdrawal of life-supporting therapy is followed by circulatory death, then the donor heart is procured and preserved via extracorporeal perfusion until transplantation.

The Australians report excellent outcomes, with rates of overall survival and rejection episodes similar to outcomes from brain-dead donors (J Am Coll Cardiol. 2019 Apr 2;73[12]:1447-59). The first U.S. heart transplant involving donation after circulatory death took place at Duke University in Durham, North Carolina. A multicenter U.S. clinical trial of this practice is underway.

If the results are positive and the practice of donation after circulatory death becomes widely implemented, the U.S. heart donor pool could increase by 30%.
 

Recent overhaul of donor heart allocation system may have backfired

The U.S. donor heart allocation system was redesigned in the fall of 2018 in an effort to reduce waiting times. One of the biggest changes involved breaking down the category with the highest urgency status into three new subcategories based upon sickness. Now, the highest-urgency category is for patients in cardiogenic shock who are supported by extracorporeal membrane oxygenation (ECMO) or other temporary mechanical circulatory support devices.

But an analysis of United Network for Organ Sharing (UNOS) data suggests this change has unintended adverse consequences for clinical outcomes.

Indeed, the investigators reported that the use of ECMO support is fourfold greater in the new system, the use of durable left ventricular assist devices (LVADs) as a bridge to transplant is down, and outcomes are worse. The 180-day rate of freedom from death or retransplantation was 77.9%, down significantly from 93.4% in the former system. In a multivariate analysis, patients transplanted in the new system had an adjusted 2.1-fold increased risk of death or retransplantation (J Heart Lung Transplant. 2020 Jan;39[1]:1-4).

“When you create a new listing system, you create new incentives, and people start to manage patients differently,” Dr. Desai observed. “Increasingly now, the path direct to transplant is through temporary mechanical circulatory support rather than durable mechanical circulatory support. Is that a good idea? We don’t know, but if you look at the best data, those on ECMO or percutaneous VADs have the worst outcomes. So the question of whether we should take the sickest of sick patients directly to transplant as a standard strategy has come under scrutiny.”
 

Improved durable LVAD technology brings impressive clinical outcomes

Results of the landmark MOMENTUM 3 randomized trial showed that 2-year clinical outcomes with the magnetically levitated centrifugal-flow HeartMate 3 LVAD now rival those of percutaneous mitral valve repair using the MitraClip device. Two-year all-cause mortality in the LVAD recipients was 22% versus 29.1% with the MitraClip in the COAPT trial and 34.9% in the MITRA-FR trial. The HeartMate 3 reduces the hemocompatibility issues that plagued earlier-generation durable LVADs, with resultant lower rates of pump thrombosis, stroke, and GI bleeding. Indeed, the outcomes in MOMENTUM 3 were so good – and so similar – with the HeartMate 3, regardless of whether the intended treatment goal was as a bridge to transplant or as lifelong destination therapy, that the investigators have recently proposed doing away with those distinctions.

“It is possible that use of arbitrary categorizations based on current or future transplant eligibility should be clinically abandoned in favor of a single preimplant strategy: to extend the survival and improve the quality of life of patients with medically refractory heart failure,” according to the investigators (JAMA Cardiol. 2020 Jan 15. doi: 10.1001/jamacardio.2019.5323).

The next step forward in LVAD technology is already on the horizon: a fully implantable device that eliminates the transcutaneous drive-line for the power supply, which is prone to infection and diminishes overall quality of life. This investigational device utilizes wireless coplanar energy transfer, with a coil ring placed around the lung and fixed to the chest wall. The implanted battery provides more than 6 hours of power without a recharge (J Heart Lung Transplant. 2019 Apr;38[4]:339-43).

“The first LVAD patient has gone swimming in Kazakhstan,” according to Dr. Desai.

Myocardial recovery in LVAD recipients remains elusive

The initial hope for LVADs was that they would not only be able to serve as a bridge to transplantation or as lifetime therapy, but that the prolonged unloading of the ventricle would enable potent medical therapy to rescue myocardial function so that the device could eventually be explanted. That does happen, but only rarely. In a large registry study, myocardial recovery occurred in only about 1% of patients on mechanical circulatory support. Attempts to enhance the process by add-on stem cell therapy have thus far been ineffective.

“For the moment, recovery is still a hope, not a reality,” the cardiologist said.

He reported serving as a consultant to more than a dozen pharmaceutical or medical device companies and receiving research grants from Alnylam, AstraZeneca, Bayer Healthcare, MyoKardia, and Novartis.

[email protected]
 

Calciphylaxis, otherwise known as calcific uremic arteriolopathy, is characterized by calcification of the tunica media of the small- to medium-sized blood vessels of the dermis and subcutis, leading to ischemia and necrosis.¹ It is a deadly disease with a 1-year mortality rate of more than 50%.² End-stage renal disease (ESRD) is the most common risk factor for calciphylaxis, with a prevalence of 1% to 4% of hemodialysis patients with calciphylaxis in the United States.^2-5 However, nonuremic calciphylaxis (NUC) has been increasingly reported in the literature and has risk factors other than ESRD, including but not limited to obesity, alcoholic liver disease, primary hyperparathyroidism, connective tissue disease, and underlying malignancy.^3,6-9 Triggers for calciphylaxis in at-risk patients include use of corticosteroids or warfarin, iron or albumin infusions, and rapid weight loss.^3,6,9-11 We report an unusual case of NUC that most likely was triggered by rapid weight loss and hypotension in a patient with multiple risk factors for calciphylaxis.

Case Report

A 75-year-old white woman with history of morbid obesity (body mass index, 40 kg/m²), unexplained weight loss of 70 lb over the last year, and polymyalgia rheumatica requiring chronic prednisone therapy presented with painful lesions on the thighs, buttocks, and right shoulder of 4 months’ duration. She had multiple hospital admissions preceding the onset of lesions for severe infections resulting in sepsis with hypotension, including Enterococcus faecalis endocarditis, extended-spectrum beta-lactamase bacteremia, and Pseudomonas aeruginosa pneumonia. Physical examination revealed large well-demarcated ulcers and necrotic eschars with surrounding violaceous induration and stellate erythema on the anterior, medial, and posterior thighs and buttocks that were exquisitely tender (Figures 1 and 2).

Notable laboratory results included hypoalbuminemia (1.3 g/dL [reference range, 3.5–5.0 g/dL]) with normal renal function, a corrected calcium level of 9.7 mg/dL (reference range, 8.2–10.2 mg/dL), a serum phosphorus level of 3.5 mg/dL (reference range, 2.3–4.7 mg/dL), a calcium-phosphate product of 27.3 mg²/dL² (reference range, <55 mg²/dL²), and a parathyroid hormone level of 49.3 pg/mL (reference range, 10–65 pg/mL). Antinuclear antibodies were negative. A hypercoagulability evaluation showed normal protein C and S levels, negative lupus anticoagulant, and negative anticardiolipin antibodies.

Telescoping punch biopsies of the indurated borders of the eschars showed prominent calcification of the small- and medium-sized vessels in the mid and deep dermis, intravascular thrombi, and necrosis of the epidermis and subcutaneous fat consistent with calciphylaxis (Figure 3).

Comment

Background on Calciphylaxis
Calciphylaxis is a rare but deadly disease that affects both ESRD patients receiving dialysis and patients without ESRD who have known risk factors for calciphylaxis, including female gender, white race, obesity, alcoholic liver disease, primary hyperparathyroidism, connective tissue disease, underlying malignancy, protein C or S deficiency, corticosteroid use, warfarin use, diabetes, iron or albumin infusions, and rapid weight loss.^3,6-9,11 Although the molecular pathogenesis of calciphylaxis is not completely understood, it is believed to be caused by local deposition of calcium in the tunica media of small- to medium-sized arterioles and venules in the skin.¹² This deposition leads to intimal proliferation and progressive narrowing of the vessels with resultant thrombosis, ischemia, and necrosis. The cutaneous manifestations and histopathology of calciphylaxis classically follow its pathogenesis. Calciphylaxis typically presents with livedo reticularis as vessels narrow and then progresses to purpura, bullae, necrosis, and eschar formation with the onset of acute thrombosis and ischemia. Histopathology is characterized by small- and medium-sized vessel calcification and thrombus, dermal necrosis, and septal panniculitis, though the histology can be highly variable.¹² Unfortunately, the already poor prognosis for calciphylaxis worsens when lesions become either ulcerative or present on the proximal extremities and trunk.^4,13 Sepsis is the leading cause of death in calciphylaxis patients, affecting more than 50% of patients.^2,3,14 The differential diagnoses for calciphylactic-appearing lesions include warfarin-induced skin necrosis, disseminated intravascular coagulation, pyoderma gangrenosum, cholesterol emboli, and various vasculitides and coagulopathies.

Risk Factors
Our case demonstrates the importance of risk factor minimization, trigger avoidance, and early intervention due to the high mortality rate of calciphylaxis. Selye et al¹⁵ coined the term calciphylaxis in 1961 based on experiments that induced calciphylaxis in rat models. Their research concluded that there were certain sensitizers (ie, risk factors) that predisposed patients to medial calcium deposition in blood vessels and other challengers (ie, triggers) that acted as inciting events to calcium deposition. Our patient presented with multiple known risk factors for calciphylaxis, including obesity (body mass index, 40 kg/m²), female gender, white race, hypoalbuminemia, and chronic corticosteroid use.¹⁶ In the presence of a milieu of risk factors, the patient’s rapid weight loss and episodes of hypotension likely were triggers for calciphylaxis.

Other case reports in the literature have suggested weight loss as a trigger for NUC. One morbidly obese patient with inactive rheumatoid arthritis had onset of calciphylaxis lesions after unintentional weight loss of approximately 50% body weight in 1 year¹⁷; however, the weight loss does not have to be drastic to trigger calciphylaxis. Another study of 16 patients with uremic calciphylaxis found that 7 of 16 (44%) patients lost 10 to 50 kg in the 6 months prior to calciphylaxis onset.¹⁴ One proposed mechanism by Munavalli et al¹⁰ is that elevated levels of matrix metalloproteinases during catabolic weight loss states enhance the deposition of calcium into elastic fibers of small vessels. The authors found elevated serum levels of matrix metalloproteinases in their patients with NUC induced by rapid weight loss.¹⁰

A meta-analysis by Nigwekar et al³ found a history of prior corticosteroid use in 61% (22/36) of NUC cases reviewed. However, it is unclear whether it is the use of corticosteroids or chronic inflammation that is implicated in NUC pathogenesis. Chronic inflammation causes downregulation of anticalcification signaling pathways.^18-20 The role of 2 vascular calcification inhibitors has been evaluated in the pathogenesis of calciphylaxis: fetuin-A and matrix gla protein (MGP).²¹ The activity of these proteins is decreased not only in calciphylaxis but also in other inflammatory states and chronic renal failure.^18-20 One study found lower fetuin-A levels in 312 hemodialysis patients compared to healthy controls and an association between low fetuin-A levels and increased C-reactive protein levels.²² Reduced fetuin-A and MGP levels may be the result of several calciphylaxis risk factors. Warfarin is believed to trigger calciphylaxis via inhibition of gamma-carboxylation of MGP, which is necessary for its anticalcification activity.²³ Hypoalbuminemia and alcoholic liver disease also are risk factors that may be explained by the fact that fetuin-A is synthesized in the liver.²⁴ Therefore, liver disease results in decreased production of fetuin-A that is permissive to vascular calcification in calciphylaxis patients.

There have been other reports of calciphylaxis patients who were originally hospitalized due to hypotension, which may serve as a trigger for calciphylaxis onset.²⁵ Because calciphylaxis lesions are more likely to occur in the fatty areas of the abdomen and proximal thighs where blood flow is slower, hypotension likely accentuates the slowing of blood flow and subsequent blood vessel calcification. This theory is supported by studies showing that established calciphylactic lesions worsen more quickly in the presence of systemic hypotension.²⁶ One patient with ESRD and calciphylaxis of the breasts had consistent systolic blood pressure readings in the high 60s to low 70s between dialysis sessions.²⁷ Due to this association, we recommend that patients with calciphylaxis have close blood pressure monitoring to aid in preventing disease progression.²⁸

Management
Calciphylaxis treatment has not yet been standardized, as it is an uncommon disease whose pathogenesis is not fully understood. Current management strategies aim to normalize metabolic abnormalities such as hypercalcemia if they are present and remove inciting agents such as warfarin and corticosteroids.²⁹ Other medical treatments that have been successfully used include sodium thiosulfate, oral steroids, and adjunctive bisphosphonates.^29-31 Sodium thiosulfate is known to cause metabolic acidosis by generating thiosulfuric acid in vivo in patients with or without renal disease; therefore, patients on sodium thiosulfate therapy should be monitored for development of metabolic acidosis and treated with oral sodium bicarbonate or dialysis as needed.^30,32 Wound care also is an important element of calciphylaxis treatment; however, the debridement of wounds is controversial. Some argue that dry intact eschars serve to protect against sepsis, which is the leading cause of death in calciphylaxis.^2,14,33 In contrast, a retrospective study of 63 calciphylaxis patients found a 1-year survival rate of 61.6% in 17 patients receiving wound debridement vs 27.4% in 46 patients who did not.² The current consensus is that debridement should be considered on a case-by-case basis, factoring in the presence of wound infection, size of wounds, stability of eschars, and treatment goals of the patient.³⁴ Future studies should be aimed at this issue, with special focus on how these factors and the decision to debride or not impact patient outcomes.

Conclusion

Calciphylaxis is a potentially fatal disease that impacts both patients with ESRD and those with nonuremic risk factors. The term calcific uremic arteriolopathy should be disregarded, as nonuremic causes are being reported with increased frequency in the literature. In such cases, patients often have multiple risk factors, including obesity, primary hyperparathyroidism, alcoholic liver disease, and underlying malignancy, among others. Certain triggers for onset of calciphylaxis should be avoided in at-risk patients, including the use of corticosteroids or warfarin; iron and albumin infusions; hypotension; and rapid weight loss. Our fatal case of NUC is a reminder to dermatologists treating at-risk patients to avoid these triggers and to keep calciphylaxis in the differential diagnosis when encountering early lesions such as livedo reticularis, as progression of these lesions has a 1-year mortality rate of more than 50% with the therapies being utilized at this time.

Calciphylaxis, otherwise known as calcific uremic arteriolopathy, is characterized by calcification of the tunica media of the small- to medium-sized blood vessels of the dermis and subcutis, leading to ischemia and necrosis.¹ It is a deadly disease with a 1-year mortality rate of more than 50%.² End-stage renal disease (ESRD) is the most common risk factor for calciphylaxis, with a prevalence of 1% to 4% of hemodialysis patients with calciphylaxis in the United States.^2-5 However, nonuremic calciphylaxis (NUC) has been increasingly reported in the literature and has risk factors other than ESRD, including but not limited to obesity, alcoholic liver disease, primary hyperparathyroidism, connective tissue disease, and underlying malignancy.^3,6-9 Triggers for calciphylaxis in at-risk patients include use of corticosteroids or warfarin, iron or albumin infusions, and rapid weight loss.^3,6,9-11 We report an unusual case of NUC that most likely was triggered by rapid weight loss and hypotension in a patient with multiple risk factors for calciphylaxis.

Case Report

A 75-year-old white woman with history of morbid obesity (body mass index, 40 kg/m²), unexplained weight loss of 70 lb over the last year, and polymyalgia rheumatica requiring chronic prednisone therapy presented with painful lesions on the thighs, buttocks, and right shoulder of 4 months’ duration. She had multiple hospital admissions preceding the onset of lesions for severe infections resulting in sepsis with hypotension, including Enterococcus faecalis endocarditis, extended-spectrum beta-lactamase bacteremia, and Pseudomonas aeruginosa pneumonia. Physical examination revealed large well-demarcated ulcers and necrotic eschars with surrounding violaceous induration and stellate erythema on the anterior, medial, and posterior thighs and buttocks that were exquisitely tender (Figures 1 and 2).

Notable laboratory results included hypoalbuminemia (1.3 g/dL [reference range, 3.5–5.0 g/dL]) with normal renal function, a corrected calcium level of 9.7 mg/dL (reference range, 8.2–10.2 mg/dL), a serum phosphorus level of 3.5 mg/dL (reference range, 2.3–4.7 mg/dL), a calcium-phosphate product of 27.3 mg²/dL² (reference range, <55 mg²/dL²), and a parathyroid hormone level of 49.3 pg/mL (reference range, 10–65 pg/mL). Antinuclear antibodies were negative. A hypercoagulability evaluation showed normal protein C and S levels, negative lupus anticoagulant, and negative anticardiolipin antibodies.

Telescoping punch biopsies of the indurated borders of the eschars showed prominent calcification of the small- and medium-sized vessels in the mid and deep dermis, intravascular thrombi, and necrosis of the epidermis and subcutaneous fat consistent with calciphylaxis (Figure 3).

Comment

Background on Calciphylaxis
Calciphylaxis is a rare but deadly disease that affects both ESRD patients receiving dialysis and patients without ESRD who have known risk factors for calciphylaxis, including female gender, white race, obesity, alcoholic liver disease, primary hyperparathyroidism, connective tissue disease, underlying malignancy, protein C or S deficiency, corticosteroid use, warfarin use, diabetes, iron or albumin infusions, and rapid weight loss.^3,6-9,11 Although the molecular pathogenesis of calciphylaxis is not completely understood, it is believed to be caused by local deposition of calcium in the tunica media of small- to medium-sized arterioles and venules in the skin.¹² This deposition leads to intimal proliferation and progressive narrowing of the vessels with resultant thrombosis, ischemia, and necrosis. The cutaneous manifestations and histopathology of calciphylaxis classically follow its pathogenesis. Calciphylaxis typically presents with livedo reticularis as vessels narrow and then progresses to purpura, bullae, necrosis, and eschar formation with the onset of acute thrombosis and ischemia. Histopathology is characterized by small- and medium-sized vessel calcification and thrombus, dermal necrosis, and septal panniculitis, though the histology can be highly variable.¹² Unfortunately, the already poor prognosis for calciphylaxis worsens when lesions become either ulcerative or present on the proximal extremities and trunk.^4,13 Sepsis is the leading cause of death in calciphylaxis patients, affecting more than 50% of patients.^2,3,14 The differential diagnoses for calciphylactic-appearing lesions include warfarin-induced skin necrosis, disseminated intravascular coagulation, pyoderma gangrenosum, cholesterol emboli, and various vasculitides and coagulopathies.

Risk Factors
Our case demonstrates the importance of risk factor minimization, trigger avoidance, and early intervention due to the high mortality rate of calciphylaxis. Selye et al¹⁵ coined the term calciphylaxis in 1961 based on experiments that induced calciphylaxis in rat models. Their research concluded that there were certain sensitizers (ie, risk factors) that predisposed patients to medial calcium deposition in blood vessels and other challengers (ie, triggers) that acted as inciting events to calcium deposition. Our patient presented with multiple known risk factors for calciphylaxis, including obesity (body mass index, 40 kg/m²), female gender, white race, hypoalbuminemia, and chronic corticosteroid use.¹⁶ In the presence of a milieu of risk factors, the patient’s rapid weight loss and episodes of hypotension likely were triggers for calciphylaxis.

Other case reports in the literature have suggested weight loss as a trigger for NUC. One morbidly obese patient with inactive rheumatoid arthritis had onset of calciphylaxis lesions after unintentional weight loss of approximately 50% body weight in 1 year¹⁷; however, the weight loss does not have to be drastic to trigger calciphylaxis. Another study of 16 patients with uremic calciphylaxis found that 7 of 16 (44%) patients lost 10 to 50 kg in the 6 months prior to calciphylaxis onset.¹⁴ One proposed mechanism by Munavalli et al¹⁰ is that elevated levels of matrix metalloproteinases during catabolic weight loss states enhance the deposition of calcium into elastic fibers of small vessels. The authors found elevated serum levels of matrix metalloproteinases in their patients with NUC induced by rapid weight loss.¹⁰

A meta-analysis by Nigwekar et al³ found a history of prior corticosteroid use in 61% (22/36) of NUC cases reviewed. However, it is unclear whether it is the use of corticosteroids or chronic inflammation that is implicated in NUC pathogenesis. Chronic inflammation causes downregulation of anticalcification signaling pathways.^18-20 The role of 2 vascular calcification inhibitors has been evaluated in the pathogenesis of calciphylaxis: fetuin-A and matrix gla protein (MGP).²¹ The activity of these proteins is decreased not only in calciphylaxis but also in other inflammatory states and chronic renal failure.^18-20 One study found lower fetuin-A levels in 312 hemodialysis patients compared to healthy controls and an association between low fetuin-A levels and increased C-reactive protein levels.²² Reduced fetuin-A and MGP levels may be the result of several calciphylaxis risk factors. Warfarin is believed to trigger calciphylaxis via inhibition of gamma-carboxylation of MGP, which is necessary for its anticalcification activity.²³ Hypoalbuminemia and alcoholic liver disease also are risk factors that may be explained by the fact that fetuin-A is synthesized in the liver.²⁴ Therefore, liver disease results in decreased production of fetuin-A that is permissive to vascular calcification in calciphylaxis patients.

There have been other reports of calciphylaxis patients who were originally hospitalized due to hypotension, which may serve as a trigger for calciphylaxis onset.²⁵ Because calciphylaxis lesions are more likely to occur in the fatty areas of the abdomen and proximal thighs where blood flow is slower, hypotension likely accentuates the slowing of blood flow and subsequent blood vessel calcification. This theory is supported by studies showing that established calciphylactic lesions worsen more quickly in the presence of systemic hypotension.²⁶ One patient with ESRD and calciphylaxis of the breasts had consistent systolic blood pressure readings in the high 60s to low 70s between dialysis sessions.²⁷ Due to this association, we recommend that patients with calciphylaxis have close blood pressure monitoring to aid in preventing disease progression.²⁸

Management
Calciphylaxis treatment has not yet been standardized, as it is an uncommon disease whose pathogenesis is not fully understood. Current management strategies aim to normalize metabolic abnormalities such as hypercalcemia if they are present and remove inciting agents such as warfarin and corticosteroids.²⁹ Other medical treatments that have been successfully used include sodium thiosulfate, oral steroids, and adjunctive bisphosphonates.^29-31 Sodium thiosulfate is known to cause metabolic acidosis by generating thiosulfuric acid in vivo in patients with or without renal disease; therefore, patients on sodium thiosulfate therapy should be monitored for development of metabolic acidosis and treated with oral sodium bicarbonate or dialysis as needed.^30,32 Wound care also is an important element of calciphylaxis treatment; however, the debridement of wounds is controversial. Some argue that dry intact eschars serve to protect against sepsis, which is the leading cause of death in calciphylaxis.^2,14,33 In contrast, a retrospective study of 63 calciphylaxis patients found a 1-year survival rate of 61.6% in 17 patients receiving wound debridement vs 27.4% in 46 patients who did not.² The current consensus is that debridement should be considered on a case-by-case basis, factoring in the presence of wound infection, size of wounds, stability of eschars, and treatment goals of the patient.³⁴ Future studies should be aimed at this issue, with special focus on how these factors and the decision to debride or not impact patient outcomes.

Conclusion

Calciphylaxis is a potentially fatal disease that impacts both patients with ESRD and those with nonuremic risk factors. The term calcific uremic arteriolopathy should be disregarded, as nonuremic causes are being reported with increased frequency in the literature. In such cases, patients often have multiple risk factors, including obesity, primary hyperparathyroidism, alcoholic liver disease, and underlying malignancy, among others. Certain triggers for onset of calciphylaxis should be avoided in at-risk patients, including the use of corticosteroids or warfarin; iron and albumin infusions; hypotension; and rapid weight loss. Our fatal case of NUC is a reminder to dermatologists treating at-risk patients to avoid these triggers and to keep calciphylaxis in the differential diagnosis when encountering early lesions such as livedo reticularis, as progression of these lesions has a 1-year mortality rate of more than 50% with the therapies being utilized at this time.

Calciphylaxis, otherwise known as calcific uremic arteriolopathy, is characterized by calcification of the tunica media of the small- to medium-sized blood vessels of the dermis and subcutis, leading to ischemia and necrosis.¹ It is a deadly disease with a 1-year mortality rate of more than 50%.² End-stage renal disease (ESRD) is the most common risk factor for calciphylaxis, with a prevalence of 1% to 4% of hemodialysis patients with calciphylaxis in the United States.^2-5 However, nonuremic calciphylaxis (NUC) has been increasingly reported in the literature and has risk factors other than ESRD, including but not limited to obesity, alcoholic liver disease, primary hyperparathyroidism, connective tissue disease, and underlying malignancy.^3,6-9 Triggers for calciphylaxis in at-risk patients include use of corticosteroids or warfarin, iron or albumin infusions, and rapid weight loss.^3,6,9-11 We report an unusual case of NUC that most likely was triggered by rapid weight loss and hypotension in a patient with multiple risk factors for calciphylaxis.

Case Report

A 75-year-old white woman with history of morbid obesity (body mass index, 40 kg/m²), unexplained weight loss of 70 lb over the last year, and polymyalgia rheumatica requiring chronic prednisone therapy presented with painful lesions on the thighs, buttocks, and right shoulder of 4 months’ duration. She had multiple hospital admissions preceding the onset of lesions for severe infections resulting in sepsis with hypotension, including Enterococcus faecalis endocarditis, extended-spectrum beta-lactamase bacteremia, and Pseudomonas aeruginosa pneumonia. Physical examination revealed large well-demarcated ulcers and necrotic eschars with surrounding violaceous induration and stellate erythema on the anterior, medial, and posterior thighs and buttocks that were exquisitely tender (Figures 1 and 2).

Notable laboratory results included hypoalbuminemia (1.3 g/dL [reference range, 3.5–5.0 g/dL]) with normal renal function, a corrected calcium level of 9.7 mg/dL (reference range, 8.2–10.2 mg/dL), a serum phosphorus level of 3.5 mg/dL (reference range, 2.3–4.7 mg/dL), a calcium-phosphate product of 27.3 mg²/dL² (reference range, <55 mg²/dL²), and a parathyroid hormone level of 49.3 pg/mL (reference range, 10–65 pg/mL). Antinuclear antibodies were negative. A hypercoagulability evaluation showed normal protein C and S levels, negative lupus anticoagulant, and negative anticardiolipin antibodies.

Telescoping punch biopsies of the indurated borders of the eschars showed prominent calcification of the small- and medium-sized vessels in the mid and deep dermis, intravascular thrombi, and necrosis of the epidermis and subcutaneous fat consistent with calciphylaxis (Figure 3).

Comment

Background on Calciphylaxis
Calciphylaxis is a rare but deadly disease that affects both ESRD patients receiving dialysis and patients without ESRD who have known risk factors for calciphylaxis, including female gender, white race, obesity, alcoholic liver disease, primary hyperparathyroidism, connective tissue disease, underlying malignancy, protein C or S deficiency, corticosteroid use, warfarin use, diabetes, iron or albumin infusions, and rapid weight loss.^3,6-9,11 Although the molecular pathogenesis of calciphylaxis is not completely understood, it is believed to be caused by local deposition of calcium in the tunica media of small- to medium-sized arterioles and venules in the skin.¹² This deposition leads to intimal proliferation and progressive narrowing of the vessels with resultant thrombosis, ischemia, and necrosis. The cutaneous manifestations and histopathology of calciphylaxis classically follow its pathogenesis. Calciphylaxis typically presents with livedo reticularis as vessels narrow and then progresses to purpura, bullae, necrosis, and eschar formation with the onset of acute thrombosis and ischemia. Histopathology is characterized by small- and medium-sized vessel calcification and thrombus, dermal necrosis, and septal panniculitis, though the histology can be highly variable.¹² Unfortunately, the already poor prognosis for calciphylaxis worsens when lesions become either ulcerative or present on the proximal extremities and trunk.^4,13 Sepsis is the leading cause of death in calciphylaxis patients, affecting more than 50% of patients.^2,3,14 The differential diagnoses for calciphylactic-appearing lesions include warfarin-induced skin necrosis, disseminated intravascular coagulation, pyoderma gangrenosum, cholesterol emboli, and various vasculitides and coagulopathies.

Risk Factors
Our case demonstrates the importance of risk factor minimization, trigger avoidance, and early intervention due to the high mortality rate of calciphylaxis. Selye et al¹⁵ coined the term calciphylaxis in 1961 based on experiments that induced calciphylaxis in rat models. Their research concluded that there were certain sensitizers (ie, risk factors) that predisposed patients to medial calcium deposition in blood vessels and other challengers (ie, triggers) that acted as inciting events to calcium deposition. Our patient presented with multiple known risk factors for calciphylaxis, including obesity (body mass index, 40 kg/m²), female gender, white race, hypoalbuminemia, and chronic corticosteroid use.¹⁶ In the presence of a milieu of risk factors, the patient’s rapid weight loss and episodes of hypotension likely were triggers for calciphylaxis.

Other case reports in the literature have suggested weight loss as a trigger for NUC. One morbidly obese patient with inactive rheumatoid arthritis had onset of calciphylaxis lesions after unintentional weight loss of approximately 50% body weight in 1 year¹⁷; however, the weight loss does not have to be drastic to trigger calciphylaxis. Another study of 16 patients with uremic calciphylaxis found that 7 of 16 (44%) patients lost 10 to 50 kg in the 6 months prior to calciphylaxis onset.¹⁴ One proposed mechanism by Munavalli et al¹⁰ is that elevated levels of matrix metalloproteinases during catabolic weight loss states enhance the deposition of calcium into elastic fibers of small vessels. The authors found elevated serum levels of matrix metalloproteinases in their patients with NUC induced by rapid weight loss.¹⁰

A meta-analysis by Nigwekar et al³ found a history of prior corticosteroid use in 61% (22/36) of NUC cases reviewed. However, it is unclear whether it is the use of corticosteroids or chronic inflammation that is implicated in NUC pathogenesis. Chronic inflammation causes downregulation of anticalcification signaling pathways.^18-20 The role of 2 vascular calcification inhibitors has been evaluated in the pathogenesis of calciphylaxis: fetuin-A and matrix gla protein (MGP).²¹ The activity of these proteins is decreased not only in calciphylaxis but also in other inflammatory states and chronic renal failure.^18-20 One study found lower fetuin-A levels in 312 hemodialysis patients compared to healthy controls and an association between low fetuin-A levels and increased C-reactive protein levels.²² Reduced fetuin-A and MGP levels may be the result of several calciphylaxis risk factors. Warfarin is believed to trigger calciphylaxis via inhibition of gamma-carboxylation of MGP, which is necessary for its anticalcification activity.²³ Hypoalbuminemia and alcoholic liver disease also are risk factors that may be explained by the fact that fetuin-A is synthesized in the liver.²⁴ Therefore, liver disease results in decreased production of fetuin-A that is permissive to vascular calcification in calciphylaxis patients.

There have been other reports of calciphylaxis patients who were originally hospitalized due to hypotension, which may serve as a trigger for calciphylaxis onset.²⁵ Because calciphylaxis lesions are more likely to occur in the fatty areas of the abdomen and proximal thighs where blood flow is slower, hypotension likely accentuates the slowing of blood flow and subsequent blood vessel calcification. This theory is supported by studies showing that established calciphylactic lesions worsen more quickly in the presence of systemic hypotension.²⁶ One patient with ESRD and calciphylaxis of the breasts had consistent systolic blood pressure readings in the high 60s to low 70s between dialysis sessions.²⁷ Due to this association, we recommend that patients with calciphylaxis have close blood pressure monitoring to aid in preventing disease progression.²⁸

Management
Calciphylaxis treatment has not yet been standardized, as it is an uncommon disease whose pathogenesis is not fully understood. Current management strategies aim to normalize metabolic abnormalities such as hypercalcemia if they are present and remove inciting agents such as warfarin and corticosteroids.²⁹ Other medical treatments that have been successfully used include sodium thiosulfate, oral steroids, and adjunctive bisphosphonates.^29-31 Sodium thiosulfate is known to cause metabolic acidosis by generating thiosulfuric acid in vivo in patients with or without renal disease; therefore, patients on sodium thiosulfate therapy should be monitored for development of metabolic acidosis and treated with oral sodium bicarbonate or dialysis as needed.^30,32 Wound care also is an important element of calciphylaxis treatment; however, the debridement of wounds is controversial. Some argue that dry intact eschars serve to protect against sepsis, which is the leading cause of death in calciphylaxis.^2,14,33 In contrast, a retrospective study of 63 calciphylaxis patients found a 1-year survival rate of 61.6% in 17 patients receiving wound debridement vs 27.4% in 46 patients who did not.² The current consensus is that debridement should be considered on a case-by-case basis, factoring in the presence of wound infection, size of wounds, stability of eschars, and treatment goals of the patient.³⁴ Future studies should be aimed at this issue, with special focus on how these factors and the decision to debride or not impact patient outcomes.

Conclusion

Calciphylaxis is a potentially fatal disease that impacts both patients with ESRD and those with nonuremic risk factors. The term calcific uremic arteriolopathy should be disregarded, as nonuremic causes are being reported with increased frequency in the literature. In such cases, patients often have multiple risk factors, including obesity, primary hyperparathyroidism, alcoholic liver disease, and underlying malignancy, among others. Certain triggers for onset of calciphylaxis should be avoided in at-risk patients, including the use of corticosteroids or warfarin; iron and albumin infusions; hypotension; and rapid weight loss. Our fatal case of NUC is a reminder to dermatologists treating at-risk patients to avoid these triggers and to keep calciphylaxis in the differential diagnosis when encountering early lesions such as livedo reticularis, as progression of these lesions has a 1-year mortality rate of more than 50% with the therapies being utilized at this time.

As the Wuhan coronavirus story unfolds, the most important thing for clinicians in the United States to do is ask patients who appear to have the flu if they, or someone they have been in contact with, recently returned from China, according to infectious disease experts.

China News Service/CC BY 3.0

“We are asking that of everyone with fever and respiratory symptoms who comes to our clinics, hospital, or emergency room. It’s a powerful screening tool,” said William Schaffner, MD, professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center, Nashville, Tenn.

In addition to fever, common signs of infection include cough, shortness of breath, and breathing difficulties. Some patients have had diarrhea, vomiting, and other gastrointestinal symptoms. In more severe cases, infection can cause pneumonia, severe acute respiratory syndrome, kidney failure, and death. The incubation period appears to be up to 2 weeks, according to the World Health Organization (WHO).

If patients exhibit symptoms and either they or a close contact has returned from China recently, take standard airborne precautions and send specimens – a serum sample, oral and nasal pharyngeal swabs, and lower respiratory tract specimens if available – to the local health department, which will forward them to the Centers for Disease Control and Prevention (CDC) for testing. Turnaround time is 24-48 hours.

Plan and rehearse

The first step to prepare is to use the CDC’s Interim Guidance for Healthcare Professionals to make a written plan specific to your practice to respond to a potential case. The plan must include notifying the local health department, the CDC liaison for testing, and tracking down patient contacts.

“It’s not good enough to just download CDC’s guidance; use it to make your own local plan and know what to do 24/7,” said Daniel Lucey, MD, an infectious disease expert at Georgetown University Medical Center, Washington, D.C.

“Know who is on call at the health department on weekends and nights,” he said. Know where the patient is going to be isolated; figure out what to do if there’s more than one, and tests come back positive. Have masks on hand, and rehearse the response. “Make a coronavirus team, and absolutely have the nurses involved,” as well as other providers who may come into contact with a case, he added.

Fatality rates

The focus right now is China. The outbreak has spread beyond Wuhan to other parts of the country, and there’s evidence of fourth-generation spread.

SARS: Lessons learned

In general, the world is much better equipped for coronavirus outbreaks than when SARS, in particular, emerged in 2003.

[email protected]

This article was updated with new case numbers on 1/26/20.

As the Wuhan coronavirus story unfolds, the most important thing for clinicians in the United States to do is ask patients who appear to have the flu if they, or someone they have been in contact with, recently returned from China, according to infectious disease experts.

China News Service/CC BY 3.0

“We are asking that of everyone with fever and respiratory symptoms who comes to our clinics, hospital, or emergency room. It’s a powerful screening tool,” said William Schaffner, MD, professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center, Nashville, Tenn.

In addition to fever, common signs of infection include cough, shortness of breath, and breathing difficulties. Some patients have had diarrhea, vomiting, and other gastrointestinal symptoms. In more severe cases, infection can cause pneumonia, severe acute respiratory syndrome, kidney failure, and death. The incubation period appears to be up to 2 weeks, according to the World Health Organization (WHO).

If patients exhibit symptoms and either they or a close contact has returned from China recently, take standard airborne precautions and send specimens – a serum sample, oral and nasal pharyngeal swabs, and lower respiratory tract specimens if available – to the local health department, which will forward them to the Centers for Disease Control and Prevention (CDC) for testing. Turnaround time is 24-48 hours.

Plan and rehearse

The first step to prepare is to use the CDC’s Interim Guidance for Healthcare Professionals to make a written plan specific to your practice to respond to a potential case. The plan must include notifying the local health department, the CDC liaison for testing, and tracking down patient contacts.

“It’s not good enough to just download CDC’s guidance; use it to make your own local plan and know what to do 24/7,” said Daniel Lucey, MD, an infectious disease expert at Georgetown University Medical Center, Washington, D.C.

“Know who is on call at the health department on weekends and nights,” he said. Know where the patient is going to be isolated; figure out what to do if there’s more than one, and tests come back positive. Have masks on hand, and rehearse the response. “Make a coronavirus team, and absolutely have the nurses involved,” as well as other providers who may come into contact with a case, he added.

Fatality rates

The focus right now is China. The outbreak has spread beyond Wuhan to other parts of the country, and there’s evidence of fourth-generation spread.

SARS: Lessons learned

In general, the world is much better equipped for coronavirus outbreaks than when SARS, in particular, emerged in 2003.

[email protected]

This article was updated with new case numbers on 1/26/20.

As the Wuhan coronavirus story unfolds, the most important thing for clinicians in the United States to do is ask patients who appear to have the flu if they, or someone they have been in contact with, recently returned from China, according to infectious disease experts.

China News Service/CC BY 3.0

“We are asking that of everyone with fever and respiratory symptoms who comes to our clinics, hospital, or emergency room. It’s a powerful screening tool,” said William Schaffner, MD, professor of preventive medicine and infectious diseases at Vanderbilt University Medical Center, Nashville, Tenn.

In addition to fever, common signs of infection include cough, shortness of breath, and breathing difficulties. Some patients have had diarrhea, vomiting, and other gastrointestinal symptoms. In more severe cases, infection can cause pneumonia, severe acute respiratory syndrome, kidney failure, and death. The incubation period appears to be up to 2 weeks, according to the World Health Organization (WHO).

If patients exhibit symptoms and either they or a close contact has returned from China recently, take standard airborne precautions and send specimens – a serum sample, oral and nasal pharyngeal swabs, and lower respiratory tract specimens if available – to the local health department, which will forward them to the Centers for Disease Control and Prevention (CDC) for testing. Turnaround time is 24-48 hours.

Plan and rehearse

The first step to prepare is to use the CDC’s Interim Guidance for Healthcare Professionals to make a written plan specific to your practice to respond to a potential case. The plan must include notifying the local health department, the CDC liaison for testing, and tracking down patient contacts.

“It’s not good enough to just download CDC’s guidance; use it to make your own local plan and know what to do 24/7,” said Daniel Lucey, MD, an infectious disease expert at Georgetown University Medical Center, Washington, D.C.

“Know who is on call at the health department on weekends and nights,” he said. Know where the patient is going to be isolated; figure out what to do if there’s more than one, and tests come back positive. Have masks on hand, and rehearse the response. “Make a coronavirus team, and absolutely have the nurses involved,” as well as other providers who may come into contact with a case, he added.

Fatality rates

The focus right now is China. The outbreak has spread beyond Wuhan to other parts of the country, and there’s evidence of fourth-generation spread.

SARS: Lessons learned

In general, the world is much better equipped for coronavirus outbreaks than when SARS, in particular, emerged in 2003.

[email protected]

This article was updated with new case numbers on 1/26/20.

Is the US Department of Defense (DoD) doing enough—or the right things—to attract and keep physicians and dentists? According to a new report by the Government Accountability Office (GAO), although the DoD is hitting the mark in some areas, there’s room for improvement in others.

It’s a crucial question. The GAO reported in 2018 that DoD officials cited “a number of challenges” that made it difficult to attract and retain physicians and dentists, such as national shortages and competition with the private sector. Indeed, military health system physicians and dentists make less than do their counterparts in the private sector, the GAO says. For 21 of 27 specialties studied in the new report, the maximum cash compensation was less than the civilian median within 4 officer pay grades (O-3 to O-6). Moreover, cash compensation even for the most senior military physicians and dentists was less than that of the civilian median at “key retention points,” such as after physicians and dentists fulfill their initial active-duty service.

The DoD provides “substantial” deferred and noncash benefits, the GAO notes, such as retirement pensions and tuition-free education, but adds that the value to service members is “difficult to determine.” The DoD also recruits with a package of incentives, including multi-year retention bonuses.

In general, the GAO found, the DoD applies several “effective human capital management” principles. For instance, it relies on clearly defined criteria on when to use incentives (such as rules-based pay plans). It also identifies and evaluates unique staffing situations. For example, to attract physicians and dentists in “critically short wartime specialties,” it offers a Critical Wartime Skills Accession Bonus.    

However, the report says, the DoD does not consistently collect information that could help inform its recruitment/retention decisions. At the time of the study, the DoD had not identified replacement costs for physicians or dentists as it does, for instance, with nuclear propulsion personnel. Nor did it gather current and historical retention information. Specifically, the GAO report says, Navy and Air Force officials said they don’t have readily available information to determine the percentage of those who accepted a retention bonus. Conversely, Army officials don’t have a framework in place that uses retention information to determine the effectiveness of retention bonuses (as do the Navy, Marine Corps, and Air Force).

Extending Service Obligations

The DoD is considering extending service obligations for students receiving DoD-funded assistance for physician or dentist education. Students in the DoD scholarship program have a 2-year minimum service obligation, with 6months of active-duty service obligations for each 6 months of benefits received. Medical students attending the Uniformed Services University of the Health Sciences (USUHS), have a 7-year active-duty service obligation.

The GAO held 8 focus groups with students and found 68% of USUHS students and 46% of scholarship students would be willing to accept 1 more year of obligation (although only 34% and 16%, respectively, would agree to 2). The participants expressed concern that longer service obligations would delay their eligibility for retention bonuses—resulting in a reduction of cash compensation over the course of a career. However, 80% and 63%, respectively, would accept an additional year of service obligation if accompanied by additional cash incentives.

Further, the GAO notes, longer obligations could have “unintended consequences.” For example, students might decide to separate and train in a civilian program after 1 or more tours as general medical officers to complete their active duty service obligation, decline further medical training and specialization via a military fellowship program, or separate from the military sooner than planned.

Potential Reductions in Health Care Force

The DoD, according to the report, also is considering reducing the overall number of active-duty physicians, including “targeted reductions” to certain specialties, raising concerns among participants in all 8 focus groups.

Given that the DoD spends millions of dollars annually to train medical and dental students and that almost half of the special pay budget is dedicated to retaining them once they’re fully trained, consistently collecting information to help inform investment decisions is “critical to ensuring the efficiency of these significant resources,” the GAO says. Collecting such information, the GAO says, and using it, would help inform its decision making. For instance, such information would help officials decide whether it would be more cost effective to focus on retaining medical personnel rather than training new staff.

Retaining “top talent,” the DoD says, is “essential to sustaining mission readiness that is adaptable and responsive.” The GAO report cites a 2012 study that found compensation for military physicians had “a large impact on the decision to remain in the military in the first unobligated year of service and just a small impact on retention in the years afterward.” 

DoD officials told the GAO that budget considerations and statutory limitations hinder their ability to change the rate of special and incentive pays. The GAO calls these “valid considerations” but suggests that collecting information on replacement costs, retention, and civilian wages would allow DoD departments to “provide greater stewardship of available funding by ensuring its efficient application.” It may be, the GAO says, that retaining fully trained physicians within the DoD is “highly economical.”. Most important, using such data to inform investment decisions will allow the DoD to “efficiently and effectively meet its mission of providing health care during times of war and peace.”

In response to the GAO findings, DoD officials have a group working on a plan to recruit and retain critical specialties, which will be released by June 2020. They also concurred with other GAO recommendations, saying changes will be made within 2 years.

Is the US Department of Defense (DoD) doing enough—or the right things—to attract and keep physicians and dentists? According to a new report by the Government Accountability Office (GAO), although the DoD is hitting the mark in some areas, there’s room for improvement in others.

It’s a crucial question. The GAO reported in 2018 that DoD officials cited “a number of challenges” that made it difficult to attract and retain physicians and dentists, such as national shortages and competition with the private sector. Indeed, military health system physicians and dentists make less than do their counterparts in the private sector, the GAO says. For 21 of 27 specialties studied in the new report, the maximum cash compensation was less than the civilian median within 4 officer pay grades (O-3 to O-6). Moreover, cash compensation even for the most senior military physicians and dentists was less than that of the civilian median at “key retention points,” such as after physicians and dentists fulfill their initial active-duty service.

The DoD provides “substantial” deferred and noncash benefits, the GAO notes, such as retirement pensions and tuition-free education, but adds that the value to service members is “difficult to determine.” The DoD also recruits with a package of incentives, including multi-year retention bonuses.

In general, the GAO found, the DoD applies several “effective human capital management” principles. For instance, it relies on clearly defined criteria on when to use incentives (such as rules-based pay plans). It also identifies and evaluates unique staffing situations. For example, to attract physicians and dentists in “critically short wartime specialties,” it offers a Critical Wartime Skills Accession Bonus.    

However, the report says, the DoD does not consistently collect information that could help inform its recruitment/retention decisions. At the time of the study, the DoD had not identified replacement costs for physicians or dentists as it does, for instance, with nuclear propulsion personnel. Nor did it gather current and historical retention information. Specifically, the GAO report says, Navy and Air Force officials said they don’t have readily available information to determine the percentage of those who accepted a retention bonus. Conversely, Army officials don’t have a framework in place that uses retention information to determine the effectiveness of retention bonuses (as do the Navy, Marine Corps, and Air Force).

Extending Service Obligations

The DoD is considering extending service obligations for students receiving DoD-funded assistance for physician or dentist education. Students in the DoD scholarship program have a 2-year minimum service obligation, with 6months of active-duty service obligations for each 6 months of benefits received. Medical students attending the Uniformed Services University of the Health Sciences (USUHS), have a 7-year active-duty service obligation.

The GAO held 8 focus groups with students and found 68% of USUHS students and 46% of scholarship students would be willing to accept 1 more year of obligation (although only 34% and 16%, respectively, would agree to 2). The participants expressed concern that longer service obligations would delay their eligibility for retention bonuses—resulting in a reduction of cash compensation over the course of a career. However, 80% and 63%, respectively, would accept an additional year of service obligation if accompanied by additional cash incentives.

Further, the GAO notes, longer obligations could have “unintended consequences.” For example, students might decide to separate and train in a civilian program after 1 or more tours as general medical officers to complete their active duty service obligation, decline further medical training and specialization via a military fellowship program, or separate from the military sooner than planned.

Potential Reductions in Health Care Force

The DoD, according to the report, also is considering reducing the overall number of active-duty physicians, including “targeted reductions” to certain specialties, raising concerns among participants in all 8 focus groups.

Given that the DoD spends millions of dollars annually to train medical and dental students and that almost half of the special pay budget is dedicated to retaining them once they’re fully trained, consistently collecting information to help inform investment decisions is “critical to ensuring the efficiency of these significant resources,” the GAO says. Collecting such information, the GAO says, and using it, would help inform its decision making. For instance, such information would help officials decide whether it would be more cost effective to focus on retaining medical personnel rather than training new staff.

Retaining “top talent,” the DoD says, is “essential to sustaining mission readiness that is adaptable and responsive.” The GAO report cites a 2012 study that found compensation for military physicians had “a large impact on the decision to remain in the military in the first unobligated year of service and just a small impact on retention in the years afterward.” 

DoD officials told the GAO that budget considerations and statutory limitations hinder their ability to change the rate of special and incentive pays. The GAO calls these “valid considerations” but suggests that collecting information on replacement costs, retention, and civilian wages would allow DoD departments to “provide greater stewardship of available funding by ensuring its efficient application.” It may be, the GAO says, that retaining fully trained physicians within the DoD is “highly economical.”. Most important, using such data to inform investment decisions will allow the DoD to “efficiently and effectively meet its mission of providing health care during times of war and peace.”

In response to the GAO findings, DoD officials have a group working on a plan to recruit and retain critical specialties, which will be released by June 2020. They also concurred with other GAO recommendations, saying changes will be made within 2 years.

Is the US Department of Defense (DoD) doing enough—or the right things—to attract and keep physicians and dentists? According to a new report by the Government Accountability Office (GAO), although the DoD is hitting the mark in some areas, there’s room for improvement in others.

It’s a crucial question. The GAO reported in 2018 that DoD officials cited “a number of challenges” that made it difficult to attract and retain physicians and dentists, such as national shortages and competition with the private sector. Indeed, military health system physicians and dentists make less than do their counterparts in the private sector, the GAO says. For 21 of 27 specialties studied in the new report, the maximum cash compensation was less than the civilian median within 4 officer pay grades (O-3 to O-6). Moreover, cash compensation even for the most senior military physicians and dentists was less than that of the civilian median at “key retention points,” such as after physicians and dentists fulfill their initial active-duty service.

The DoD provides “substantial” deferred and noncash benefits, the GAO notes, such as retirement pensions and tuition-free education, but adds that the value to service members is “difficult to determine.” The DoD also recruits with a package of incentives, including multi-year retention bonuses.

In general, the GAO found, the DoD applies several “effective human capital management” principles. For instance, it relies on clearly defined criteria on when to use incentives (such as rules-based pay plans). It also identifies and evaluates unique staffing situations. For example, to attract physicians and dentists in “critically short wartime specialties,” it offers a Critical Wartime Skills Accession Bonus.    

However, the report says, the DoD does not consistently collect information that could help inform its recruitment/retention decisions. At the time of the study, the DoD had not identified replacement costs for physicians or dentists as it does, for instance, with nuclear propulsion personnel. Nor did it gather current and historical retention information. Specifically, the GAO report says, Navy and Air Force officials said they don’t have readily available information to determine the percentage of those who accepted a retention bonus. Conversely, Army officials don’t have a framework in place that uses retention information to determine the effectiveness of retention bonuses (as do the Navy, Marine Corps, and Air Force).

Extending Service Obligations

The DoD is considering extending service obligations for students receiving DoD-funded assistance for physician or dentist education. Students in the DoD scholarship program have a 2-year minimum service obligation, with 6months of active-duty service obligations for each 6 months of benefits received. Medical students attending the Uniformed Services University of the Health Sciences (USUHS), have a 7-year active-duty service obligation.

The GAO held 8 focus groups with students and found 68% of USUHS students and 46% of scholarship students would be willing to accept 1 more year of obligation (although only 34% and 16%, respectively, would agree to 2). The participants expressed concern that longer service obligations would delay their eligibility for retention bonuses—resulting in a reduction of cash compensation over the course of a career. However, 80% and 63%, respectively, would accept an additional year of service obligation if accompanied by additional cash incentives.

Further, the GAO notes, longer obligations could have “unintended consequences.” For example, students might decide to separate and train in a civilian program after 1 or more tours as general medical officers to complete their active duty service obligation, decline further medical training and specialization via a military fellowship program, or separate from the military sooner than planned.

Potential Reductions in Health Care Force

The DoD, according to the report, also is considering reducing the overall number of active-duty physicians, including “targeted reductions” to certain specialties, raising concerns among participants in all 8 focus groups.

Given that the DoD spends millions of dollars annually to train medical and dental students and that almost half of the special pay budget is dedicated to retaining them once they’re fully trained, consistently collecting information to help inform investment decisions is “critical to ensuring the efficiency of these significant resources,” the GAO says. Collecting such information, the GAO says, and using it, would help inform its decision making. For instance, such information would help officials decide whether it would be more cost effective to focus on retaining medical personnel rather than training new staff.

Retaining “top talent,” the DoD says, is “essential to sustaining mission readiness that is adaptable and responsive.” The GAO report cites a 2012 study that found compensation for military physicians had “a large impact on the decision to remain in the military in the first unobligated year of service and just a small impact on retention in the years afterward.” 

DoD officials told the GAO that budget considerations and statutory limitations hinder their ability to change the rate of special and incentive pays. The GAO calls these “valid considerations” but suggests that collecting information on replacement costs, retention, and civilian wages would allow DoD departments to “provide greater stewardship of available funding by ensuring its efficient application.” It may be, the GAO says, that retaining fully trained physicians within the DoD is “highly economical.”. Most important, using such data to inform investment decisions will allow the DoD to “efficiently and effectively meet its mission of providing health care during times of war and peace.”

In response to the GAO findings, DoD officials have a group working on a plan to recruit and retain critical specialties, which will be released by June 2020. They also concurred with other GAO recommendations, saying changes will be made within 2 years.

The Food and Drug Administration has issued a warning that certain GE Healthcare Clinical Information Central Stations and Telemetry Servers have cybersecurity vulnerabilities that may introduce risk to monitored patients.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

A security firm identified several vulnerabilities in the GE devices that allow attackers to remotely take control of the medical device, silence alarms, generate false alarms, and interfere with alarms of patient monitors connected to these devices, according to an “Urgent Medical Device Correction” letter issued by GE Healthcare in November 2019.

The affected devices are the ApexPro Telemetry Server and CARESCAPE Telemetry Server, the CARESCAPE Central Station (CSCS) version 1, and the CIC Pro Clinical Information Center Central Station version 1. These devices are used in health care facilities for displaying information, such as the patient’s physiological parameters, and for monitoring patient status from a central location in a facility.

No adverse events related to the vulnerabilities have been reported to the FDA. Health care facility staff should update their devices when GE Healthcare issues a software patch that addresses the vulnerability, separate the network connecting patient monitors using affected devices from the rest of the hospital, and use firewalls and other means to minimize the risk of remote or local network attacks.

“The FDA takes reports of cybersecurity vulnerabilities in medical devices seriously and will continue to work with GE Healthcare as the firm develops software patches to correct these vulnerabilities as soon as possible. The FDA will continue to assess new information concerning the vulnerabilities and will keep the public informed if significant new information becomes available,” the FDA said in the Safety Communication.

[email protected]

The Food and Drug Administration has issued a warning that certain GE Healthcare Clinical Information Central Stations and Telemetry Servers have cybersecurity vulnerabilities that may introduce risk to monitored patients.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

A security firm identified several vulnerabilities in the GE devices that allow attackers to remotely take control of the medical device, silence alarms, generate false alarms, and interfere with alarms of patient monitors connected to these devices, according to an “Urgent Medical Device Correction” letter issued by GE Healthcare in November 2019.

The affected devices are the ApexPro Telemetry Server and CARESCAPE Telemetry Server, the CARESCAPE Central Station (CSCS) version 1, and the CIC Pro Clinical Information Center Central Station version 1. These devices are used in health care facilities for displaying information, such as the patient’s physiological parameters, and for monitoring patient status from a central location in a facility.

No adverse events related to the vulnerabilities have been reported to the FDA. Health care facility staff should update their devices when GE Healthcare issues a software patch that addresses the vulnerability, separate the network connecting patient monitors using affected devices from the rest of the hospital, and use firewalls and other means to minimize the risk of remote or local network attacks.

“The FDA takes reports of cybersecurity vulnerabilities in medical devices seriously and will continue to work with GE Healthcare as the firm develops software patches to correct these vulnerabilities as soon as possible. The FDA will continue to assess new information concerning the vulnerabilities and will keep the public informed if significant new information becomes available,” the FDA said in the Safety Communication.

[email protected]

The Food and Drug Administration has issued a warning that certain GE Healthcare Clinical Information Central Stations and Telemetry Servers have cybersecurity vulnerabilities that may introduce risk to monitored patients.

Wikimedia Commons/FitzColinGerald/ Creative Commons License

A security firm identified several vulnerabilities in the GE devices that allow attackers to remotely take control of the medical device, silence alarms, generate false alarms, and interfere with alarms of patient monitors connected to these devices, according to an “Urgent Medical Device Correction” letter issued by GE Healthcare in November 2019.

The affected devices are the ApexPro Telemetry Server and CARESCAPE Telemetry Server, the CARESCAPE Central Station (CSCS) version 1, and the CIC Pro Clinical Information Center Central Station version 1. These devices are used in health care facilities for displaying information, such as the patient’s physiological parameters, and for monitoring patient status from a central location in a facility.

No adverse events related to the vulnerabilities have been reported to the FDA. Health care facility staff should update their devices when GE Healthcare issues a software patch that addresses the vulnerability, separate the network connecting patient monitors using affected devices from the rest of the hospital, and use firewalls and other means to minimize the risk of remote or local network attacks.

“The FDA takes reports of cybersecurity vulnerabilities in medical devices seriously and will continue to work with GE Healthcare as the firm develops software patches to correct these vulnerabilities as soon as possible. The FDA will continue to assess new information concerning the vulnerabilities and will keep the public informed if significant new information becomes available,” the FDA said in the Safety Communication.

[email protected]

Hospital medicine groups (HMGs) nationally are confronted with a host of challenging issues: increased patient volume/complexities, resident duty-hour restrictions, and a rise in provider burnout. Many are turning to advanced practice providers (APPs) to help lighten these burdens.

But no practical guidelines exist around how to successfully incorporate APPs in a way that meets the needs of the patients, the providers, the HMG, and the health system, according to Kasey Bowden, MSN, FNP, AG-ACNP, lead author of a HM19 abstract on that subject.

“Much of the recent literature around APP utilization involves descriptive anecdotes on how individual HMGs have utilized APPs, and what metrics this helped them to achieve,” she said. “While these stories are often compelling, they provide no tangible value to HMGs looking to incorporate APPs into practice, as they do not address unique elements that limit successful APP integration, including diverse educational backgrounds of APPs and exceedingly high turnover rates (12.6% nationally).”

Ms. Bowden and coauthors created a conceptual framework, which recognizes that, without taking a holistic approach, many HMGs will fail to successfully integrate APPs. “Our hope is that by utilizing this framework to define APP-physician best practices, we will be able to create a useful tool for all HMGs that will promote successful APP-physician collaborative practice models.”

She thinks that hospitalists could also use this framework to examine their current practice models and to see where there may be opportunity for improvement. For example, a group may look at their own APP turnover rate. “If turnover rate is high in the first year, it may suggest inadequate onboarding/training, if it is high after 3 years, this may suggest minimal opportunities for professional growth and advancement,” Ms. Bowden said. “I would love to see a consensus group form within SHM of physician and APP leaders to utilize this framework to establish ‘APP-Physician best practices,’ and create a guideline available to all HMGs so that they can successfully incorporate APPs into their practice,” she said.

Reference

1. Bowden K et al. Creation of APP-physician best practices: A necessary tool for the growing APP workforce. Hospital Medicine 2019, Abstract 436.

Hospital medicine groups (HMGs) nationally are confronted with a host of challenging issues: increased patient volume/complexities, resident duty-hour restrictions, and a rise in provider burnout. Many are turning to advanced practice providers (APPs) to help lighten these burdens.

But no practical guidelines exist around how to successfully incorporate APPs in a way that meets the needs of the patients, the providers, the HMG, and the health system, according to Kasey Bowden, MSN, FNP, AG-ACNP, lead author of a HM19 abstract on that subject.

“Much of the recent literature around APP utilization involves descriptive anecdotes on how individual HMGs have utilized APPs, and what metrics this helped them to achieve,” she said. “While these stories are often compelling, they provide no tangible value to HMGs looking to incorporate APPs into practice, as they do not address unique elements that limit successful APP integration, including diverse educational backgrounds of APPs and exceedingly high turnover rates (12.6% nationally).”

Ms. Bowden and coauthors created a conceptual framework, which recognizes that, without taking a holistic approach, many HMGs will fail to successfully integrate APPs. “Our hope is that by utilizing this framework to define APP-physician best practices, we will be able to create a useful tool for all HMGs that will promote successful APP-physician collaborative practice models.”

She thinks that hospitalists could also use this framework to examine their current practice models and to see where there may be opportunity for improvement. For example, a group may look at their own APP turnover rate. “If turnover rate is high in the first year, it may suggest inadequate onboarding/training, if it is high after 3 years, this may suggest minimal opportunities for professional growth and advancement,” Ms. Bowden said. “I would love to see a consensus group form within SHM of physician and APP leaders to utilize this framework to establish ‘APP-Physician best practices,’ and create a guideline available to all HMGs so that they can successfully incorporate APPs into their practice,” she said.

Reference

1. Bowden K et al. Creation of APP-physician best practices: A necessary tool for the growing APP workforce. Hospital Medicine 2019, Abstract 436.

Hospital medicine groups (HMGs) nationally are confronted with a host of challenging issues: increased patient volume/complexities, resident duty-hour restrictions, and a rise in provider burnout. Many are turning to advanced practice providers (APPs) to help lighten these burdens.

But no practical guidelines exist around how to successfully incorporate APPs in a way that meets the needs of the patients, the providers, the HMG, and the health system, according to Kasey Bowden, MSN, FNP, AG-ACNP, lead author of a HM19 abstract on that subject.

“Much of the recent literature around APP utilization involves descriptive anecdotes on how individual HMGs have utilized APPs, and what metrics this helped them to achieve,” she said. “While these stories are often compelling, they provide no tangible value to HMGs looking to incorporate APPs into practice, as they do not address unique elements that limit successful APP integration, including diverse educational backgrounds of APPs and exceedingly high turnover rates (12.6% nationally).”

Ms. Bowden and coauthors created a conceptual framework, which recognizes that, without taking a holistic approach, many HMGs will fail to successfully integrate APPs. “Our hope is that by utilizing this framework to define APP-physician best practices, we will be able to create a useful tool for all HMGs that will promote successful APP-physician collaborative practice models.”

She thinks that hospitalists could also use this framework to examine their current practice models and to see where there may be opportunity for improvement. For example, a group may look at their own APP turnover rate. “If turnover rate is high in the first year, it may suggest inadequate onboarding/training, if it is high after 3 years, this may suggest minimal opportunities for professional growth and advancement,” Ms. Bowden said. “I would love to see a consensus group form within SHM of physician and APP leaders to utilize this framework to establish ‘APP-Physician best practices,’ and create a guideline available to all HMGs so that they can successfully incorporate APPs into their practice,” she said.

Reference

1. Bowden K et al. Creation of APP-physician best practices: A necessary tool for the growing APP workforce. Hospital Medicine 2019, Abstract 436.

The health consequences of diet don’t largely depend on whether a person eats a high or low level of carbohydrates or a diet high or low in fat. What’s much more important is where the carbs and fats come from, according to an analysis that related diet and mortality rates in more than 37,000 American adults.

“Unhealthy low carbohydrate diet [LCD] and low-fat diet [LFD] scores were associated with higher total mortality, whereas healthy LCD and LFD scores were associated with lower total mortality,” Zhilei Shan, MD, and associates wrote in an article (JAMA Intern Med. 2020 Jan 21; doi: 10.1001/jamainternmed.2019.6980). The findings “suggest that the association of LCDs and LFDs with mortality may depend on the quality of food sources of macronutrients,” said the researchers, based at the Harvard T.H. Chan School of Public Health in Boston.

The analysis included follow-up of almost 300,000 person-years. It showed that, for every 20-percentile increase in a person’s unhealthy LCD score, their relative rate of total mortality increased by a statistically significant 7%; and for every 20-percentile rise in unhealthy LFD score, the relative, total mortality rate rose by a statistically significant 6%, after adjustment for several demographic and clinical measures and family and personal histories of diabetes, cancer, and heart disease. In contrast, for each 20-percentile increase in healthy LCD score relative, total mortality fell by 9%, and similar increases in healthy LFD score linked with an 11% relative drop in total mortality, also statistically significant associations in these confounder-adjusted analyses.

The findings “extend the previous evidence” for these links, and the data suggest that “the health benefits of an LCD or LFD may depend not only on the types of protein and fat or carbohydrate but also on the quality of carbohydrate or fat remaining in the diet,” the researchers wrote. They cited the documented health problems caused by eating significant amounts of low-quality carbohydrates such as refined grains and added sugars, which provide limited nutrition and introduce a high glycemic load, and can produce high levels of postprandial glucose and insulin, inflammation, insulin resistance, and dyslipidemia.

The foods people ate that produced healthy diet scores and linked with better survival were diets high in plant protein and unsaturated fat, and low in carbohydrates from refined grains, added sugar, starchy vegetables, and similar sources as part of a low carbohydrate diet. The foods that formed a healthy LFD included whole grains, whole fruit, legumes, and nonstarchy vegetables, along with higher intake of plant protein and low levels of saturated fat.

The study used data from 24-hour diet-recall surveys completed by 37,233 American adults collected by the National Health and Nutrition Examination Survey (NHANES) during 1999-2014, and linked the diet scores calculated for these people with U.S. national death records collected by the National Death Index through the end of 2015. The people included averaged about 50 years of age at the time of their dietary interview, and 53% were women. During 297,768 person-years of follow-up, 4,866 total deaths occurred, including 849 from heart disease and 1,068 from cancer. The analyses found no statistically significant links between overall LCD or LFD scores and mortality; the significant links only existed when the researchers further classified the diet scores into healthy and unhealthy subtypes.

The results also showed statistically significant links or strong trends between high or low levels of healthy or unhealthy LCD and LFD scores and cancer deaths. A 20-percentile increase in unhealthy LCD score linked with an 11% relative increase in cancer deaths, while a 20-percentile increase in the healthy LCD score linked with a 10% decrease in cancer deaths. A 20-percentile increase in the healthy LFD score linked with a 15% relative decrease in cancer mortality.

The study received no commercial fundings, and the authors had no commercial disclosures.

[email protected]

SOURCE: Shan Z et al. JAMA Intern Med. 2020 Jan 21; doi: 10.1001/jamainternmed.2019.6980.

The health consequences of diet don’t largely depend on whether a person eats a high or low level of carbohydrates or a diet high or low in fat. What’s much more important is where the carbs and fats come from, according to an analysis that related diet and mortality rates in more than 37,000 American adults.

“Unhealthy low carbohydrate diet [LCD] and low-fat diet [LFD] scores were associated with higher total mortality, whereas healthy LCD and LFD scores were associated with lower total mortality,” Zhilei Shan, MD, and associates wrote in an article (JAMA Intern Med. 2020 Jan 21; doi: 10.1001/jamainternmed.2019.6980). The findings “suggest that the association of LCDs and LFDs with mortality may depend on the quality of food sources of macronutrients,” said the researchers, based at the Harvard T.H. Chan School of Public Health in Boston.

The analysis included follow-up of almost 300,000 person-years. It showed that, for every 20-percentile increase in a person’s unhealthy LCD score, their relative rate of total mortality increased by a statistically significant 7%; and for every 20-percentile rise in unhealthy LFD score, the relative, total mortality rate rose by a statistically significant 6%, after adjustment for several demographic and clinical measures and family and personal histories of diabetes, cancer, and heart disease. In contrast, for each 20-percentile increase in healthy LCD score relative, total mortality fell by 9%, and similar increases in healthy LFD score linked with an 11% relative drop in total mortality, also statistically significant associations in these confounder-adjusted analyses.

The findings “extend the previous evidence” for these links, and the data suggest that “the health benefits of an LCD or LFD may depend not only on the types of protein and fat or carbohydrate but also on the quality of carbohydrate or fat remaining in the diet,” the researchers wrote. They cited the documented health problems caused by eating significant amounts of low-quality carbohydrates such as refined grains and added sugars, which provide limited nutrition and introduce a high glycemic load, and can produce high levels of postprandial glucose and insulin, inflammation, insulin resistance, and dyslipidemia.

The foods people ate that produced healthy diet scores and linked with better survival were diets high in plant protein and unsaturated fat, and low in carbohydrates from refined grains, added sugar, starchy vegetables, and similar sources as part of a low carbohydrate diet. The foods that formed a healthy LFD included whole grains, whole fruit, legumes, and nonstarchy vegetables, along with higher intake of plant protein and low levels of saturated fat.

The study used data from 24-hour diet-recall surveys completed by 37,233 American adults collected by the National Health and Nutrition Examination Survey (NHANES) during 1999-2014, and linked the diet scores calculated for these people with U.S. national death records collected by the National Death Index through the end of 2015. The people included averaged about 50 years of age at the time of their dietary interview, and 53% were women. During 297,768 person-years of follow-up, 4,866 total deaths occurred, including 849 from heart disease and 1,068 from cancer. The analyses found no statistically significant links between overall LCD or LFD scores and mortality; the significant links only existed when the researchers further classified the diet scores into healthy and unhealthy subtypes.

The results also showed statistically significant links or strong trends between high or low levels of healthy or unhealthy LCD and LFD scores and cancer deaths. A 20-percentile increase in unhealthy LCD score linked with an 11% relative increase in cancer deaths, while a 20-percentile increase in the healthy LCD score linked with a 10% decrease in cancer deaths. A 20-percentile increase in the healthy LFD score linked with a 15% relative decrease in cancer mortality.

The study received no commercial fundings, and the authors had no commercial disclosures.

[email protected]

SOURCE: Shan Z et al. JAMA Intern Med. 2020 Jan 21; doi: 10.1001/jamainternmed.2019.6980.

The health consequences of diet don’t largely depend on whether a person eats a high or low level of carbohydrates or a diet high or low in fat. What’s much more important is where the carbs and fats come from, according to an analysis that related diet and mortality rates in more than 37,000 American adults.

“Unhealthy low carbohydrate diet [LCD] and low-fat diet [LFD] scores were associated with higher total mortality, whereas healthy LCD and LFD scores were associated with lower total mortality,” Zhilei Shan, MD, and associates wrote in an article (JAMA Intern Med. 2020 Jan 21; doi: 10.1001/jamainternmed.2019.6980). The findings “suggest that the association of LCDs and LFDs with mortality may depend on the quality of food sources of macronutrients,” said the researchers, based at the Harvard T.H. Chan School of Public Health in Boston.

The analysis included follow-up of almost 300,000 person-years. It showed that, for every 20-percentile increase in a person’s unhealthy LCD score, their relative rate of total mortality increased by a statistically significant 7%; and for every 20-percentile rise in unhealthy LFD score, the relative, total mortality rate rose by a statistically significant 6%, after adjustment for several demographic and clinical measures and family and personal histories of diabetes, cancer, and heart disease. In contrast, for each 20-percentile increase in healthy LCD score relative, total mortality fell by 9%, and similar increases in healthy LFD score linked with an 11% relative drop in total mortality, also statistically significant associations in these confounder-adjusted analyses.

The findings “extend the previous evidence” for these links, and the data suggest that “the health benefits of an LCD or LFD may depend not only on the types of protein and fat or carbohydrate but also on the quality of carbohydrate or fat remaining in the diet,” the researchers wrote. They cited the documented health problems caused by eating significant amounts of low-quality carbohydrates such as refined grains and added sugars, which provide limited nutrition and introduce a high glycemic load, and can produce high levels of postprandial glucose and insulin, inflammation, insulin resistance, and dyslipidemia.

The foods people ate that produced healthy diet scores and linked with better survival were diets high in plant protein and unsaturated fat, and low in carbohydrates from refined grains, added sugar, starchy vegetables, and similar sources as part of a low carbohydrate diet. The foods that formed a healthy LFD included whole grains, whole fruit, legumes, and nonstarchy vegetables, along with higher intake of plant protein and low levels of saturated fat.

The study used data from 24-hour diet-recall surveys completed by 37,233 American adults collected by the National Health and Nutrition Examination Survey (NHANES) during 1999-2014, and linked the diet scores calculated for these people with U.S. national death records collected by the National Death Index through the end of 2015. The people included averaged about 50 years of age at the time of their dietary interview, and 53% were women. During 297,768 person-years of follow-up, 4,866 total deaths occurred, including 849 from heart disease and 1,068 from cancer. The analyses found no statistically significant links between overall LCD or LFD scores and mortality; the significant links only existed when the researchers further classified the diet scores into healthy and unhealthy subtypes.

The results also showed statistically significant links or strong trends between high or low levels of healthy or unhealthy LCD and LFD scores and cancer deaths. A 20-percentile increase in unhealthy LCD score linked with an 11% relative increase in cancer deaths, while a 20-percentile increase in the healthy LCD score linked with a 10% decrease in cancer deaths. A 20-percentile increase in the healthy LFD score linked with a 15% relative decrease in cancer mortality.

The study received no commercial fundings, and the authors had no commercial disclosures.

[email protected]

SOURCE: Shan Z et al. JAMA Intern Med. 2020 Jan 21; doi: 10.1001/jamainternmed.2019.6980.

The first issue of Skin & Allergy News, now Dermatology News, was published in January 1970. One front-page story highlighted the "continued improvement and more widespread use of steroids" as the most important development of the 1960s in dermatology. Another covered the launch of a national program for dermatology "to design a pattern for its future instead of simply drifting and letting its fate be determined by others."

Throughout 2020, look for articles and features marking the publication's golden anniversary. And read the first ever issue in the PDF above.

The first issue of Skin & Allergy News, now Dermatology News, was published in January 1970. One front-page story highlighted the "continued improvement and more widespread use of steroids" as the most important development of the 1960s in dermatology. Another covered the launch of a national program for dermatology "to design a pattern for its future instead of simply drifting and letting its fate be determined by others."

Throughout 2020, look for articles and features marking the publication's golden anniversary. And read the first ever issue in the PDF above.

The first issue of Skin & Allergy News, now Dermatology News, was published in January 1970. One front-page story highlighted the "continued improvement and more widespread use of steroids" as the most important development of the 1960s in dermatology. Another covered the launch of a national program for dermatology "to design a pattern for its future instead of simply drifting and letting its fate be determined by others."

Throughout 2020, look for articles and features marking the publication's golden anniversary. And read the first ever issue in the PDF above.

Six active ingredients used in sunscreen products in the United States showed systemic skin absorption with geometric mean plasma concentrations greater than 0.5 ng/mL in a randomized trial including four product types. The results were published in JAMA.

The testing was done as part of a proposed rule on sunscreen, published in February 2019, which requested additional information on sunscreen ingredients. Murali K. Matta, PhD, of the Food and Drug Administration and coauthors wrote that these plasma concentrations “surpassed the FDA threshold for potentially waiving additional safety studies for sunscreens.” But, they added, the findings “do not indicate that individuals should refrain from the use of sunscreen.”

This was a follow-up study to a smaller study of 24 health volunteers published last year that determined that the sunscreen active ingredients tested were absorbed systemically (JAMA. 2019;321[21]:2082-91). “This follow-up study expanded the sample size, tested additional sunscreen active ingredients and formulations, and confirmed the finding that sunscreen active ingredients are systemically absorbed,” the authors wrote.

To gather information on the absorption of active ingredients in sunscreens, the investigators randomized 48 adults to one of four sunscreen products (lotion, aerosol spray, nonaerosol spray, or pump spray) with one of six active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate). Not all products contained each of the ingredients.

The participants applied the products in amounts of 2 mg/cm² to 75% of body surface area at baseline, no use on day 1 and four times a day at 2-hour intervals on days 2 through 4. The researchers collected blood samples over 21 days and measured the maximum plasma concentrations. The average age of the participants was 37 years, and half were women. The study was conducted in a clinical pharmacology unit.

The geometric mean maximum plasma concentrations for the primary endpoint of avobenzone in lotion, aerosol spray, nonaerosol spray, and pump spray were 7.1 ng/mL, 3.5 ng/mL, 3.5 ng/mL, and 3.3 ng/mL, respectively.

For oxybenzone, the concentrations were 258.1 ng/mL and 180.1 ng/mL, respectively, for lotion and aerosol spray. The concentrations for octocrylene were 7.8 ng/mL, 6.6 ng/mL, and 6.6 ng/mL, respectively, for lotion, aerosol spray, and nonaerosol spray.

For homosalate, the geometric mean plasma concentrations were 23.1 ng/mL for aerosol spray, 17.9 for nonaerosol spray, and 13.9 for pump spray. For octisalate, the concentrations were 5.1 ng/mL, 5.8 ng/mL, and 4.6 ng/mL, respectively, for aerosol spray, nonaerosol spray, and pump spray. For octinoxate, the concentrations were 7.9 ng/mL for nonaerosol spray and 5.2 ng/mL for pump spray.

“The systemic exposures, as measured by geometric mean maximum plasma concentrations, of all the tested active ingredients were higher than 0.5 ng/mL after a single application,” the researchers noted.

Overall, the most common event was rash, which was reported in 14 participants.

The study findings were limited by several factors including the use of an indoor clinical setting, rather than outdoor exposure; the inability to assess absorption differences by formulation and Fitzpatrick skin type; and the variation in amounts of ingredients among products, the researchers noted. However, the results can be used to design additional studies needed to research the effects of systemic exposure to sunscreen ingredients, they said.

In an accompanying editorial (JAMA. 2020;323:223-4), Adewole S. Adamson, MD, of the University of Texas at Austin, and Kanade Shinkai, MD, of the University of California, San Francisco, wrote that “the study did not address key questions about sunscreen safety,” including the length of time it takes “for plasma concentrations of sunscreen ingredients to fall below the FDA threshold for safety testing.” Dr. Shinkai is also editor in chief of JAMA Dermatology.

“In making an informed decision, clinicians must determine whether the magnitude of the benefit exceeds the risk of potential harm for a specific individual,” they said. “Importantly, this balance may be different, depending on characteristics of the sunscreen user (e.g., for individuals with darker skin types and for children) and may depend on the frequency and duration of application (e.g., daily vs. intermittent use; starting in infancy or later in life),” they noted.

“In the absence of clear data demonstrating harm, the use of chemical sunscreen may still be considered appropriate; the use of mineral-based sunscreen is a well-established safe alternative,” although the potential harms remain uncertain until the sunscreen industry conducts the safety studies recommended by the FDA, Dr. Adamson and Dr. Shinkai concluded.

In a statement released by the FDA on Jan 21, the day the study was published, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said that, considering the “recognized public health benefits” of using sunscreen, the FDA “urges Americans to use sunscreens in conjunction with other sun protective measures (such as protective clothing).”

Commenting on the study, she said, “results from our study released today show there is evidence that some sunscreen active ingredients may be absorbed. However, the fact that an ingredient is absorbed through the skin and into the body does not mean that the ingredient is unsafe, nor does the FDA seeking further information indicate such. Rather, this finding calls for further industry testing to determine the safety and effect of systemic exposure of sunscreen ingredients, especially with chronic use.”

The study was supported by the FDA. The researchers and editorial authors had no financial conflicts to disclose.

SOURCES: Matta MK et al. JAMA. 2020;323:256-267.

Six active ingredients used in sunscreen products in the United States showed systemic skin absorption with geometric mean plasma concentrations greater than 0.5 ng/mL in a randomized trial including four product types. The results were published in JAMA.

The testing was done as part of a proposed rule on sunscreen, published in February 2019, which requested additional information on sunscreen ingredients. Murali K. Matta, PhD, of the Food and Drug Administration and coauthors wrote that these plasma concentrations “surpassed the FDA threshold for potentially waiving additional safety studies for sunscreens.” But, they added, the findings “do not indicate that individuals should refrain from the use of sunscreen.”

This was a follow-up study to a smaller study of 24 health volunteers published last year that determined that the sunscreen active ingredients tested were absorbed systemically (JAMA. 2019;321[21]:2082-91). “This follow-up study expanded the sample size, tested additional sunscreen active ingredients and formulations, and confirmed the finding that sunscreen active ingredients are systemically absorbed,” the authors wrote.

To gather information on the absorption of active ingredients in sunscreens, the investigators randomized 48 adults to one of four sunscreen products (lotion, aerosol spray, nonaerosol spray, or pump spray) with one of six active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate). Not all products contained each of the ingredients.

The participants applied the products in amounts of 2 mg/cm² to 75% of body surface area at baseline, no use on day 1 and four times a day at 2-hour intervals on days 2 through 4. The researchers collected blood samples over 21 days and measured the maximum plasma concentrations. The average age of the participants was 37 years, and half were women. The study was conducted in a clinical pharmacology unit.

The geometric mean maximum plasma concentrations for the primary endpoint of avobenzone in lotion, aerosol spray, nonaerosol spray, and pump spray were 7.1 ng/mL, 3.5 ng/mL, 3.5 ng/mL, and 3.3 ng/mL, respectively.

For oxybenzone, the concentrations were 258.1 ng/mL and 180.1 ng/mL, respectively, for lotion and aerosol spray. The concentrations for octocrylene were 7.8 ng/mL, 6.6 ng/mL, and 6.6 ng/mL, respectively, for lotion, aerosol spray, and nonaerosol spray.

For homosalate, the geometric mean plasma concentrations were 23.1 ng/mL for aerosol spray, 17.9 for nonaerosol spray, and 13.9 for pump spray. For octisalate, the concentrations were 5.1 ng/mL, 5.8 ng/mL, and 4.6 ng/mL, respectively, for aerosol spray, nonaerosol spray, and pump spray. For octinoxate, the concentrations were 7.9 ng/mL for nonaerosol spray and 5.2 ng/mL for pump spray.

“The systemic exposures, as measured by geometric mean maximum plasma concentrations, of all the tested active ingredients were higher than 0.5 ng/mL after a single application,” the researchers noted.

Overall, the most common event was rash, which was reported in 14 participants.

The study findings were limited by several factors including the use of an indoor clinical setting, rather than outdoor exposure; the inability to assess absorption differences by formulation and Fitzpatrick skin type; and the variation in amounts of ingredients among products, the researchers noted. However, the results can be used to design additional studies needed to research the effects of systemic exposure to sunscreen ingredients, they said.

In an accompanying editorial (JAMA. 2020;323:223-4), Adewole S. Adamson, MD, of the University of Texas at Austin, and Kanade Shinkai, MD, of the University of California, San Francisco, wrote that “the study did not address key questions about sunscreen safety,” including the length of time it takes “for plasma concentrations of sunscreen ingredients to fall below the FDA threshold for safety testing.” Dr. Shinkai is also editor in chief of JAMA Dermatology.

“In making an informed decision, clinicians must determine whether the magnitude of the benefit exceeds the risk of potential harm for a specific individual,” they said. “Importantly, this balance may be different, depending on characteristics of the sunscreen user (e.g., for individuals with darker skin types and for children) and may depend on the frequency and duration of application (e.g., daily vs. intermittent use; starting in infancy or later in life),” they noted.

“In the absence of clear data demonstrating harm, the use of chemical sunscreen may still be considered appropriate; the use of mineral-based sunscreen is a well-established safe alternative,” although the potential harms remain uncertain until the sunscreen industry conducts the safety studies recommended by the FDA, Dr. Adamson and Dr. Shinkai concluded.

In a statement released by the FDA on Jan 21, the day the study was published, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said that, considering the “recognized public health benefits” of using sunscreen, the FDA “urges Americans to use sunscreens in conjunction with other sun protective measures (such as protective clothing).”

Commenting on the study, she said, “results from our study released today show there is evidence that some sunscreen active ingredients may be absorbed. However, the fact that an ingredient is absorbed through the skin and into the body does not mean that the ingredient is unsafe, nor does the FDA seeking further information indicate such. Rather, this finding calls for further industry testing to determine the safety and effect of systemic exposure of sunscreen ingredients, especially with chronic use.”

The study was supported by the FDA. The researchers and editorial authors had no financial conflicts to disclose.

SOURCES: Matta MK et al. JAMA. 2020;323:256-267.

Six active ingredients used in sunscreen products in the United States showed systemic skin absorption with geometric mean plasma concentrations greater than 0.5 ng/mL in a randomized trial including four product types. The results were published in JAMA.

The testing was done as part of a proposed rule on sunscreen, published in February 2019, which requested additional information on sunscreen ingredients. Murali K. Matta, PhD, of the Food and Drug Administration and coauthors wrote that these plasma concentrations “surpassed the FDA threshold for potentially waiving additional safety studies for sunscreens.” But, they added, the findings “do not indicate that individuals should refrain from the use of sunscreen.”

This was a follow-up study to a smaller study of 24 health volunteers published last year that determined that the sunscreen active ingredients tested were absorbed systemically (JAMA. 2019;321[21]:2082-91). “This follow-up study expanded the sample size, tested additional sunscreen active ingredients and formulations, and confirmed the finding that sunscreen active ingredients are systemically absorbed,” the authors wrote.

To gather information on the absorption of active ingredients in sunscreens, the investigators randomized 48 adults to one of four sunscreen products (lotion, aerosol spray, nonaerosol spray, or pump spray) with one of six active ingredients (avobenzone, oxybenzone, octocrylene, homosalate, octisalate, and octinoxate). Not all products contained each of the ingredients.

The participants applied the products in amounts of 2 mg/cm² to 75% of body surface area at baseline, no use on day 1 and four times a day at 2-hour intervals on days 2 through 4. The researchers collected blood samples over 21 days and measured the maximum plasma concentrations. The average age of the participants was 37 years, and half were women. The study was conducted in a clinical pharmacology unit.

The geometric mean maximum plasma concentrations for the primary endpoint of avobenzone in lotion, aerosol spray, nonaerosol spray, and pump spray were 7.1 ng/mL, 3.5 ng/mL, 3.5 ng/mL, and 3.3 ng/mL, respectively.

For oxybenzone, the concentrations were 258.1 ng/mL and 180.1 ng/mL, respectively, for lotion and aerosol spray. The concentrations for octocrylene were 7.8 ng/mL, 6.6 ng/mL, and 6.6 ng/mL, respectively, for lotion, aerosol spray, and nonaerosol spray.

For homosalate, the geometric mean plasma concentrations were 23.1 ng/mL for aerosol spray, 17.9 for nonaerosol spray, and 13.9 for pump spray. For octisalate, the concentrations were 5.1 ng/mL, 5.8 ng/mL, and 4.6 ng/mL, respectively, for aerosol spray, nonaerosol spray, and pump spray. For octinoxate, the concentrations were 7.9 ng/mL for nonaerosol spray and 5.2 ng/mL for pump spray.

“The systemic exposures, as measured by geometric mean maximum plasma concentrations, of all the tested active ingredients were higher than 0.5 ng/mL after a single application,” the researchers noted.

Overall, the most common event was rash, which was reported in 14 participants.

The study findings were limited by several factors including the use of an indoor clinical setting, rather than outdoor exposure; the inability to assess absorption differences by formulation and Fitzpatrick skin type; and the variation in amounts of ingredients among products, the researchers noted. However, the results can be used to design additional studies needed to research the effects of systemic exposure to sunscreen ingredients, they said.

In an accompanying editorial (JAMA. 2020;323:223-4), Adewole S. Adamson, MD, of the University of Texas at Austin, and Kanade Shinkai, MD, of the University of California, San Francisco, wrote that “the study did not address key questions about sunscreen safety,” including the length of time it takes “for plasma concentrations of sunscreen ingredients to fall below the FDA threshold for safety testing.” Dr. Shinkai is also editor in chief of JAMA Dermatology.

“In making an informed decision, clinicians must determine whether the magnitude of the benefit exceeds the risk of potential harm for a specific individual,” they said. “Importantly, this balance may be different, depending on characteristics of the sunscreen user (e.g., for individuals with darker skin types and for children) and may depend on the frequency and duration of application (e.g., daily vs. intermittent use; starting in infancy or later in life),” they noted.

“In the absence of clear data demonstrating harm, the use of chemical sunscreen may still be considered appropriate; the use of mineral-based sunscreen is a well-established safe alternative,” although the potential harms remain uncertain until the sunscreen industry conducts the safety studies recommended by the FDA, Dr. Adamson and Dr. Shinkai concluded.

In a statement released by the FDA on Jan 21, the day the study was published, Janet Woodcock, MD, director of the FDA’s Center for Drug Evaluation and Research, said that, considering the “recognized public health benefits” of using sunscreen, the FDA “urges Americans to use sunscreens in conjunction with other sun protective measures (such as protective clothing).”

Commenting on the study, she said, “results from our study released today show there is evidence that some sunscreen active ingredients may be absorbed. However, the fact that an ingredient is absorbed through the skin and into the body does not mean that the ingredient is unsafe, nor does the FDA seeking further information indicate such. Rather, this finding calls for further industry testing to determine the safety and effect of systemic exposure of sunscreen ingredients, especially with chronic use.”

The study was supported by the FDA. The researchers and editorial authors had no financial conflicts to disclose.

SOURCES: Matta MK et al. JAMA. 2020;323:256-267.

Groceries, maybe a new shirt, and now some veterans can fit in some shopping at their next health care visit. In a pilot project, the US Department of Veterans Affairs (VA) is partnering with Walmart to offer veterans easy access to health care at 5 sites.

The VA-led ATLAS (Accessing telehealth through local area stations) program is part of the VA Anywhere to Anywhere telehealth initiative, which aims to provide care to veterans no matter where they live. Other telehealth pilot sites are in Wisconsin, Michigan, and Iowa. In addition to Walmart, ATLAS sites are located at American Legion posts and Veterans of Foreign Wars (VFW) posts.

The local VA facility associated with the ATLAS site determines which clinical services the site offers. The health care services do not require hands-on exams. Clinical services may include, for instance, primary care, mental health counseling, clinical pharmacy, nutrition services, and social work. On-site attendants provide information, help the veterans get started, troubleshoot technical issues, and clean the space between appointments. Walmart donated equipment and space, where veterans can meet with a VA provider in a private room via video technology.

Last year, nearly 500,000 veterans logged > 1.3 million VA video telehealth encounters. It is the “way of the future,” says VA Secretary Robert Wilkie. “Veterans need the expansion of choice, and this partnership is vital to affording them convenient access to VA health care services where they live.”

Daryl Risinger, Chief Growth Officer for Walmart US Health and Wellness, is a veteran of the Air Force, and has a son and son-in-law serving. He says, “I know firsthand how important support and access is for our military, especially when it comes to health care. …This is another way we are helping our communities live better.”

For a veteran to attend an appointment at an ATLAS site, the site must be associated with the VA Medical Center where the veteran is enrolled. Family members who receive care through the VA can also visit ATLAS sites for select appointments.

Groceries, maybe a new shirt, and now some veterans can fit in some shopping at their next health care visit. In a pilot project, the US Department of Veterans Affairs (VA) is partnering with Walmart to offer veterans easy access to health care at 5 sites.

The VA-led ATLAS (Accessing telehealth through local area stations) program is part of the VA Anywhere to Anywhere telehealth initiative, which aims to provide care to veterans no matter where they live. Other telehealth pilot sites are in Wisconsin, Michigan, and Iowa. In addition to Walmart, ATLAS sites are located at American Legion posts and Veterans of Foreign Wars (VFW) posts.

The local VA facility associated with the ATLAS site determines which clinical services the site offers. The health care services do not require hands-on exams. Clinical services may include, for instance, primary care, mental health counseling, clinical pharmacy, nutrition services, and social work. On-site attendants provide information, help the veterans get started, troubleshoot technical issues, and clean the space between appointments. Walmart donated equipment and space, where veterans can meet with a VA provider in a private room via video technology.

Last year, nearly 500,000 veterans logged > 1.3 million VA video telehealth encounters. It is the “way of the future,” says VA Secretary Robert Wilkie. “Veterans need the expansion of choice, and this partnership is vital to affording them convenient access to VA health care services where they live.”

Daryl Risinger, Chief Growth Officer for Walmart US Health and Wellness, is a veteran of the Air Force, and has a son and son-in-law serving. He says, “I know firsthand how important support and access is for our military, especially when it comes to health care. …This is another way we are helping our communities live better.”

For a veteran to attend an appointment at an ATLAS site, the site must be associated with the VA Medical Center where the veteran is enrolled. Family members who receive care through the VA can also visit ATLAS sites for select appointments.

Groceries, maybe a new shirt, and now some veterans can fit in some shopping at their next health care visit. In a pilot project, the US Department of Veterans Affairs (VA) is partnering with Walmart to offer veterans easy access to health care at 5 sites.

The VA-led ATLAS (Accessing telehealth through local area stations) program is part of the VA Anywhere to Anywhere telehealth initiative, which aims to provide care to veterans no matter where they live. Other telehealth pilot sites are in Wisconsin, Michigan, and Iowa. In addition to Walmart, ATLAS sites are located at American Legion posts and Veterans of Foreign Wars (VFW) posts.

The local VA facility associated with the ATLAS site determines which clinical services the site offers. The health care services do not require hands-on exams. Clinical services may include, for instance, primary care, mental health counseling, clinical pharmacy, nutrition services, and social work. On-site attendants provide information, help the veterans get started, troubleshoot technical issues, and clean the space between appointments. Walmart donated equipment and space, where veterans can meet with a VA provider in a private room via video technology.

Last year, nearly 500,000 veterans logged > 1.3 million VA video telehealth encounters. It is the “way of the future,” says VA Secretary Robert Wilkie. “Veterans need the expansion of choice, and this partnership is vital to affording them convenient access to VA health care services where they live.”

Daryl Risinger, Chief Growth Officer for Walmart US Health and Wellness, is a veteran of the Air Force, and has a son and son-in-law serving. He says, “I know firsthand how important support and access is for our military, especially when it comes to health care. …This is another way we are helping our communities live better.”

For a veteran to attend an appointment at an ATLAS site, the site must be associated with the VA Medical Center where the veteran is enrolled. Family members who receive care through the VA can also visit ATLAS sites for select appointments.