Mixed Topics

A team of surgeons successfully transplanted genetically engineered pig hearts into two recently deceased people whose bodies were being maintained on ventilatory support – not in the hope of restoring life, but as a proof-of-concept experiment in xenotransplantation that could eventually help to ease the critical shortage of donor organs.

The surgeries were performed on June 16 and July 6, 2022, using porcine hearts from animals genetically engineered to prevent organ rejection and promote adaptive immunity by human recipients

“From the very beginning our goal was to be able to create a model where we actually mimicked what is now done clinically in human transplantation, without utilizing unapproved devices or techniques or medications,” said Nader Moazami, MD, surgical director of heart transplantation and chief of the division of heart and lung transplantation and mechanical circulatory support at NYU Langone Health, New York.

Joe Carrotta for NYU Langone Health

Through 72 hours of postoperative monitoring “we evaluated the heart for functionality and the heart function was completely normal with excellent contractility,” he said at a press briefing announcing early results of the experimental program.

He acknowledged that for the first of the two procedures some surgical modification of the pig heart was required, primarily because of size differences between the donor and recipient.

“Nevertheless, we learned a tremendous amount from the first operation, and when that experience was translated into the second operation it even performed better,” he said.

Alex Reyentovich, MD, medical director of heart transplantation and director of the NYU Langone advanced heart failure program noted that “there are 6 million individuals with heart failure in the United States. About 100,000 of those individuals have end-stage heart failure, and we only do about 3,500 heart transplants a year in the United States, so we have a tremendous deficiency in organs, and there are many people dying waiting for a heart.”

Infection protocols

To date there has been only one xenotransplant of a genetically modified pig heart into a living human recipient, David Bennett Sr., age 57. The surgery, performed at the University of Maryland in January 2022, was initially successful, with the patient able to sit up in bed a few days after the procedure, and the heart performing like a “rock star” according to transplant surgeon Bartley Griffith, MD.

However, Mr. Bennett died 2 months after the procedure from compromise of the organ by an as yet undetermined cause, of which one may have been the heart's infection by porcine cytomegalovirus (CMV).

Joe Carrotta for NYU Langone Health

The NYU team, mindful of this potential setback, used more sensitive assays to screen the donor organs for porcine CMV, and implemented protocols to prevent and to monitor for potential zoonotic transmission of porcine endogenous retrovirus.

The procedure used a dedicated operating room and equipment that will not be used for clinical procedures, the team emphasized.

An organ transplant specialist who was not involved in the study commented that there can be unwelcome surprises even with the most rigorous infection prophylaxis protocols.

“I think these are important steps, but they don’t resolve the question of infectious risk. Sometimes viruses or latent infections are only manifested later,” said Jay A. Fishman, MD, associate director of the Massachusetts General Hospital Transplant Center and director of the transplant infectious diseases and compromised host program at the hospital, which is in Boston.

“I think these are important steps, but as you may recall from the Maryland heart transplant experience, when porcine cytomegalovirus was activated, it was a long way into that patient’s course, and so we just don’t know whether something would have been reactivated later,” he said in an interview.

Dr. Fishman noted that experience with xenotransplantation at the University of Maryland and other centers has suggested that immunosuppressive regimens used for human-to-human transplants may not be suited for animal-to-human grafts.

The hearts were taken from pigs genetically modified with knockouts of four porcine genes to prevent rejection – including a gene for a growth hormone that would otherwise cause the heart to continue to expand in the recipient’s chest – and with the addition of six human transgenes encoding for expression of proteins regulating biologic pathways that might be disrupted by incompatibilities across species.

Vietnam veteran

The organ recipients were recently deceased patients who had expressed the clear wish to be organ donors but whose organs were for clinical reasons unsuitable for transplant.

The first recipient was Lawrence Kelly, a Vietnam War veteran and welder who died from heart failure at the age of 72.

“He was an organ donor, and would be so happy to know how much his contribution to this research will help people like him with this heart disease. He was a hero his whole life, and he went out a hero,” said Alice Michael, Mr. Kelly’s partner of 33 years, who also spoke at the briefing.

“It was, I think, one of the most incredible things to see a pig heart pounding away and beating inside the chest of a human being,” said Robert A. Montgomery, MD, DPhil, director of the NYU Transplant Institute, and himself a heart transplant recipient.

Dr. Fishman said he had no relevant conflicts of interest.

This article was updated on 7/12/22 and 7/14/22.

A team of surgeons successfully transplanted genetically engineered pig hearts into two recently deceased people whose bodies were being maintained on ventilatory support – not in the hope of restoring life, but as a proof-of-concept experiment in xenotransplantation that could eventually help to ease the critical shortage of donor organs.

The surgeries were performed on June 16 and July 6, 2022, using porcine hearts from animals genetically engineered to prevent organ rejection and promote adaptive immunity by human recipients

“From the very beginning our goal was to be able to create a model where we actually mimicked what is now done clinically in human transplantation, without utilizing unapproved devices or techniques or medications,” said Nader Moazami, MD, surgical director of heart transplantation and chief of the division of heart and lung transplantation and mechanical circulatory support at NYU Langone Health, New York.

Joe Carrotta for NYU Langone Health

Through 72 hours of postoperative monitoring “we evaluated the heart for functionality and the heart function was completely normal with excellent contractility,” he said at a press briefing announcing early results of the experimental program.

He acknowledged that for the first of the two procedures some surgical modification of the pig heart was required, primarily because of size differences between the donor and recipient.

“Nevertheless, we learned a tremendous amount from the first operation, and when that experience was translated into the second operation it even performed better,” he said.

Alex Reyentovich, MD, medical director of heart transplantation and director of the NYU Langone advanced heart failure program noted that “there are 6 million individuals with heart failure in the United States. About 100,000 of those individuals have end-stage heart failure, and we only do about 3,500 heart transplants a year in the United States, so we have a tremendous deficiency in organs, and there are many people dying waiting for a heart.”

Infection protocols

To date there has been only one xenotransplant of a genetically modified pig heart into a living human recipient, David Bennett Sr., age 57. The surgery, performed at the University of Maryland in January 2022, was initially successful, with the patient able to sit up in bed a few days after the procedure, and the heart performing like a “rock star” according to transplant surgeon Bartley Griffith, MD.

However, Mr. Bennett died 2 months after the procedure from compromise of the organ by an as yet undetermined cause, of which one may have been the heart's infection by porcine cytomegalovirus (CMV).

Joe Carrotta for NYU Langone Health

The NYU team, mindful of this potential setback, used more sensitive assays to screen the donor organs for porcine CMV, and implemented protocols to prevent and to monitor for potential zoonotic transmission of porcine endogenous retrovirus.

The procedure used a dedicated operating room and equipment that will not be used for clinical procedures, the team emphasized.

An organ transplant specialist who was not involved in the study commented that there can be unwelcome surprises even with the most rigorous infection prophylaxis protocols.

“I think these are important steps, but they don’t resolve the question of infectious risk. Sometimes viruses or latent infections are only manifested later,” said Jay A. Fishman, MD, associate director of the Massachusetts General Hospital Transplant Center and director of the transplant infectious diseases and compromised host program at the hospital, which is in Boston.

“I think these are important steps, but as you may recall from the Maryland heart transplant experience, when porcine cytomegalovirus was activated, it was a long way into that patient’s course, and so we just don’t know whether something would have been reactivated later,” he said in an interview.

Dr. Fishman noted that experience with xenotransplantation at the University of Maryland and other centers has suggested that immunosuppressive regimens used for human-to-human transplants may not be suited for animal-to-human grafts.

The hearts were taken from pigs genetically modified with knockouts of four porcine genes to prevent rejection – including a gene for a growth hormone that would otherwise cause the heart to continue to expand in the recipient’s chest – and with the addition of six human transgenes encoding for expression of proteins regulating biologic pathways that might be disrupted by incompatibilities across species.

Vietnam veteran

The organ recipients were recently deceased patients who had expressed the clear wish to be organ donors but whose organs were for clinical reasons unsuitable for transplant.

The first recipient was Lawrence Kelly, a Vietnam War veteran and welder who died from heart failure at the age of 72.

“He was an organ donor, and would be so happy to know how much his contribution to this research will help people like him with this heart disease. He was a hero his whole life, and he went out a hero,” said Alice Michael, Mr. Kelly’s partner of 33 years, who also spoke at the briefing.

“It was, I think, one of the most incredible things to see a pig heart pounding away and beating inside the chest of a human being,” said Robert A. Montgomery, MD, DPhil, director of the NYU Transplant Institute, and himself a heart transplant recipient.

Dr. Fishman said he had no relevant conflicts of interest.

This article was updated on 7/12/22 and 7/14/22.

A team of surgeons successfully transplanted genetically engineered pig hearts into two recently deceased people whose bodies were being maintained on ventilatory support – not in the hope of restoring life, but as a proof-of-concept experiment in xenotransplantation that could eventually help to ease the critical shortage of donor organs.

The surgeries were performed on June 16 and July 6, 2022, using porcine hearts from animals genetically engineered to prevent organ rejection and promote adaptive immunity by human recipients

“From the very beginning our goal was to be able to create a model where we actually mimicked what is now done clinically in human transplantation, without utilizing unapproved devices or techniques or medications,” said Nader Moazami, MD, surgical director of heart transplantation and chief of the division of heart and lung transplantation and mechanical circulatory support at NYU Langone Health, New York.

Joe Carrotta for NYU Langone Health

Through 72 hours of postoperative monitoring “we evaluated the heart for functionality and the heart function was completely normal with excellent contractility,” he said at a press briefing announcing early results of the experimental program.

He acknowledged that for the first of the two procedures some surgical modification of the pig heart was required, primarily because of size differences between the donor and recipient.

“Nevertheless, we learned a tremendous amount from the first operation, and when that experience was translated into the second operation it even performed better,” he said.

Alex Reyentovich, MD, medical director of heart transplantation and director of the NYU Langone advanced heart failure program noted that “there are 6 million individuals with heart failure in the United States. About 100,000 of those individuals have end-stage heart failure, and we only do about 3,500 heart transplants a year in the United States, so we have a tremendous deficiency in organs, and there are many people dying waiting for a heart.”

Infection protocols

To date there has been only one xenotransplant of a genetically modified pig heart into a living human recipient, David Bennett Sr., age 57. The surgery, performed at the University of Maryland in January 2022, was initially successful, with the patient able to sit up in bed a few days after the procedure, and the heart performing like a “rock star” according to transplant surgeon Bartley Griffith, MD.

However, Mr. Bennett died 2 months after the procedure from compromise of the organ by an as yet undetermined cause, of which one may have been the heart's infection by porcine cytomegalovirus (CMV).

Joe Carrotta for NYU Langone Health

The NYU team, mindful of this potential setback, used more sensitive assays to screen the donor organs for porcine CMV, and implemented protocols to prevent and to monitor for potential zoonotic transmission of porcine endogenous retrovirus.

The procedure used a dedicated operating room and equipment that will not be used for clinical procedures, the team emphasized.

An organ transplant specialist who was not involved in the study commented that there can be unwelcome surprises even with the most rigorous infection prophylaxis protocols.

“I think these are important steps, but they don’t resolve the question of infectious risk. Sometimes viruses or latent infections are only manifested later,” said Jay A. Fishman, MD, associate director of the Massachusetts General Hospital Transplant Center and director of the transplant infectious diseases and compromised host program at the hospital, which is in Boston.

“I think these are important steps, but as you may recall from the Maryland heart transplant experience, when porcine cytomegalovirus was activated, it was a long way into that patient’s course, and so we just don’t know whether something would have been reactivated later,” he said in an interview.

Dr. Fishman noted that experience with xenotransplantation at the University of Maryland and other centers has suggested that immunosuppressive regimens used for human-to-human transplants may not be suited for animal-to-human grafts.

The hearts were taken from pigs genetically modified with knockouts of four porcine genes to prevent rejection – including a gene for a growth hormone that would otherwise cause the heart to continue to expand in the recipient’s chest – and with the addition of six human transgenes encoding for expression of proteins regulating biologic pathways that might be disrupted by incompatibilities across species.

Vietnam veteran

The organ recipients were recently deceased patients who had expressed the clear wish to be organ donors but whose organs were for clinical reasons unsuitable for transplant.

The first recipient was Lawrence Kelly, a Vietnam War veteran and welder who died from heart failure at the age of 72.

“He was an organ donor, and would be so happy to know how much his contribution to this research will help people like him with this heart disease. He was a hero his whole life, and he went out a hero,” said Alice Michael, Mr. Kelly’s partner of 33 years, who also spoke at the briefing.

“It was, I think, one of the most incredible things to see a pig heart pounding away and beating inside the chest of a human being,” said Robert A. Montgomery, MD, DPhil, director of the NYU Transplant Institute, and himself a heart transplant recipient.

Dr. Fishman said he had no relevant conflicts of interest.

This article was updated on 7/12/22 and 7/14/22.

Insulin injection therapy is one of the most widely used health care interventions to manage both type 1 and type 2 diabetes mellitus (T1DM/T2DM). Globally, more than 150 to 200 million people inject insulin into their upper posterior arms, buttocks, anterior and lateral thighs, or abdomen.^1,2 In an ideal world, every patient would be using the correct site and rotating their insulin injection sites in accordance with health care professional (HCP) recommendations—systematic injections in one general body location, at least 1 cm away from the previous injection.² Unfortunately, same-site insulin injection (repeatedly in the same region within 1 cm of previous injections) is a common mistake made by patients with DM—in one study, 63% of participants either did not rotate sites correctly or failed to do so at all.

Insulin-resistant cutaneous complications may occur as a result of same-site insulin injections. The most common is lipohypertrophy, reported in some studies in nearly 50% of patients with DM on insulin therapy.⁴ Other common cutaneous complications include lipoatrophy and amyloidosis. Injection-site acanthosis nigricans, although uncommon, has been reported in 18 cases in the literature.

Most articles suggest that same-site insulin injections decrease local insulin sensitivity and result in tissue hypertrophy because of the anabolic properties of insulin and increase in insulin binding to insulin-like growth factor-1 (IGF-1) receptor.^5-20 The hyperkeratotic growth and varying insulin absorption rates associated with these cutaneous complications increase chances of either hyper- or hypoglycemic episodes in patients.^10,11,13 It is the responsibility of the DM care professional to provide proper insulin-injection technique education and perform routine inspection of injection sites to reduce cutaneous complications of insulin therapy. The purpose of this article is to (1) describe a case of acanthosis nigricans resulting from insulin injection at the same site; (2) review case reports in the literature describing injection-site acanthosis nigricans resulting from same-site insulin injections; (3) describe localized cutaneous complications associated with the use of insulin; and (4) discuss clinical implications and lessons learned from the literature.

Case Presentation

A 75-year-old patient with an 8-year history of T2DM, as well as stable coronary artery disease, atrial fibrillation, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, and stage 3 chronic kidney disease, presented with 2 discrete abdominal hyperpigmented plaques. At the time of the initial clinic visit, the patient was taking metformin 1000 mg twice daily and insulin glargine 40 units once daily. When insulin was initiated 7 years prior, the patient received neutral protamine Hagedorn (NPH) insulin for the first year and transitioned to insulin glargine. After 4 years of insulin therapy, insulin aspart was added and discontinued after 2 years. The patient’s hemoglobin A_1c (HbA_1c) was 6.8%, suggesting good glycemic control.

The patient reported 5 years of progressive, asymptomatic hyperpigmentation of the skin surrounding his insulin glargine injection sites and injecting in these same sites daily without rotation. He reported no additional skin changes or symptoms. He had noticed no skin changes while using NPH insulin during his first year of insulin therapy. On examination, the abdominal wall skin demonstrated 2 well-demarcated, nearly black, soft, velvety plaques, measuring 9 × 8 cm on the left side and 4 × 3.5 cm on the right, suggesting acanthosis nigricans (Figure 1A). The remainder of the skin examination, including the flexures, was normal. Of note, the patient received biweekly intramuscular testosterone injections in the gluteal region for secondary hypogonadism with no adverse dermatologic effects. A skin punch biopsy was performed and revealed epidermal papillomatosis and hyperkeratosis, confirming the clinical diagnosis of acanthosis nigricans (Figure 2).

After a review of insulin-injection technique at his clinic visit, the patient started rotating insulin injection sites over his entire abdomen, and the acanthosis nigricans partially improved. A few months later, the patient stopped rotating the insulin injection site, and the acanthosis nigricans worsened again. Because of worsening glycemic control, the patient was then started on insulin aspart. He did not develop any skin changes at the insulin aspart injection site, although he was not rotating its site of injection.

Subsequently, with reeducation and proper injection-site rotation, the patient had resolution of his acanthosis nigricans (Figure 1b).

Discussion

A review of the literature revealed 18 reported cases of acanthosis nigricans at sites of repeated insulin injection (Table).^5-20 Acanthosis nigricans at the site of insulin injection afflicts patients of any age, with cases observed in patients aged 14 to 75 years. Sixteen (84%) of 19 cases were male. Fourteen cases (73%) had T2DM; the rest of the patients had T1DM. The duration of insulin injection therapy prior to onset ranged from immediate to 13 years (median 4 years). Fourteen cases (73%) were reported on the abdomen; however, other sites, such as thighs and upper arm, also were reported. Lesions size varied from 12 to 360 cm². Two cases had associated amyloidosis. The average HbA_1c reported at presentation was 10%. Following insulin injection-site rotation, most of the cases reported improvement of both glycemic control and acanthosis nigricans appearance.

In the case described by Kudo and colleagues, a 59-year-old male patient with T2DM had been injecting insulin into the same spot on his abdomen for 10 years. He developed acanthosis nigricans and an amyloidoma so large and firm that it bent the needle when he injected insulin.¹¹

Most of the cases we found in the literature were after 2005 and associated with the use of human or analog insulin. These cases may be related to a bias, as cases may be easier to find in digital archives in the later years, when human or analog insulins have been in common use. Also noteworthy, in cases that reported dosage, most were not very high, and the highest daily dose was 240 IU/d. Ten reports of injection-site acanthosis nigricans were in dermatology journals; only 5 reports were in endocrinology journals and 3 in general medical journals, indicating possible less awareness of this phenomenon in other HCPs who care for patients with DM.

Complications of Same-Site Injections

Acanthosis nigricans. Commonly found in the armpits, neck folds, and groin, acanthosis nigricans is known as one of the calling cards for insulin resistance, obesity, and hyperinsulinemia.²¹ Acanthosis nigricans can be seen in people with or without DM and is not limited to those on insulin therapy. However, same-site insulin injections for 4 to 6 years also may result in injection-site acanthosis nigricans–like lesions because of factors such as insulin exposure at the local tissue level.¹⁶

Acanthosis nigricans development is characterized by hyperpigmented, hyperkeratotic, velvety, and sometimes verrucous plaques.⁶ Acanthosis nigricans surrounding repeated injection sites is hypothesized to develop as a result of localized hyperinsulinemia secondary to insulin resistance, which increases the stimulation of IGF, thereby causing epidermal hypertrophy.^5-20 If insulin injection therapy continues to be administered through the acanthosis nigricans lesion, it results in decreased insulin absorption, leading to poor glycemic control.¹³

Acanthosis nigricans associated with insulin injection is reversible. After rotation of injection sites, lesions either decrease in size or severity of appearance.^5-8,11 Also, by avoiding injection into the hyperkeratotic plaques and using normal subcutaneous tissue for injection, patients’ response to insulin improves, as measured by HbA_1c and by decreased daily insulin requirement.^{6-8,10,12,18-20}

Lipohypertrophy. This is characterized by an increase in localized adipose tissue and is the most common cutaneous complication of insulin therapy.² Lipohypertrophy presents as a firm, rubbery mass in the location of same-site insulin injections.²² Development of lipohypertrophy is suspected to be the result of either (1) anabolic effect of insulin on local adipocytes, promoting fat and protein synthesis; (2) an autoimmune response by immunoglobulin (Ig) G or IgE antibodies to insulin, immune response to insulin of different species, or to insulin injection techniques; or (3) repeated trauma to the injection site from repeated needle usage.^4,23

In a study assessing the prevalence of lipohypertrophy and its relation to insulin technique, 49.1% of participants with lipohypertrophy had glycemic variability compared with 6.5% of participants without lipohypertrophy.³ Johansson and colleagues described an impairment of insulin absorption in lipohypertrophic tissues, causing a 25% lower plasma insulin concentration compared with that of normal tissues.⁴ These findings suggest a significant effect of lipohypertrophy on insulin absorption—unnecessarily increasing insulin consumption and worsening glycemic control.

Primary prevention measures include injection site inspection and patient education about rotation and abstaining from needle reuse.²² If a patient already has signs of lipohypertrophy, data supports education and insulin injection technique practice as simple and effective means to reduce insulin action variability and increase glycemic control.²⁴

Lipoatrophy. Lipoatrophy is described as a local loss of subcutaneous adipose tissue often in the face, buttocks, legs and arm regions and can be rooted in genetic, immune, or drug-associated etiologies.²⁵ Insulin-induced lipoatrophy is suspected to be the result of tumor necrosis factor-α hyperproduction in reaction to insulin crystal presence at the injection site.^26,27 Overall, lipoatrophy development has decreased since the use of recombinant human insulin and analog insulin therapy.²⁸ The decrease is hypothesized to be due to increased subcutaneous tissue absorption rate of human insulin and its analog, decreasing overall adipocyte exposure to localized high insulin concentration.²⁷ Treatments for same-site insulin-derived lipoatrophy include changing injection sites and preparation of insulin.²⁶ When injection into the lipoatrophic site was avoided, glycemic control and lipoatrophy appearance improved.²⁶

Amyloidosis. Amyloidosis indicates the presence of an extracellular bundle of insoluble polymeric protein fibrils in tissues and organs.²⁹ Insulin-induced amyloidosis presents as a hard mass or ball near the injection site.²⁹ Insulin is one of many hormones that can form amyloid fibrils, and there have been several dozen cases reported of amyloid formation at the site of insulin injection.^29-31 Although insulin-derived amyloidosis is rare, it may be misdiagnosed as lipohypertrophy due to a lack of histopathologic testing or general awareness of the complication.²⁹

In a case series of 7 patients with amyloidosis, all patients had a mean HbA_1c of 9.3% (range, 8.5-10.2%) and averaged 1 IU/kg bodyweight before intervention.³⁰ After the discovery of the mass, participants were instructed to avoid injection into the amyloidoma, and average insulin requirements decreased to 0.48 IU/kg body weight (P = .40).³⁰ Patients with amyloidosis who rotated their injection sites experienced better glycemic control and decreased insulin requirements.³⁰

Pathophysiology of Localized Insulin Resistance

Insulin regulates glucose homeostasis in skeletal muscle and adipose tissue, increases hepatic and adipocyte lipid synthesis, and decreases adipocyte fatty acid release.³² Generalized insulin resistance occurs when target tissues have decreased glucose uptake in response to circulating insulin.³² Insulin resistance increases the amount of free insulin in surrounding tissues. At high concentrations, insulin fosters tissue growth by binding to IGF-1 receptors, stimulating hypertrophy and reproduction of keratinocytes and fibroblasts.³³ This pathophysiology helps explain the origin of localized acanthosis nigricans at same-site insulin injections.

Conclusions

Cutaneous complications are a local adverse effect of long-term failure to rotate insulin injection sites. Our case serves as a call to action for HCPs to improve education regarding insulin injection-site rotation, conduct routine injection-site inspection, and actively document cases as they occur to increase public awareness of these important complications.

If a patient with DM presents with unexplained poor glycemic control, consider questioning the patient about injection-site location and how often they are rotating the insulin injection site. Inspect the site for cutaneous complications. Of note, if a patient has a cutaneous complication due to insulin injection, adjust or decrease the insulin dosage when rotating sites to mitigate the risk of hypoglycemic episodes.

Improvement of glycemic control, cosmetic appearance of injection site, and insulin use all begin with skin inspection, injection technique education, and periodic review by a HCP.

Insulin injection therapy is one of the most widely used health care interventions to manage both type 1 and type 2 diabetes mellitus (T1DM/T2DM). Globally, more than 150 to 200 million people inject insulin into their upper posterior arms, buttocks, anterior and lateral thighs, or abdomen.^1,2 In an ideal world, every patient would be using the correct site and rotating their insulin injection sites in accordance with health care professional (HCP) recommendations—systematic injections in one general body location, at least 1 cm away from the previous injection.² Unfortunately, same-site insulin injection (repeatedly in the same region within 1 cm of previous injections) is a common mistake made by patients with DM—in one study, 63% of participants either did not rotate sites correctly or failed to do so at all.

Insulin-resistant cutaneous complications may occur as a result of same-site insulin injections. The most common is lipohypertrophy, reported in some studies in nearly 50% of patients with DM on insulin therapy.⁴ Other common cutaneous complications include lipoatrophy and amyloidosis. Injection-site acanthosis nigricans, although uncommon, has been reported in 18 cases in the literature.

Most articles suggest that same-site insulin injections decrease local insulin sensitivity and result in tissue hypertrophy because of the anabolic properties of insulin and increase in insulin binding to insulin-like growth factor-1 (IGF-1) receptor.^5-20 The hyperkeratotic growth and varying insulin absorption rates associated with these cutaneous complications increase chances of either hyper- or hypoglycemic episodes in patients.^10,11,13 It is the responsibility of the DM care professional to provide proper insulin-injection technique education and perform routine inspection of injection sites to reduce cutaneous complications of insulin therapy. The purpose of this article is to (1) describe a case of acanthosis nigricans resulting from insulin injection at the same site; (2) review case reports in the literature describing injection-site acanthosis nigricans resulting from same-site insulin injections; (3) describe localized cutaneous complications associated with the use of insulin; and (4) discuss clinical implications and lessons learned from the literature.

Case Presentation

A 75-year-old patient with an 8-year history of T2DM, as well as stable coronary artery disease, atrial fibrillation, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, and stage 3 chronic kidney disease, presented with 2 discrete abdominal hyperpigmented plaques. At the time of the initial clinic visit, the patient was taking metformin 1000 mg twice daily and insulin glargine 40 units once daily. When insulin was initiated 7 years prior, the patient received neutral protamine Hagedorn (NPH) insulin for the first year and transitioned to insulin glargine. After 4 years of insulin therapy, insulin aspart was added and discontinued after 2 years. The patient’s hemoglobin A_1c (HbA_1c) was 6.8%, suggesting good glycemic control.

The patient reported 5 years of progressive, asymptomatic hyperpigmentation of the skin surrounding his insulin glargine injection sites and injecting in these same sites daily without rotation. He reported no additional skin changes or symptoms. He had noticed no skin changes while using NPH insulin during his first year of insulin therapy. On examination, the abdominal wall skin demonstrated 2 well-demarcated, nearly black, soft, velvety plaques, measuring 9 × 8 cm on the left side and 4 × 3.5 cm on the right, suggesting acanthosis nigricans (Figure 1A). The remainder of the skin examination, including the flexures, was normal. Of note, the patient received biweekly intramuscular testosterone injections in the gluteal region for secondary hypogonadism with no adverse dermatologic effects. A skin punch biopsy was performed and revealed epidermal papillomatosis and hyperkeratosis, confirming the clinical diagnosis of acanthosis nigricans (Figure 2).

After a review of insulin-injection technique at his clinic visit, the patient started rotating insulin injection sites over his entire abdomen, and the acanthosis nigricans partially improved. A few months later, the patient stopped rotating the insulin injection site, and the acanthosis nigricans worsened again. Because of worsening glycemic control, the patient was then started on insulin aspart. He did not develop any skin changes at the insulin aspart injection site, although he was not rotating its site of injection.

Subsequently, with reeducation and proper injection-site rotation, the patient had resolution of his acanthosis nigricans (Figure 1b).

Discussion

A review of the literature revealed 18 reported cases of acanthosis nigricans at sites of repeated insulin injection (Table).^5-20 Acanthosis nigricans at the site of insulin injection afflicts patients of any age, with cases observed in patients aged 14 to 75 years. Sixteen (84%) of 19 cases were male. Fourteen cases (73%) had T2DM; the rest of the patients had T1DM. The duration of insulin injection therapy prior to onset ranged from immediate to 13 years (median 4 years). Fourteen cases (73%) were reported on the abdomen; however, other sites, such as thighs and upper arm, also were reported. Lesions size varied from 12 to 360 cm². Two cases had associated amyloidosis. The average HbA_1c reported at presentation was 10%. Following insulin injection-site rotation, most of the cases reported improvement of both glycemic control and acanthosis nigricans appearance.

In the case described by Kudo and colleagues, a 59-year-old male patient with T2DM had been injecting insulin into the same spot on his abdomen for 10 years. He developed acanthosis nigricans and an amyloidoma so large and firm that it bent the needle when he injected insulin.¹¹

Most of the cases we found in the literature were after 2005 and associated with the use of human or analog insulin. These cases may be related to a bias, as cases may be easier to find in digital archives in the later years, when human or analog insulins have been in common use. Also noteworthy, in cases that reported dosage, most were not very high, and the highest daily dose was 240 IU/d. Ten reports of injection-site acanthosis nigricans were in dermatology journals; only 5 reports were in endocrinology journals and 3 in general medical journals, indicating possible less awareness of this phenomenon in other HCPs who care for patients with DM.

Complications of Same-Site Injections

Acanthosis nigricans. Commonly found in the armpits, neck folds, and groin, acanthosis nigricans is known as one of the calling cards for insulin resistance, obesity, and hyperinsulinemia.²¹ Acanthosis nigricans can be seen in people with or without DM and is not limited to those on insulin therapy. However, same-site insulin injections for 4 to 6 years also may result in injection-site acanthosis nigricans–like lesions because of factors such as insulin exposure at the local tissue level.¹⁶

Acanthosis nigricans development is characterized by hyperpigmented, hyperkeratotic, velvety, and sometimes verrucous plaques.⁶ Acanthosis nigricans surrounding repeated injection sites is hypothesized to develop as a result of localized hyperinsulinemia secondary to insulin resistance, which increases the stimulation of IGF, thereby causing epidermal hypertrophy.^5-20 If insulin injection therapy continues to be administered through the acanthosis nigricans lesion, it results in decreased insulin absorption, leading to poor glycemic control.¹³

Acanthosis nigricans associated with insulin injection is reversible. After rotation of injection sites, lesions either decrease in size or severity of appearance.^5-8,11 Also, by avoiding injection into the hyperkeratotic plaques and using normal subcutaneous tissue for injection, patients’ response to insulin improves, as measured by HbA_1c and by decreased daily insulin requirement.^{6-8,10,12,18-20}

Lipohypertrophy. This is characterized by an increase in localized adipose tissue and is the most common cutaneous complication of insulin therapy.² Lipohypertrophy presents as a firm, rubbery mass in the location of same-site insulin injections.²² Development of lipohypertrophy is suspected to be the result of either (1) anabolic effect of insulin on local adipocytes, promoting fat and protein synthesis; (2) an autoimmune response by immunoglobulin (Ig) G or IgE antibodies to insulin, immune response to insulin of different species, or to insulin injection techniques; or (3) repeated trauma to the injection site from repeated needle usage.^4,23

In a study assessing the prevalence of lipohypertrophy and its relation to insulin technique, 49.1% of participants with lipohypertrophy had glycemic variability compared with 6.5% of participants without lipohypertrophy.³ Johansson and colleagues described an impairment of insulin absorption in lipohypertrophic tissues, causing a 25% lower plasma insulin concentration compared with that of normal tissues.⁴ These findings suggest a significant effect of lipohypertrophy on insulin absorption—unnecessarily increasing insulin consumption and worsening glycemic control.

Primary prevention measures include injection site inspection and patient education about rotation and abstaining from needle reuse.²² If a patient already has signs of lipohypertrophy, data supports education and insulin injection technique practice as simple and effective means to reduce insulin action variability and increase glycemic control.²⁴

Lipoatrophy. Lipoatrophy is described as a local loss of subcutaneous adipose tissue often in the face, buttocks, legs and arm regions and can be rooted in genetic, immune, or drug-associated etiologies.²⁵ Insulin-induced lipoatrophy is suspected to be the result of tumor necrosis factor-α hyperproduction in reaction to insulin crystal presence at the injection site.^26,27 Overall, lipoatrophy development has decreased since the use of recombinant human insulin and analog insulin therapy.²⁸ The decrease is hypothesized to be due to increased subcutaneous tissue absorption rate of human insulin and its analog, decreasing overall adipocyte exposure to localized high insulin concentration.²⁷ Treatments for same-site insulin-derived lipoatrophy include changing injection sites and preparation of insulin.²⁶ When injection into the lipoatrophic site was avoided, glycemic control and lipoatrophy appearance improved.²⁶

Amyloidosis. Amyloidosis indicates the presence of an extracellular bundle of insoluble polymeric protein fibrils in tissues and organs.²⁹ Insulin-induced amyloidosis presents as a hard mass or ball near the injection site.²⁹ Insulin is one of many hormones that can form amyloid fibrils, and there have been several dozen cases reported of amyloid formation at the site of insulin injection.^29-31 Although insulin-derived amyloidosis is rare, it may be misdiagnosed as lipohypertrophy due to a lack of histopathologic testing or general awareness of the complication.²⁹

In a case series of 7 patients with amyloidosis, all patients had a mean HbA_1c of 9.3% (range, 8.5-10.2%) and averaged 1 IU/kg bodyweight before intervention.³⁰ After the discovery of the mass, participants were instructed to avoid injection into the amyloidoma, and average insulin requirements decreased to 0.48 IU/kg body weight (P = .40).³⁰ Patients with amyloidosis who rotated their injection sites experienced better glycemic control and decreased insulin requirements.³⁰

Pathophysiology of Localized Insulin Resistance

Insulin regulates glucose homeostasis in skeletal muscle and adipose tissue, increases hepatic and adipocyte lipid synthesis, and decreases adipocyte fatty acid release.³² Generalized insulin resistance occurs when target tissues have decreased glucose uptake in response to circulating insulin.³² Insulin resistance increases the amount of free insulin in surrounding tissues. At high concentrations, insulin fosters tissue growth by binding to IGF-1 receptors, stimulating hypertrophy and reproduction of keratinocytes and fibroblasts.³³ This pathophysiology helps explain the origin of localized acanthosis nigricans at same-site insulin injections.

Conclusions

Cutaneous complications are a local adverse effect of long-term failure to rotate insulin injection sites. Our case serves as a call to action for HCPs to improve education regarding insulin injection-site rotation, conduct routine injection-site inspection, and actively document cases as they occur to increase public awareness of these important complications.

If a patient with DM presents with unexplained poor glycemic control, consider questioning the patient about injection-site location and how often they are rotating the insulin injection site. Inspect the site for cutaneous complications. Of note, if a patient has a cutaneous complication due to insulin injection, adjust or decrease the insulin dosage when rotating sites to mitigate the risk of hypoglycemic episodes.

Improvement of glycemic control, cosmetic appearance of injection site, and insulin use all begin with skin inspection, injection technique education, and periodic review by a HCP.

Insulin injection therapy is one of the most widely used health care interventions to manage both type 1 and type 2 diabetes mellitus (T1DM/T2DM). Globally, more than 150 to 200 million people inject insulin into their upper posterior arms, buttocks, anterior and lateral thighs, or abdomen.^1,2 In an ideal world, every patient would be using the correct site and rotating their insulin injection sites in accordance with health care professional (HCP) recommendations—systematic injections in one general body location, at least 1 cm away from the previous injection.² Unfortunately, same-site insulin injection (repeatedly in the same region within 1 cm of previous injections) is a common mistake made by patients with DM—in one study, 63% of participants either did not rotate sites correctly or failed to do so at all.

Insulin-resistant cutaneous complications may occur as a result of same-site insulin injections. The most common is lipohypertrophy, reported in some studies in nearly 50% of patients with DM on insulin therapy.⁴ Other common cutaneous complications include lipoatrophy and amyloidosis. Injection-site acanthosis nigricans, although uncommon, has been reported in 18 cases in the literature.

Most articles suggest that same-site insulin injections decrease local insulin sensitivity and result in tissue hypertrophy because of the anabolic properties of insulin and increase in insulin binding to insulin-like growth factor-1 (IGF-1) receptor.^5-20 The hyperkeratotic growth and varying insulin absorption rates associated with these cutaneous complications increase chances of either hyper- or hypoglycemic episodes in patients.^10,11,13 It is the responsibility of the DM care professional to provide proper insulin-injection technique education and perform routine inspection of injection sites to reduce cutaneous complications of insulin therapy. The purpose of this article is to (1) describe a case of acanthosis nigricans resulting from insulin injection at the same site; (2) review case reports in the literature describing injection-site acanthosis nigricans resulting from same-site insulin injections; (3) describe localized cutaneous complications associated with the use of insulin; and (4) discuss clinical implications and lessons learned from the literature.

Case Presentation

A 75-year-old patient with an 8-year history of T2DM, as well as stable coronary artery disease, atrial fibrillation, hypertension, hyperlipidemia, chronic obstructive pulmonary disease, and stage 3 chronic kidney disease, presented with 2 discrete abdominal hyperpigmented plaques. At the time of the initial clinic visit, the patient was taking metformin 1000 mg twice daily and insulin glargine 40 units once daily. When insulin was initiated 7 years prior, the patient received neutral protamine Hagedorn (NPH) insulin for the first year and transitioned to insulin glargine. After 4 years of insulin therapy, insulin aspart was added and discontinued after 2 years. The patient’s hemoglobin A_1c (HbA_1c) was 6.8%, suggesting good glycemic control.

The patient reported 5 years of progressive, asymptomatic hyperpigmentation of the skin surrounding his insulin glargine injection sites and injecting in these same sites daily without rotation. He reported no additional skin changes or symptoms. He had noticed no skin changes while using NPH insulin during his first year of insulin therapy. On examination, the abdominal wall skin demonstrated 2 well-demarcated, nearly black, soft, velvety plaques, measuring 9 × 8 cm on the left side and 4 × 3.5 cm on the right, suggesting acanthosis nigricans (Figure 1A). The remainder of the skin examination, including the flexures, was normal. Of note, the patient received biweekly intramuscular testosterone injections in the gluteal region for secondary hypogonadism with no adverse dermatologic effects. A skin punch biopsy was performed and revealed epidermal papillomatosis and hyperkeratosis, confirming the clinical diagnosis of acanthosis nigricans (Figure 2).

After a review of insulin-injection technique at his clinic visit, the patient started rotating insulin injection sites over his entire abdomen, and the acanthosis nigricans partially improved. A few months later, the patient stopped rotating the insulin injection site, and the acanthosis nigricans worsened again. Because of worsening glycemic control, the patient was then started on insulin aspart. He did not develop any skin changes at the insulin aspart injection site, although he was not rotating its site of injection.

Subsequently, with reeducation and proper injection-site rotation, the patient had resolution of his acanthosis nigricans (Figure 1b).

Discussion

A review of the literature revealed 18 reported cases of acanthosis nigricans at sites of repeated insulin injection (Table).^5-20 Acanthosis nigricans at the site of insulin injection afflicts patients of any age, with cases observed in patients aged 14 to 75 years. Sixteen (84%) of 19 cases were male. Fourteen cases (73%) had T2DM; the rest of the patients had T1DM. The duration of insulin injection therapy prior to onset ranged from immediate to 13 years (median 4 years). Fourteen cases (73%) were reported on the abdomen; however, other sites, such as thighs and upper arm, also were reported. Lesions size varied from 12 to 360 cm². Two cases had associated amyloidosis. The average HbA_1c reported at presentation was 10%. Following insulin injection-site rotation, most of the cases reported improvement of both glycemic control and acanthosis nigricans appearance.

In the case described by Kudo and colleagues, a 59-year-old male patient with T2DM had been injecting insulin into the same spot on his abdomen for 10 years. He developed acanthosis nigricans and an amyloidoma so large and firm that it bent the needle when he injected insulin.¹¹

Most of the cases we found in the literature were after 2005 and associated with the use of human or analog insulin. These cases may be related to a bias, as cases may be easier to find in digital archives in the later years, when human or analog insulins have been in common use. Also noteworthy, in cases that reported dosage, most were not very high, and the highest daily dose was 240 IU/d. Ten reports of injection-site acanthosis nigricans were in dermatology journals; only 5 reports were in endocrinology journals and 3 in general medical journals, indicating possible less awareness of this phenomenon in other HCPs who care for patients with DM.

Complications of Same-Site Injections

Acanthosis nigricans. Commonly found in the armpits, neck folds, and groin, acanthosis nigricans is known as one of the calling cards for insulin resistance, obesity, and hyperinsulinemia.²¹ Acanthosis nigricans can be seen in people with or without DM and is not limited to those on insulin therapy. However, same-site insulin injections for 4 to 6 years also may result in injection-site acanthosis nigricans–like lesions because of factors such as insulin exposure at the local tissue level.¹⁶

Acanthosis nigricans development is characterized by hyperpigmented, hyperkeratotic, velvety, and sometimes verrucous plaques.⁶ Acanthosis nigricans surrounding repeated injection sites is hypothesized to develop as a result of localized hyperinsulinemia secondary to insulin resistance, which increases the stimulation of IGF, thereby causing epidermal hypertrophy.^5-20 If insulin injection therapy continues to be administered through the acanthosis nigricans lesion, it results in decreased insulin absorption, leading to poor glycemic control.¹³

Acanthosis nigricans associated with insulin injection is reversible. After rotation of injection sites, lesions either decrease in size or severity of appearance.^5-8,11 Also, by avoiding injection into the hyperkeratotic plaques and using normal subcutaneous tissue for injection, patients’ response to insulin improves, as measured by HbA_1c and by decreased daily insulin requirement.^{6-8,10,12,18-20}

Lipohypertrophy. This is characterized by an increase in localized adipose tissue and is the most common cutaneous complication of insulin therapy.² Lipohypertrophy presents as a firm, rubbery mass in the location of same-site insulin injections.²² Development of lipohypertrophy is suspected to be the result of either (1) anabolic effect of insulin on local adipocytes, promoting fat and protein synthesis; (2) an autoimmune response by immunoglobulin (Ig) G or IgE antibodies to insulin, immune response to insulin of different species, or to insulin injection techniques; or (3) repeated trauma to the injection site from repeated needle usage.^4,23

In a study assessing the prevalence of lipohypertrophy and its relation to insulin technique, 49.1% of participants with lipohypertrophy had glycemic variability compared with 6.5% of participants without lipohypertrophy.³ Johansson and colleagues described an impairment of insulin absorption in lipohypertrophic tissues, causing a 25% lower plasma insulin concentration compared with that of normal tissues.⁴ These findings suggest a significant effect of lipohypertrophy on insulin absorption—unnecessarily increasing insulin consumption and worsening glycemic control.

Primary prevention measures include injection site inspection and patient education about rotation and abstaining from needle reuse.²² If a patient already has signs of lipohypertrophy, data supports education and insulin injection technique practice as simple and effective means to reduce insulin action variability and increase glycemic control.²⁴

Lipoatrophy. Lipoatrophy is described as a local loss of subcutaneous adipose tissue often in the face, buttocks, legs and arm regions and can be rooted in genetic, immune, or drug-associated etiologies.²⁵ Insulin-induced lipoatrophy is suspected to be the result of tumor necrosis factor-α hyperproduction in reaction to insulin crystal presence at the injection site.^26,27 Overall, lipoatrophy development has decreased since the use of recombinant human insulin and analog insulin therapy.²⁸ The decrease is hypothesized to be due to increased subcutaneous tissue absorption rate of human insulin and its analog, decreasing overall adipocyte exposure to localized high insulin concentration.²⁷ Treatments for same-site insulin-derived lipoatrophy include changing injection sites and preparation of insulin.²⁶ When injection into the lipoatrophic site was avoided, glycemic control and lipoatrophy appearance improved.²⁶

Amyloidosis. Amyloidosis indicates the presence of an extracellular bundle of insoluble polymeric protein fibrils in tissues and organs.²⁹ Insulin-induced amyloidosis presents as a hard mass or ball near the injection site.²⁹ Insulin is one of many hormones that can form amyloid fibrils, and there have been several dozen cases reported of amyloid formation at the site of insulin injection.^29-31 Although insulin-derived amyloidosis is rare, it may be misdiagnosed as lipohypertrophy due to a lack of histopathologic testing or general awareness of the complication.²⁹

In a case series of 7 patients with amyloidosis, all patients had a mean HbA_1c of 9.3% (range, 8.5-10.2%) and averaged 1 IU/kg bodyweight before intervention.³⁰ After the discovery of the mass, participants were instructed to avoid injection into the amyloidoma, and average insulin requirements decreased to 0.48 IU/kg body weight (P = .40).³⁰ Patients with amyloidosis who rotated their injection sites experienced better glycemic control and decreased insulin requirements.³⁰

Pathophysiology of Localized Insulin Resistance

Insulin regulates glucose homeostasis in skeletal muscle and adipose tissue, increases hepatic and adipocyte lipid synthesis, and decreases adipocyte fatty acid release.³² Generalized insulin resistance occurs when target tissues have decreased glucose uptake in response to circulating insulin.³² Insulin resistance increases the amount of free insulin in surrounding tissues. At high concentrations, insulin fosters tissue growth by binding to IGF-1 receptors, stimulating hypertrophy and reproduction of keratinocytes and fibroblasts.³³ This pathophysiology helps explain the origin of localized acanthosis nigricans at same-site insulin injections.

Conclusions

Cutaneous complications are a local adverse effect of long-term failure to rotate insulin injection sites. Our case serves as a call to action for HCPs to improve education regarding insulin injection-site rotation, conduct routine injection-site inspection, and actively document cases as they occur to increase public awareness of these important complications.

If a patient with DM presents with unexplained poor glycemic control, consider questioning the patient about injection-site location and how often they are rotating the insulin injection site. Inspect the site for cutaneous complications. Of note, if a patient has a cutaneous complication due to insulin injection, adjust or decrease the insulin dosage when rotating sites to mitigate the risk of hypoglycemic episodes.

Improvement of glycemic control, cosmetic appearance of injection site, and insulin use all begin with skin inspection, injection technique education, and periodic review by a HCP.

Patients with rheumatoid arthritis or inflammatory bowel disease (IBD) taking a tumor necrosis factor–alpha inhibitor (TNFi) have about a two-fold higher risk of developing psoriasis, compared with patients receiving conventional treatment, according to a new study published in JAMA Dermatology.

Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.

They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.

The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.

Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.

The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).

Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
 

Best evidence to date on risk

Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.

The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.

Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”

For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”

In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”

However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.

The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.

What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2­-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.

“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”

He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”

The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.

Patients with rheumatoid arthritis or inflammatory bowel disease (IBD) taking a tumor necrosis factor–alpha inhibitor (TNFi) have about a two-fold higher risk of developing psoriasis, compared with patients receiving conventional treatment, according to a new study published in JAMA Dermatology.

Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.

They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.

The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.

Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.

The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).

Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
 

Best evidence to date on risk

Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.

The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.

Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”

For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”

In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”

However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.

The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.

What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2­-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.

“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”

He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”

The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.

Patients with rheumatoid arthritis or inflammatory bowel disease (IBD) taking a tumor necrosis factor–alpha inhibitor (TNFi) have about a two-fold higher risk of developing psoriasis, compared with patients receiving conventional treatment, according to a new study published in JAMA Dermatology.

Despite this finding, the authors of the large Danish nationwide cohort study noted that TNFi-induced psoriasis is still a rare adverse event. “Practitioners and patients should be aware and observant of the potential for TNFi-associated psoriasis during TNFi treatment but keep in mind that the absolute risk appears to be low,” David Thein, MB, of the department of dermatology at Bispebjerg Hospital, University of Copenhagen, and colleagues wrote in the study.

They analyzed 109,085 patients with RA and IBD enrolled in Danish national registries between 1995 and 2018 without a previous diagnosis of psoriasis, who received either TNFi (20,910 patients) or conventional treatments (108,024 patients) and were followed for 5 years. They were a mean of 50 years old when they started treatment, 62% were women, with 87.8% of patients in the TNFi group receiving prior conventional therapy and 1% of patients in the conventional therapy group receiving prior TNFi treatment.

The investigators assessed the risk of developing any psoriasis, nonpustular psoriasis, and pustular psoriasis in the two groups using ICD-10 codes as well as a record of two consecutive prescriptions for topical vitamin D analogs.

Overall, 1,471 patients (1.4%) developed psoriasis of any type; 1,332 had non-pustular psoriasis, 127 had palmoplantar pustulosis, and 12 had generalized pustulosis.

The incidence rate of developing any psoriasis was 3.0 per 1,000 patient-years (95% confidence interval, 2.9-3.2) for patients receiving conventional therapy and 7.8 per 1,000 patient-years (95% CI, 7.5-8.9) for patients receiving TNFi treatment. Compared with conventional treatment, the risk of developing nonpustular psoriasis was twofold higher among patients receiving TNFi treatment (hazard ratio, 2.12; 95% CI, 1.87-2.40; P < .001). The risk of developing pustular psoriasis was more than sixfold higher among those on a TNFi (HR, 6.50; 95% CI, 4.60-9.23; P < .001).

Dr. Thein and colleagues estimated that the exposure needed to harm 1 additional patient was 241 patient-years for any psoriasis type, 342 patient-years for nonpustular psoriasis, and 909 patient-years for pustular psoriasis, with an estimated absolute risk difference of 5 per 1,000 patient-years.
 

Best evidence to date on risk

Asked to comment on the study findings, Anthony Fernandez, MD, PhD, director of medical dermatology at the Cleveland Clinic, said that he applauded the researchers for performing this well-designed study to determine the risk of TNF inhibitor–induced psoriasis in patients with RA and IBD.

The strengths of the study include excluding patients with a history of psoriasis to rule out disease recurrence and having a large comparator group of patients with IBD and RA who were taking medications other than TNF inhibitors, while one limitation was the potential accuracy of the ICD-10 codes used as the basis for diagnosing psoriasis. “It’s probably closer to the truth of what the true risk is compared to studies done in the past,” he said in an interview.

Dr. Fernandez noted that the results aren’t likely to change how dermatologists, rheumatologists, or gastroenterologists practice, but the message to stay the course in initially treating TNFi-induced psoriasis also holds value. “We don’t need to change anything in our clinical practice when it comes to TNF-alpha inhibitors.”

For patients with RA or IBD who develop TNFi-induced psoriasis with disease that is well controlled with TNFi treatment, keeping them on that treatment is a priority, Dr. Fernandez explained. “The first and foremost goal is, if the TNF inhibitor is working very well to control the disease that it was prescribed for, then you exhaust your efforts to try to control the psoriasis and allow those patients to stay on the TNF inhibitor.”

In his experience, most patients with RA and IBD who develop TNFi-induced psoriasis are controlled with topical medications. Switching to another TNFi is not recommended, he noted, as patients are “likely to have that reaction with any TNF inhibitor.”

However, Dr. Fernandez said that won’t be an option for all patients with RA and IBD. “In some patients you do simply have to stop the TNF inhibitor” and try an alternative treatment with a different mechanism of action.

The cause of TNFi-induced psoriasis is still not well understood. “There certainly is evidence to support that interferon alpha production by plasmacytoid dendritic cells is playing some role in this phenomenon,” but there is “more to the story” and unanswered questions remain, Dr. Fernandez said.

What’s most interesting about this phenomenon, he added, is that “patients can develop it at any time when exposed to a TNF inhibitor.” For instance, most patients develop drug reactions within 2­-3 weeks of starting a treatment, but TNFi-induced psoriasis can appear after a single dose or several years after initiating treatment.

“Why so few patients, and why is there such variability in terms of how long they’re on the TNF inhibitor before the reaction occurs?” he asked. “That really points to ... some other trigger besides exposure to the TNF inhibitor needed for the initiation of this reaction.”

He noted that it would be valuable to identify triggers – or the most likely triggers – which would be challenging, but could “potentially impact clinical practice.”

The authors reported personal and institutional relationships in the form of personal and institutional research grants, honoraria, personal fees, investigator fees paid to university, consultancies, and speaker’s bureau positions for a variety of pharmaceutical companies, data companies, hospitals, and foundations. Dr. Fernandez reported he has nonbranded speaking, consulting, and research relationships with AbbVie and Novartis; and is a consultant for UCB, Bristol-Myers Squibb, and Boehringer Ingelheim on related products.

For many Americans – especially those too young to know much about the Cold War or Hiroshima – Russia’s invasion of Ukraine might mark the first time they’ve truly considered the dangers of nuclear weapons. But dozens of hematologists in the United States already know the drill and have placed themselves on the front lines. These physicians stand prepared to treat patients exposed to radiation caused by nuclear accidents or attacks on U.S. soil.

They work nationwide at 74 medical centers that make up the Radiation Injury Treatment Network, ready to manage cases of acute radiation syndrome (ARS) during disasters. While RITN keeps a low profile, it’s been in the news lately amid anxieties about the Ukraine conflict, nuclear plant accidents, and the potential launching of nuclear weapons by foreign adversaries.

Wikimedia Commons

“The Radiation Injury Treatment Network helps plan responses for disaster scenarios where a person’s cells would be damaged after having been exposed to ionizing radiation,” program director Cullen Case Jr., MPA, said in an interview.

A U.S. Army veteran who took part in hurricane response early in his career, Mr. Case now oversees preparedness activities among all RITN hospitals, blood donor centers, and cord blood banks, in readiness for a mass casualty radiological incident. He also serves as a senior manager of the National Marrow Donor Program/Be a Match Marrow Registry.

Intense preparation for nuclear attacks or accidents is necessary, Mr. Case said, despite the doomsday scenarios disseminated on television shows and movies.

“The most frequent misconception we hear is that a nuclear disaster will encompass the whole world and be so complete that preparedness isn’t useful. However, many planning scenarios include smaller-scale incidents where survivors will need prompt and expert care,” he said.

In the wake of 9/11, the National Marrow Donor Program and the American Society for Blood and Marrow Transplantation established the RITN in 2006, with a mission to prepare for nuclear disaster and help manage the response if one occurs.

National Archives/Wikimedia commons

“The widespread availability of radioactive material has made future exposure events, accidental or intentional, nearly inevitable,” RITN leaders warned in a 2008 report. “Hematologists, oncologists, and HSCT [hematopoietic stem cell transplantation] physicians are uniquely suited to care for victims of radiation exposure, creating a collective responsibility to prepare for a variety of contingencies.”

RITN doesn’t just train physicians, Mr. Case noted. All medical centers within the RITN are required to conduct an annual tabletop exercise where a radiation disaster scenario and a set of discussion questions are presented to the team.
 

Hematologists specially equipped to treat radiation injuries

Why are hematologists involved in treating people exposed to dangerously high levels of radiation? The answer has to do with how radiation harms the body, said Dr. Ann A. Jakubowski, a hematologist/oncologist and transplant physician at Memorial Sloan Kettering Cancer Center, New York, who serves as a medical director for RITN.

“One of the most common toxicities from radiation exposure and a major player in acute radiation syndrome is hematologic toxicity– damage to the bone marrow by the radiation, with a resultant decrease in peripheral blood counts,” she said in an interview. “This is similar to what is often seen in the treatment of cancers with radiation and/or chemotherapy.”

In cases of severe and nonreversible radiation damage to the bone marrow, Dr. Jakubowski noted, “patients can be considered for a stem cell transplant to provide new healthy cells to repopulate the bone marrow, which provides recovery of peripheral blood counts. Hematologist/oncologists are the physicians who manage stem cell transplants.”

The crucial role of hematologists in radiation injuries is not new. In fact, these physicians have been closely intertwined with nuclear research since the dawn of the atomic age. The work of developing atomic bombs also led investigators to an understanding of the structure and processes of hematopoiesis and helped them to identify hematopoietic stem cells and prove their existence in humans.
 

Disaster response poses multiple challenges

As noted in a recent article in ASH Clinical News, the challenges of treating radiation injuries would be intense, especially in the event of a nuclear accident or attack that affects a wide area. For starters, how quickly can medical professionals be mobilized, and will there be enough physicians comfortable treating patients? Fortunately, irradiated patients should not pose a direct risk to medical professionals who treat them.

“The expectation is that the patients will all be decontaminated,” said Nelson Chao, MD, MBA, one of the founders of RITN and a hematologist/oncologist and transplant physician at Duke University, Durham, N.C.

Dr. Jakubowski questions whether there will be adequate resources to handle the influx of patients who need more intensive treatment, as well as outpatients who “received lower doses of radiation and may experience a period of low blood counts but are expected to eventually recover blood counts.”

AFP/Getty Images

And if many people are injured, Dr. Chao asks, how will physicians “adopt altered standards of care to treat large numbers of patients?”

There will also be a need for physicians who aren’t hematologists, Dr. Jakubowski said. “There may be many victims who have both radiation exposure and traumatic or burn injuries, which need to be addressed first, before the hematologist can start addressing the consequences of ARS. Traumatic and burn injuries will require surgical resources.”

In addition, ARS affects the gastrointestinal track and central nervous system/cardiovascular, and it has multiple stages, she noted.

“Although we have methods of supporting the hematopoietic system – transfusions and growth factors – and even replacing it with a stem cell transplant, this will not necessarily fix the badly damaged other organs, Dr. Jakubowski said. “Also, not all radioactive isotopes are equal in their effects, nor are the various types of radiation exposure.”
 

Training goes beyond transplants and drugs

RITN offers individual hematologists specialized education about treating radiation injuries through annual exercises, modules, and “just-in-time” training.

For example, the RITN webpage devoted to triage includes guidelines for transferring radiation injury patients, triage guidelines for cytokine administration in cases of ARS, an exposure and symptom triage tool, and more. The treatment page includes details about subjects such as when human leukocyte antigen typing of casualties is appropriate and how to keep yourself safe while treating patients.

Another focus is teaching hematologists to react quickly in disasters, Mr. Case said. “The vast majority of hematologists have little to no experience in responding to disasters and making decisions with imperfect or incomplete information, as emergency medicine practitioners must do regularly.”

“Some of the RITN tabletop exercises present physicians and advanced practitioners with an incomplete set of patient information and ask physicians to then determine and prioritize their care,” Mr. Case said. “The resulting discussions help to lay the groundwork for being able to shift to the crisis standards of care mindset that would be necessary during a radiological disaster.”
 

Here’s how hematologists can get involved

If you want to help improve the nation’s response to radiation injuries, Mr. Case suggests checking RITN’s list of participating hospitals. If your facility is already part of this network, he said, contact its bone marrow transplant unit for more information.

In such cases, Dr. Jakubowski suggests that you “consider periodically giving a presentation to staff on the basics of radiation injury and the center’s role in RITN.” And if you’re not part of RITN, she said, consider contacting the network about becoming a member.

Hematologists, Mr. Case said, can also take advantage of RITN’s free short overview courses, review the RITN Treatment Guidelines, or watch short videos on the RITN’s YouTube channel.

He highlighted the Radiation Emergency Medical Management website administered by the Department of Health & Human Services, the Center for Disease Control’s radiation emergencies webpage, and the Department of Energy’s Radiation Emergency Assistance Center/Training Site.

For many Americans – especially those too young to know much about the Cold War or Hiroshima – Russia’s invasion of Ukraine might mark the first time they’ve truly considered the dangers of nuclear weapons. But dozens of hematologists in the United States already know the drill and have placed themselves on the front lines. These physicians stand prepared to treat patients exposed to radiation caused by nuclear accidents or attacks on U.S. soil.

They work nationwide at 74 medical centers that make up the Radiation Injury Treatment Network, ready to manage cases of acute radiation syndrome (ARS) during disasters. While RITN keeps a low profile, it’s been in the news lately amid anxieties about the Ukraine conflict, nuclear plant accidents, and the potential launching of nuclear weapons by foreign adversaries.

Wikimedia Commons

“The Radiation Injury Treatment Network helps plan responses for disaster scenarios where a person’s cells would be damaged after having been exposed to ionizing radiation,” program director Cullen Case Jr., MPA, said in an interview.

A U.S. Army veteran who took part in hurricane response early in his career, Mr. Case now oversees preparedness activities among all RITN hospitals, blood donor centers, and cord blood banks, in readiness for a mass casualty radiological incident. He also serves as a senior manager of the National Marrow Donor Program/Be a Match Marrow Registry.

Intense preparation for nuclear attacks or accidents is necessary, Mr. Case said, despite the doomsday scenarios disseminated on television shows and movies.

“The most frequent misconception we hear is that a nuclear disaster will encompass the whole world and be so complete that preparedness isn’t useful. However, many planning scenarios include smaller-scale incidents where survivors will need prompt and expert care,” he said.

In the wake of 9/11, the National Marrow Donor Program and the American Society for Blood and Marrow Transplantation established the RITN in 2006, with a mission to prepare for nuclear disaster and help manage the response if one occurs.

National Archives/Wikimedia commons

“The widespread availability of radioactive material has made future exposure events, accidental or intentional, nearly inevitable,” RITN leaders warned in a 2008 report. “Hematologists, oncologists, and HSCT [hematopoietic stem cell transplantation] physicians are uniquely suited to care for victims of radiation exposure, creating a collective responsibility to prepare for a variety of contingencies.”

RITN doesn’t just train physicians, Mr. Case noted. All medical centers within the RITN are required to conduct an annual tabletop exercise where a radiation disaster scenario and a set of discussion questions are presented to the team.
 

Hematologists specially equipped to treat radiation injuries

Why are hematologists involved in treating people exposed to dangerously high levels of radiation? The answer has to do with how radiation harms the body, said Dr. Ann A. Jakubowski, a hematologist/oncologist and transplant physician at Memorial Sloan Kettering Cancer Center, New York, who serves as a medical director for RITN.

“One of the most common toxicities from radiation exposure and a major player in acute radiation syndrome is hematologic toxicity– damage to the bone marrow by the radiation, with a resultant decrease in peripheral blood counts,” she said in an interview. “This is similar to what is often seen in the treatment of cancers with radiation and/or chemotherapy.”

In cases of severe and nonreversible radiation damage to the bone marrow, Dr. Jakubowski noted, “patients can be considered for a stem cell transplant to provide new healthy cells to repopulate the bone marrow, which provides recovery of peripheral blood counts. Hematologist/oncologists are the physicians who manage stem cell transplants.”

The crucial role of hematologists in radiation injuries is not new. In fact, these physicians have been closely intertwined with nuclear research since the dawn of the atomic age. The work of developing atomic bombs also led investigators to an understanding of the structure and processes of hematopoiesis and helped them to identify hematopoietic stem cells and prove their existence in humans.
 

Disaster response poses multiple challenges

As noted in a recent article in ASH Clinical News, the challenges of treating radiation injuries would be intense, especially in the event of a nuclear accident or attack that affects a wide area. For starters, how quickly can medical professionals be mobilized, and will there be enough physicians comfortable treating patients? Fortunately, irradiated patients should not pose a direct risk to medical professionals who treat them.

“The expectation is that the patients will all be decontaminated,” said Nelson Chao, MD, MBA, one of the founders of RITN and a hematologist/oncologist and transplant physician at Duke University, Durham, N.C.

Dr. Jakubowski questions whether there will be adequate resources to handle the influx of patients who need more intensive treatment, as well as outpatients who “received lower doses of radiation and may experience a period of low blood counts but are expected to eventually recover blood counts.”

AFP/Getty Images

And if many people are injured, Dr. Chao asks, how will physicians “adopt altered standards of care to treat large numbers of patients?”

There will also be a need for physicians who aren’t hematologists, Dr. Jakubowski said. “There may be many victims who have both radiation exposure and traumatic or burn injuries, which need to be addressed first, before the hematologist can start addressing the consequences of ARS. Traumatic and burn injuries will require surgical resources.”

In addition, ARS affects the gastrointestinal track and central nervous system/cardiovascular, and it has multiple stages, she noted.

“Although we have methods of supporting the hematopoietic system – transfusions and growth factors – and even replacing it with a stem cell transplant, this will not necessarily fix the badly damaged other organs, Dr. Jakubowski said. “Also, not all radioactive isotopes are equal in their effects, nor are the various types of radiation exposure.”
 

Training goes beyond transplants and drugs

RITN offers individual hematologists specialized education about treating radiation injuries through annual exercises, modules, and “just-in-time” training.

For example, the RITN webpage devoted to triage includes guidelines for transferring radiation injury patients, triage guidelines for cytokine administration in cases of ARS, an exposure and symptom triage tool, and more. The treatment page includes details about subjects such as when human leukocyte antigen typing of casualties is appropriate and how to keep yourself safe while treating patients.

Another focus is teaching hematologists to react quickly in disasters, Mr. Case said. “The vast majority of hematologists have little to no experience in responding to disasters and making decisions with imperfect or incomplete information, as emergency medicine practitioners must do regularly.”

“Some of the RITN tabletop exercises present physicians and advanced practitioners with an incomplete set of patient information and ask physicians to then determine and prioritize their care,” Mr. Case said. “The resulting discussions help to lay the groundwork for being able to shift to the crisis standards of care mindset that would be necessary during a radiological disaster.”
 

Here’s how hematologists can get involved

If you want to help improve the nation’s response to radiation injuries, Mr. Case suggests checking RITN’s list of participating hospitals. If your facility is already part of this network, he said, contact its bone marrow transplant unit for more information.

In such cases, Dr. Jakubowski suggests that you “consider periodically giving a presentation to staff on the basics of radiation injury and the center’s role in RITN.” And if you’re not part of RITN, she said, consider contacting the network about becoming a member.

Hematologists, Mr. Case said, can also take advantage of RITN’s free short overview courses, review the RITN Treatment Guidelines, or watch short videos on the RITN’s YouTube channel.

He highlighted the Radiation Emergency Medical Management website administered by the Department of Health & Human Services, the Center for Disease Control’s radiation emergencies webpage, and the Department of Energy’s Radiation Emergency Assistance Center/Training Site.

For many Americans – especially those too young to know much about the Cold War or Hiroshima – Russia’s invasion of Ukraine might mark the first time they’ve truly considered the dangers of nuclear weapons. But dozens of hematologists in the United States already know the drill and have placed themselves on the front lines. These physicians stand prepared to treat patients exposed to radiation caused by nuclear accidents or attacks on U.S. soil.

They work nationwide at 74 medical centers that make up the Radiation Injury Treatment Network, ready to manage cases of acute radiation syndrome (ARS) during disasters. While RITN keeps a low profile, it’s been in the news lately amid anxieties about the Ukraine conflict, nuclear plant accidents, and the potential launching of nuclear weapons by foreign adversaries.

Wikimedia Commons

“The Radiation Injury Treatment Network helps plan responses for disaster scenarios where a person’s cells would be damaged after having been exposed to ionizing radiation,” program director Cullen Case Jr., MPA, said in an interview.

A U.S. Army veteran who took part in hurricane response early in his career, Mr. Case now oversees preparedness activities among all RITN hospitals, blood donor centers, and cord blood banks, in readiness for a mass casualty radiological incident. He also serves as a senior manager of the National Marrow Donor Program/Be a Match Marrow Registry.

Intense preparation for nuclear attacks or accidents is necessary, Mr. Case said, despite the doomsday scenarios disseminated on television shows and movies.

“The most frequent misconception we hear is that a nuclear disaster will encompass the whole world and be so complete that preparedness isn’t useful. However, many planning scenarios include smaller-scale incidents where survivors will need prompt and expert care,” he said.

In the wake of 9/11, the National Marrow Donor Program and the American Society for Blood and Marrow Transplantation established the RITN in 2006, with a mission to prepare for nuclear disaster and help manage the response if one occurs.

National Archives/Wikimedia commons

“The widespread availability of radioactive material has made future exposure events, accidental or intentional, nearly inevitable,” RITN leaders warned in a 2008 report. “Hematologists, oncologists, and HSCT [hematopoietic stem cell transplantation] physicians are uniquely suited to care for victims of radiation exposure, creating a collective responsibility to prepare for a variety of contingencies.”

RITN doesn’t just train physicians, Mr. Case noted. All medical centers within the RITN are required to conduct an annual tabletop exercise where a radiation disaster scenario and a set of discussion questions are presented to the team.
 

Hematologists specially equipped to treat radiation injuries

Why are hematologists involved in treating people exposed to dangerously high levels of radiation? The answer has to do with how radiation harms the body, said Dr. Ann A. Jakubowski, a hematologist/oncologist and transplant physician at Memorial Sloan Kettering Cancer Center, New York, who serves as a medical director for RITN.

“One of the most common toxicities from radiation exposure and a major player in acute radiation syndrome is hematologic toxicity– damage to the bone marrow by the radiation, with a resultant decrease in peripheral blood counts,” she said in an interview. “This is similar to what is often seen in the treatment of cancers with radiation and/or chemotherapy.”

In cases of severe and nonreversible radiation damage to the bone marrow, Dr. Jakubowski noted, “patients can be considered for a stem cell transplant to provide new healthy cells to repopulate the bone marrow, which provides recovery of peripheral blood counts. Hematologist/oncologists are the physicians who manage stem cell transplants.”

The crucial role of hematologists in radiation injuries is not new. In fact, these physicians have been closely intertwined with nuclear research since the dawn of the atomic age. The work of developing atomic bombs also led investigators to an understanding of the structure and processes of hematopoiesis and helped them to identify hematopoietic stem cells and prove their existence in humans.
 

Disaster response poses multiple challenges

As noted in a recent article in ASH Clinical News, the challenges of treating radiation injuries would be intense, especially in the event of a nuclear accident or attack that affects a wide area. For starters, how quickly can medical professionals be mobilized, and will there be enough physicians comfortable treating patients? Fortunately, irradiated patients should not pose a direct risk to medical professionals who treat them.

“The expectation is that the patients will all be decontaminated,” said Nelson Chao, MD, MBA, one of the founders of RITN and a hematologist/oncologist and transplant physician at Duke University, Durham, N.C.

Dr. Jakubowski questions whether there will be adequate resources to handle the influx of patients who need more intensive treatment, as well as outpatients who “received lower doses of radiation and may experience a period of low blood counts but are expected to eventually recover blood counts.”

AFP/Getty Images

And if many people are injured, Dr. Chao asks, how will physicians “adopt altered standards of care to treat large numbers of patients?”

There will also be a need for physicians who aren’t hematologists, Dr. Jakubowski said. “There may be many victims who have both radiation exposure and traumatic or burn injuries, which need to be addressed first, before the hematologist can start addressing the consequences of ARS. Traumatic and burn injuries will require surgical resources.”

In addition, ARS affects the gastrointestinal track and central nervous system/cardiovascular, and it has multiple stages, she noted.

“Although we have methods of supporting the hematopoietic system – transfusions and growth factors – and even replacing it with a stem cell transplant, this will not necessarily fix the badly damaged other organs, Dr. Jakubowski said. “Also, not all radioactive isotopes are equal in their effects, nor are the various types of radiation exposure.”
 

Training goes beyond transplants and drugs

RITN offers individual hematologists specialized education about treating radiation injuries through annual exercises, modules, and “just-in-time” training.

For example, the RITN webpage devoted to triage includes guidelines for transferring radiation injury patients, triage guidelines for cytokine administration in cases of ARS, an exposure and symptom triage tool, and more. The treatment page includes details about subjects such as when human leukocyte antigen typing of casualties is appropriate and how to keep yourself safe while treating patients.

Another focus is teaching hematologists to react quickly in disasters, Mr. Case said. “The vast majority of hematologists have little to no experience in responding to disasters and making decisions with imperfect or incomplete information, as emergency medicine practitioners must do regularly.”

“Some of the RITN tabletop exercises present physicians and advanced practitioners with an incomplete set of patient information and ask physicians to then determine and prioritize their care,” Mr. Case said. “The resulting discussions help to lay the groundwork for being able to shift to the crisis standards of care mindset that would be necessary during a radiological disaster.”
 

Here’s how hematologists can get involved

If you want to help improve the nation’s response to radiation injuries, Mr. Case suggests checking RITN’s list of participating hospitals. If your facility is already part of this network, he said, contact its bone marrow transplant unit for more information.

In such cases, Dr. Jakubowski suggests that you “consider periodically giving a presentation to staff on the basics of radiation injury and the center’s role in RITN.” And if you’re not part of RITN, she said, consider contacting the network about becoming a member.

Hematologists, Mr. Case said, can also take advantage of RITN’s free short overview courses, review the RITN Treatment Guidelines, or watch short videos on the RITN’s YouTube channel.

He highlighted the Radiation Emergency Medical Management website administered by the Department of Health & Human Services, the Center for Disease Control’s radiation emergencies webpage, and the Department of Energy’s Radiation Emergency Assistance Center/Training Site.

GLASGOW – Dermatologists do not feel confident in independently prescribing antipsychotic medications for patients with delusional infestation, shows a U.K. survey that also indicated there is a clear demand for training in prescribing these drugs.

Delusional infestation is a rare disorder characterized by an individual’s belief that his or her skin, body, or immediate environment is infested by small, living pathogens, despite a lack of any medical evidence. Most of these patients require antipsychotic medication to alleviate symptoms.

The survey of almost 80 dermatologists found that almost 90% had not prescribed antipsychotics in the previous month for patients with psychodermatology conditions and that the most common barrier to prescribing was lack of experience with the drugs.

This was reflected in only 10% of survey respondents who said they were “happy to” prescribe antipsychotics without consulting either dermatology or psychiatric colleagues, and less than half having attended a related course.

Yet the research, presented at the annual meeting of the British Association of Dermatologists, indicated that more than 75% of respondents would attend such a course to increase their confidence.

This finding, said study presenter Ling Li, MD, Churchill Hospital, Oxford (England) University Hospitals NHS Foundation Trust, shows that there is a “clear demand for training, particularly among all the registrars [residents] who we surveyed.”

Dr. Li noted that the UK’s Joint Royal Colleges of Physicians Training Board’s latest curriculum for dermatology training highlights psychocutaneous medicine as a key area, and “that will include antipsychotic medication.”

The BAD also recently published guidelines for the management of adults with delusional infestation, which includes a recommendation to conduct a survey on attitudes toward antipsychotic prescribing for the condition among U.K. dermatologists.

Heeding that call, Dr. Li and colleagues sent an email containing a 10-question online survey to members of the BAD and the British Society for Medical Dermatology. Questions covered familiarity with antipsychotics and frequency of prescribing, confidence around antipsychotics, and current training and future needs. Responses were received between February through April 2021.

Among the 79 respondents, 51 (65%) were consultants and 20 (25%) were dermatology registrars, with the remainder dermatology clinical fellows, foundation doctors, or other doctors. A total of 31 respondents had an average of more than 50 visits with patients per week, 18 had an average of 41-50 patient visits, and 13 had an average of 31-40 visits per week; the remainder had an average of 11-30 visits per week.

Most of the respondents (39) said they had seen 2-5 patients with psychodermatology conditions in the last 6 months, while 17 said they had seen 1 patient, 13 said they had seen more than 10 patients, and 6 said they had seen 6-10 patients (4 had seen none and 1 could not remember).

The most commonly prescribed antipsychotics for psychodermatology patients in the past 6 months were risperidone (Risperdal; prescribed by five respondents), followed by olanzapine (Zyprexa; by four respondents). Seventy respondents had not prescribed any antipsychotics.

Asked about how confident they felt about prescribing antipsychotic medication for patients with delusional infestation, 8 (10%) said they were happy to prescribe independently, while 42 (54%) said they were not at all confident. Another 10 (13%) respondents said they would be happy to prescribe the medications after liaising with a dermatology colleague, while 17 (22%) said they would prefer to consult with the psychiatry team.

The most common barrier to prescribing antipsychotic medications was a lack of experience with the drugs, cited by 66 respondents, followed by concerns over drug monitoring, cited by 43 respondents.

In addition, 42 respondents highlighted concerns over adverse effects, 36 cited lack of experience in psychodermatology clinics, and 19 cited lack of experience in discussing psychodermatologic conditions with patients. Other barriers mentioned by the respondents included difficulties with patient acceptance of a psychiatric medication prescribed by a dermatologist.

An audience member went further, saying that clinicians have been told not to “confront” such patients and that the temptation is therefore to cloak the discussion of antipsychotics in nonthreatening language so that it is more acceptable to the patient.

However, under the U.K. system, a letter with the results of the consultation, including information that an antipsychotic has been prescribed, must be sent to the patient’s family doctor along with a copy that goes to the patient. “The situation is almost impossible,” the audience member said, adding that there “must be some arrangement where in certain circumstances dermatologists could be allowed not to write to the patient” or alternatively, “write an entirely different letter” to the family doctor.

Session cochair Susannah Baron, MD, a consultant dermatologist at St. John’s Institute of Dermatology, Guy’s and St. Thomas’ Hospital, London, said that, in these situations, it is “really helpful to talk about doses” with patients.

She explained that she uses the analogy of aspirin, which has different effects depending on the dose given, giving pain relief at high doses but primarily an antiplatelet effect at low doses.

In the case of an antipsychotic, it is helpful to explain to the patient that “you don’t think they’re psychotic, and you’re prescribing it in a very low dose, because what it can do is help with their symptoms,” Dr. Baron added. “You have to be very open because if you’re not, they go to the pharmacy, and the pharmacist says: ‘Why are you on an antipsychotic?’ ”

Further results from the survey revealed that 56 (71%) respondents did not have access to a specialist psychodermatology clinic, whereas 36 (46%) had not yet attended a psychodermatology course.

Despite these responses, 60 (77%) respondents said they would be interested in attending a training course for prescribing antipsychotics, which included all 20 of the registrars who took part in the survey. a psychodermatologist at Frimley Health Foundation Trust, Windsor, England, and lead author of the BAD guidelines, commented from the audience that the survey results were “sort of what we expected.”

She explained that the intention of the authors when developing the guidelines “was to be able to help our junior colleagues and our peers to be able to feel competent to discuss antipsychotics with patients with delusional infestation and also initiate management.”

Dr. Ahmed added: “Why we’re encouraging our colleagues to prescribe antipsychotics is the longer you leave this type of psychotic illness untreated, the worse the prognosis.”

No funding or relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

GLASGOW – Dermatologists do not feel confident in independently prescribing antipsychotic medications for patients with delusional infestation, shows a U.K. survey that also indicated there is a clear demand for training in prescribing these drugs.

Delusional infestation is a rare disorder characterized by an individual’s belief that his or her skin, body, or immediate environment is infested by small, living pathogens, despite a lack of any medical evidence. Most of these patients require antipsychotic medication to alleviate symptoms.

The survey of almost 80 dermatologists found that almost 90% had not prescribed antipsychotics in the previous month for patients with psychodermatology conditions and that the most common barrier to prescribing was lack of experience with the drugs.

This was reflected in only 10% of survey respondents who said they were “happy to” prescribe antipsychotics without consulting either dermatology or psychiatric colleagues, and less than half having attended a related course.

Yet the research, presented at the annual meeting of the British Association of Dermatologists, indicated that more than 75% of respondents would attend such a course to increase their confidence.

This finding, said study presenter Ling Li, MD, Churchill Hospital, Oxford (England) University Hospitals NHS Foundation Trust, shows that there is a “clear demand for training, particularly among all the registrars [residents] who we surveyed.”

Dr. Li noted that the UK’s Joint Royal Colleges of Physicians Training Board’s latest curriculum for dermatology training highlights psychocutaneous medicine as a key area, and “that will include antipsychotic medication.”

The BAD also recently published guidelines for the management of adults with delusional infestation, which includes a recommendation to conduct a survey on attitudes toward antipsychotic prescribing for the condition among U.K. dermatologists.

Heeding that call, Dr. Li and colleagues sent an email containing a 10-question online survey to members of the BAD and the British Society for Medical Dermatology. Questions covered familiarity with antipsychotics and frequency of prescribing, confidence around antipsychotics, and current training and future needs. Responses were received between February through April 2021.

Among the 79 respondents, 51 (65%) were consultants and 20 (25%) were dermatology registrars, with the remainder dermatology clinical fellows, foundation doctors, or other doctors. A total of 31 respondents had an average of more than 50 visits with patients per week, 18 had an average of 41-50 patient visits, and 13 had an average of 31-40 visits per week; the remainder had an average of 11-30 visits per week.

Most of the respondents (39) said they had seen 2-5 patients with psychodermatology conditions in the last 6 months, while 17 said they had seen 1 patient, 13 said they had seen more than 10 patients, and 6 said they had seen 6-10 patients (4 had seen none and 1 could not remember).

The most commonly prescribed antipsychotics for psychodermatology patients in the past 6 months were risperidone (Risperdal; prescribed by five respondents), followed by olanzapine (Zyprexa; by four respondents). Seventy respondents had not prescribed any antipsychotics.

Asked about how confident they felt about prescribing antipsychotic medication for patients with delusional infestation, 8 (10%) said they were happy to prescribe independently, while 42 (54%) said they were not at all confident. Another 10 (13%) respondents said they would be happy to prescribe the medications after liaising with a dermatology colleague, while 17 (22%) said they would prefer to consult with the psychiatry team.

The most common barrier to prescribing antipsychotic medications was a lack of experience with the drugs, cited by 66 respondents, followed by concerns over drug monitoring, cited by 43 respondents.

In addition, 42 respondents highlighted concerns over adverse effects, 36 cited lack of experience in psychodermatology clinics, and 19 cited lack of experience in discussing psychodermatologic conditions with patients. Other barriers mentioned by the respondents included difficulties with patient acceptance of a psychiatric medication prescribed by a dermatologist.

An audience member went further, saying that clinicians have been told not to “confront” such patients and that the temptation is therefore to cloak the discussion of antipsychotics in nonthreatening language so that it is more acceptable to the patient.

However, under the U.K. system, a letter with the results of the consultation, including information that an antipsychotic has been prescribed, must be sent to the patient’s family doctor along with a copy that goes to the patient. “The situation is almost impossible,” the audience member said, adding that there “must be some arrangement where in certain circumstances dermatologists could be allowed not to write to the patient” or alternatively, “write an entirely different letter” to the family doctor.

Session cochair Susannah Baron, MD, a consultant dermatologist at St. John’s Institute of Dermatology, Guy’s and St. Thomas’ Hospital, London, said that, in these situations, it is “really helpful to talk about doses” with patients.

She explained that she uses the analogy of aspirin, which has different effects depending on the dose given, giving pain relief at high doses but primarily an antiplatelet effect at low doses.

In the case of an antipsychotic, it is helpful to explain to the patient that “you don’t think they’re psychotic, and you’re prescribing it in a very low dose, because what it can do is help with their symptoms,” Dr. Baron added. “You have to be very open because if you’re not, they go to the pharmacy, and the pharmacist says: ‘Why are you on an antipsychotic?’ ”

Further results from the survey revealed that 56 (71%) respondents did not have access to a specialist psychodermatology clinic, whereas 36 (46%) had not yet attended a psychodermatology course.

Despite these responses, 60 (77%) respondents said they would be interested in attending a training course for prescribing antipsychotics, which included all 20 of the registrars who took part in the survey. a psychodermatologist at Frimley Health Foundation Trust, Windsor, England, and lead author of the BAD guidelines, commented from the audience that the survey results were “sort of what we expected.”

She explained that the intention of the authors when developing the guidelines “was to be able to help our junior colleagues and our peers to be able to feel competent to discuss antipsychotics with patients with delusional infestation and also initiate management.”

Dr. Ahmed added: “Why we’re encouraging our colleagues to prescribe antipsychotics is the longer you leave this type of psychotic illness untreated, the worse the prognosis.”

No funding or relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

GLASGOW – Dermatologists do not feel confident in independently prescribing antipsychotic medications for patients with delusional infestation, shows a U.K. survey that also indicated there is a clear demand for training in prescribing these drugs.

Delusional infestation is a rare disorder characterized by an individual’s belief that his or her skin, body, or immediate environment is infested by small, living pathogens, despite a lack of any medical evidence. Most of these patients require antipsychotic medication to alleviate symptoms.

The survey of almost 80 dermatologists found that almost 90% had not prescribed antipsychotics in the previous month for patients with psychodermatology conditions and that the most common barrier to prescribing was lack of experience with the drugs.

This was reflected in only 10% of survey respondents who said they were “happy to” prescribe antipsychotics without consulting either dermatology or psychiatric colleagues, and less than half having attended a related course.

Yet the research, presented at the annual meeting of the British Association of Dermatologists, indicated that more than 75% of respondents would attend such a course to increase their confidence.

This finding, said study presenter Ling Li, MD, Churchill Hospital, Oxford (England) University Hospitals NHS Foundation Trust, shows that there is a “clear demand for training, particularly among all the registrars [residents] who we surveyed.”

Dr. Li noted that the UK’s Joint Royal Colleges of Physicians Training Board’s latest curriculum for dermatology training highlights psychocutaneous medicine as a key area, and “that will include antipsychotic medication.”

The BAD also recently published guidelines for the management of adults with delusional infestation, which includes a recommendation to conduct a survey on attitudes toward antipsychotic prescribing for the condition among U.K. dermatologists.

Heeding that call, Dr. Li and colleagues sent an email containing a 10-question online survey to members of the BAD and the British Society for Medical Dermatology. Questions covered familiarity with antipsychotics and frequency of prescribing, confidence around antipsychotics, and current training and future needs. Responses were received between February through April 2021.

Among the 79 respondents, 51 (65%) were consultants and 20 (25%) were dermatology registrars, with the remainder dermatology clinical fellows, foundation doctors, or other doctors. A total of 31 respondents had an average of more than 50 visits with patients per week, 18 had an average of 41-50 patient visits, and 13 had an average of 31-40 visits per week; the remainder had an average of 11-30 visits per week.

Most of the respondents (39) said they had seen 2-5 patients with psychodermatology conditions in the last 6 months, while 17 said they had seen 1 patient, 13 said they had seen more than 10 patients, and 6 said they had seen 6-10 patients (4 had seen none and 1 could not remember).

The most commonly prescribed antipsychotics for psychodermatology patients in the past 6 months were risperidone (Risperdal; prescribed by five respondents), followed by olanzapine (Zyprexa; by four respondents). Seventy respondents had not prescribed any antipsychotics.

Asked about how confident they felt about prescribing antipsychotic medication for patients with delusional infestation, 8 (10%) said they were happy to prescribe independently, while 42 (54%) said they were not at all confident. Another 10 (13%) respondents said they would be happy to prescribe the medications after liaising with a dermatology colleague, while 17 (22%) said they would prefer to consult with the psychiatry team.

The most common barrier to prescribing antipsychotic medications was a lack of experience with the drugs, cited by 66 respondents, followed by concerns over drug monitoring, cited by 43 respondents.

In addition, 42 respondents highlighted concerns over adverse effects, 36 cited lack of experience in psychodermatology clinics, and 19 cited lack of experience in discussing psychodermatologic conditions with patients. Other barriers mentioned by the respondents included difficulties with patient acceptance of a psychiatric medication prescribed by a dermatologist.

An audience member went further, saying that clinicians have been told not to “confront” such patients and that the temptation is therefore to cloak the discussion of antipsychotics in nonthreatening language so that it is more acceptable to the patient.

However, under the U.K. system, a letter with the results of the consultation, including information that an antipsychotic has been prescribed, must be sent to the patient’s family doctor along with a copy that goes to the patient. “The situation is almost impossible,” the audience member said, adding that there “must be some arrangement where in certain circumstances dermatologists could be allowed not to write to the patient” or alternatively, “write an entirely different letter” to the family doctor.

Session cochair Susannah Baron, MD, a consultant dermatologist at St. John’s Institute of Dermatology, Guy’s and St. Thomas’ Hospital, London, said that, in these situations, it is “really helpful to talk about doses” with patients.

She explained that she uses the analogy of aspirin, which has different effects depending on the dose given, giving pain relief at high doses but primarily an antiplatelet effect at low doses.

In the case of an antipsychotic, it is helpful to explain to the patient that “you don’t think they’re psychotic, and you’re prescribing it in a very low dose, because what it can do is help with their symptoms,” Dr. Baron added. “You have to be very open because if you’re not, they go to the pharmacy, and the pharmacist says: ‘Why are you on an antipsychotic?’ ”

Further results from the survey revealed that 56 (71%) respondents did not have access to a specialist psychodermatology clinic, whereas 36 (46%) had not yet attended a psychodermatology course.

Despite these responses, 60 (77%) respondents said they would be interested in attending a training course for prescribing antipsychotics, which included all 20 of the registrars who took part in the survey. a psychodermatologist at Frimley Health Foundation Trust, Windsor, England, and lead author of the BAD guidelines, commented from the audience that the survey results were “sort of what we expected.”

She explained that the intention of the authors when developing the guidelines “was to be able to help our junior colleagues and our peers to be able to feel competent to discuss antipsychotics with patients with delusional infestation and also initiate management.”

Dr. Ahmed added: “Why we’re encouraging our colleagues to prescribe antipsychotics is the longer you leave this type of psychotic illness untreated, the worse the prognosis.”

No funding or relevant financial relationships were declared.

A version of this article first appeared on Medscape.com.

Only a small number of research clinical trials for cancer drugs actually show benefit in quality of life, according to a study published in JAMA Oncology.

The study found trials that failed to show improved quality of life often reported their quality of life outcomes more favorably. Non–immunotherapy-targeted drugs were found to lead to worse quality of life outcomes more often than did cytotoxic agents. And, while there is an association between quality of life benefit and overall survival, no such association was found with progression-free survival.

“In this study, we evaluated the outcomes of cancer drug trials with regard to patients’ quality of life and found that only a quarter of phase 3 cancer drug trials in the advanced-disease setting demonstrated improved quality of life,” wrote authors who were led by Bishal Gyawali, MD, PhD, of the Cancer Research Institute, Queen’s University, Kingston, Ont.

“Improved quality of life outcomes were associated with improved overall survival but not with improved progression-free survival. Importantly, almost half of the cancer drugs drug trials that showed improved progression-free survival showed no improved overall survival or quality of life (i.e., PFS-only benefit). Some reports included conclusions regarding quality of life (QOL) findings that were not directly supported by the trial data, particularly for inferior or non–statistically significant QOL outcomes, thereby framing the findings in a favorable light or downplaying detrimental effects of the study intervention on QOL. Furthermore, contrary to common perception, inferior QOL outcomes were more common with targeted drugs than cytotoxic drugs. Taken together, these findings have important policy implications,” the authors wrote.

These findings are based on the results of a cohort study of 45 phase 3 research clinical trials of 24,806 patients. Only a small percentage of patients showed QOL benefits. The study found that industry-funded clinical trial reports often framed QOL findings more favorably than was warranted by the data.

The study found improved QOL with experimental agents in 11 of 45 randomized controlled trials (24.4%). Studies that reported improved QOL were more likely to also show improved overall survival as compared with trials in which quality of life was not improved (7 of 11 [64%] versus 10 of 34 [29%] trials). For improved progression-free survival, however, there was no positive association (6 of 11 [55%] trials versus 17 of 34 [50%] trials without improved QOL). Among six trials reporting worsening QOL, three (50%) were trials of targeted drugs. Among 11 trials reporting improved QOL, 6 (55%) were trials of immunotherapy drugs. Among the 34 trials in which QOL was not improved compared with controls, the findings were framed favorably (versus neutrally or negatively) in the abstract or conclusions in 16 (47%), an observation that was statistically significantly associated with industry funding (chi-squared = 6.35; P = .01).

“It is important to clearly understand and communicate the effects of cancer drugs”

To fulfill the obligation to inform patients about proposed treatments, the authors wrote that it is important to clearly understand and communicate the effects of cancer drugs on patient quality of life alongside their effects on overall survival and intermediate end points such as progression-free survival. “Patients with advanced cancer expect treatment to help them live longer or have better lives,” the authors wrote. In that respect, in clinical trials of cancer medicines, overall survival and quality of life are the most important measures. Toxicity profiles and disease progression delays do not reliably predict quality of life, and studies have shown poor correlations between quality of life, overall survival, and progression-free survival. This raises the question of validity of progression-free survival as a surrogate endpoint. “Progression-free survival is meaningless without overall survival or quality of life gains,” Dr. Gyawali said in an interview.

Writing in The Lancet Oncology in March, Dr. Gyawali stated that, because progression free survival “does not directly measure how a patient feels or functions, or how long a patient lives, progression-free survival was not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. However, over the past 2 decades, it has become the most common primary endpoint in oncology clinical trials. We are deeply worried about how the term survival in this phrase can influence clinical practice and patient choices. We propose replacing the phrase progression-free survival with a less ambiguous term: progression-free interval.”

In JAMA Oncology, Dr. Gyawali aimed to elucidate relationships between QOL, overall survival, and progression-free survival, and to assess, as well, how QOL results are framed, especially in industry-sponsored research. When drug trials they analyzed showed no change in QOL but reported that QOL did not worsen or QOL was maintained rather than stating that QOL did not improve, or if there was downplaying of worse QOL outcomes, the study had favorable interpretation, Dr. Gyawali and associates wrote. The expectation of patients receiving cancer drugs would be improved QOL rather than “not worse” QOL, Dr. Gyawali said.

Regarding the finding that QOL outcomes were described as favorable in 47% of trials with unimproved QOL outcomes, Dr. Gyawali said, “the bias in reporting should be corrected by the reviewers and editors of journals. Also, quality of life reporting should be made mandatory. Without unbiased quality of life information, informed decision making on whether or not to use a certain drug is impossible. Patients and physicians need to know that information. Regulators can demand that this should be mandatory in all trials in noncurative settings.”

He remarked further on the worsening QOL in some targeted drug trials, “People tout chemo-free regimens as automatically having better quality of life, but that doesn’t seem to be the case. Targeted drugs can have a severe impact on quality of life, probably due to prolonged duration of side effects. Quality of life should be measured and reported for all drugs.”

Dr. Gyawali and associates noted the limitation in that several studies with negative QOL results are not published at all or are published after a considerable delay, so the present observations may understate the issues that have been raised.

Dr. Gyawali declared that he received no funding and disclosed no conflicts of interest for this study.

Only a small number of research clinical trials for cancer drugs actually show benefit in quality of life, according to a study published in JAMA Oncology.

The study found trials that failed to show improved quality of life often reported their quality of life outcomes more favorably. Non–immunotherapy-targeted drugs were found to lead to worse quality of life outcomes more often than did cytotoxic agents. And, while there is an association between quality of life benefit and overall survival, no such association was found with progression-free survival.

“In this study, we evaluated the outcomes of cancer drug trials with regard to patients’ quality of life and found that only a quarter of phase 3 cancer drug trials in the advanced-disease setting demonstrated improved quality of life,” wrote authors who were led by Bishal Gyawali, MD, PhD, of the Cancer Research Institute, Queen’s University, Kingston, Ont.

“Improved quality of life outcomes were associated with improved overall survival but not with improved progression-free survival. Importantly, almost half of the cancer drugs drug trials that showed improved progression-free survival showed no improved overall survival or quality of life (i.e., PFS-only benefit). Some reports included conclusions regarding quality of life (QOL) findings that were not directly supported by the trial data, particularly for inferior or non–statistically significant QOL outcomes, thereby framing the findings in a favorable light or downplaying detrimental effects of the study intervention on QOL. Furthermore, contrary to common perception, inferior QOL outcomes were more common with targeted drugs than cytotoxic drugs. Taken together, these findings have important policy implications,” the authors wrote.

These findings are based on the results of a cohort study of 45 phase 3 research clinical trials of 24,806 patients. Only a small percentage of patients showed QOL benefits. The study found that industry-funded clinical trial reports often framed QOL findings more favorably than was warranted by the data.

The study found improved QOL with experimental agents in 11 of 45 randomized controlled trials (24.4%). Studies that reported improved QOL were more likely to also show improved overall survival as compared with trials in which quality of life was not improved (7 of 11 [64%] versus 10 of 34 [29%] trials). For improved progression-free survival, however, there was no positive association (6 of 11 [55%] trials versus 17 of 34 [50%] trials without improved QOL). Among six trials reporting worsening QOL, three (50%) were trials of targeted drugs. Among 11 trials reporting improved QOL, 6 (55%) were trials of immunotherapy drugs. Among the 34 trials in which QOL was not improved compared with controls, the findings were framed favorably (versus neutrally or negatively) in the abstract or conclusions in 16 (47%), an observation that was statistically significantly associated with industry funding (chi-squared = 6.35; P = .01).

“It is important to clearly understand and communicate the effects of cancer drugs”

To fulfill the obligation to inform patients about proposed treatments, the authors wrote that it is important to clearly understand and communicate the effects of cancer drugs on patient quality of life alongside their effects on overall survival and intermediate end points such as progression-free survival. “Patients with advanced cancer expect treatment to help them live longer or have better lives,” the authors wrote. In that respect, in clinical trials of cancer medicines, overall survival and quality of life are the most important measures. Toxicity profiles and disease progression delays do not reliably predict quality of life, and studies have shown poor correlations between quality of life, overall survival, and progression-free survival. This raises the question of validity of progression-free survival as a surrogate endpoint. “Progression-free survival is meaningless without overall survival or quality of life gains,” Dr. Gyawali said in an interview.

Writing in The Lancet Oncology in March, Dr. Gyawali stated that, because progression free survival “does not directly measure how a patient feels or functions, or how long a patient lives, progression-free survival was not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. However, over the past 2 decades, it has become the most common primary endpoint in oncology clinical trials. We are deeply worried about how the term survival in this phrase can influence clinical practice and patient choices. We propose replacing the phrase progression-free survival with a less ambiguous term: progression-free interval.”

In JAMA Oncology, Dr. Gyawali aimed to elucidate relationships between QOL, overall survival, and progression-free survival, and to assess, as well, how QOL results are framed, especially in industry-sponsored research. When drug trials they analyzed showed no change in QOL but reported that QOL did not worsen or QOL was maintained rather than stating that QOL did not improve, or if there was downplaying of worse QOL outcomes, the study had favorable interpretation, Dr. Gyawali and associates wrote. The expectation of patients receiving cancer drugs would be improved QOL rather than “not worse” QOL, Dr. Gyawali said.

Regarding the finding that QOL outcomes were described as favorable in 47% of trials with unimproved QOL outcomes, Dr. Gyawali said, “the bias in reporting should be corrected by the reviewers and editors of journals. Also, quality of life reporting should be made mandatory. Without unbiased quality of life information, informed decision making on whether or not to use a certain drug is impossible. Patients and physicians need to know that information. Regulators can demand that this should be mandatory in all trials in noncurative settings.”

He remarked further on the worsening QOL in some targeted drug trials, “People tout chemo-free regimens as automatically having better quality of life, but that doesn’t seem to be the case. Targeted drugs can have a severe impact on quality of life, probably due to prolonged duration of side effects. Quality of life should be measured and reported for all drugs.”

Dr. Gyawali and associates noted the limitation in that several studies with negative QOL results are not published at all or are published after a considerable delay, so the present observations may understate the issues that have been raised.

Dr. Gyawali declared that he received no funding and disclosed no conflicts of interest for this study.

Only a small number of research clinical trials for cancer drugs actually show benefit in quality of life, according to a study published in JAMA Oncology.

The study found trials that failed to show improved quality of life often reported their quality of life outcomes more favorably. Non–immunotherapy-targeted drugs were found to lead to worse quality of life outcomes more often than did cytotoxic agents. And, while there is an association between quality of life benefit and overall survival, no such association was found with progression-free survival.

“In this study, we evaluated the outcomes of cancer drug trials with regard to patients’ quality of life and found that only a quarter of phase 3 cancer drug trials in the advanced-disease setting demonstrated improved quality of life,” wrote authors who were led by Bishal Gyawali, MD, PhD, of the Cancer Research Institute, Queen’s University, Kingston, Ont.

“Improved quality of life outcomes were associated with improved overall survival but not with improved progression-free survival. Importantly, almost half of the cancer drugs drug trials that showed improved progression-free survival showed no improved overall survival or quality of life (i.e., PFS-only benefit). Some reports included conclusions regarding quality of life (QOL) findings that were not directly supported by the trial data, particularly for inferior or non–statistically significant QOL outcomes, thereby framing the findings in a favorable light or downplaying detrimental effects of the study intervention on QOL. Furthermore, contrary to common perception, inferior QOL outcomes were more common with targeted drugs than cytotoxic drugs. Taken together, these findings have important policy implications,” the authors wrote.

These findings are based on the results of a cohort study of 45 phase 3 research clinical trials of 24,806 patients. Only a small percentage of patients showed QOL benefits. The study found that industry-funded clinical trial reports often framed QOL findings more favorably than was warranted by the data.

The study found improved QOL with experimental agents in 11 of 45 randomized controlled trials (24.4%). Studies that reported improved QOL were more likely to also show improved overall survival as compared with trials in which quality of life was not improved (7 of 11 [64%] versus 10 of 34 [29%] trials). For improved progression-free survival, however, there was no positive association (6 of 11 [55%] trials versus 17 of 34 [50%] trials without improved QOL). Among six trials reporting worsening QOL, three (50%) were trials of targeted drugs. Among 11 trials reporting improved QOL, 6 (55%) were trials of immunotherapy drugs. Among the 34 trials in which QOL was not improved compared with controls, the findings were framed favorably (versus neutrally or negatively) in the abstract or conclusions in 16 (47%), an observation that was statistically significantly associated with industry funding (chi-squared = 6.35; P = .01).

“It is important to clearly understand and communicate the effects of cancer drugs”

To fulfill the obligation to inform patients about proposed treatments, the authors wrote that it is important to clearly understand and communicate the effects of cancer drugs on patient quality of life alongside their effects on overall survival and intermediate end points such as progression-free survival. “Patients with advanced cancer expect treatment to help them live longer or have better lives,” the authors wrote. In that respect, in clinical trials of cancer medicines, overall survival and quality of life are the most important measures. Toxicity profiles and disease progression delays do not reliably predict quality of life, and studies have shown poor correlations between quality of life, overall survival, and progression-free survival. This raises the question of validity of progression-free survival as a surrogate endpoint. “Progression-free survival is meaningless without overall survival or quality of life gains,” Dr. Gyawali said in an interview.

Writing in The Lancet Oncology in March, Dr. Gyawali stated that, because progression free survival “does not directly measure how a patient feels or functions, or how long a patient lives, progression-free survival was not intended to inform clinical practice or establish whether a new therapy provides clinically meaningful benefits for patients. However, over the past 2 decades, it has become the most common primary endpoint in oncology clinical trials. We are deeply worried about how the term survival in this phrase can influence clinical practice and patient choices. We propose replacing the phrase progression-free survival with a less ambiguous term: progression-free interval.”

In JAMA Oncology, Dr. Gyawali aimed to elucidate relationships between QOL, overall survival, and progression-free survival, and to assess, as well, how QOL results are framed, especially in industry-sponsored research. When drug trials they analyzed showed no change in QOL but reported that QOL did not worsen or QOL was maintained rather than stating that QOL did not improve, or if there was downplaying of worse QOL outcomes, the study had favorable interpretation, Dr. Gyawali and associates wrote. The expectation of patients receiving cancer drugs would be improved QOL rather than “not worse” QOL, Dr. Gyawali said.

Regarding the finding that QOL outcomes were described as favorable in 47% of trials with unimproved QOL outcomes, Dr. Gyawali said, “the bias in reporting should be corrected by the reviewers and editors of journals. Also, quality of life reporting should be made mandatory. Without unbiased quality of life information, informed decision making on whether or not to use a certain drug is impossible. Patients and physicians need to know that information. Regulators can demand that this should be mandatory in all trials in noncurative settings.”

He remarked further on the worsening QOL in some targeted drug trials, “People tout chemo-free regimens as automatically having better quality of life, but that doesn’t seem to be the case. Targeted drugs can have a severe impact on quality of life, probably due to prolonged duration of side effects. Quality of life should be measured and reported for all drugs.”

Dr. Gyawali and associates noted the limitation in that several studies with negative QOL results are not published at all or are published after a considerable delay, so the present observations may understate the issues that have been raised.

Dr. Gyawali declared that he received no funding and disclosed no conflicts of interest for this study.

Physician-musician Cleveland Francis, MD, responded to the recent mass shooting in Buffalo, New York, which left 10 dead, in the only way he knew how. He wrote and recorded a song to honor the victims as “a plea to the other side to recognize us as people,” the Black cardiologist told this news organization.

He couldn’t sleep after the shooting, and “this song was just in my head.” In the 1990s, Dr. Francis took a 3-year sabbatical from medicine to perform and tour as a country singer. He leveraged his Nashville connections to get “Buffalo” produced and recorded.

Acclaimed artist James Threalkill created the accompanying art, titled “The Heavenly Escort of the Buffalo 10,” after listening to a scratch demo.

Dr. Francis doesn’t want people to overlook the massacre as just another gun violence incident because this was “overt hate-crime racism,” he said.

According to the affidavit submitted by FBI agent Christopher J. Dlugokinski, the suspect’s “motive for the mass shooting was to prevent Black people from replacing White people and eliminating the White race, and to inspire others to commit similar attacks.”

Dr. Francis views the Buffalo shooting as distinct from cases like the murder of George Floyd that involved crime or police. It immediately made him think of the Mother Emanuel Church shooting in Charleston, South Carolina. “Having a black skin is now a death warrant,” he said.

The song is also an appeal for White people to fight racism. Dr. Francis is concerned about young men caught up in white supremacy and suggests that we be more alert to children or grandchildren who disconnect from their families, spend time on the dark web, and access guns. The lyrics deliberately don’t mention guns because Dr. Francis wanted to stay out of that debate. “I just sang: ‘What else do I have to do to prove to you that I’m human too?’ ”

Despite his country credentials, Dr. Francis wrote “Buffalo” as a Gospel song because that genre “connects with Black people more and because that civil rights movement was through the church with Dr. Martin Luther King,” he explained. Although he sings all styles of music, the song is performed by Nashville-based singer Michael Lusk so that it’s not a “Cleve Francis thing,” he said, referring to his stage name.

Songwriter Norman Kerner collaborated on the song. The music was produced and recorded by David Thein and mixed by Bob Bullock of Nashville, who Dr. Francis had worked with when he was an artist on Capitol Records.

They sent the video and artwork to the Mayor of Buffalo, Byron Brown, but have yet to hear back. Dr. Francis hopes it could be part of their healing, noting that some people used the song in their Juneteenth celebrations.

The Louisiana native grew up during segregation and was one of two Black students in the Medical College of Virginia class of 1973. After completing his cardiology fellowship, no one would hire him, so Dr. Francis set up his own practice in Northern Virginia. He now works at Inova Heart and Vascular Institute in Alexandria, Va. He remains optimistic about race relations in America and would love a Black pop or Gospel star to record “Buffalo” and bring it to a wider audience.

Dr. Francis is a regular blogger for Medscape. His contribution to country music is recognized in the National Museum of African American History and Culture in Washington, DC. You can find more of his music on YouTube.

A version of this article first appeared on Medscape.com.

Physician-musician Cleveland Francis, MD, responded to the recent mass shooting in Buffalo, New York, which left 10 dead, in the only way he knew how. He wrote and recorded a song to honor the victims as “a plea to the other side to recognize us as people,” the Black cardiologist told this news organization.

He couldn’t sleep after the shooting, and “this song was just in my head.” In the 1990s, Dr. Francis took a 3-year sabbatical from medicine to perform and tour as a country singer. He leveraged his Nashville connections to get “Buffalo” produced and recorded.

Acclaimed artist James Threalkill created the accompanying art, titled “The Heavenly Escort of the Buffalo 10,” after listening to a scratch demo.

Dr. Francis doesn’t want people to overlook the massacre as just another gun violence incident because this was “overt hate-crime racism,” he said.

According to the affidavit submitted by FBI agent Christopher J. Dlugokinski, the suspect’s “motive for the mass shooting was to prevent Black people from replacing White people and eliminating the White race, and to inspire others to commit similar attacks.”

Dr. Francis views the Buffalo shooting as distinct from cases like the murder of George Floyd that involved crime or police. It immediately made him think of the Mother Emanuel Church shooting in Charleston, South Carolina. “Having a black skin is now a death warrant,” he said.

The song is also an appeal for White people to fight racism. Dr. Francis is concerned about young men caught up in white supremacy and suggests that we be more alert to children or grandchildren who disconnect from their families, spend time on the dark web, and access guns. The lyrics deliberately don’t mention guns because Dr. Francis wanted to stay out of that debate. “I just sang: ‘What else do I have to do to prove to you that I’m human too?’ ”

Despite his country credentials, Dr. Francis wrote “Buffalo” as a Gospel song because that genre “connects with Black people more and because that civil rights movement was through the church with Dr. Martin Luther King,” he explained. Although he sings all styles of music, the song is performed by Nashville-based singer Michael Lusk so that it’s not a “Cleve Francis thing,” he said, referring to his stage name.

Songwriter Norman Kerner collaborated on the song. The music was produced and recorded by David Thein and mixed by Bob Bullock of Nashville, who Dr. Francis had worked with when he was an artist on Capitol Records.

They sent the video and artwork to the Mayor of Buffalo, Byron Brown, but have yet to hear back. Dr. Francis hopes it could be part of their healing, noting that some people used the song in their Juneteenth celebrations.

The Louisiana native grew up during segregation and was one of two Black students in the Medical College of Virginia class of 1973. After completing his cardiology fellowship, no one would hire him, so Dr. Francis set up his own practice in Northern Virginia. He now works at Inova Heart and Vascular Institute in Alexandria, Va. He remains optimistic about race relations in America and would love a Black pop or Gospel star to record “Buffalo” and bring it to a wider audience.

Dr. Francis is a regular blogger for Medscape. His contribution to country music is recognized in the National Museum of African American History and Culture in Washington, DC. You can find more of his music on YouTube.

A version of this article first appeared on Medscape.com.

Physician-musician Cleveland Francis, MD, responded to the recent mass shooting in Buffalo, New York, which left 10 dead, in the only way he knew how. He wrote and recorded a song to honor the victims as “a plea to the other side to recognize us as people,” the Black cardiologist told this news organization.

He couldn’t sleep after the shooting, and “this song was just in my head.” In the 1990s, Dr. Francis took a 3-year sabbatical from medicine to perform and tour as a country singer. He leveraged his Nashville connections to get “Buffalo” produced and recorded.

Acclaimed artist James Threalkill created the accompanying art, titled “The Heavenly Escort of the Buffalo 10,” after listening to a scratch demo.

Dr. Francis doesn’t want people to overlook the massacre as just another gun violence incident because this was “overt hate-crime racism,” he said.

According to the affidavit submitted by FBI agent Christopher J. Dlugokinski, the suspect’s “motive for the mass shooting was to prevent Black people from replacing White people and eliminating the White race, and to inspire others to commit similar attacks.”

Dr. Francis views the Buffalo shooting as distinct from cases like the murder of George Floyd that involved crime or police. It immediately made him think of the Mother Emanuel Church shooting in Charleston, South Carolina. “Having a black skin is now a death warrant,” he said.

The song is also an appeal for White people to fight racism. Dr. Francis is concerned about young men caught up in white supremacy and suggests that we be more alert to children or grandchildren who disconnect from their families, spend time on the dark web, and access guns. The lyrics deliberately don’t mention guns because Dr. Francis wanted to stay out of that debate. “I just sang: ‘What else do I have to do to prove to you that I’m human too?’ ”

Despite his country credentials, Dr. Francis wrote “Buffalo” as a Gospel song because that genre “connects with Black people more and because that civil rights movement was through the church with Dr. Martin Luther King,” he explained. Although he sings all styles of music, the song is performed by Nashville-based singer Michael Lusk so that it’s not a “Cleve Francis thing,” he said, referring to his stage name.

Songwriter Norman Kerner collaborated on the song. The music was produced and recorded by David Thein and mixed by Bob Bullock of Nashville, who Dr. Francis had worked with when he was an artist on Capitol Records.

They sent the video and artwork to the Mayor of Buffalo, Byron Brown, but have yet to hear back. Dr. Francis hopes it could be part of their healing, noting that some people used the song in their Juneteenth celebrations.

The Louisiana native grew up during segregation and was one of two Black students in the Medical College of Virginia class of 1973. After completing his cardiology fellowship, no one would hire him, so Dr. Francis set up his own practice in Northern Virginia. He now works at Inova Heart and Vascular Institute in Alexandria, Va. He remains optimistic about race relations in America and would love a Black pop or Gospel star to record “Buffalo” and bring it to a wider audience.

Dr. Francis is a regular blogger for Medscape. His contribution to country music is recognized in the National Museum of African American History and Culture in Washington, DC. You can find more of his music on YouTube.

A version of this article first appeared on Medscape.com.

These viruses want mosquitoes with good taste

Taste can be a pretty subjective sense. Not everyone agrees on what tastes good and what tastes bad. Most people would agree that freshly baked cookies taste good, but what about lima beans? And what about mosquitoes? What tastes good to a mosquito?

The answer? Blood. Blood tastes good to a mosquito. That really wasn’t a very hard question, was it? You did know the answer, didn’t you? They don’t care about cookies, and they certainly don’t care about lima beans. It’s blood that they love.

©Mathisa_s/ThinkStock

That brings us back to subjectivity, because it is possible for blood to taste even better. The secret ingredient is dengue … and Zika.

A study just published in Cell demonstrates that mice infected with dengue and Zika viruses release a volatile compound called acetophenone. “We found that flavivirus [like dengue and Zika] can utilize the increased release of acetophenone to help itself achieve its lifecycles more effectively by making their hosts more attractive to mosquito vectors,” senior author Gong Cheng of Tsinghua University, Beijing, said in a written statement.

How do they do it? The viruses, he explained, promote the proliferation of acetophenone-producing skin bacteria. “As a result, some bacteria overreplicate and produce more acetophenone. Suddenly, these sick individuals smell as delicious to mosquitoes as a tray of freshly baked cookies to a group of five-year-old children,” the statement said.

And how do you stop a group of tiny, flying 5-year-olds? That’s right, with acne medication. Really? You knew that one but not the blood one before? The investigators fed isotretinoin to the infected mice, which led to reduced acetophenone release from skin bacteria and made the animals no more attractive to the mosquitoes than their uninfected counterparts.

The investigators are planning to take the next step – feeding isotretinoin to people with dengue and Zika – having gotten the official fictional taste-test approval of celebrity chef Gordon Ramsay, who said, “You’re going to feed this #$^% to sick people? ARE YOU &%*$@#& KIDDING ME?”

Okay, so maybe approval isn’t quite the right word.
 

Welcome to bladders of the rich and famous!

Don’t you hate it when you’re driving out to your multimillion-dollar second home in the Hamptons and traffic is so bad you absolutely have to find a place to “rest” along the way? But wouldn’t you know it, there just isn’t anywhere to stop! Geez, how do we live?

That’s where David Shusterman, MD, a urologist in New York City and a true American hero, comes in. He’s identified a market and positioned himself as the king of both bladder surgery and “bladder Botox” for the wealthy New Yorkers who regularly make long journeys from the city out to their second homes in the Hamptons. Traffic has increased dramatically on Long Island roads in recent years, and the journey can now taking upward of 4 hours. Some people just can’t make it that long without a bathroom break, and there are very few places to stop along the way.

National Park Service/Rawpixel

Dr. Shusterman understands the plight of the Hamptons vacationer, as he told Insider.com: “I can’t tell you how many arguments I personally get into – I’ve lost three friends because I’m the driver and refuse to stop for them.” A tragedy worthy of Shakespeare himself.

During the summer season, Dr. Shusterman performs about 10 prostate artery embolizations a week, an hour-long procedure that shrinks the prostate, which is great for 50- to 60-year-old men with enlarged prostates that cause more frequent bathroom trips. He also performs Botox injections into the bladder once or twice a week for women, which reduces the need to urinate for roughly 6 months. The perfect amount of time to get them through the summer season.

These procedures are sometimes covered by insurance but can cost as much as $20,000 if paid out of pocket. That’s a lot of money to us, but if you’re the sort of person who has a second home in the Hamptons, $20,000 is chump change, especially if it means you won’t have to go 2 entire minutes out of your way to use a gas-station bathroom. Then again, having seen a more than a few gas-station bathrooms in our time, maybe they have a point.
 

Ditch the apples. Go for the avocados

We’ve all heard about “an apple a day,” but instead of apples you might want to go with avocados.

tookapic/Pixabay

Avocados are generally thought to be a healthy fat. A study just published in the Journal of the American Heart Association proves that they actually don’t do anything for your waistline but will work wonders on your cholesterol level. The study involved 923 participants who were considered overweight/obese split into two groups: One was asked to consume an avocado a day, and the other continued their usual diets and were asked to consume fewer than two avocados a month.

At the end of the 6 months, the researchers found total cholesterol decreased by an additional 2.9 mg/dL and LDL cholesterol by 2.5 mg/dL in those who ate one avocado every day, compared with the usual-diet group. And even though avocados have a lot of calories, there was no clinical evidence that it impacted weight gain or any cardiometabolic risk factors, according to a statement from Penn State University.

Avocados, then, can be considered a guilt-free food. The findings from this study suggest it can give a substantial boost to your overall quality of diet, in turn lessening your risk of developing type 2 diabetes and some cancers, Kristina Peterson, PhD, assistant professor of nutritional sciences at Texas Tech University, said in the statement.

So get creative with your avocado recipes. You can only eat so much guacamole.
 

Your nose knows a good friend for you

You’ve probably noticed how dogs sniff other dogs and people before becoming friends. It would be pretty comical if people did the same thing, right? Just walked up to strangers and started sniffing them like dogs?

Well, apparently humans do go by smell when it comes to making friends, and they prefer people who smell like them. Maybe you’ve noticed that your friends look like you, share your values, and think the same way as you. You’re probably right, seeing as previous research has pointed to this.

For the current study, done to show how smell affects human behavior, researchers recruited people who befriended each other quickly, before knowing much about each other. They assumed that the relationships between these same-sex, nonromantic “click friends” relied more on physiological traits, including smell. After collecting samples from the click friends, researchers used an eNose to scan chemical signatures. In another experiment, human volunteers sniffed samples to determine if any were similar. Both experiments showed that click friends had more similar smells than pairs of random people.

Weizmann Institute of Science

These viruses want mosquitoes with good taste

Taste can be a pretty subjective sense. Not everyone agrees on what tastes good and what tastes bad. Most people would agree that freshly baked cookies taste good, but what about lima beans? And what about mosquitoes? What tastes good to a mosquito?

The answer? Blood. Blood tastes good to a mosquito. That really wasn’t a very hard question, was it? You did know the answer, didn’t you? They don’t care about cookies, and they certainly don’t care about lima beans. It’s blood that they love.

©Mathisa_s/ThinkStock

That brings us back to subjectivity, because it is possible for blood to taste even better. The secret ingredient is dengue … and Zika.

A study just published in Cell demonstrates that mice infected with dengue and Zika viruses release a volatile compound called acetophenone. “We found that flavivirus [like dengue and Zika] can utilize the increased release of acetophenone to help itself achieve its lifecycles more effectively by making their hosts more attractive to mosquito vectors,” senior author Gong Cheng of Tsinghua University, Beijing, said in a written statement.

How do they do it? The viruses, he explained, promote the proliferation of acetophenone-producing skin bacteria. “As a result, some bacteria overreplicate and produce more acetophenone. Suddenly, these sick individuals smell as delicious to mosquitoes as a tray of freshly baked cookies to a group of five-year-old children,” the statement said.

And how do you stop a group of tiny, flying 5-year-olds? That’s right, with acne medication. Really? You knew that one but not the blood one before? The investigators fed isotretinoin to the infected mice, which led to reduced acetophenone release from skin bacteria and made the animals no more attractive to the mosquitoes than their uninfected counterparts.

The investigators are planning to take the next step – feeding isotretinoin to people with dengue and Zika – having gotten the official fictional taste-test approval of celebrity chef Gordon Ramsay, who said, “You’re going to feed this #$^% to sick people? ARE YOU &%*$@#& KIDDING ME?”

Okay, so maybe approval isn’t quite the right word.
 

Welcome to bladders of the rich and famous!

Don’t you hate it when you’re driving out to your multimillion-dollar second home in the Hamptons and traffic is so bad you absolutely have to find a place to “rest” along the way? But wouldn’t you know it, there just isn’t anywhere to stop! Geez, how do we live?

That’s where David Shusterman, MD, a urologist in New York City and a true American hero, comes in. He’s identified a market and positioned himself as the king of both bladder surgery and “bladder Botox” for the wealthy New Yorkers who regularly make long journeys from the city out to their second homes in the Hamptons. Traffic has increased dramatically on Long Island roads in recent years, and the journey can now taking upward of 4 hours. Some people just can’t make it that long without a bathroom break, and there are very few places to stop along the way.

National Park Service/Rawpixel

Dr. Shusterman understands the plight of the Hamptons vacationer, as he told Insider.com: “I can’t tell you how many arguments I personally get into – I’ve lost three friends because I’m the driver and refuse to stop for them.” A tragedy worthy of Shakespeare himself.

During the summer season, Dr. Shusterman performs about 10 prostate artery embolizations a week, an hour-long procedure that shrinks the prostate, which is great for 50- to 60-year-old men with enlarged prostates that cause more frequent bathroom trips. He also performs Botox injections into the bladder once or twice a week for women, which reduces the need to urinate for roughly 6 months. The perfect amount of time to get them through the summer season.

These procedures are sometimes covered by insurance but can cost as much as $20,000 if paid out of pocket. That’s a lot of money to us, but if you’re the sort of person who has a second home in the Hamptons, $20,000 is chump change, especially if it means you won’t have to go 2 entire minutes out of your way to use a gas-station bathroom. Then again, having seen a more than a few gas-station bathrooms in our time, maybe they have a point.
 

Ditch the apples. Go for the avocados

We’ve all heard about “an apple a day,” but instead of apples you might want to go with avocados.

tookapic/Pixabay

Avocados are generally thought to be a healthy fat. A study just published in the Journal of the American Heart Association proves that they actually don’t do anything for your waistline but will work wonders on your cholesterol level. The study involved 923 participants who were considered overweight/obese split into two groups: One was asked to consume an avocado a day, and the other continued their usual diets and were asked to consume fewer than two avocados a month.

At the end of the 6 months, the researchers found total cholesterol decreased by an additional 2.9 mg/dL and LDL cholesterol by 2.5 mg/dL in those who ate one avocado every day, compared with the usual-diet group. And even though avocados have a lot of calories, there was no clinical evidence that it impacted weight gain or any cardiometabolic risk factors, according to a statement from Penn State University.

Avocados, then, can be considered a guilt-free food. The findings from this study suggest it can give a substantial boost to your overall quality of diet, in turn lessening your risk of developing type 2 diabetes and some cancers, Kristina Peterson, PhD, assistant professor of nutritional sciences at Texas Tech University, said in the statement.

So get creative with your avocado recipes. You can only eat so much guacamole.
 

Your nose knows a good friend for you

You’ve probably noticed how dogs sniff other dogs and people before becoming friends. It would be pretty comical if people did the same thing, right? Just walked up to strangers and started sniffing them like dogs?

Well, apparently humans do go by smell when it comes to making friends, and they prefer people who smell like them. Maybe you’ve noticed that your friends look like you, share your values, and think the same way as you. You’re probably right, seeing as previous research has pointed to this.

For the current study, done to show how smell affects human behavior, researchers recruited people who befriended each other quickly, before knowing much about each other. They assumed that the relationships between these same-sex, nonromantic “click friends” relied more on physiological traits, including smell. After collecting samples from the click friends, researchers used an eNose to scan chemical signatures. In another experiment, human volunteers sniffed samples to determine if any were similar. Both experiments showed that click friends had more similar smells than pairs of random people.

Weizmann Institute of Science

These viruses want mosquitoes with good taste

Taste can be a pretty subjective sense. Not everyone agrees on what tastes good and what tastes bad. Most people would agree that freshly baked cookies taste good, but what about lima beans? And what about mosquitoes? What tastes good to a mosquito?

The answer? Blood. Blood tastes good to a mosquito. That really wasn’t a very hard question, was it? You did know the answer, didn’t you? They don’t care about cookies, and they certainly don’t care about lima beans. It’s blood that they love.

©Mathisa_s/ThinkStock

That brings us back to subjectivity, because it is possible for blood to taste even better. The secret ingredient is dengue … and Zika.

A study just published in Cell demonstrates that mice infected with dengue and Zika viruses release a volatile compound called acetophenone. “We found that flavivirus [like dengue and Zika] can utilize the increased release of acetophenone to help itself achieve its lifecycles more effectively by making their hosts more attractive to mosquito vectors,” senior author Gong Cheng of Tsinghua University, Beijing, said in a written statement.

How do they do it? The viruses, he explained, promote the proliferation of acetophenone-producing skin bacteria. “As a result, some bacteria overreplicate and produce more acetophenone. Suddenly, these sick individuals smell as delicious to mosquitoes as a tray of freshly baked cookies to a group of five-year-old children,” the statement said.

And how do you stop a group of tiny, flying 5-year-olds? That’s right, with acne medication. Really? You knew that one but not the blood one before? The investigators fed isotretinoin to the infected mice, which led to reduced acetophenone release from skin bacteria and made the animals no more attractive to the mosquitoes than their uninfected counterparts.

The investigators are planning to take the next step – feeding isotretinoin to people with dengue and Zika – having gotten the official fictional taste-test approval of celebrity chef Gordon Ramsay, who said, “You’re going to feed this #$^% to sick people? ARE YOU &%*$@#& KIDDING ME?”

Okay, so maybe approval isn’t quite the right word.
 

Welcome to bladders of the rich and famous!

Don’t you hate it when you’re driving out to your multimillion-dollar second home in the Hamptons and traffic is so bad you absolutely have to find a place to “rest” along the way? But wouldn’t you know it, there just isn’t anywhere to stop! Geez, how do we live?

That’s where David Shusterman, MD, a urologist in New York City and a true American hero, comes in. He’s identified a market and positioned himself as the king of both bladder surgery and “bladder Botox” for the wealthy New Yorkers who regularly make long journeys from the city out to their second homes in the Hamptons. Traffic has increased dramatically on Long Island roads in recent years, and the journey can now taking upward of 4 hours. Some people just can’t make it that long without a bathroom break, and there are very few places to stop along the way.

National Park Service/Rawpixel

Dr. Shusterman understands the plight of the Hamptons vacationer, as he told Insider.com: “I can’t tell you how many arguments I personally get into – I’ve lost three friends because I’m the driver and refuse to stop for them.” A tragedy worthy of Shakespeare himself.

During the summer season, Dr. Shusterman performs about 10 prostate artery embolizations a week, an hour-long procedure that shrinks the prostate, which is great for 50- to 60-year-old men with enlarged prostates that cause more frequent bathroom trips. He also performs Botox injections into the bladder once or twice a week for women, which reduces the need to urinate for roughly 6 months. The perfect amount of time to get them through the summer season.

These procedures are sometimes covered by insurance but can cost as much as $20,000 if paid out of pocket. That’s a lot of money to us, but if you’re the sort of person who has a second home in the Hamptons, $20,000 is chump change, especially if it means you won’t have to go 2 entire minutes out of your way to use a gas-station bathroom. Then again, having seen a more than a few gas-station bathrooms in our time, maybe they have a point.
 

Ditch the apples. Go for the avocados

We’ve all heard about “an apple a day,” but instead of apples you might want to go with avocados.

tookapic/Pixabay

Avocados are generally thought to be a healthy fat. A study just published in the Journal of the American Heart Association proves that they actually don’t do anything for your waistline but will work wonders on your cholesterol level. The study involved 923 participants who were considered overweight/obese split into two groups: One was asked to consume an avocado a day, and the other continued their usual diets and were asked to consume fewer than two avocados a month.

At the end of the 6 months, the researchers found total cholesterol decreased by an additional 2.9 mg/dL and LDL cholesterol by 2.5 mg/dL in those who ate one avocado every day, compared with the usual-diet group. And even though avocados have a lot of calories, there was no clinical evidence that it impacted weight gain or any cardiometabolic risk factors, according to a statement from Penn State University.

Avocados, then, can be considered a guilt-free food. The findings from this study suggest it can give a substantial boost to your overall quality of diet, in turn lessening your risk of developing type 2 diabetes and some cancers, Kristina Peterson, PhD, assistant professor of nutritional sciences at Texas Tech University, said in the statement.

So get creative with your avocado recipes. You can only eat so much guacamole.
 

Your nose knows a good friend for you

You’ve probably noticed how dogs sniff other dogs and people before becoming friends. It would be pretty comical if people did the same thing, right? Just walked up to strangers and started sniffing them like dogs?

Well, apparently humans do go by smell when it comes to making friends, and they prefer people who smell like them. Maybe you’ve noticed that your friends look like you, share your values, and think the same way as you. You’re probably right, seeing as previous research has pointed to this.

For the current study, done to show how smell affects human behavior, researchers recruited people who befriended each other quickly, before knowing much about each other. They assumed that the relationships between these same-sex, nonromantic “click friends” relied more on physiological traits, including smell. After collecting samples from the click friends, researchers used an eNose to scan chemical signatures. In another experiment, human volunteers sniffed samples to determine if any were similar. Both experiments showed that click friends had more similar smells than pairs of random people.

Weizmann Institute of Science

A weekend, for most of us in solo practice, doesn’t really signify time off from work. It just means we’re not seeing patients at the office.

There’s always business stuff to do (like payroll and paying bills), legal cases to review, the never-ending forms for a million things, and all the other stuff there never seems to be enough time to do on weekdays.

So this weekend I started attacking the pile after dinner on Friday and found myself done by Saturday afternoon. Which is rare, usually I spend the better part of a weekend at my desk.

And then, unexpectedly faced with an empty desk, I found myself wondering what to do.

Boredom is one of the odder human conditions. Certainly, there are more ways to waste time now than there ever have been. TV, Netflix, phone games, TikTok, books, just to name a few.

But do we always have to be entertained? Many great scientists have said that world-changing ideas have come to them when they weren’t working, such as while showering or riding to work. Leo Szilard was crossing a London street in 1933 when he suddenly saw how a nuclear chain reaction would be self-sustaining once initiated. (Fortunately, he wasn’t hit by a car in the process.)

But I’m not Szilard. So I rationalized a reason not to exercise and sat on the couch with a book.

The remarkable human brain doesn’t shut down easily. With nothing else to do, most other mammals tend to doze off. But not us. It’s always on, trying to think of the next goal, the next move, the next whatever.

Having nothing to do sounds like a great idea, until you have nothing to do. It may be fine for a few days, but after a while you realize there’s only so long you can stare at the waves or mountains before your mind turns back to “what’s next.” Many patients tell me how retirement sounded good until they got there, then found themselves volunteering or taking new jobs just to keep busy.

This isn’t a bad thing. Being bored is probably constructive. Without realizing it we use it to form new ideas and start new plans.

Maybe this is why we’re here. The mind that keeps working is a powerful tool, driving us forward in all walks of life. Perhaps it’s this feature that pushed the development of intelligence further and led us to form civilizations.

Perhaps it’s the real reason we keep moving forward.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A weekend, for most of us in solo practice, doesn’t really signify time off from work. It just means we’re not seeing patients at the office.

There’s always business stuff to do (like payroll and paying bills), legal cases to review, the never-ending forms for a million things, and all the other stuff there never seems to be enough time to do on weekdays.

So this weekend I started attacking the pile after dinner on Friday and found myself done by Saturday afternoon. Which is rare, usually I spend the better part of a weekend at my desk.

And then, unexpectedly faced with an empty desk, I found myself wondering what to do.

Boredom is one of the odder human conditions. Certainly, there are more ways to waste time now than there ever have been. TV, Netflix, phone games, TikTok, books, just to name a few.

But do we always have to be entertained? Many great scientists have said that world-changing ideas have come to them when they weren’t working, such as while showering or riding to work. Leo Szilard was crossing a London street in 1933 when he suddenly saw how a nuclear chain reaction would be self-sustaining once initiated. (Fortunately, he wasn’t hit by a car in the process.)

But I’m not Szilard. So I rationalized a reason not to exercise and sat on the couch with a book.

The remarkable human brain doesn’t shut down easily. With nothing else to do, most other mammals tend to doze off. But not us. It’s always on, trying to think of the next goal, the next move, the next whatever.

Having nothing to do sounds like a great idea, until you have nothing to do. It may be fine for a few days, but after a while you realize there’s only so long you can stare at the waves or mountains before your mind turns back to “what’s next.” Many patients tell me how retirement sounded good until they got there, then found themselves volunteering or taking new jobs just to keep busy.

This isn’t a bad thing. Being bored is probably constructive. Without realizing it we use it to form new ideas and start new plans.

Maybe this is why we’re here. The mind that keeps working is a powerful tool, driving us forward in all walks of life. Perhaps it’s this feature that pushed the development of intelligence further and led us to form civilizations.

Perhaps it’s the real reason we keep moving forward.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

A weekend, for most of us in solo practice, doesn’t really signify time off from work. It just means we’re not seeing patients at the office.

There’s always business stuff to do (like payroll and paying bills), legal cases to review, the never-ending forms for a million things, and all the other stuff there never seems to be enough time to do on weekdays.

So this weekend I started attacking the pile after dinner on Friday and found myself done by Saturday afternoon. Which is rare, usually I spend the better part of a weekend at my desk.

And then, unexpectedly faced with an empty desk, I found myself wondering what to do.

Boredom is one of the odder human conditions. Certainly, there are more ways to waste time now than there ever have been. TV, Netflix, phone games, TikTok, books, just to name a few.

But do we always have to be entertained? Many great scientists have said that world-changing ideas have come to them when they weren’t working, such as while showering or riding to work. Leo Szilard was crossing a London street in 1933 when he suddenly saw how a nuclear chain reaction would be self-sustaining once initiated. (Fortunately, he wasn’t hit by a car in the process.)

But I’m not Szilard. So I rationalized a reason not to exercise and sat on the couch with a book.

The remarkable human brain doesn’t shut down easily. With nothing else to do, most other mammals tend to doze off. But not us. It’s always on, trying to think of the next goal, the next move, the next whatever.

Having nothing to do sounds like a great idea, until you have nothing to do. It may be fine for a few days, but after a while you realize there’s only so long you can stare at the waves or mountains before your mind turns back to “what’s next.” Many patients tell me how retirement sounded good until they got there, then found themselves volunteering or taking new jobs just to keep busy.

This isn’t a bad thing. Being bored is probably constructive. Without realizing it we use it to form new ideas and start new plans.

Maybe this is why we’re here. The mind that keeps working is a powerful tool, driving us forward in all walks of life. Perhaps it’s this feature that pushed the development of intelligence further and led us to form civilizations.

Perhaps it’s the real reason we keep moving forward.

Dr. Block has a solo neurology practice in Scottsdale, Ariz.

Sunil Khushalani and Antonio DePaolo,

“Transforming Mental Healthcare: Applying Performance Improvement Methods to Mental Healthcare”

(London: Routledge, Taylor & Francis, 2022)

Since the publication of our book, “Lean Behavioral Health: The Kings County Hospital Story” (Oxford, England: Oxford University Press, 2014) almost a decade ago, “Transforming Mental Healthcare” is the first major book published about the use of a system for quality improvement across the health care continuum. That it has taken this long is probably surprising to those of us who have spent careers on trying to improve what is universally described as a system that is “broken” and in need of a major overhaul.

Routledge, Taylor &amp; Francis Group

Every news cycle that reports mass violence typically spends a good bit of time talking about the failures of the mental health care system. One important lesson I learned when taking over the beleaguered Kings County (N.Y.) psychiatry service in 2009 (a department that has made extraordinary improvements over the years and is now exclaimed by the U.S. Department of Justice as “a model program”), is that the employees on the front line are often erroneously blamed for such failures.

The failure is systemic and usually starts at the top of the table of organization, not at the bottom. Dr. Khushalani and Dr. DePaolo have produced an excellent volume that should be purchased by every mental health care CEO and given “with thanks” to the local leaders overseeing the direct care of some of our nation’s most vulnerable patient populations.

The first part of “Transforming Mental Healthcare” provides an excellent overview of the current state of our mental health care system and its too numerous to name problems. This section could be a primer for all our legislators so their eyes can be opened to the failures on the ground that require their help in correcting. Many of the “failures” of our mental health care are societal failures – lack of affordable housing, access to care, reimbursement for care, gun access, etc. – and cannot be “fixed” by providers of care. Such problems are societal problems that call for societal and governmental solutions, and not only at the local level but from coast to coast.

The remainder of this easy to read and follow text provides many rich resources for the deliverers of mental health care. Focusing on quality improvement at the systemic level and providing a basic and fundamental teaching about the lean improvement methodology, readers learn about each of the foundational tools (e.g., plan-do-act, standard work, and A3 thinking).

Dr. Joseph Merlino

The closing section focuses on leadership and culture – often overlooked to the detriment of any organization that doesn’t pay close attention to supporting both. Culture is cultivated and nourished by the organization’s leaders. Culture empowers staff to become problem solvers and agents of improvement. Empowered staff support and enrich their culture. Together a workplace that brings out the best of all its people is created, and burnout is held at bay.

“Transforming Mental Healthcare: Applying Performance Improvement Methods to Mental Healthcare” is a welcome and essential addition to the current morass, which is our mental health care delivery system, an oasis in the desert from which perhaps the lotus flower can emerge.

Dr. Merlino is emeritus professor of psychiatry, SUNY Downstate College of Medicine, Rhinebeck, N.Y., and formerly director of psychiatry at Kings County Hospital Center, Brooklyn, NY. He is the coauthor of “Lean Behavioral Health: The Kings County Hospital Story.” .

Sunil Khushalani and Antonio DePaolo,

“Transforming Mental Healthcare: Applying Performance Improvement Methods to Mental Healthcare”

(London: Routledge, Taylor & Francis, 2022)

Since the publication of our book, “Lean Behavioral Health: The Kings County Hospital Story” (Oxford, England: Oxford University Press, 2014) almost a decade ago, “Transforming Mental Healthcare” is the first major book published about the use of a system for quality improvement across the health care continuum. That it has taken this long is probably surprising to those of us who have spent careers on trying to improve what is universally described as a system that is “broken” and in need of a major overhaul.

Routledge, Taylor &amp; Francis Group

Every news cycle that reports mass violence typically spends a good bit of time talking about the failures of the mental health care system. One important lesson I learned when taking over the beleaguered Kings County (N.Y.) psychiatry service in 2009 (a department that has made extraordinary improvements over the years and is now exclaimed by the U.S. Department of Justice as “a model program”), is that the employees on the front line are often erroneously blamed for such failures.

The failure is systemic and usually starts at the top of the table of organization, not at the bottom. Dr. Khushalani and Dr. DePaolo have produced an excellent volume that should be purchased by every mental health care CEO and given “with thanks” to the local leaders overseeing the direct care of some of our nation’s most vulnerable patient populations.

The first part of “Transforming Mental Healthcare” provides an excellent overview of the current state of our mental health care system and its too numerous to name problems. This section could be a primer for all our legislators so their eyes can be opened to the failures on the ground that require their help in correcting. Many of the “failures” of our mental health care are societal failures – lack of affordable housing, access to care, reimbursement for care, gun access, etc. – and cannot be “fixed” by providers of care. Such problems are societal problems that call for societal and governmental solutions, and not only at the local level but from coast to coast.

The remainder of this easy to read and follow text provides many rich resources for the deliverers of mental health care. Focusing on quality improvement at the systemic level and providing a basic and fundamental teaching about the lean improvement methodology, readers learn about each of the foundational tools (e.g., plan-do-act, standard work, and A3 thinking).

Dr. Joseph Merlino

The closing section focuses on leadership and culture – often overlooked to the detriment of any organization that doesn’t pay close attention to supporting both. Culture is cultivated and nourished by the organization’s leaders. Culture empowers staff to become problem solvers and agents of improvement. Empowered staff support and enrich their culture. Together a workplace that brings out the best of all its people is created, and burnout is held at bay.

“Transforming Mental Healthcare: Applying Performance Improvement Methods to Mental Healthcare” is a welcome and essential addition to the current morass, which is our mental health care delivery system, an oasis in the desert from which perhaps the lotus flower can emerge.

Dr. Merlino is emeritus professor of psychiatry, SUNY Downstate College of Medicine, Rhinebeck, N.Y., and formerly director of psychiatry at Kings County Hospital Center, Brooklyn, NY. He is the coauthor of “Lean Behavioral Health: The Kings County Hospital Story.” .

Sunil Khushalani and Antonio DePaolo,

“Transforming Mental Healthcare: Applying Performance Improvement Methods to Mental Healthcare”

(London: Routledge, Taylor & Francis, 2022)

Since the publication of our book, “Lean Behavioral Health: The Kings County Hospital Story” (Oxford, England: Oxford University Press, 2014) almost a decade ago, “Transforming Mental Healthcare” is the first major book published about the use of a system for quality improvement across the health care continuum. That it has taken this long is probably surprising to those of us who have spent careers on trying to improve what is universally described as a system that is “broken” and in need of a major overhaul.

Routledge, Taylor &amp; Francis Group

Every news cycle that reports mass violence typically spends a good bit of time talking about the failures of the mental health care system. One important lesson I learned when taking over the beleaguered Kings County (N.Y.) psychiatry service in 2009 (a department that has made extraordinary improvements over the years and is now exclaimed by the U.S. Department of Justice as “a model program”), is that the employees on the front line are often erroneously blamed for such failures.

The failure is systemic and usually starts at the top of the table of organization, not at the bottom. Dr. Khushalani and Dr. DePaolo have produced an excellent volume that should be purchased by every mental health care CEO and given “with thanks” to the local leaders overseeing the direct care of some of our nation’s most vulnerable patient populations.

The first part of “Transforming Mental Healthcare” provides an excellent overview of the current state of our mental health care system and its too numerous to name problems. This section could be a primer for all our legislators so their eyes can be opened to the failures on the ground that require their help in correcting. Many of the “failures” of our mental health care are societal failures – lack of affordable housing, access to care, reimbursement for care, gun access, etc. – and cannot be “fixed” by providers of care. Such problems are societal problems that call for societal and governmental solutions, and not only at the local level but from coast to coast.

The remainder of this easy to read and follow text provides many rich resources for the deliverers of mental health care. Focusing on quality improvement at the systemic level and providing a basic and fundamental teaching about the lean improvement methodology, readers learn about each of the foundational tools (e.g., plan-do-act, standard work, and A3 thinking).

Dr. Joseph Merlino

The closing section focuses on leadership and culture – often overlooked to the detriment of any organization that doesn’t pay close attention to supporting both. Culture is cultivated and nourished by the organization’s leaders. Culture empowers staff to become problem solvers and agents of improvement. Empowered staff support and enrich their culture. Together a workplace that brings out the best of all its people is created, and burnout is held at bay.

“Transforming Mental Healthcare: Applying Performance Improvement Methods to Mental Healthcare” is a welcome and essential addition to the current morass, which is our mental health care delivery system, an oasis in the desert from which perhaps the lotus flower can emerge.

Dr. Merlino is emeritus professor of psychiatry, SUNY Downstate College of Medicine, Rhinebeck, N.Y., and formerly director of psychiatry at Kings County Hospital Center, Brooklyn, NY. He is the coauthor of “Lean Behavioral Health: The Kings County Hospital Story.” .