Mounting evidence suggests that a higher density of Demodex mites on the skin may play a role in the development of papules and pustules associated with rosacea, a narrative review proposes.

According to the author, Fabienne Forton, MD, PhD, a dermatologist based in Brussels, recent studies suggest that Demodex induces two opposite actions on host immunity: A defensive immune response aimed at eliminating the mite and an immunosuppressive action aimed at favoring its own proliferation. “Moreover, the initial defensive immune response is likely diverted towards benefit for the mite, via T-cell exhaustion induced by the immunosuppressive properties of vascular endothelial growth factor (VEGF), which may also explain the favorable influence that the altered vascular background of rosacea seems to exert on Demodex proliferation,” she wrote in the review, which was published in JEADV, the Journal of the European Academy of Dermatology and Venereology.

Courtesy National Rosacea Society

She presented several arguments for and against a causal role of Demodex in rosacea. Three on the “for” side are:

High Demodex densities (Dds) are observed in almost all cases of rosacea with papulopustules (PPR). Dr. Forton pointed out that Demodex proliferation presents in as many as 98.6% of cases of PPR when two consecutive standardized skin surface biopsies (SSSBs) are performed (Acta Derm Venereol. 2017;97:242-8). “Dds in patients with PPR are as high as those in patients with demodicosis, much higher than in healthy skin and other facial dermatoses (except when these are associated with demodicosis [as is often the case with seborrheic dermatitis and acne vulgaris]),” she wrote.

The Demodex mite has the elements necessary to stimulate the host’s innate and adaptative immune system. Dr. Forton characterized Demodex as “the only microorganism found in abundance in almost all subjects with PPR, which can, in addition, alter the skin barrier. To feed and move around, Demodex mites attack the epidermal wall of the pilosebaceous follicles mechanically (via their stylets, mouth palps and motor palps) and chemically (through enzymes secreted from salivary glands for pre-oral digestion).”

The Demodex mite stimulates the immune system (which ultimately results in phymatous changes). A healthy immune system, including T helper 17 cells, seems necessary to adequately control mite proliferation. Dr. Forton noted that researchers have observed a perivascular and perifollicular infiltrate in people with rosacea, “which invades the epidermis and is often associated with the presence of Demodex. The lympho-histiocytic perifollicular infiltrate is correlated with the presence and the numbers of mites inside the follicles, and giant cell granulomas can be seen around intradermal Demodex mites, which attempt to phagocytize the mites.”

The three arguments that she presented against a causal role of Demodex in rosacea are the following:

No relationship with the mite was observed in two early histological studies. Rosacea biopsies conducted in these two analyses, published in 1969 and 1988, showed only mild infiltrate, with few parasites and no inflammation around the infested follicles.

However, she countered, “these data are now obsolete, because it has since been clearly demonstrated that the perifollicular infiltrate is a characteristic of rosacea, that this infiltrate is statistically related to the presence and the number of Demodex mites, and that high Dds are observed in almost all subjects with PPR.”

Demodex is not always associated with inflammatory symptoms. This argument holds that Demodex is present in all individuals and can be observed in very high densities without causing significant symptoms. Studies that support this viewpoint include the following: J Eur Acad Dermatol Venereol. 2001;15:441–4 and J Zhejiang Univ Sci B. 2011;12:998-1007.

However, Dr. Forton pointed out that the normal, low-density presence of Demodex in the skin “does not contradict a pathogenic effect when it proliferates excessively or penetrates into the dermis. The absence of intense inflammatory symptoms when the Dd is very high does not negate its potential pathogenicity.”

Demodex proliferation could be a consequence rather than a cause. Dr. Forton cited a study, suggesting that inflammation could be responsible for alteration of the skin barrier, “which, secondarily, would favor proliferation of the parasites, as with skin affected by atopic dermatitis that becomes superinfected by Staphylococcus aureus”. On the other hand, she argued, “unlike S. aureus, Demodex does not require alteration of the skin barrier to implant or proliferate. It also does not require an inflammatory background.” She added that if mite proliferation was a consequence of clinical lesions, “the Demodex mite should logically proliferate in other inflammatory facial skin conditions, which is not the case.”

A Sept. 14 National Rosacea Society (NRS) press release featured the paper by Dr. Forton, titled, “Which Comes First, The Rosacea Blemish or The Mite?” In the release, Richard Gallo, MD, PhD, who chaired the NRS Expert Committee that updated the standard classification of rosacea in 2018, said that “growing knowledge of rosacea’s pathophysiology has established that a consistent multivariate disease process underlies its potential manifestations, and the clinical significance of each of these elements is increasing as more is understood.”

While the potential role of Demodex in rosacea has been controversial in the past, “these new insights suggest where it may play a role as a meaningful cofactor in the development of the disorder,” added Dr. Gallo, chair of the department of dermatology at the University of California, San Diego.

Dr. Forton reported having no financial disclosures.

Mounting evidence suggests that a higher density of Demodex mites on the skin may play a role in the development of papules and pustules associated with rosacea, a narrative review proposes.

According to the author, Fabienne Forton, MD, PhD, a dermatologist based in Brussels, recent studies suggest that Demodex induces two opposite actions on host immunity: A defensive immune response aimed at eliminating the mite and an immunosuppressive action aimed at favoring its own proliferation. “Moreover, the initial defensive immune response is likely diverted towards benefit for the mite, via T-cell exhaustion induced by the immunosuppressive properties of vascular endothelial growth factor (VEGF), which may also explain the favorable influence that the altered vascular background of rosacea seems to exert on Demodex proliferation,” she wrote in the review, which was published in JEADV, the Journal of the European Academy of Dermatology and Venereology.

Courtesy National Rosacea Society

She presented several arguments for and against a causal role of Demodex in rosacea. Three on the “for” side are:

High Demodex densities (Dds) are observed in almost all cases of rosacea with papulopustules (PPR). Dr. Forton pointed out that Demodex proliferation presents in as many as 98.6% of cases of PPR when two consecutive standardized skin surface biopsies (SSSBs) are performed (Acta Derm Venereol. 2017;97:242-8). “Dds in patients with PPR are as high as those in patients with demodicosis, much higher than in healthy skin and other facial dermatoses (except when these are associated with demodicosis [as is often the case with seborrheic dermatitis and acne vulgaris]),” she wrote.

The Demodex mite has the elements necessary to stimulate the host’s innate and adaptative immune system. Dr. Forton characterized Demodex as “the only microorganism found in abundance in almost all subjects with PPR, which can, in addition, alter the skin barrier. To feed and move around, Demodex mites attack the epidermal wall of the pilosebaceous follicles mechanically (via their stylets, mouth palps and motor palps) and chemically (through enzymes secreted from salivary glands for pre-oral digestion).”

The Demodex mite stimulates the immune system (which ultimately results in phymatous changes). A healthy immune system, including T helper 17 cells, seems necessary to adequately control mite proliferation. Dr. Forton noted that researchers have observed a perivascular and perifollicular infiltrate in people with rosacea, “which invades the epidermis and is often associated with the presence of Demodex. The lympho-histiocytic perifollicular infiltrate is correlated with the presence and the numbers of mites inside the follicles, and giant cell granulomas can be seen around intradermal Demodex mites, which attempt to phagocytize the mites.”

The three arguments that she presented against a causal role of Demodex in rosacea are the following:

No relationship with the mite was observed in two early histological studies. Rosacea biopsies conducted in these two analyses, published in 1969 and 1988, showed only mild infiltrate, with few parasites and no inflammation around the infested follicles.

However, she countered, “these data are now obsolete, because it has since been clearly demonstrated that the perifollicular infiltrate is a characteristic of rosacea, that this infiltrate is statistically related to the presence and the number of Demodex mites, and that high Dds are observed in almost all subjects with PPR.”

Demodex is not always associated with inflammatory symptoms. This argument holds that Demodex is present in all individuals and can be observed in very high densities without causing significant symptoms. Studies that support this viewpoint include the following: J Eur Acad Dermatol Venereol. 2001;15:441–4 and J Zhejiang Univ Sci B. 2011;12:998-1007.

However, Dr. Forton pointed out that the normal, low-density presence of Demodex in the skin “does not contradict a pathogenic effect when it proliferates excessively or penetrates into the dermis. The absence of intense inflammatory symptoms when the Dd is very high does not negate its potential pathogenicity.”

Demodex proliferation could be a consequence rather than a cause. Dr. Forton cited a study, suggesting that inflammation could be responsible for alteration of the skin barrier, “which, secondarily, would favor proliferation of the parasites, as with skin affected by atopic dermatitis that becomes superinfected by Staphylococcus aureus”. On the other hand, she argued, “unlike S. aureus, Demodex does not require alteration of the skin barrier to implant or proliferate. It also does not require an inflammatory background.” She added that if mite proliferation was a consequence of clinical lesions, “the Demodex mite should logically proliferate in other inflammatory facial skin conditions, which is not the case.”

A Sept. 14 National Rosacea Society (NRS) press release featured the paper by Dr. Forton, titled, “Which Comes First, The Rosacea Blemish or The Mite?” In the release, Richard Gallo, MD, PhD, who chaired the NRS Expert Committee that updated the standard classification of rosacea in 2018, said that “growing knowledge of rosacea’s pathophysiology has established that a consistent multivariate disease process underlies its potential manifestations, and the clinical significance of each of these elements is increasing as more is understood.”

While the potential role of Demodex in rosacea has been controversial in the past, “these new insights suggest where it may play a role as a meaningful cofactor in the development of the disorder,” added Dr. Gallo, chair of the department of dermatology at the University of California, San Diego.

Dr. Forton reported having no financial disclosures.

Mounting evidence suggests that a higher density of Demodex mites on the skin may play a role in the development of papules and pustules associated with rosacea, a narrative review proposes.

According to the author, Fabienne Forton, MD, PhD, a dermatologist based in Brussels, recent studies suggest that Demodex induces two opposite actions on host immunity: A defensive immune response aimed at eliminating the mite and an immunosuppressive action aimed at favoring its own proliferation. “Moreover, the initial defensive immune response is likely diverted towards benefit for the mite, via T-cell exhaustion induced by the immunosuppressive properties of vascular endothelial growth factor (VEGF), which may also explain the favorable influence that the altered vascular background of rosacea seems to exert on Demodex proliferation,” she wrote in the review, which was published in JEADV, the Journal of the European Academy of Dermatology and Venereology.

Courtesy National Rosacea Society

She presented several arguments for and against a causal role of Demodex in rosacea. Three on the “for” side are:

High Demodex densities (Dds) are observed in almost all cases of rosacea with papulopustules (PPR). Dr. Forton pointed out that Demodex proliferation presents in as many as 98.6% of cases of PPR when two consecutive standardized skin surface biopsies (SSSBs) are performed (Acta Derm Venereol. 2017;97:242-8). “Dds in patients with PPR are as high as those in patients with demodicosis, much higher than in healthy skin and other facial dermatoses (except when these are associated with demodicosis [as is often the case with seborrheic dermatitis and acne vulgaris]),” she wrote.

The Demodex mite has the elements necessary to stimulate the host’s innate and adaptative immune system. Dr. Forton characterized Demodex as “the only microorganism found in abundance in almost all subjects with PPR, which can, in addition, alter the skin barrier. To feed and move around, Demodex mites attack the epidermal wall of the pilosebaceous follicles mechanically (via their stylets, mouth palps and motor palps) and chemically (through enzymes secreted from salivary glands for pre-oral digestion).”

The Demodex mite stimulates the immune system (which ultimately results in phymatous changes). A healthy immune system, including T helper 17 cells, seems necessary to adequately control mite proliferation. Dr. Forton noted that researchers have observed a perivascular and perifollicular infiltrate in people with rosacea, “which invades the epidermis and is often associated with the presence of Demodex. The lympho-histiocytic perifollicular infiltrate is correlated with the presence and the numbers of mites inside the follicles, and giant cell granulomas can be seen around intradermal Demodex mites, which attempt to phagocytize the mites.”

The three arguments that she presented against a causal role of Demodex in rosacea are the following:

No relationship with the mite was observed in two early histological studies. Rosacea biopsies conducted in these two analyses, published in 1969 and 1988, showed only mild infiltrate, with few parasites and no inflammation around the infested follicles.

However, she countered, “these data are now obsolete, because it has since been clearly demonstrated that the perifollicular infiltrate is a characteristic of rosacea, that this infiltrate is statistically related to the presence and the number of Demodex mites, and that high Dds are observed in almost all subjects with PPR.”

Demodex is not always associated with inflammatory symptoms. This argument holds that Demodex is present in all individuals and can be observed in very high densities without causing significant symptoms. Studies that support this viewpoint include the following: J Eur Acad Dermatol Venereol. 2001;15:441–4 and J Zhejiang Univ Sci B. 2011;12:998-1007.

However, Dr. Forton pointed out that the normal, low-density presence of Demodex in the skin “does not contradict a pathogenic effect when it proliferates excessively or penetrates into the dermis. The absence of intense inflammatory symptoms when the Dd is very high does not negate its potential pathogenicity.”

Demodex proliferation could be a consequence rather than a cause. Dr. Forton cited a study, suggesting that inflammation could be responsible for alteration of the skin barrier, “which, secondarily, would favor proliferation of the parasites, as with skin affected by atopic dermatitis that becomes superinfected by Staphylococcus aureus”. On the other hand, she argued, “unlike S. aureus, Demodex does not require alteration of the skin barrier to implant or proliferate. It also does not require an inflammatory background.” She added that if mite proliferation was a consequence of clinical lesions, “the Demodex mite should logically proliferate in other inflammatory facial skin conditions, which is not the case.”

A Sept. 14 National Rosacea Society (NRS) press release featured the paper by Dr. Forton, titled, “Which Comes First, The Rosacea Blemish or The Mite?” In the release, Richard Gallo, MD, PhD, who chaired the NRS Expert Committee that updated the standard classification of rosacea in 2018, said that “growing knowledge of rosacea’s pathophysiology has established that a consistent multivariate disease process underlies its potential manifestations, and the clinical significance of each of these elements is increasing as more is understood.”

While the potential role of Demodex in rosacea has been controversial in the past, “these new insights suggest where it may play a role as a meaningful cofactor in the development of the disorder,” added Dr. Gallo, chair of the department of dermatology at the University of California, San Diego.

Dr. Forton reported having no financial disclosures.

We now know that the effects of COVID-19 don’t always end when the infection seems over. Long COVID—the postacute sequelae—can encompass a wide range of extrapulmonary organ dysfunctions. Most studies on COVID-19 have had follow-ups of 6 months or less with a narrow selection of neurologic outcomes, say Evan Xu, Yan Xie, PhD, and Ziyad Al-Aly, MD of the US Department of Veterans Affairs (VA) St. Louis Health Care System in Missouri. The 12-month study of 11,652,484 people published in Nature Medicine sounds an alert: Get ready to care for more patients with long-term, even chronic, neurologic disorders from migraine to stroke.

The researchers “leveraged the breadth and depth” of the VA’s national health care databases to build 3 groups: 154,068 people who survived the first 30 days of COVID-19; 5,638,795 VA users with no evidence of COVID-19 infection; and 5,859,621 VA users during 2017 (ie, prepandemic). Altogether, the groups corresponded to 14,064,985 person-years of follow-up.

The findings, which the researchers termed robust, revealed substantial risks and burdens beyond the first 30 days of COVID-19 infection, including “an array of neurologic disorders spanning several disease categories.”

Patients were at greater risk for stroke (both ischemic and hemorrhagic), cognition and memory disorders, peripheral nervous system disorders, episodic disorders like migraine and seizures, extrapyramidal and movement disorders, mental health disorders, musculoskeletal disorders, sensory disorders, Guillain-Barré syndrome, and encephalitis or encephalopathy.

The researchers estimated the hazard ratio of any neurological sequelae as 1.42. The risks were elevated even in people who did not require hospitalization during acute COVID-19 and increased according to the care setting of the acute phase of the disease from nonhospitalized to hospitalized and admitted to intensive care.

“Given the colossal scale of the pandemic,” the researchers say, governments and health systems should consider these findings when devising policy for continued management and developing plans for a postpandemic world. Some of the disorders they report on, they note, “are serious chronic conditions that will impact some people for a lifetime.” They point to 2 key findings: first, regardless of age, people with COVID-19 had a higher risk of all the neurologic outcomes examined, and second, the analyses suggest that the effects on risk were stronger in younger adults.

“The effects of these disorders on younger lives are profound and cannot be overstated,” the researchers say. Equally troubling, they note, is the stronger effect of COVID-19 on mental health, musculoskeletal, and episodic disorders in older adults, “highlighting their vulnerability” to these disorders following COVID-19 infection.

“It is imperative,” the researchers conclude, “that we recognize the enormous challenges posed by long COVID and all its downstream long-term consequences” and design capacity planning and clinical care pathways to address the needs of people who make it past the acute phase of COVID-19

We now know that the effects of COVID-19 don’t always end when the infection seems over. Long COVID—the postacute sequelae—can encompass a wide range of extrapulmonary organ dysfunctions. Most studies on COVID-19 have had follow-ups of 6 months or less with a narrow selection of neurologic outcomes, say Evan Xu, Yan Xie, PhD, and Ziyad Al-Aly, MD of the US Department of Veterans Affairs (VA) St. Louis Health Care System in Missouri. The 12-month study of 11,652,484 people published in Nature Medicine sounds an alert: Get ready to care for more patients with long-term, even chronic, neurologic disorders from migraine to stroke.

The researchers “leveraged the breadth and depth” of the VA’s national health care databases to build 3 groups: 154,068 people who survived the first 30 days of COVID-19; 5,638,795 VA users with no evidence of COVID-19 infection; and 5,859,621 VA users during 2017 (ie, prepandemic). Altogether, the groups corresponded to 14,064,985 person-years of follow-up.

The findings, which the researchers termed robust, revealed substantial risks and burdens beyond the first 30 days of COVID-19 infection, including “an array of neurologic disorders spanning several disease categories.”

Patients were at greater risk for stroke (both ischemic and hemorrhagic), cognition and memory disorders, peripheral nervous system disorders, episodic disorders like migraine and seizures, extrapyramidal and movement disorders, mental health disorders, musculoskeletal disorders, sensory disorders, Guillain-Barré syndrome, and encephalitis or encephalopathy.

The researchers estimated the hazard ratio of any neurological sequelae as 1.42. The risks were elevated even in people who did not require hospitalization during acute COVID-19 and increased according to the care setting of the acute phase of the disease from nonhospitalized to hospitalized and admitted to intensive care.

“Given the colossal scale of the pandemic,” the researchers say, governments and health systems should consider these findings when devising policy for continued management and developing plans for a postpandemic world. Some of the disorders they report on, they note, “are serious chronic conditions that will impact some people for a lifetime.” They point to 2 key findings: first, regardless of age, people with COVID-19 had a higher risk of all the neurologic outcomes examined, and second, the analyses suggest that the effects on risk were stronger in younger adults.

“The effects of these disorders on younger lives are profound and cannot be overstated,” the researchers say. Equally troubling, they note, is the stronger effect of COVID-19 on mental health, musculoskeletal, and episodic disorders in older adults, “highlighting their vulnerability” to these disorders following COVID-19 infection.

“It is imperative,” the researchers conclude, “that we recognize the enormous challenges posed by long COVID and all its downstream long-term consequences” and design capacity planning and clinical care pathways to address the needs of people who make it past the acute phase of COVID-19

We now know that the effects of COVID-19 don’t always end when the infection seems over. Long COVID—the postacute sequelae—can encompass a wide range of extrapulmonary organ dysfunctions. Most studies on COVID-19 have had follow-ups of 6 months or less with a narrow selection of neurologic outcomes, say Evan Xu, Yan Xie, PhD, and Ziyad Al-Aly, MD of the US Department of Veterans Affairs (VA) St. Louis Health Care System in Missouri. The 12-month study of 11,652,484 people published in Nature Medicine sounds an alert: Get ready to care for more patients with long-term, even chronic, neurologic disorders from migraine to stroke.

The researchers “leveraged the breadth and depth” of the VA’s national health care databases to build 3 groups: 154,068 people who survived the first 30 days of COVID-19; 5,638,795 VA users with no evidence of COVID-19 infection; and 5,859,621 VA users during 2017 (ie, prepandemic). Altogether, the groups corresponded to 14,064,985 person-years of follow-up.

The findings, which the researchers termed robust, revealed substantial risks and burdens beyond the first 30 days of COVID-19 infection, including “an array of neurologic disorders spanning several disease categories.”

Patients were at greater risk for stroke (both ischemic and hemorrhagic), cognition and memory disorders, peripheral nervous system disorders, episodic disorders like migraine and seizures, extrapyramidal and movement disorders, mental health disorders, musculoskeletal disorders, sensory disorders, Guillain-Barré syndrome, and encephalitis or encephalopathy.

The researchers estimated the hazard ratio of any neurological sequelae as 1.42. The risks were elevated even in people who did not require hospitalization during acute COVID-19 and increased according to the care setting of the acute phase of the disease from nonhospitalized to hospitalized and admitted to intensive care.

“Given the colossal scale of the pandemic,” the researchers say, governments and health systems should consider these findings when devising policy for continued management and developing plans for a postpandemic world. Some of the disorders they report on, they note, “are serious chronic conditions that will impact some people for a lifetime.” They point to 2 key findings: first, regardless of age, people with COVID-19 had a higher risk of all the neurologic outcomes examined, and second, the analyses suggest that the effects on risk were stronger in younger adults.

“The effects of these disorders on younger lives are profound and cannot be overstated,” the researchers say. Equally troubling, they note, is the stronger effect of COVID-19 on mental health, musculoskeletal, and episodic disorders in older adults, “highlighting their vulnerability” to these disorders following COVID-19 infection.

“It is imperative,” the researchers conclude, “that we recognize the enormous challenges posed by long COVID and all its downstream long-term consequences” and design capacity planning and clinical care pathways to address the needs of people who make it past the acute phase of COVID-19

Shortening the duration of dual-antiplatelet therapy (DAPT) and continuing with a P2Y12 inhibitor alone after percutaneous coronary intervention (PCI) was associated with a similar rate of ischemic events but with less bleeding than prolonged DAPT after 3 years of follow-up in the SMART-CHOICE trial.

“The current results of extended follow-up from the SMART-CHOICE trial support evidence of an aspirin dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” the investigators, with lead author Ki Hong Choi, MD, division of cardiology, department of medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, conclude.

The 3-year results from the study were published online in JAMA Cardiology.

The authors explain that although dual therapy with aspirin and a P2Y12 inhibitor after PCI with a drug-eluting stent (DES) is crucial to reduce the risk of ischemic events, it raises concerns about increased risk of bleeding, and the antiplatelet strategy after PCI is currently shifting to reduce the duration of DAPT.

Several recent randomized studies have consistently shown that a short duration of DAPT (1-3 months) followed by P2Y12 inhibitor monotherapy had ischemia protection effects comparable with that of DAPT of longer duration, and it was associated with a significantly reduced risk of bleeding events in patients who underwent PCI, they note. However, these studies have so far reported only 1-year outcomes, and long-term results are not yet available.

The SMART-CHOICE trial compared two antiplatelet strategies – 3 months of DAPT followed by long-term P2Y12 inhibitor monotherapy (mainly with clopidogrel) or prolonged DAPT for 12 months or longer – in 2,993 patients who had undergone PCI with a drug-eluting stent. Results at 12 months showed a similar rate of ischemic events with both strategies but a lower rate of bleeding in the group that received shortened DAPT.

The SMART-CHOICE investigators now report the 3-year results showing similar outcomes.

At 3 years, the primary endpoint, a composite of all-cause death, myocardial infarction, or stroke, had occurred in 6.3% of the shortened DAPT group and 6.1% in the prolonged DAPT group, giving a hazard ratio of 1.06 (95% confidence interval, 0.79-1.44).

But in the shortened DAPT group, the risk of bleeding was reduced. Bleeding Academic Research Consortium (BARC) types 2-5 bleeding had occurred in 3.2% of the shortened DAPT group and in 8.2% of the prolonged DAPT group (hazard ratio, 0.39; 95% CI, 0.28-0.55). Major bleeding, BARC types 3-5, occurred in 1.2% of the shortened DAPT group and in 2.4% of the prolonged DAPT group (HR, 0.56; 95% CI 0.31-0.99).

The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.

The researchers point out that this is the first trial to report on the long-term safety and efficacy of P2Y12-inhibitor monotherapy as long-term maintenance therapy for stable patients treated with PCI.

“Especially considering that extended DAPT significantly reduced the risks of ischemic events compared with aspirin monotherapy in a couple of trials, comparison between P2Y12-inhibitor monotherapy and prolonged DAPT for recurrent ischemic events over a longer period beyond 1 year is of great importance,” they say.

They cite two other trials – HOST-EXAM and GLOBAL LEADERS – which have shown P2Y12-inhibitor monotherapy to be superior to aspirin monotherapy in preventing both ischemic and bleeding events during the long-term maintenance period after PCI.

“Combining the results of the current study, HOST-EXAM trial, and landmark analysis of the GLOBAL LEADERS trial, long-term P2Y12-inhibitor monotherapy after a minimum period of DAPT might be the most reliable option from among aspirin monotherapy, P2Y12 monotherapy, and extended DAPT for maintenance therapy after stabilizing patients who have undergone PCI with a current-generation DES,” they conclude.

They note that the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines for coronary artery revascularization newly recommends a shorter course of DAPT followed by P2Y12 monotherapy as a class IIa indication. The recommendation is based on results of five large, randomized clinical trials, including SMART-CHOICE, TWILIGHT, STOPDAPT-2, TICO, and GLOBAL LEADERS.

“The current results of extended follow-up from the SMART-CHOICE trial support evidence of aspirin-dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” they say.

They point out that two further trials, A-CLOSE in high-risk patients and SMART-CHOICE III, will be helpful to confirm these findings.
 

P2Y12-inhibitor monotherapy ‘attractive concept’

In an accompanying editor’s note, Ajay Kirtane, MD, Columbia University Irving Medical Center/New York–Presbyterian Hospital, New York, and Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai and the Cardiovascular Research Foundation, New York, note that current guidelines recommend 3-6 months of DAPT following PCI with current-generation drug-eluting stents in stable patients and 6-12 months or longer for those with acute coronary syndromes. For patients at higher risk of bleeding, even shorter DAPT durations can be considered on a case-by-case basis.

Historically, the component of DAPT subject to discontinuation decisions was the P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor), but more recent trials have further explored whether discontinuation of the aspirin component of DAPT can mitigate bleeding while preserving anti-ischemic efficacy.

The editorialists explain that the concept of P2Y1-inhibitor monotherapy is attractive because it may optimize antiplatelet effects through a single agent that can avoid the gastrointestinal toxicity of aspirin as well as the increased bleeding that comes with combing multiple antithrombotic agents.

They suggest that the long-term results from the SMART-CHOICE trial “should lead clinicians to consider a strategy of monotherapy after a short period of DAPT as a viable one to mitigate bleeding risk,” although they also point out that SMART-CHOICE was underpowered to rigorously assess ischemic differences, so caution is warranted.

“For patients at greatest risk for recurrent ischemic events, the role of continued DAPT is always an option, but these data (and other consistent trials) give clinicians more options to pursue individualized treatment decisions,” they write.

“To some, the continually moving field of post-PCI antiplatelet therapy has provided too many choices, which can at times be dizzying. To us, every patient is different, and thoughtful evidence-based consideration is increasingly possible for many of our treatment decisions,” they conclude.

The SMART-CHOICE study was supported by unrestricted grants from the Korean Society of Interventional Cardiology, Abbott Vascular, Biotronik, and Boston Scientific.

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

Shortening the duration of dual-antiplatelet therapy (DAPT) and continuing with a P2Y12 inhibitor alone after percutaneous coronary intervention (PCI) was associated with a similar rate of ischemic events but with less bleeding than prolonged DAPT after 3 years of follow-up in the SMART-CHOICE trial.

“The current results of extended follow-up from the SMART-CHOICE trial support evidence of an aspirin dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” the investigators, with lead author Ki Hong Choi, MD, division of cardiology, department of medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, conclude.

The 3-year results from the study were published online in JAMA Cardiology.

The authors explain that although dual therapy with aspirin and a P2Y12 inhibitor after PCI with a drug-eluting stent (DES) is crucial to reduce the risk of ischemic events, it raises concerns about increased risk of bleeding, and the antiplatelet strategy after PCI is currently shifting to reduce the duration of DAPT.

Several recent randomized studies have consistently shown that a short duration of DAPT (1-3 months) followed by P2Y12 inhibitor monotherapy had ischemia protection effects comparable with that of DAPT of longer duration, and it was associated with a significantly reduced risk of bleeding events in patients who underwent PCI, they note. However, these studies have so far reported only 1-year outcomes, and long-term results are not yet available.

The SMART-CHOICE trial compared two antiplatelet strategies – 3 months of DAPT followed by long-term P2Y12 inhibitor monotherapy (mainly with clopidogrel) or prolonged DAPT for 12 months or longer – in 2,993 patients who had undergone PCI with a drug-eluting stent. Results at 12 months showed a similar rate of ischemic events with both strategies but a lower rate of bleeding in the group that received shortened DAPT.

The SMART-CHOICE investigators now report the 3-year results showing similar outcomes.

At 3 years, the primary endpoint, a composite of all-cause death, myocardial infarction, or stroke, had occurred in 6.3% of the shortened DAPT group and 6.1% in the prolonged DAPT group, giving a hazard ratio of 1.06 (95% confidence interval, 0.79-1.44).

But in the shortened DAPT group, the risk of bleeding was reduced. Bleeding Academic Research Consortium (BARC) types 2-5 bleeding had occurred in 3.2% of the shortened DAPT group and in 8.2% of the prolonged DAPT group (hazard ratio, 0.39; 95% CI, 0.28-0.55). Major bleeding, BARC types 3-5, occurred in 1.2% of the shortened DAPT group and in 2.4% of the prolonged DAPT group (HR, 0.56; 95% CI 0.31-0.99).

The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.

The researchers point out that this is the first trial to report on the long-term safety and efficacy of P2Y12-inhibitor monotherapy as long-term maintenance therapy for stable patients treated with PCI.

“Especially considering that extended DAPT significantly reduced the risks of ischemic events compared with aspirin monotherapy in a couple of trials, comparison between P2Y12-inhibitor monotherapy and prolonged DAPT for recurrent ischemic events over a longer period beyond 1 year is of great importance,” they say.

They cite two other trials – HOST-EXAM and GLOBAL LEADERS – which have shown P2Y12-inhibitor monotherapy to be superior to aspirin monotherapy in preventing both ischemic and bleeding events during the long-term maintenance period after PCI.

“Combining the results of the current study, HOST-EXAM trial, and landmark analysis of the GLOBAL LEADERS trial, long-term P2Y12-inhibitor monotherapy after a minimum period of DAPT might be the most reliable option from among aspirin monotherapy, P2Y12 monotherapy, and extended DAPT for maintenance therapy after stabilizing patients who have undergone PCI with a current-generation DES,” they conclude.

They note that the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines for coronary artery revascularization newly recommends a shorter course of DAPT followed by P2Y12 monotherapy as a class IIa indication. The recommendation is based on results of five large, randomized clinical trials, including SMART-CHOICE, TWILIGHT, STOPDAPT-2, TICO, and GLOBAL LEADERS.

“The current results of extended follow-up from the SMART-CHOICE trial support evidence of aspirin-dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” they say.

They point out that two further trials, A-CLOSE in high-risk patients and SMART-CHOICE III, will be helpful to confirm these findings.
 

P2Y12-inhibitor monotherapy ‘attractive concept’

In an accompanying editor’s note, Ajay Kirtane, MD, Columbia University Irving Medical Center/New York–Presbyterian Hospital, New York, and Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai and the Cardiovascular Research Foundation, New York, note that current guidelines recommend 3-6 months of DAPT following PCI with current-generation drug-eluting stents in stable patients and 6-12 months or longer for those with acute coronary syndromes. For patients at higher risk of bleeding, even shorter DAPT durations can be considered on a case-by-case basis.

Historically, the component of DAPT subject to discontinuation decisions was the P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor), but more recent trials have further explored whether discontinuation of the aspirin component of DAPT can mitigate bleeding while preserving anti-ischemic efficacy.

The editorialists explain that the concept of P2Y1-inhibitor monotherapy is attractive because it may optimize antiplatelet effects through a single agent that can avoid the gastrointestinal toxicity of aspirin as well as the increased bleeding that comes with combing multiple antithrombotic agents.

They suggest that the long-term results from the SMART-CHOICE trial “should lead clinicians to consider a strategy of monotherapy after a short period of DAPT as a viable one to mitigate bleeding risk,” although they also point out that SMART-CHOICE was underpowered to rigorously assess ischemic differences, so caution is warranted.

“For patients at greatest risk for recurrent ischemic events, the role of continued DAPT is always an option, but these data (and other consistent trials) give clinicians more options to pursue individualized treatment decisions,” they write.

“To some, the continually moving field of post-PCI antiplatelet therapy has provided too many choices, which can at times be dizzying. To us, every patient is different, and thoughtful evidence-based consideration is increasingly possible for many of our treatment decisions,” they conclude.

The SMART-CHOICE study was supported by unrestricted grants from the Korean Society of Interventional Cardiology, Abbott Vascular, Biotronik, and Boston Scientific.

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

Shortening the duration of dual-antiplatelet therapy (DAPT) and continuing with a P2Y12 inhibitor alone after percutaneous coronary intervention (PCI) was associated with a similar rate of ischemic events but with less bleeding than prolonged DAPT after 3 years of follow-up in the SMART-CHOICE trial.

“The current results of extended follow-up from the SMART-CHOICE trial support evidence of an aspirin dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” the investigators, with lead author Ki Hong Choi, MD, division of cardiology, department of medicine, Samsung Medical Center, Sungkyunkwan University, Seoul, South Korea, conclude.

The 3-year results from the study were published online in JAMA Cardiology.

The authors explain that although dual therapy with aspirin and a P2Y12 inhibitor after PCI with a drug-eluting stent (DES) is crucial to reduce the risk of ischemic events, it raises concerns about increased risk of bleeding, and the antiplatelet strategy after PCI is currently shifting to reduce the duration of DAPT.

Several recent randomized studies have consistently shown that a short duration of DAPT (1-3 months) followed by P2Y12 inhibitor monotherapy had ischemia protection effects comparable with that of DAPT of longer duration, and it was associated with a significantly reduced risk of bleeding events in patients who underwent PCI, they note. However, these studies have so far reported only 1-year outcomes, and long-term results are not yet available.

The SMART-CHOICE trial compared two antiplatelet strategies – 3 months of DAPT followed by long-term P2Y12 inhibitor monotherapy (mainly with clopidogrel) or prolonged DAPT for 12 months or longer – in 2,993 patients who had undergone PCI with a drug-eluting stent. Results at 12 months showed a similar rate of ischemic events with both strategies but a lower rate of bleeding in the group that received shortened DAPT.

The SMART-CHOICE investigators now report the 3-year results showing similar outcomes.

At 3 years, the primary endpoint, a composite of all-cause death, myocardial infarction, or stroke, had occurred in 6.3% of the shortened DAPT group and 6.1% in the prolonged DAPT group, giving a hazard ratio of 1.06 (95% confidence interval, 0.79-1.44).

But in the shortened DAPT group, the risk of bleeding was reduced. Bleeding Academic Research Consortium (BARC) types 2-5 bleeding had occurred in 3.2% of the shortened DAPT group and in 8.2% of the prolonged DAPT group (hazard ratio, 0.39; 95% CI, 0.28-0.55). Major bleeding, BARC types 3-5, occurred in 1.2% of the shortened DAPT group and in 2.4% of the prolonged DAPT group (HR, 0.56; 95% CI 0.31-0.99).

The landmark analyses between 3 months and 3 years and per-protocol analyses showed consistent results.

The researchers point out that this is the first trial to report on the long-term safety and efficacy of P2Y12-inhibitor monotherapy as long-term maintenance therapy for stable patients treated with PCI.

“Especially considering that extended DAPT significantly reduced the risks of ischemic events compared with aspirin monotherapy in a couple of trials, comparison between P2Y12-inhibitor monotherapy and prolonged DAPT for recurrent ischemic events over a longer period beyond 1 year is of great importance,” they say.

They cite two other trials – HOST-EXAM and GLOBAL LEADERS – which have shown P2Y12-inhibitor monotherapy to be superior to aspirin monotherapy in preventing both ischemic and bleeding events during the long-term maintenance period after PCI.

“Combining the results of the current study, HOST-EXAM trial, and landmark analysis of the GLOBAL LEADERS trial, long-term P2Y12-inhibitor monotherapy after a minimum period of DAPT might be the most reliable option from among aspirin monotherapy, P2Y12 monotherapy, and extended DAPT for maintenance therapy after stabilizing patients who have undergone PCI with a current-generation DES,” they conclude.

They note that the American College of Cardiology/American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines for coronary artery revascularization newly recommends a shorter course of DAPT followed by P2Y12 monotherapy as a class IIa indication. The recommendation is based on results of five large, randomized clinical trials, including SMART-CHOICE, TWILIGHT, STOPDAPT-2, TICO, and GLOBAL LEADERS.

“The current results of extended follow-up from the SMART-CHOICE trial support evidence of aspirin-dropping strategy with indefinite use of P2Y12 inhibitor after minimum use of DAPT in patients who underwent PCI,” they say.

They point out that two further trials, A-CLOSE in high-risk patients and SMART-CHOICE III, will be helpful to confirm these findings.
 

P2Y12-inhibitor monotherapy ‘attractive concept’

In an accompanying editor’s note, Ajay Kirtane, MD, Columbia University Irving Medical Center/New York–Presbyterian Hospital, New York, and Roxana Mehran, MD, Icahn School of Medicine at Mount Sinai and the Cardiovascular Research Foundation, New York, note that current guidelines recommend 3-6 months of DAPT following PCI with current-generation drug-eluting stents in stable patients and 6-12 months or longer for those with acute coronary syndromes. For patients at higher risk of bleeding, even shorter DAPT durations can be considered on a case-by-case basis.

Historically, the component of DAPT subject to discontinuation decisions was the P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor), but more recent trials have further explored whether discontinuation of the aspirin component of DAPT can mitigate bleeding while preserving anti-ischemic efficacy.

The editorialists explain that the concept of P2Y1-inhibitor monotherapy is attractive because it may optimize antiplatelet effects through a single agent that can avoid the gastrointestinal toxicity of aspirin as well as the increased bleeding that comes with combing multiple antithrombotic agents.

They suggest that the long-term results from the SMART-CHOICE trial “should lead clinicians to consider a strategy of monotherapy after a short period of DAPT as a viable one to mitigate bleeding risk,” although they also point out that SMART-CHOICE was underpowered to rigorously assess ischemic differences, so caution is warranted.

“For patients at greatest risk for recurrent ischemic events, the role of continued DAPT is always an option, but these data (and other consistent trials) give clinicians more options to pursue individualized treatment decisions,” they write.

“To some, the continually moving field of post-PCI antiplatelet therapy has provided too many choices, which can at times be dizzying. To us, every patient is different, and thoughtful evidence-based consideration is increasingly possible for many of our treatment decisions,” they conclude.

The SMART-CHOICE study was supported by unrestricted grants from the Korean Society of Interventional Cardiology, Abbott Vascular, Biotronik, and Boston Scientific.

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

The study covered in this summary was published on medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaway

• Absolute lesion control rate with image-guided superficial radiation therapy (IGSRT) for early-stage nonmelanoma skin cancer was achieved in nearly all patients.

Why this matters

• IGSRT is a newer radiation technique for skin cancer, an alternative to Mohs micrographic surgery and other surgical options.
• The ultrasound imaging used during IGSRT allows for precise targeting of cancer cells while sparing surrounding tissue.
• IGSRT is currently recommended for early-stage nonmelanoma skin cancer among patients who refuse or cannot tolerate surgery.
• Given the safety, lack of surgical disfigurement, cost-effectiveness, and high cure rate, IGSRT should be considered more broadly as a first-line option for early-stage nonmelanoma skin cancer, the researchers concluded.

Study design

• The investigators reviewed 1,899 early-stage nonmelanoma skin cancer lesions in 1,243 patients treated with IGSRT at an outpatient dermatology clinic in Dallas.
• Energies ranged from 50 to 100 kV, with a mean treatment dose of 5,364.4 cGy over an average of 20.2 fractions.
• Treatment duration was a mean of 7.5 weeks and followed for a mean of 65.5 weeks.

Key results

• Absolute lesion control was achieved in 99.7% of patients, with a stable control rate of 99.6% past 12 months.
• At a 5-year follow-up, local control was 99.4%.
• Local control for both basal and squamous cell carcinoma at 5 years was 99%; local control for squamous cell carcinoma in situ was 100% at 5 years.
• The most common side effects were erythema, dryness, and dry desquamation. Some patients had ulceration and moist desquamation, but it did not affect lesion control.
• The procedure was well tolerated, with a grade 1 Radiation Treatment Oncology Group toxicity score in 72% of lesions.
• The results compare favorably with Mohs surgery.

Limitations

• No study limitations were noted.

Disclosures

• No funding source was reported.
• Senior investigator Lio Yu, MD, reported research, speaking and/or consulting for SkinCure Oncology, a developer of IGSRT technology.

This is a summary of a preprint research study, “Analysis of Image-Guided Superficial Radiation Therapy (IGSRT) on the Treatment of Early Stage Non-Melanoma Skin Cancer (NMSC) in the Outpatient Dermatology Setting,” led by Alison Tran, MD, of Baylor University Medical Center, Dallas. The study has not been peer reviewed. The full text can be found at medRxiv.org.

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

The study covered in this summary was published on medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaway

• Absolute lesion control rate with image-guided superficial radiation therapy (IGSRT) for early-stage nonmelanoma skin cancer was achieved in nearly all patients.

Why this matters

• IGSRT is a newer radiation technique for skin cancer, an alternative to Mohs micrographic surgery and other surgical options.
• The ultrasound imaging used during IGSRT allows for precise targeting of cancer cells while sparing surrounding tissue.
• IGSRT is currently recommended for early-stage nonmelanoma skin cancer among patients who refuse or cannot tolerate surgery.
• Given the safety, lack of surgical disfigurement, cost-effectiveness, and high cure rate, IGSRT should be considered more broadly as a first-line option for early-stage nonmelanoma skin cancer, the researchers concluded.

Study design

• The investigators reviewed 1,899 early-stage nonmelanoma skin cancer lesions in 1,243 patients treated with IGSRT at an outpatient dermatology clinic in Dallas.
• Energies ranged from 50 to 100 kV, with a mean treatment dose of 5,364.4 cGy over an average of 20.2 fractions.
• Treatment duration was a mean of 7.5 weeks and followed for a mean of 65.5 weeks.

Key results

• Absolute lesion control was achieved in 99.7% of patients, with a stable control rate of 99.6% past 12 months.
• At a 5-year follow-up, local control was 99.4%.
• Local control for both basal and squamous cell carcinoma at 5 years was 99%; local control for squamous cell carcinoma in situ was 100% at 5 years.
• The most common side effects were erythema, dryness, and dry desquamation. Some patients had ulceration and moist desquamation, but it did not affect lesion control.
• The procedure was well tolerated, with a grade 1 Radiation Treatment Oncology Group toxicity score in 72% of lesions.
• The results compare favorably with Mohs surgery.

Limitations

• No study limitations were noted.

Disclosures

• No funding source was reported.
• Senior investigator Lio Yu, MD, reported research, speaking and/or consulting for SkinCure Oncology, a developer of IGSRT technology.

This is a summary of a preprint research study, “Analysis of Image-Guided Superficial Radiation Therapy (IGSRT) on the Treatment of Early Stage Non-Melanoma Skin Cancer (NMSC) in the Outpatient Dermatology Setting,” led by Alison Tran, MD, of Baylor University Medical Center, Dallas. The study has not been peer reviewed. The full text can be found at medRxiv.org.

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

The study covered in this summary was published on medRxiv.org as a preprint and has not yet been peer reviewed.

Key takeaway

• Absolute lesion control rate with image-guided superficial radiation therapy (IGSRT) for early-stage nonmelanoma skin cancer was achieved in nearly all patients.

Why this matters

• IGSRT is a newer radiation technique for skin cancer, an alternative to Mohs micrographic surgery and other surgical options.
• The ultrasound imaging used during IGSRT allows for precise targeting of cancer cells while sparing surrounding tissue.
• IGSRT is currently recommended for early-stage nonmelanoma skin cancer among patients who refuse or cannot tolerate surgery.
• Given the safety, lack of surgical disfigurement, cost-effectiveness, and high cure rate, IGSRT should be considered more broadly as a first-line option for early-stage nonmelanoma skin cancer, the researchers concluded.

Study design

• The investigators reviewed 1,899 early-stage nonmelanoma skin cancer lesions in 1,243 patients treated with IGSRT at an outpatient dermatology clinic in Dallas.
• Energies ranged from 50 to 100 kV, with a mean treatment dose of 5,364.4 cGy over an average of 20.2 fractions.
• Treatment duration was a mean of 7.5 weeks and followed for a mean of 65.5 weeks.

Key results

• Absolute lesion control was achieved in 99.7% of patients, with a stable control rate of 99.6% past 12 months.
• At a 5-year follow-up, local control was 99.4%.
• Local control for both basal and squamous cell carcinoma at 5 years was 99%; local control for squamous cell carcinoma in situ was 100% at 5 years.
• The most common side effects were erythema, dryness, and dry desquamation. Some patients had ulceration and moist desquamation, but it did not affect lesion control.
• The procedure was well tolerated, with a grade 1 Radiation Treatment Oncology Group toxicity score in 72% of lesions.
• The results compare favorably with Mohs surgery.

Limitations

• No study limitations were noted.

Disclosures

• No funding source was reported.
• Senior investigator Lio Yu, MD, reported research, speaking and/or consulting for SkinCure Oncology, a developer of IGSRT technology.

This is a summary of a preprint research study, “Analysis of Image-Guided Superficial Radiation Therapy (IGSRT) on the Treatment of Early Stage Non-Melanoma Skin Cancer (NMSC) in the Outpatient Dermatology Setting,” led by Alison Tran, MD, of Baylor University Medical Center, Dallas. The study has not been peer reviewed. The full text can be found at medRxiv.org.

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

I hear other doctors talk about online reviews, both good and bad.

I recently read a piece where a practice gave doctors a bonus for getting 5-star reviews, though it doesn’t say if they were penalized for getting bad reviews. I assume the latter docs got a good “talking to” by someone in administration, or marketing, or both.

I get my share of them, too, both good and bad, scattered across at least a dozen sites that profess to offer accurate ratings.

I tend to ignore all of them.

Bad ratings mean nothing. They might be reasonable. They can also be from patients whom I fired for noncompliance, or from patients I refused to give an early narcotic refill to. They can also be from people who aren’t patients, such as a neighbor angry at the way I voted at a home owners association meeting, or a person who never saw me but was upset because I don’t take their insurance, or someone at the hospital whom I had to hang up on after being put on hold for 10 minutes.

Good reviews also don’t mean much, either. They might be from patients. They could also be from well-meaning family and friends. Or the waiter I left an extra-large tip for the other night.

One of my 1-star reviews even goes on to describe me in glowing terms (the lady called my office to apologize, saying the site confused her).

There’s also a whole cottage industry around this: Like restaurants, you can pay people to give you good reviews. They’re on Craig’s list and other sites. Some are freelancers. Others are actually well-organized companies, offering to give you X number of good reviews per month for a regular fee. I see ads for the latter online, usually describing themselves as “reputation recovery services.”

There was even a recent post on Sermo about this. A doctor noted he’d gotten a string of bad reviews from nonpatients, and shortly afterward was contacted by a reputation recovery service to help. He wondered if the crappy reviews were intentionally written by that business before they called him. He also questioned if it was an unspoken blackmail tactic – pay us or we’ll write more bad reviews.

Unlike a restaurant, we can’t respond because of patient confidentiality. Unless it’s something meaninglessly generic like “thank you” or “sorry you had a bad experience.”

A friend of mine (not in medicine) said that picking your doctor from online reviews is like selecting a wine recommended by a guy who lives at the train yard.

While there are pros and cons to the whole online review thing, in medicine there are mostly cons. Many reviews are anonymous, with no way to trace them. Unless details are provided, you don’t know if the reviewer is really a patient (or even a human in this bot era). Neither does the general public, reading them and presumably making decisions about who to see.

Like many things about the Internet, online reviews are the wild west. There are minimal (if any) rules, no law enforcement, and no one knows who the good guys and bad guys really are.

And there’s nothing we can do about it, either.

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

I hear other doctors talk about online reviews, both good and bad.

I recently read a piece where a practice gave doctors a bonus for getting 5-star reviews, though it doesn’t say if they were penalized for getting bad reviews. I assume the latter docs got a good “talking to” by someone in administration, or marketing, or both.

I get my share of them, too, both good and bad, scattered across at least a dozen sites that profess to offer accurate ratings.

I tend to ignore all of them.

Bad ratings mean nothing. They might be reasonable. They can also be from patients whom I fired for noncompliance, or from patients I refused to give an early narcotic refill to. They can also be from people who aren’t patients, such as a neighbor angry at the way I voted at a home owners association meeting, or a person who never saw me but was upset because I don’t take their insurance, or someone at the hospital whom I had to hang up on after being put on hold for 10 minutes.

Good reviews also don’t mean much, either. They might be from patients. They could also be from well-meaning family and friends. Or the waiter I left an extra-large tip for the other night.

One of my 1-star reviews even goes on to describe me in glowing terms (the lady called my office to apologize, saying the site confused her).

There’s also a whole cottage industry around this: Like restaurants, you can pay people to give you good reviews. They’re on Craig’s list and other sites. Some are freelancers. Others are actually well-organized companies, offering to give you X number of good reviews per month for a regular fee. I see ads for the latter online, usually describing themselves as “reputation recovery services.”

There was even a recent post on Sermo about this. A doctor noted he’d gotten a string of bad reviews from nonpatients, and shortly afterward was contacted by a reputation recovery service to help. He wondered if the crappy reviews were intentionally written by that business before they called him. He also questioned if it was an unspoken blackmail tactic – pay us or we’ll write more bad reviews.

Unlike a restaurant, we can’t respond because of patient confidentiality. Unless it’s something meaninglessly generic like “thank you” or “sorry you had a bad experience.”

A friend of mine (not in medicine) said that picking your doctor from online reviews is like selecting a wine recommended by a guy who lives at the train yard.

While there are pros and cons to the whole online review thing, in medicine there are mostly cons. Many reviews are anonymous, with no way to trace them. Unless details are provided, you don’t know if the reviewer is really a patient (or even a human in this bot era). Neither does the general public, reading them and presumably making decisions about who to see.

Like many things about the Internet, online reviews are the wild west. There are minimal (if any) rules, no law enforcement, and no one knows who the good guys and bad guys really are.

And there’s nothing we can do about it, either.

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

I hear other doctors talk about online reviews, both good and bad.

I recently read a piece where a practice gave doctors a bonus for getting 5-star reviews, though it doesn’t say if they were penalized for getting bad reviews. I assume the latter docs got a good “talking to” by someone in administration, or marketing, or both.

I get my share of them, too, both good and bad, scattered across at least a dozen sites that profess to offer accurate ratings.

I tend to ignore all of them.

Bad ratings mean nothing. They might be reasonable. They can also be from patients whom I fired for noncompliance, or from patients I refused to give an early narcotic refill to. They can also be from people who aren’t patients, such as a neighbor angry at the way I voted at a home owners association meeting, or a person who never saw me but was upset because I don’t take their insurance, or someone at the hospital whom I had to hang up on after being put on hold for 10 minutes.

Good reviews also don’t mean much, either. They might be from patients. They could also be from well-meaning family and friends. Or the waiter I left an extra-large tip for the other night.

One of my 1-star reviews even goes on to describe me in glowing terms (the lady called my office to apologize, saying the site confused her).

There’s also a whole cottage industry around this: Like restaurants, you can pay people to give you good reviews. They’re on Craig’s list and other sites. Some are freelancers. Others are actually well-organized companies, offering to give you X number of good reviews per month for a regular fee. I see ads for the latter online, usually describing themselves as “reputation recovery services.”

There was even a recent post on Sermo about this. A doctor noted he’d gotten a string of bad reviews from nonpatients, and shortly afterward was contacted by a reputation recovery service to help. He wondered if the crappy reviews were intentionally written by that business before they called him. He also questioned if it was an unspoken blackmail tactic – pay us or we’ll write more bad reviews.

Unlike a restaurant, we can’t respond because of patient confidentiality. Unless it’s something meaninglessly generic like “thank you” or “sorry you had a bad experience.”

A friend of mine (not in medicine) said that picking your doctor from online reviews is like selecting a wine recommended by a guy who lives at the train yard.

While there are pros and cons to the whole online review thing, in medicine there are mostly cons. Many reviews are anonymous, with no way to trace them. Unless details are provided, you don’t know if the reviewer is really a patient (or even a human in this bot era). Neither does the general public, reading them and presumably making decisions about who to see.

Like many things about the Internet, online reviews are the wild west. There are minimal (if any) rules, no law enforcement, and no one knows who the good guys and bad guys really are.

And there’s nothing we can do about it, either.

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

STOCKHOLM – Recent study results confirm that two agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class can significantly cut the incidence of adverse cardiovascular events in patients with heart failure with reduced ejection fraction (HFpEF), a disease especially common in people with type 2 diabetes, obesity, or both.

And findings from secondary analyses of the studies – including one reported at the annual meeting of the European Association for the Study of Diabetes – show that these SGLT2 inhibitors work as well for cutting incident adverse events (cardiovascular death or worsening heart failure) in patients with HFpEF and diabetes as they do for people with normal blood glucose levels.

But delivering treatment with these proven agents, dapagliflozin (Farxiga) and empagliflozin (Jardiance), first requires diagnosis of HFpEF, a task that clinicians have historically fallen short in accomplishing.

When in 2021, results from the EMPEROR-Preserved trial with empagliflozin and when in September 2022 results from the DELIVER trial with dapagliflozin established the efficacy of these two SGLT2 inhibitors as the first treatments proven to benefit patients with HFpEF, they also raised the stakes for clinicians to be much more diligent and systematic in evaluating people at high risk for developing HFpEF because of having type 2 diabetes or obesity, two of the most potent risk factors for this form of heart failure.
 

‘Vigilance ... needs to increase’

“Vigilance for HFpEF needs to increase because we can now help these patients,” declared Lars H. Lund, MD, PhD, speaking at the meeting. “Type 2 diabetes dramatically increases the incidence of HFpEF,” and the mechanisms by which it does this are “especially amenable to treatment with SGLT2 inhibitors,” said Dr. Lund, a cardiologist and heart failure specialist at the Karolinska Institute, Stockholm.

HFpEF has a history of going undetected in people with type 2 diabetes, an ironic situation given its high incidence as well as the elevated rate of adverse cardiovascular events when heart failure occurs in patients with type 2 diabetes compared with patients who do not have diabetes.

The key, say experts, is for clinicians to maintain a high index of suspicion for signs and symptoms of heart failure in people with type 2 diabetes and to regularly assess them, starting with just a few simple questions that probe for the presence of dyspnea, exertional fatigue, or both, an approach not widely employed up to now.

Clinicians who care for people with type 2 diabetes must become “alert to thinking about heart failure and alert to asking questions about signs and symptoms” that flag the presence of HFpEF, advised Naveed Sattar, MBChB, PhD, a professor of metabolic medicine at the University of Glasgow.

Soon, medical groups will issue guidelines for appropriate assessment for the presence of HFpEF in people with type 2 diabetes, Dr. Sattar predicted in an interview.
 

A need to probe

“You can’t simply ask patients with type 2 diabetes whether they have shortness of breath or exertional fatigue and stop there,” because often their first response will be no.

“Commonly, patients will initially say they have no dyspnea, but when you probe further, you find symptoms,” noted Mikhail N. Kosiborod, MD, codirector of Saint Luke’s Cardiometabolic Center of Excellence in Kansas City, Mo.

These people are often sedentary, so they frequently don’t experience shortness of breath at baseline, Dr. Kosiborod said in an interview. In some cases, they may limit their activity because of their exertional intolerance.

Once a person’s suggestive symptoms become known, the next step is to measure the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker considered to be a generally reliable signal of existing heart failure when elevated.

Any value above 125 pg/mL is suggestive of prevalent heart failure and should lead to the next diagnostic step of echocardiography, Dr. Sattar said.

Elevated NT-proBNP has such good positive predictive value for identifying heart failure that it is tempting to use it broadly in people with type 2 diabetes. A 2022 consensus report from the American Diabetes Association says that “measurement of a natriuretic peptide [such as NT-proBNP] or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest HF [heart failure] stages and implement strategies to prevent transition to symptomatic HF.”
 

Test costs require targeting

But because of the relatively high current price for an NT-proBNP test, the cost-benefit ratio for widespread annual testing of all people with type 2 diabetes would be poor, some experts caution.

“Screening everyone may not be the right answer. Hundreds of millions of people worldwide” have type 2 diabetes. “You first need to target evaluation to people with symptoms,” advised Dr. Kosiborod.

He also warned that a low NT-proBNP level does not always rule out HFpEF, especially among people with type 2 diabetes who also have overweight or obesity, because NT-proBNP levels can be “artificially low” in people with obesity.

Other potential aids to diagnosis are assessment scores that researchers have developed, such as the H2FPEF score, which relies on variables that include age, obesity, and the presence of atrial fibrillation and hypertension.

However, this score also requires an echocardiography examination, another test that would have a questionable cost-benefit ratio if performed widely for patients with type 2 diabetes without targeting, Dr. Kosiborod said.
 

SGLT2 inhibitors benefit HFpEF regardless of glucose levels

A prespecified analysis of the DELIVER results that divided the study cohort on the basis of their glycemic status proved the efficacy of the SGLT2 inhibitor dapagliflozin for patients with HFpEF regardless of whether or not they had type 2 diabetes, prediabetes, or were normoglycemic at entry into the study, Silvio E. Inzucchi, MD, reported at the EASD meeting.

Mitchel L. Zoler/MDedge News

Treatment with dapagliflozin cut the incidence of the trial’s primary outcome of cardiovascular death or worsening heart failure by a significant 18% relative to placebo among all enrolled patients.

The new analysis reported by Dr. Inzucchi showed that treatment was associated with a 23% relative risk reduction among those with normoglycemia, a 13% reduction among those with prediabetes, and a 19% reduction among those with type 2 diabetes, with no signal of a significant difference among the three subgroups.

“There was no statistical interaction between categorical glycemic subgrouping and dapagliflozin’s treatment effect,” concluded Dr. Inzucchi, director of the Yale Medicine Diabetes Center, New Haven, Conn.

He also reported that, among the 6,259 people in the trial with HFpEF, 50% had diabetes, 31% had prediabetes, and a scant 19% had normoglycemia. The finding highlights once again the high prevalence of dysglycemia among people with HFpEF.

Previously, a prespecified secondary analysis of data from the EMPEROR-Preserved trial yielded similar findings for empagliflozin that showed the agent’s efficacy for people with HFpEF across the range of glucose levels.

The DELIVER trial was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). The EMPEROR-Preserved trial was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Lund has been a consultant to AstraZeneca and Boehringer Ingelheim and to numerous other companies, and he is a stockholder in AnaCardio. Dr. Sattar has been a consultant to and has received research support from AstraZeneca and Boehringer Ingelheim, and he has been a consultant with numerous companies. Dr. Kosiborod has been a consultant to and has received research funding from AstraZeneca and Boehringer Ingelheim and has been a consultant to Eli Lilly and numerous other companies. Dr. Inzucchi has been a consultant to, given talks on behalf of, or served on trial committees for Abbott, AstraZeneca, Boehringer Ingelheim, Esperion, Lexicon, Merck, Novo Nordisk, Pfizer, and vTv Therapetics.

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

STOCKHOLM – Recent study results confirm that two agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class can significantly cut the incidence of adverse cardiovascular events in patients with heart failure with reduced ejection fraction (HFpEF), a disease especially common in people with type 2 diabetes, obesity, or both.

And findings from secondary analyses of the studies – including one reported at the annual meeting of the European Association for the Study of Diabetes – show that these SGLT2 inhibitors work as well for cutting incident adverse events (cardiovascular death or worsening heart failure) in patients with HFpEF and diabetes as they do for people with normal blood glucose levels.

But delivering treatment with these proven agents, dapagliflozin (Farxiga) and empagliflozin (Jardiance), first requires diagnosis of HFpEF, a task that clinicians have historically fallen short in accomplishing.

When in 2021, results from the EMPEROR-Preserved trial with empagliflozin and when in September 2022 results from the DELIVER trial with dapagliflozin established the efficacy of these two SGLT2 inhibitors as the first treatments proven to benefit patients with HFpEF, they also raised the stakes for clinicians to be much more diligent and systematic in evaluating people at high risk for developing HFpEF because of having type 2 diabetes or obesity, two of the most potent risk factors for this form of heart failure.
 

‘Vigilance ... needs to increase’

“Vigilance for HFpEF needs to increase because we can now help these patients,” declared Lars H. Lund, MD, PhD, speaking at the meeting. “Type 2 diabetes dramatically increases the incidence of HFpEF,” and the mechanisms by which it does this are “especially amenable to treatment with SGLT2 inhibitors,” said Dr. Lund, a cardiologist and heart failure specialist at the Karolinska Institute, Stockholm.

HFpEF has a history of going undetected in people with type 2 diabetes, an ironic situation given its high incidence as well as the elevated rate of adverse cardiovascular events when heart failure occurs in patients with type 2 diabetes compared with patients who do not have diabetes.

The key, say experts, is for clinicians to maintain a high index of suspicion for signs and symptoms of heart failure in people with type 2 diabetes and to regularly assess them, starting with just a few simple questions that probe for the presence of dyspnea, exertional fatigue, or both, an approach not widely employed up to now.

Clinicians who care for people with type 2 diabetes must become “alert to thinking about heart failure and alert to asking questions about signs and symptoms” that flag the presence of HFpEF, advised Naveed Sattar, MBChB, PhD, a professor of metabolic medicine at the University of Glasgow.

Soon, medical groups will issue guidelines for appropriate assessment for the presence of HFpEF in people with type 2 diabetes, Dr. Sattar predicted in an interview.
 

A need to probe

“You can’t simply ask patients with type 2 diabetes whether they have shortness of breath or exertional fatigue and stop there,” because often their first response will be no.

“Commonly, patients will initially say they have no dyspnea, but when you probe further, you find symptoms,” noted Mikhail N. Kosiborod, MD, codirector of Saint Luke’s Cardiometabolic Center of Excellence in Kansas City, Mo.

These people are often sedentary, so they frequently don’t experience shortness of breath at baseline, Dr. Kosiborod said in an interview. In some cases, they may limit their activity because of their exertional intolerance.

Once a person’s suggestive symptoms become known, the next step is to measure the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker considered to be a generally reliable signal of existing heart failure when elevated.

Any value above 125 pg/mL is suggestive of prevalent heart failure and should lead to the next diagnostic step of echocardiography, Dr. Sattar said.

Elevated NT-proBNP has such good positive predictive value for identifying heart failure that it is tempting to use it broadly in people with type 2 diabetes. A 2022 consensus report from the American Diabetes Association says that “measurement of a natriuretic peptide [such as NT-proBNP] or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest HF [heart failure] stages and implement strategies to prevent transition to symptomatic HF.”
 

Test costs require targeting

But because of the relatively high current price for an NT-proBNP test, the cost-benefit ratio for widespread annual testing of all people with type 2 diabetes would be poor, some experts caution.

“Screening everyone may not be the right answer. Hundreds of millions of people worldwide” have type 2 diabetes. “You first need to target evaluation to people with symptoms,” advised Dr. Kosiborod.

He also warned that a low NT-proBNP level does not always rule out HFpEF, especially among people with type 2 diabetes who also have overweight or obesity, because NT-proBNP levels can be “artificially low” in people with obesity.

Other potential aids to diagnosis are assessment scores that researchers have developed, such as the H2FPEF score, which relies on variables that include age, obesity, and the presence of atrial fibrillation and hypertension.

However, this score also requires an echocardiography examination, another test that would have a questionable cost-benefit ratio if performed widely for patients with type 2 diabetes without targeting, Dr. Kosiborod said.
 

SGLT2 inhibitors benefit HFpEF regardless of glucose levels

A prespecified analysis of the DELIVER results that divided the study cohort on the basis of their glycemic status proved the efficacy of the SGLT2 inhibitor dapagliflozin for patients with HFpEF regardless of whether or not they had type 2 diabetes, prediabetes, or were normoglycemic at entry into the study, Silvio E. Inzucchi, MD, reported at the EASD meeting.

Mitchel L. Zoler/MDedge News

Treatment with dapagliflozin cut the incidence of the trial’s primary outcome of cardiovascular death or worsening heart failure by a significant 18% relative to placebo among all enrolled patients.

The new analysis reported by Dr. Inzucchi showed that treatment was associated with a 23% relative risk reduction among those with normoglycemia, a 13% reduction among those with prediabetes, and a 19% reduction among those with type 2 diabetes, with no signal of a significant difference among the three subgroups.

“There was no statistical interaction between categorical glycemic subgrouping and dapagliflozin’s treatment effect,” concluded Dr. Inzucchi, director of the Yale Medicine Diabetes Center, New Haven, Conn.

He also reported that, among the 6,259 people in the trial with HFpEF, 50% had diabetes, 31% had prediabetes, and a scant 19% had normoglycemia. The finding highlights once again the high prevalence of dysglycemia among people with HFpEF.

Previously, a prespecified secondary analysis of data from the EMPEROR-Preserved trial yielded similar findings for empagliflozin that showed the agent’s efficacy for people with HFpEF across the range of glucose levels.

The DELIVER trial was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). The EMPEROR-Preserved trial was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Lund has been a consultant to AstraZeneca and Boehringer Ingelheim and to numerous other companies, and he is a stockholder in AnaCardio. Dr. Sattar has been a consultant to and has received research support from AstraZeneca and Boehringer Ingelheim, and he has been a consultant with numerous companies. Dr. Kosiborod has been a consultant to and has received research funding from AstraZeneca and Boehringer Ingelheim and has been a consultant to Eli Lilly and numerous other companies. Dr. Inzucchi has been a consultant to, given talks on behalf of, or served on trial committees for Abbott, AstraZeneca, Boehringer Ingelheim, Esperion, Lexicon, Merck, Novo Nordisk, Pfizer, and vTv Therapetics.

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

STOCKHOLM – Recent study results confirm that two agents from the sodium-glucose cotransporter 2 (SGLT2) inhibitor class can significantly cut the incidence of adverse cardiovascular events in patients with heart failure with reduced ejection fraction (HFpEF), a disease especially common in people with type 2 diabetes, obesity, or both.

And findings from secondary analyses of the studies – including one reported at the annual meeting of the European Association for the Study of Diabetes – show that these SGLT2 inhibitors work as well for cutting incident adverse events (cardiovascular death or worsening heart failure) in patients with HFpEF and diabetes as they do for people with normal blood glucose levels.

But delivering treatment with these proven agents, dapagliflozin (Farxiga) and empagliflozin (Jardiance), first requires diagnosis of HFpEF, a task that clinicians have historically fallen short in accomplishing.

When in 2021, results from the EMPEROR-Preserved trial with empagliflozin and when in September 2022 results from the DELIVER trial with dapagliflozin established the efficacy of these two SGLT2 inhibitors as the first treatments proven to benefit patients with HFpEF, they also raised the stakes for clinicians to be much more diligent and systematic in evaluating people at high risk for developing HFpEF because of having type 2 diabetes or obesity, two of the most potent risk factors for this form of heart failure.
 

‘Vigilance ... needs to increase’

“Vigilance for HFpEF needs to increase because we can now help these patients,” declared Lars H. Lund, MD, PhD, speaking at the meeting. “Type 2 diabetes dramatically increases the incidence of HFpEF,” and the mechanisms by which it does this are “especially amenable to treatment with SGLT2 inhibitors,” said Dr. Lund, a cardiologist and heart failure specialist at the Karolinska Institute, Stockholm.

HFpEF has a history of going undetected in people with type 2 diabetes, an ironic situation given its high incidence as well as the elevated rate of adverse cardiovascular events when heart failure occurs in patients with type 2 diabetes compared with patients who do not have diabetes.

The key, say experts, is for clinicians to maintain a high index of suspicion for signs and symptoms of heart failure in people with type 2 diabetes and to regularly assess them, starting with just a few simple questions that probe for the presence of dyspnea, exertional fatigue, or both, an approach not widely employed up to now.

Clinicians who care for people with type 2 diabetes must become “alert to thinking about heart failure and alert to asking questions about signs and symptoms” that flag the presence of HFpEF, advised Naveed Sattar, MBChB, PhD, a professor of metabolic medicine at the University of Glasgow.

Soon, medical groups will issue guidelines for appropriate assessment for the presence of HFpEF in people with type 2 diabetes, Dr. Sattar predicted in an interview.
 

A need to probe

“You can’t simply ask patients with type 2 diabetes whether they have shortness of breath or exertional fatigue and stop there,” because often their first response will be no.

“Commonly, patients will initially say they have no dyspnea, but when you probe further, you find symptoms,” noted Mikhail N. Kosiborod, MD, codirector of Saint Luke’s Cardiometabolic Center of Excellence in Kansas City, Mo.

These people are often sedentary, so they frequently don’t experience shortness of breath at baseline, Dr. Kosiborod said in an interview. In some cases, they may limit their activity because of their exertional intolerance.

Once a person’s suggestive symptoms become known, the next step is to measure the serum level of N-terminal pro-B-type natriuretic peptide (NT-proBNP), a biomarker considered to be a generally reliable signal of existing heart failure when elevated.

Any value above 125 pg/mL is suggestive of prevalent heart failure and should lead to the next diagnostic step of echocardiography, Dr. Sattar said.

Elevated NT-proBNP has such good positive predictive value for identifying heart failure that it is tempting to use it broadly in people with type 2 diabetes. A 2022 consensus report from the American Diabetes Association says that “measurement of a natriuretic peptide [such as NT-proBNP] or high-sensitivity cardiac troponin is recommended on at least a yearly basis to identify the earliest HF [heart failure] stages and implement strategies to prevent transition to symptomatic HF.”
 

Test costs require targeting

But because of the relatively high current price for an NT-proBNP test, the cost-benefit ratio for widespread annual testing of all people with type 2 diabetes would be poor, some experts caution.

“Screening everyone may not be the right answer. Hundreds of millions of people worldwide” have type 2 diabetes. “You first need to target evaluation to people with symptoms,” advised Dr. Kosiborod.

He also warned that a low NT-proBNP level does not always rule out HFpEF, especially among people with type 2 diabetes who also have overweight or obesity, because NT-proBNP levels can be “artificially low” in people with obesity.

Other potential aids to diagnosis are assessment scores that researchers have developed, such as the H2FPEF score, which relies on variables that include age, obesity, and the presence of atrial fibrillation and hypertension.

However, this score also requires an echocardiography examination, another test that would have a questionable cost-benefit ratio if performed widely for patients with type 2 diabetes without targeting, Dr. Kosiborod said.
 

SGLT2 inhibitors benefit HFpEF regardless of glucose levels

A prespecified analysis of the DELIVER results that divided the study cohort on the basis of their glycemic status proved the efficacy of the SGLT2 inhibitor dapagliflozin for patients with HFpEF regardless of whether or not they had type 2 diabetes, prediabetes, or were normoglycemic at entry into the study, Silvio E. Inzucchi, MD, reported at the EASD meeting.

Mitchel L. Zoler/MDedge News

Treatment with dapagliflozin cut the incidence of the trial’s primary outcome of cardiovascular death or worsening heart failure by a significant 18% relative to placebo among all enrolled patients.

The new analysis reported by Dr. Inzucchi showed that treatment was associated with a 23% relative risk reduction among those with normoglycemia, a 13% reduction among those with prediabetes, and a 19% reduction among those with type 2 diabetes, with no signal of a significant difference among the three subgroups.

“There was no statistical interaction between categorical glycemic subgrouping and dapagliflozin’s treatment effect,” concluded Dr. Inzucchi, director of the Yale Medicine Diabetes Center, New Haven, Conn.

He also reported that, among the 6,259 people in the trial with HFpEF, 50% had diabetes, 31% had prediabetes, and a scant 19% had normoglycemia. The finding highlights once again the high prevalence of dysglycemia among people with HFpEF.

Previously, a prespecified secondary analysis of data from the EMPEROR-Preserved trial yielded similar findings for empagliflozin that showed the agent’s efficacy for people with HFpEF across the range of glucose levels.

The DELIVER trial was funded by AstraZeneca, the company that markets dapagliflozin (Farxiga). The EMPEROR-Preserved trial was sponsored by Boehringer Ingelheim and Eli Lilly, the companies that jointly market empagliflozin (Jardiance). Dr. Lund has been a consultant to AstraZeneca and Boehringer Ingelheim and to numerous other companies, and he is a stockholder in AnaCardio. Dr. Sattar has been a consultant to and has received research support from AstraZeneca and Boehringer Ingelheim, and he has been a consultant with numerous companies. Dr. Kosiborod has been a consultant to and has received research funding from AstraZeneca and Boehringer Ingelheim and has been a consultant to Eli Lilly and numerous other companies. Dr. Inzucchi has been a consultant to, given talks on behalf of, or served on trial committees for Abbott, AstraZeneca, Boehringer Ingelheim, Esperion, Lexicon, Merck, Novo Nordisk, Pfizer, and vTv Therapetics.

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

The Asia-Pacific Colorectal Screening (APCS) scoring system, combined with a stool DNA test, could improve the detection of advanced colorectal neoplasms and limit colonoscopy use, according to a new study published in Clinical Gastroenterology and Hepatology.

Although a colonoscopy can detect both colorectal cancer and precancerous lesions, using it as the primary screening tool can cause barriers due to high costs, limited resources, and low compliance, wrote Junfeng Xu of the gastroenterology department at the First Medical Center of Chinese PLA General Hospital, Beijing, and colleagues.

ChrisChrisW/iStock/Getty Images

Avoiding complications

“Colonoscopy is expensive and time consuming for both the patient and the health care system. Colonoscopy is also not without risk since bowel perforation, post-procedural bleeding, and sedation-related complications all occur at low but measurable rates,” said Reid Ness, MD, associate professor of medicine and gastroenterologist at Vanderbilt University Medical Center, Nashville, Tenn.

“The primary strength of the study was that all patients eventually received colonoscopy, allowing for the best estimate of strategy sensitivity for advanced colorectal neoplasia,” he said.

At the same time, the cross-sectional study was unable to estimate the benefit of using this type of screening strategy over time, Dr. Ness said. With limited endoscopic resources available in many countries, however, clinicians need better modalities and strategies for noninvasive identification of advanced colorectal neoplasia, he added.

“Since less than 5% of the population will eventually develop colorectal cancer, the overwhelming majority can only be discomfited and possibly injured through colonoscopy screening,” he said. “For these reasons, the use of a CRC screening strategy that minimizes the use of colonoscopy without compromising the identification rate for advanced colorectal neoplasia is best for both the patient and the health care system.”

The study was supported by grants from the Beijing Municipal Science and Technology Commission. The authors declared no conflicts of interest. Dr. Ness reported no relevant disclosures.

This article was updated Oct. 4, 2022.

The Asia-Pacific Colorectal Screening (APCS) scoring system, combined with a stool DNA test, could improve the detection of advanced colorectal neoplasms and limit colonoscopy use, according to a new study published in Clinical Gastroenterology and Hepatology.

Although a colonoscopy can detect both colorectal cancer and precancerous lesions, using it as the primary screening tool can cause barriers due to high costs, limited resources, and low compliance, wrote Junfeng Xu of the gastroenterology department at the First Medical Center of Chinese PLA General Hospital, Beijing, and colleagues.

ChrisChrisW/iStock/Getty Images

Avoiding complications

“Colonoscopy is expensive and time consuming for both the patient and the health care system. Colonoscopy is also not without risk since bowel perforation, post-procedural bleeding, and sedation-related complications all occur at low but measurable rates,” said Reid Ness, MD, associate professor of medicine and gastroenterologist at Vanderbilt University Medical Center, Nashville, Tenn.

“The primary strength of the study was that all patients eventually received colonoscopy, allowing for the best estimate of strategy sensitivity for advanced colorectal neoplasia,” he said.

At the same time, the cross-sectional study was unable to estimate the benefit of using this type of screening strategy over time, Dr. Ness said. With limited endoscopic resources available in many countries, however, clinicians need better modalities and strategies for noninvasive identification of advanced colorectal neoplasia, he added.

“Since less than 5% of the population will eventually develop colorectal cancer, the overwhelming majority can only be discomfited and possibly injured through colonoscopy screening,” he said. “For these reasons, the use of a CRC screening strategy that minimizes the use of colonoscopy without compromising the identification rate for advanced colorectal neoplasia is best for both the patient and the health care system.”

The study was supported by grants from the Beijing Municipal Science and Technology Commission. The authors declared no conflicts of interest. Dr. Ness reported no relevant disclosures.

This article was updated Oct. 4, 2022.

The Asia-Pacific Colorectal Screening (APCS) scoring system, combined with a stool DNA test, could improve the detection of advanced colorectal neoplasms and limit colonoscopy use, according to a new study published in Clinical Gastroenterology and Hepatology.

Although a colonoscopy can detect both colorectal cancer and precancerous lesions, using it as the primary screening tool can cause barriers due to high costs, limited resources, and low compliance, wrote Junfeng Xu of the gastroenterology department at the First Medical Center of Chinese PLA General Hospital, Beijing, and colleagues.

ChrisChrisW/iStock/Getty Images

Avoiding complications

“Colonoscopy is expensive and time consuming for both the patient and the health care system. Colonoscopy is also not without risk since bowel perforation, post-procedural bleeding, and sedation-related complications all occur at low but measurable rates,” said Reid Ness, MD, associate professor of medicine and gastroenterologist at Vanderbilt University Medical Center, Nashville, Tenn.

“The primary strength of the study was that all patients eventually received colonoscopy, allowing for the best estimate of strategy sensitivity for advanced colorectal neoplasia,” he said.

At the same time, the cross-sectional study was unable to estimate the benefit of using this type of screening strategy over time, Dr. Ness said. With limited endoscopic resources available in many countries, however, clinicians need better modalities and strategies for noninvasive identification of advanced colorectal neoplasia, he added.

“Since less than 5% of the population will eventually develop colorectal cancer, the overwhelming majority can only be discomfited and possibly injured through colonoscopy screening,” he said. “For these reasons, the use of a CRC screening strategy that minimizes the use of colonoscopy without compromising the identification rate for advanced colorectal neoplasia is best for both the patient and the health care system.”

The study was supported by grants from the Beijing Municipal Science and Technology Commission. The authors declared no conflicts of interest. Dr. Ness reported no relevant disclosures.

This article was updated Oct. 4, 2022.

John worked as a handyman and lived on a small sailboat in a marina. When he was diagnosed with metastatic kidney cancer at age 48, he quickly fell through the cracks. He failed to show to appointments and took oral anticancer treatments, but just sporadically. He had Medicaid, so insurance wasn’t the issue. It was everything else.

John was behind on his slip fees; he hadn’t been able to work for some time because of his progressive weakness and pain. He was chronically in danger of getting kicked out of his makeshift home aboard the boat. He had no reliable transportation to the clinic and so he didn’t come to appointments regularly. The specialty pharmacy refused to deliver his expensive oral chemotherapy to his address at the marina. He went days without eating full meals because he was too weak to cook for himself. Plus, he was estranged from his family who were unaware of his illness. His oncologist was overwhelmed trying to take care of him. He had a reasonable chance of achieving disease control on first-line oral therapy, but his problems seemed to hinder these chances at every turn. She was distraught – what could she do?

Enter the team approach. John’s oncologist reached out to our palliative care program for help. We recognized that this was a job too big for us alone so we connected John with the Extensivist Medicine program at UCLA Health, a high-intensity primary care program led by a physician specializing in primary care for high-risk individuals. The program provides wraparound outpatient services for chronically and seriously ill patients, like John, who are at risk for falling through the cracks. John went from receiving very little support to now having an entire team of caring professionals focused on helping him achieve his best possible outcome despite the seriousness of his disease.

He now had the support of a high-functioning team with clearly defined roles. Social work connected him with housing, food, and transportation resources. A nurse called him every day to check in and make sure he was taking medications and reminded him about his upcoming appointments. Case management helped him get needed equipment, such as grab bars and a walker. As his palliative care nurse practitioner, I counseled him on understanding his prognosis and planning ahead for medical emergencies. Our psycho-oncology clinicians helped John reconcile with his family, who were more than willing to take him in once they realized how ill he was. Once these social factors were addressed, John could more easily stay current with his oral chemotherapy, giving him the best chance possible to achieve a robust treatment response that could buy him more time.

And, John did get that time – he got 6 months of improved quality of life, during which he reconnected with his family, including his children, and rebuilt these important relationships. Eventually treatment failed him. His disease, already widely metastatic, became more active and painful. He accepted hospice care at his sister’s house and we transitioned him from our team to the hospice team. He died peacefully surrounded by family.
 

Interprofessional teamwork is fundamental to treat ‘total pain’

None of this would have been possible without the work of high-functioning teams. It is a commonly held belief that interprofessional teamwork is fundamental to the care of patients and families living with serious illness. But why? How did this idea come about? And what evidence is there to support teamwork?

Dame Cicely Saunders, who founded the modern hospice movement in mid-20th century England, embodied the interdisciplinary team by working first as a nurse, then a social worker, and finally as a physician. She wrote about patients’ “total pain,” the crisis of physical, spiritual, social, and emotional distress that many people have at the end of life. She understood that no single health care discipline was adequate to the task of addressing each of these domains equally well. Thus, hospice became synonymous with care provided by a quartet of specialists – physicians, nurses, social workers, and chaplains. Nowadays, there are other specialists that are added to the mix – home health aides, pharmacists, physical and occupational therapists, music and pet therapists, and so on.

But in medicine, like all areas of science, convention and tradition only go so far. What evidence is there to support the work of an interdisciplinary team in managing the distress of patients and families living with advanced illnesses? It turns out that there is good evidence to support the use of high-functioning interdisciplinary teams in the care of the seriously ill. Palliative care is associated with improved patient outcomes, including improvements in symptom control, quality of life, and end of life care, when it is delivered by an interdisciplinary team rather than by a solo practitioner.

You may think that teamwork is most useful for patients like John who have seemingly intractable social barriers. But it is also true that for even patients with many more social advantages teamwork improves quality of life. I got to see this up close recently in my own life.
 

Teamwork improves quality of life

My father recently passed away after a 9-month battle with advanced cancer. He had every advantage possible – financial stability, high health literacy, an incredibly devoted spouse who happens to be an RN, good insurance, and access to top-notch medical care. Yet, even he benefited from a team approach. It started small, with the oncologist and oncology NP providing excellent, patient-centered care. Then it grew to include myself as the daughter/palliative care nurse practitioner who made recommendations for treating his nausea and ensured that his advance directive was completed and uploaded to his chart. When my dad needed physical therapy, the home health agency sent a wonderful physical therapist, who brought all sorts of equipment that kept him more functional than he would have been otherwise. Other family members helped out – my sisters helped connect my dad with a priest who came to the home to provide spiritual care, which was crucial to ensuring that he was at peace. And, in his final days, my dad had the hospice team to help manage his symptoms and his family members to provide hands-on care.

Cancer, as one of my patients once remarked to me, is a “full-contact sport.” Living with advanced cancer touches nearly every aspect of a person’s life. The complexity of cancer care has long necessitated a team approach to planning cancer treatment – known as a tumor board – with medical oncology, radiation oncology, surgery, and pathology all weighing in. It makes sense that patients and their families would also need a team of clinicians representing different specialty areas to assist with the wide array of physical, psychosocial, practical, and spiritual concerns that arise throughout the cancer disease trajectory.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

John worked as a handyman and lived on a small sailboat in a marina. When he was diagnosed with metastatic kidney cancer at age 48, he quickly fell through the cracks. He failed to show to appointments and took oral anticancer treatments, but just sporadically. He had Medicaid, so insurance wasn’t the issue. It was everything else.

John was behind on his slip fees; he hadn’t been able to work for some time because of his progressive weakness and pain. He was chronically in danger of getting kicked out of his makeshift home aboard the boat. He had no reliable transportation to the clinic and so he didn’t come to appointments regularly. The specialty pharmacy refused to deliver his expensive oral chemotherapy to his address at the marina. He went days without eating full meals because he was too weak to cook for himself. Plus, he was estranged from his family who were unaware of his illness. His oncologist was overwhelmed trying to take care of him. He had a reasonable chance of achieving disease control on first-line oral therapy, but his problems seemed to hinder these chances at every turn. She was distraught – what could she do?

Enter the team approach. John’s oncologist reached out to our palliative care program for help. We recognized that this was a job too big for us alone so we connected John with the Extensivist Medicine program at UCLA Health, a high-intensity primary care program led by a physician specializing in primary care for high-risk individuals. The program provides wraparound outpatient services for chronically and seriously ill patients, like John, who are at risk for falling through the cracks. John went from receiving very little support to now having an entire team of caring professionals focused on helping him achieve his best possible outcome despite the seriousness of his disease.

He now had the support of a high-functioning team with clearly defined roles. Social work connected him with housing, food, and transportation resources. A nurse called him every day to check in and make sure he was taking medications and reminded him about his upcoming appointments. Case management helped him get needed equipment, such as grab bars and a walker. As his palliative care nurse practitioner, I counseled him on understanding his prognosis and planning ahead for medical emergencies. Our psycho-oncology clinicians helped John reconcile with his family, who were more than willing to take him in once they realized how ill he was. Once these social factors were addressed, John could more easily stay current with his oral chemotherapy, giving him the best chance possible to achieve a robust treatment response that could buy him more time.

And, John did get that time – he got 6 months of improved quality of life, during which he reconnected with his family, including his children, and rebuilt these important relationships. Eventually treatment failed him. His disease, already widely metastatic, became more active and painful. He accepted hospice care at his sister’s house and we transitioned him from our team to the hospice team. He died peacefully surrounded by family.
 

Interprofessional teamwork is fundamental to treat ‘total pain’

None of this would have been possible without the work of high-functioning teams. It is a commonly held belief that interprofessional teamwork is fundamental to the care of patients and families living with serious illness. But why? How did this idea come about? And what evidence is there to support teamwork?

Dame Cicely Saunders, who founded the modern hospice movement in mid-20th century England, embodied the interdisciplinary team by working first as a nurse, then a social worker, and finally as a physician. She wrote about patients’ “total pain,” the crisis of physical, spiritual, social, and emotional distress that many people have at the end of life. She understood that no single health care discipline was adequate to the task of addressing each of these domains equally well. Thus, hospice became synonymous with care provided by a quartet of specialists – physicians, nurses, social workers, and chaplains. Nowadays, there are other specialists that are added to the mix – home health aides, pharmacists, physical and occupational therapists, music and pet therapists, and so on.

But in medicine, like all areas of science, convention and tradition only go so far. What evidence is there to support the work of an interdisciplinary team in managing the distress of patients and families living with advanced illnesses? It turns out that there is good evidence to support the use of high-functioning interdisciplinary teams in the care of the seriously ill. Palliative care is associated with improved patient outcomes, including improvements in symptom control, quality of life, and end of life care, when it is delivered by an interdisciplinary team rather than by a solo practitioner.

You may think that teamwork is most useful for patients like John who have seemingly intractable social barriers. But it is also true that for even patients with many more social advantages teamwork improves quality of life. I got to see this up close recently in my own life.
 

Teamwork improves quality of life

My father recently passed away after a 9-month battle with advanced cancer. He had every advantage possible – financial stability, high health literacy, an incredibly devoted spouse who happens to be an RN, good insurance, and access to top-notch medical care. Yet, even he benefited from a team approach. It started small, with the oncologist and oncology NP providing excellent, patient-centered care. Then it grew to include myself as the daughter/palliative care nurse practitioner who made recommendations for treating his nausea and ensured that his advance directive was completed and uploaded to his chart. When my dad needed physical therapy, the home health agency sent a wonderful physical therapist, who brought all sorts of equipment that kept him more functional than he would have been otherwise. Other family members helped out – my sisters helped connect my dad with a priest who came to the home to provide spiritual care, which was crucial to ensuring that he was at peace. And, in his final days, my dad had the hospice team to help manage his symptoms and his family members to provide hands-on care.

Cancer, as one of my patients once remarked to me, is a “full-contact sport.” Living with advanced cancer touches nearly every aspect of a person’s life. The complexity of cancer care has long necessitated a team approach to planning cancer treatment – known as a tumor board – with medical oncology, radiation oncology, surgery, and pathology all weighing in. It makes sense that patients and their families would also need a team of clinicians representing different specialty areas to assist with the wide array of physical, psychosocial, practical, and spiritual concerns that arise throughout the cancer disease trajectory.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

John worked as a handyman and lived on a small sailboat in a marina. When he was diagnosed with metastatic kidney cancer at age 48, he quickly fell through the cracks. He failed to show to appointments and took oral anticancer treatments, but just sporadically. He had Medicaid, so insurance wasn’t the issue. It was everything else.

John was behind on his slip fees; he hadn’t been able to work for some time because of his progressive weakness and pain. He was chronically in danger of getting kicked out of his makeshift home aboard the boat. He had no reliable transportation to the clinic and so he didn’t come to appointments regularly. The specialty pharmacy refused to deliver his expensive oral chemotherapy to his address at the marina. He went days without eating full meals because he was too weak to cook for himself. Plus, he was estranged from his family who were unaware of his illness. His oncologist was overwhelmed trying to take care of him. He had a reasonable chance of achieving disease control on first-line oral therapy, but his problems seemed to hinder these chances at every turn. She was distraught – what could she do?

Enter the team approach. John’s oncologist reached out to our palliative care program for help. We recognized that this was a job too big for us alone so we connected John with the Extensivist Medicine program at UCLA Health, a high-intensity primary care program led by a physician specializing in primary care for high-risk individuals. The program provides wraparound outpatient services for chronically and seriously ill patients, like John, who are at risk for falling through the cracks. John went from receiving very little support to now having an entire team of caring professionals focused on helping him achieve his best possible outcome despite the seriousness of his disease.

He now had the support of a high-functioning team with clearly defined roles. Social work connected him with housing, food, and transportation resources. A nurse called him every day to check in and make sure he was taking medications and reminded him about his upcoming appointments. Case management helped him get needed equipment, such as grab bars and a walker. As his palliative care nurse practitioner, I counseled him on understanding his prognosis and planning ahead for medical emergencies. Our psycho-oncology clinicians helped John reconcile with his family, who were more than willing to take him in once they realized how ill he was. Once these social factors were addressed, John could more easily stay current with his oral chemotherapy, giving him the best chance possible to achieve a robust treatment response that could buy him more time.

And, John did get that time – he got 6 months of improved quality of life, during which he reconnected with his family, including his children, and rebuilt these important relationships. Eventually treatment failed him. His disease, already widely metastatic, became more active and painful. He accepted hospice care at his sister’s house and we transitioned him from our team to the hospice team. He died peacefully surrounded by family.
 

Interprofessional teamwork is fundamental to treat ‘total pain’

None of this would have been possible without the work of high-functioning teams. It is a commonly held belief that interprofessional teamwork is fundamental to the care of patients and families living with serious illness. But why? How did this idea come about? And what evidence is there to support teamwork?

Dame Cicely Saunders, who founded the modern hospice movement in mid-20th century England, embodied the interdisciplinary team by working first as a nurse, then a social worker, and finally as a physician. She wrote about patients’ “total pain,” the crisis of physical, spiritual, social, and emotional distress that many people have at the end of life. She understood that no single health care discipline was adequate to the task of addressing each of these domains equally well. Thus, hospice became synonymous with care provided by a quartet of specialists – physicians, nurses, social workers, and chaplains. Nowadays, there are other specialists that are added to the mix – home health aides, pharmacists, physical and occupational therapists, music and pet therapists, and so on.

But in medicine, like all areas of science, convention and tradition only go so far. What evidence is there to support the work of an interdisciplinary team in managing the distress of patients and families living with advanced illnesses? It turns out that there is good evidence to support the use of high-functioning interdisciplinary teams in the care of the seriously ill. Palliative care is associated with improved patient outcomes, including improvements in symptom control, quality of life, and end of life care, when it is delivered by an interdisciplinary team rather than by a solo practitioner.

You may think that teamwork is most useful for patients like John who have seemingly intractable social barriers. But it is also true that for even patients with many more social advantages teamwork improves quality of life. I got to see this up close recently in my own life.
 

Teamwork improves quality of life

My father recently passed away after a 9-month battle with advanced cancer. He had every advantage possible – financial stability, high health literacy, an incredibly devoted spouse who happens to be an RN, good insurance, and access to top-notch medical care. Yet, even he benefited from a team approach. It started small, with the oncologist and oncology NP providing excellent, patient-centered care. Then it grew to include myself as the daughter/palliative care nurse practitioner who made recommendations for treating his nausea and ensured that his advance directive was completed and uploaded to his chart. When my dad needed physical therapy, the home health agency sent a wonderful physical therapist, who brought all sorts of equipment that kept him more functional than he would have been otherwise. Other family members helped out – my sisters helped connect my dad with a priest who came to the home to provide spiritual care, which was crucial to ensuring that he was at peace. And, in his final days, my dad had the hospice team to help manage his symptoms and his family members to provide hands-on care.

Cancer, as one of my patients once remarked to me, is a “full-contact sport.” Living with advanced cancer touches nearly every aspect of a person’s life. The complexity of cancer care has long necessitated a team approach to planning cancer treatment – known as a tumor board – with medical oncology, radiation oncology, surgery, and pathology all weighing in. It makes sense that patients and their families would also need a team of clinicians representing different specialty areas to assist with the wide array of physical, psychosocial, practical, and spiritual concerns that arise throughout the cancer disease trajectory.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

MILAN – In the current spread of monkeypox among countries outside of Africa, this zoonotic orthopox DNA virus is sexually transmitted in more than 90% of cases, mostly among men having sex with men (MSM), and can produce severe skin and systemic symptoms but is rarely fatal, according to a breaking news presentation at the annual congress of the European Academy of Dermatology and Venereology.

Synthesizing data from 185 cases in Spain with several sets of recently published data, Alba Català, MD, a dermatologist at Centro Médico Teknon, Barcelona, said at the meeting that there have been only two deaths in Spain in the current epidemic. (As of Sept. 30, after the EADV meeting had concluded, a total of three deaths related to monkeypox in Spain and one death in the United States had been reported, according to the Centers for Disease Control and Prevention).

Hospitalizations have been uncommon, and in Spain, there were only four hospitalizations, according to data collected from the beginning of May through early August, she said. Almost all cases in this Spanish series were from men having high-risk sex with men. Upon screening, 76% had another sexually transmitted disease, including 41% infected with human immunodeficiency virus.
 

More than 40% of patients with monkeypox have HIV

These data are consistent with several other recently published studies, such as one that evaluated 528 infections in 16 non-African countries, including those in North America, South America, Europe, the Mideast, as well as Australia. In that survey, published in the New England Journal of Medicine, and covering cases between late April and late June, 2022, 41% were HIV positive. Of those who were HIV negative, 57% were taking a pre-exposure prophylaxis regimen of antiretroviral drugs to prevent HIV infection.

However, these data do not preclude a significant risk of nonsexual transmission, according to Dr. Català, who noted that respiratory transmission and transmission through nonsexual skin contact is well documented in endemic areas.

“The virus has no preference for a sexual orientation,” Dr. Català cautioned. Despite the consistency of the data in regard to a largely MSM transmission in the epidemic so far, “these data may change with further spread of infection in the community.”

Typically, the incubation period of monkeypox lasts several days before the invasive period, which is commonly accompanied by systemic complaints, particularly fever, headache, and often lymphadenopathy. These systemic features usually but not always precede cutaneous involvement, which is seen in more than 90% of patients, according to Dr. Català. In the Spanish series, mucocutaneous involvement was recorded in 100% of patients.

Monkeypox and smallpox

“The differential diagnosis might include other vesicular eruptions, such as those caused by varicella or smallpox,” reported Dr. Català, who noted that monkeypox and smallpox are related.

Cutaneous lesions often appear first at the site of infection, such as the genitalia, but typically spread in a secondary eruption that is pruritic and may take days to resolve, according to Dr. Català. She reported that single lesions are less common but do occur. While hundreds of lesions have been reported among cases in endemic areas, most patients had 25 lesions or fewer in the Spanish epidemic and other recent series.

Even though there is a common progression in which lesions begin in a papular stage before the vesicular and pustular stages in a given area, new eruptions can occur before a prior eruption develops scabs.

“Frequently, not all the patient’s lesions are in the same stage of development,” said Dr. Català, who explained that disease activity and its complications, such as proctitis, pharyngitis, and penile edema, can take weeks to resolve. Because of the highly invasive nature of monkeypox, it is appropriate to be alert to less common manifestations, such as ocular involvement.

Many of these and other complications, such as secondary bacterial infections, will require targeted treatment, but the mainstay of therapy for the dermatologic manifestations of monkeypox is symptomatic treatment that includes nonsteroidal anti-inflammatory drugs and analgesics.
 

Re-epithelialization reduces transmission risk

“A clean, moist environment can mitigate transmission potential by covering infectious sores and promoting the re-epithelialization of the damaged exanthem,” Dr. Català advised. Tecovirimat (TPOXX, ST-246), an antiviral drug for smallpox, is approved for treating monkeypox in Europe but not in the United States (but it is approved for smallpox in the United States). Another antiviral drug, brincidofovir (CMX001 or Tembexa), is approved for smallpox in the United States, but not in Europe, according to Dr. Català. (In the United States, no treatment is specifically approved for treating monkeypox, but antivirals developed for smallpox “may prove beneficial against monkeypox,” according to the CDC.)

But she advised weighing the risks and benefits of using either drug in any individual patient.

The data suggest that the risk of viral shedding persists until the late stages of the disease trajectory. “A person is considered infectious from the onset of clinical manifestations until all skin lesions have scabbed over and re-epithelization has occurred,” Dr. Català said.

The prolonged period of contagion might be one reason to expect monkeypox to be transmitted more generally than it is now, according to Boghuma K. Titanji, MD, PhD, assistant professor of infectious diseases, Emory University, Atlanta.

“The longer the outbreak persists, the more likely we will see cases reported in groups other than MSM who have been most affected so far,” said Dr. Titanji, the first author of a recently published review article on monkeypox in Open Forum Infectious Diseases.

However, he acknowledged that a COVID-like spread is not expected. “The spread of monkeypox requires close and prolonged contact and is generally inefficient via fomites and droplet modes of transmission,” Dr. Titanji said in an interview. “Spread in heterosexual networks and congregate settings like crowded jails where close contact is unavoidable remains a concern that we need to educate the public about and maintain a high level of vigilance for.”

Dr. Català and Dr. Titanji report no potential conflicts of interest.

MILAN – In the current spread of monkeypox among countries outside of Africa, this zoonotic orthopox DNA virus is sexually transmitted in more than 90% of cases, mostly among men having sex with men (MSM), and can produce severe skin and systemic symptoms but is rarely fatal, according to a breaking news presentation at the annual congress of the European Academy of Dermatology and Venereology.

Synthesizing data from 185 cases in Spain with several sets of recently published data, Alba Català, MD, a dermatologist at Centro Médico Teknon, Barcelona, said at the meeting that there have been only two deaths in Spain in the current epidemic. (As of Sept. 30, after the EADV meeting had concluded, a total of three deaths related to monkeypox in Spain and one death in the United States had been reported, according to the Centers for Disease Control and Prevention).

Hospitalizations have been uncommon, and in Spain, there were only four hospitalizations, according to data collected from the beginning of May through early August, she said. Almost all cases in this Spanish series were from men having high-risk sex with men. Upon screening, 76% had another sexually transmitted disease, including 41% infected with human immunodeficiency virus.
 

More than 40% of patients with monkeypox have HIV

These data are consistent with several other recently published studies, such as one that evaluated 528 infections in 16 non-African countries, including those in North America, South America, Europe, the Mideast, as well as Australia. In that survey, published in the New England Journal of Medicine, and covering cases between late April and late June, 2022, 41% were HIV positive. Of those who were HIV negative, 57% were taking a pre-exposure prophylaxis regimen of antiretroviral drugs to prevent HIV infection.

However, these data do not preclude a significant risk of nonsexual transmission, according to Dr. Català, who noted that respiratory transmission and transmission through nonsexual skin contact is well documented in endemic areas.

“The virus has no preference for a sexual orientation,” Dr. Català cautioned. Despite the consistency of the data in regard to a largely MSM transmission in the epidemic so far, “these data may change with further spread of infection in the community.”

Typically, the incubation period of monkeypox lasts several days before the invasive period, which is commonly accompanied by systemic complaints, particularly fever, headache, and often lymphadenopathy. These systemic features usually but not always precede cutaneous involvement, which is seen in more than 90% of patients, according to Dr. Català. In the Spanish series, mucocutaneous involvement was recorded in 100% of patients.

Monkeypox and smallpox

“The differential diagnosis might include other vesicular eruptions, such as those caused by varicella or smallpox,” reported Dr. Català, who noted that monkeypox and smallpox are related.

Cutaneous lesions often appear first at the site of infection, such as the genitalia, but typically spread in a secondary eruption that is pruritic and may take days to resolve, according to Dr. Català. She reported that single lesions are less common but do occur. While hundreds of lesions have been reported among cases in endemic areas, most patients had 25 lesions or fewer in the Spanish epidemic and other recent series.

Even though there is a common progression in which lesions begin in a papular stage before the vesicular and pustular stages in a given area, new eruptions can occur before a prior eruption develops scabs.

“Frequently, not all the patient’s lesions are in the same stage of development,” said Dr. Català, who explained that disease activity and its complications, such as proctitis, pharyngitis, and penile edema, can take weeks to resolve. Because of the highly invasive nature of monkeypox, it is appropriate to be alert to less common manifestations, such as ocular involvement.

Many of these and other complications, such as secondary bacterial infections, will require targeted treatment, but the mainstay of therapy for the dermatologic manifestations of monkeypox is symptomatic treatment that includes nonsteroidal anti-inflammatory drugs and analgesics.
 

Re-epithelialization reduces transmission risk

“A clean, moist environment can mitigate transmission potential by covering infectious sores and promoting the re-epithelialization of the damaged exanthem,” Dr. Català advised. Tecovirimat (TPOXX, ST-246), an antiviral drug for smallpox, is approved for treating monkeypox in Europe but not in the United States (but it is approved for smallpox in the United States). Another antiviral drug, brincidofovir (CMX001 or Tembexa), is approved for smallpox in the United States, but not in Europe, according to Dr. Català. (In the United States, no treatment is specifically approved for treating monkeypox, but antivirals developed for smallpox “may prove beneficial against monkeypox,” according to the CDC.)

But she advised weighing the risks and benefits of using either drug in any individual patient.

The data suggest that the risk of viral shedding persists until the late stages of the disease trajectory. “A person is considered infectious from the onset of clinical manifestations until all skin lesions have scabbed over and re-epithelization has occurred,” Dr. Català said.

The prolonged period of contagion might be one reason to expect monkeypox to be transmitted more generally than it is now, according to Boghuma K. Titanji, MD, PhD, assistant professor of infectious diseases, Emory University, Atlanta.

“The longer the outbreak persists, the more likely we will see cases reported in groups other than MSM who have been most affected so far,” said Dr. Titanji, the first author of a recently published review article on monkeypox in Open Forum Infectious Diseases.

However, he acknowledged that a COVID-like spread is not expected. “The spread of monkeypox requires close and prolonged contact and is generally inefficient via fomites and droplet modes of transmission,” Dr. Titanji said in an interview. “Spread in heterosexual networks and congregate settings like crowded jails where close contact is unavoidable remains a concern that we need to educate the public about and maintain a high level of vigilance for.”

Dr. Català and Dr. Titanji report no potential conflicts of interest.

MILAN – In the current spread of monkeypox among countries outside of Africa, this zoonotic orthopox DNA virus is sexually transmitted in more than 90% of cases, mostly among men having sex with men (MSM), and can produce severe skin and systemic symptoms but is rarely fatal, according to a breaking news presentation at the annual congress of the European Academy of Dermatology and Venereology.

Synthesizing data from 185 cases in Spain with several sets of recently published data, Alba Català, MD, a dermatologist at Centro Médico Teknon, Barcelona, said at the meeting that there have been only two deaths in Spain in the current epidemic. (As of Sept. 30, after the EADV meeting had concluded, a total of three deaths related to monkeypox in Spain and one death in the United States had been reported, according to the Centers for Disease Control and Prevention).

Hospitalizations have been uncommon, and in Spain, there were only four hospitalizations, according to data collected from the beginning of May through early August, she said. Almost all cases in this Spanish series were from men having high-risk sex with men. Upon screening, 76% had another sexually transmitted disease, including 41% infected with human immunodeficiency virus.
 

More than 40% of patients with monkeypox have HIV

These data are consistent with several other recently published studies, such as one that evaluated 528 infections in 16 non-African countries, including those in North America, South America, Europe, the Mideast, as well as Australia. In that survey, published in the New England Journal of Medicine, and covering cases between late April and late June, 2022, 41% were HIV positive. Of those who were HIV negative, 57% were taking a pre-exposure prophylaxis regimen of antiretroviral drugs to prevent HIV infection.

However, these data do not preclude a significant risk of nonsexual transmission, according to Dr. Català, who noted that respiratory transmission and transmission through nonsexual skin contact is well documented in endemic areas.

“The virus has no preference for a sexual orientation,” Dr. Català cautioned. Despite the consistency of the data in regard to a largely MSM transmission in the epidemic so far, “these data may change with further spread of infection in the community.”

Typically, the incubation period of monkeypox lasts several days before the invasive period, which is commonly accompanied by systemic complaints, particularly fever, headache, and often lymphadenopathy. These systemic features usually but not always precede cutaneous involvement, which is seen in more than 90% of patients, according to Dr. Català. In the Spanish series, mucocutaneous involvement was recorded in 100% of patients.

Monkeypox and smallpox

“The differential diagnosis might include other vesicular eruptions, such as those caused by varicella or smallpox,” reported Dr. Català, who noted that monkeypox and smallpox are related.

Cutaneous lesions often appear first at the site of infection, such as the genitalia, but typically spread in a secondary eruption that is pruritic and may take days to resolve, according to Dr. Català. She reported that single lesions are less common but do occur. While hundreds of lesions have been reported among cases in endemic areas, most patients had 25 lesions or fewer in the Spanish epidemic and other recent series.

Even though there is a common progression in which lesions begin in a papular stage before the vesicular and pustular stages in a given area, new eruptions can occur before a prior eruption develops scabs.

“Frequently, not all the patient’s lesions are in the same stage of development,” said Dr. Català, who explained that disease activity and its complications, such as proctitis, pharyngitis, and penile edema, can take weeks to resolve. Because of the highly invasive nature of monkeypox, it is appropriate to be alert to less common manifestations, such as ocular involvement.

Many of these and other complications, such as secondary bacterial infections, will require targeted treatment, but the mainstay of therapy for the dermatologic manifestations of monkeypox is symptomatic treatment that includes nonsteroidal anti-inflammatory drugs and analgesics.
 

Re-epithelialization reduces transmission risk

“A clean, moist environment can mitigate transmission potential by covering infectious sores and promoting the re-epithelialization of the damaged exanthem,” Dr. Català advised. Tecovirimat (TPOXX, ST-246), an antiviral drug for smallpox, is approved for treating monkeypox in Europe but not in the United States (but it is approved for smallpox in the United States). Another antiviral drug, brincidofovir (CMX001 or Tembexa), is approved for smallpox in the United States, but not in Europe, according to Dr. Català. (In the United States, no treatment is specifically approved for treating monkeypox, but antivirals developed for smallpox “may prove beneficial against monkeypox,” according to the CDC.)

But she advised weighing the risks and benefits of using either drug in any individual patient.

The data suggest that the risk of viral shedding persists until the late stages of the disease trajectory. “A person is considered infectious from the onset of clinical manifestations until all skin lesions have scabbed over and re-epithelization has occurred,” Dr. Català said.

The prolonged period of contagion might be one reason to expect monkeypox to be transmitted more generally than it is now, according to Boghuma K. Titanji, MD, PhD, assistant professor of infectious diseases, Emory University, Atlanta.

“The longer the outbreak persists, the more likely we will see cases reported in groups other than MSM who have been most affected so far,” said Dr. Titanji, the first author of a recently published review article on monkeypox in Open Forum Infectious Diseases.

However, he acknowledged that a COVID-like spread is not expected. “The spread of monkeypox requires close and prolonged contact and is generally inefficient via fomites and droplet modes of transmission,” Dr. Titanji said in an interview. “Spread in heterosexual networks and congregate settings like crowded jails where close contact is unavoidable remains a concern that we need to educate the public about and maintain a high level of vigilance for.”

Dr. Català and Dr. Titanji report no potential conflicts of interest.

While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.

Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children. Now, a large clinical trial launched by the Leukemia & Lymphoma Society (LLS) seeks to revolutionize pediatric AML care by testing multiple experimental treatments across the globe. Its goal goes beyond simply boosting survival.

“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”

The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).

The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.

“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”

In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”

In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.

“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”

Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.

The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”

In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”

In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”

In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.

What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”

As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.

”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”

Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.

While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.

Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children. Now, a large clinical trial launched by the Leukemia & Lymphoma Society (LLS) seeks to revolutionize pediatric AML care by testing multiple experimental treatments across the globe. Its goal goes beyond simply boosting survival.

“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”

The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).

The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.

“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”

In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”

In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.

“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”

Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.

The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”

In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”

In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”

In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.

What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”

As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.

”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”

Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.

While great strides have been made in children’s leukemia care during the past 50 years, statistics have remained grim. For acute myeloid leukemia (AML), the most common type, 5-year survival rates were just 69% for children younger than 15 between 2009 and 2015. Patients who do survive past adolescence face high risks of future complications.

Specialists say the challenges hindering more progress include a lack of clinical research, an emphasis on competition over cooperation, and sparse insight into how best to adjust adult leukemia treatments to children. Now, a large clinical trial launched by the Leukemia & Lymphoma Society (LLS) seeks to revolutionize pediatric AML care by testing multiple experimental treatments across the globe. Its goal goes beyond simply boosting survival.

“Our project aims to find better treatments, more targeted treatments, that will leave children with fewer long-term health problems as adults. We want them to not just survive but thrive,” Gwen Nichols, MD, chief medical officer of LLS, said in an interview. “What we’ve had was not working for anybody. So we have to try a different approach.”

The LLS Pediatric Acute Leukemia (PedAL) Master Trial launched in spring of 2022. Seventy-five study locations from Nova Scotia to Hawaii are now recruiting patients up to age 22 with known or suspected relapsed/refractory AML, mixed phenotype acute leukemia, or relapsed acute lymphoblastic leukemia (ALL).

The 5-year trial expects to recruit 960 participants in the United States and Canada. Clinics in Europe, Australia, and New Zealand also are taking part.

“Pediatric oncologists should know that PedAL, for the first time, is providing a cooperative, seamless way to interrogate [the genomics of] a child’s leukemia,” hematologist/oncologist Todd Cooper, DO, section chief of pediatric oncology at Seattle Children’s Cancer and Blood Disorders Center, said in an interview. “It is also providing a seamless and efficient way for children to be assigned to clinical trials that are going to be tailored towards a particular child’s leukemia. This is something that’s never been done.”

In North America, all trial participants with relapsed AML will undergo genetic sequencing for free as part of the screening process. Clinics “can’t always access genomic screening for their patients,” Dr. Nichols said. “We’re providing that even if they don’t participate in any other part of the trial, even if they go and get another available therapy or go on a different trial. We want them to know that this is available, and they will get the results. And if they’re looking for a trial when they get those results, we have trained oncology nurses who will help them navigate and find clinical trials.”

In PedAL itself, one subtrial is now in progress: An open-label phase 3 randomized multicenter analysis of whether the oral leukemia drug venetoclax combined with the intensive infused chemotherapy treatment FLA+GO (fludarabine, high-dose cytarabine, and gemtuzumab ozogamicin) will improve overall survival compared to FLA+GO alone. Ninety-eight subjects are expected to join the 5-year subtrial.

“We expect within the next year to open three or four different subtrials of targeted therapies for specific groups of patients,” E. Anders Kolb, MD, chief of oncology and hematology at Nemours Children’s Health in Delaware and cochair of the PedAL trial, said in an interview. “Over the course of the next few years, we’re going to learn a lot about the natural history of relapsed leukemia – we don’t have a ton of data on that – and then how targeted therapies may alter some of those outcomes.”

Discussions with multiple drugmakers are in progress regarding the potential subtrials, he said.

The PedAL strategy addresses the lack of new drugs for children with AML, Seattle Children’s Dr. Cooper said. One main reason for the gap is that childhood leukemia is much less common than the adult form, he said, so a lot of drug development is geared toward adults. As a result, he said, new drugs “are geared towards adults whose leukemia is not as aggressive. Whereas in children, the acute leukemias, especially AML, are quite aggressive and need therapies that are often more intense.”

In addition, he said, “we have only recently become aware of how AML is biologically much different than in adults.”

In AML, Delaware’s Dr. Kolb explained, “there are many different phenotypes – ways that these cells can look and behave. But we treat them with a single regimen. What I like to tell families is that we’ve got a few tools in our toolbox, but they all happen to be sledgehammers. The key to the challenge in AML is that it is a molecular disease, but we’re treating it with therapies that were developed 40-50 years ago.”

In PedAL, the goal is to figure out the best ways to target therapy for the specific types that patients have. On this front, the genomic screening in the trial is crucial because it will identify which patients express certain targets and allow them to be assigned to appropriate sub-trials, Dr. Coooper said.

What’s next? “LLS has planned for this to be ongoing for the next 5 to 7 years, so that we can get a number of studies up and running,” Dr. Nichols said. “After that, those studies will continue. We will hope that most of them can be self-funded by then.”

As for cost, she noted that the PedAL trial is part of the society’s Dare to Dream Project, formerly known as the Children’s Initiative, which focuses on pediatric blood cancers. The project, with a fundraising goal of $175 million, focuses on research, patient services and survivorship.

”We have a whole range of services, travel assistance, copay programs and educational resources that doctors may want to use as a valid source of information,” she said. ‘When I was in practice, patients were always asking me, ‘Do you have anything I can read or take home to give my son something about his disease?’ LLS has good-quality, patient-level information for patients. We welcome people contacting us or going to our website and taking advantage of that for free.”

Dr. Nichols and Dr. Kolb report no disclosures. Dr. Cooper reports academic funding from LLS.