The Diagnosis: Circumscribed Palmar Hypokeratosis

Circumscribed palmar hypokeratosis is a rare, benign, acquired dermatosis that was first described by Pérez et al¹ in 2002 and is characterized by annular plaques with an atrophic center and hyperkeratotic edges. Classically, the lesions present on the thenar and hypothenar eminences of the palms.² The condition predominantly affects women (4:1 ratio), with a mean age of onset of 65 years.³

Although the pathogenesis of circumscribed palmar hypokeratosis is unknown, local trauma generally is considered to be the causative factor. Other hypotheses include human papillomaviruses 4 and 6 infection and primary abnormal keratinization in the epidermis.³ Immunohistochemical studies have demonstrated increased expression of keratin 16 and Ki-67 in cutaneous lesions, which is postulated to be responsible for keratinocyte fragility associated with epidermal hyperproliferation. Other reported cases have shown diminished keratin 9, keratin 2e, and connexin 26 expression, which normally are abundant in the acral epidermis. Abnormal expression of antigens associated with epidermal proliferation and differentiation also have been reported,³ suggesting that there is an altered regulation of the cutaneous desquamation process.

Histologically, circumscribed palmar hypokeratosis is characterized by an abrupt reduction in the stratum corneum (Figure), forming a step between the lesion and the perilesional normal skin.^2,3 The clinical appearance of erythema is due to visualization of dermal blood circulation in the area of corneal thinning and is not a result of vasodilation. The dermis is uninvolved, and inflammation is absent. The differential diagnosis includes psoriasis, Bowen disease, porokeratosis, and dermatophytosis.³

Circumscribed palmar hypokeratosis is a chronic condition, and there are no known reports of development of malignancy. Treatment is not required but may include cryotherapy; topical therapy with corticosteroids, retinoids, urea, and calcipotriene; and photodynamic therapy. Circumscribed hypokeratosis should be included in the differential diagnosis of palmar lesions.

The Diagnosis: Circumscribed Palmar Hypokeratosis

Circumscribed palmar hypokeratosis is a rare, benign, acquired dermatosis that was first described by Pérez et al¹ in 2002 and is characterized by annular plaques with an atrophic center and hyperkeratotic edges. Classically, the lesions present on the thenar and hypothenar eminences of the palms.² The condition predominantly affects women (4:1 ratio), with a mean age of onset of 65 years.³

Although the pathogenesis of circumscribed palmar hypokeratosis is unknown, local trauma generally is considered to be the causative factor. Other hypotheses include human papillomaviruses 4 and 6 infection and primary abnormal keratinization in the epidermis.³ Immunohistochemical studies have demonstrated increased expression of keratin 16 and Ki-67 in cutaneous lesions, which is postulated to be responsible for keratinocyte fragility associated with epidermal hyperproliferation. Other reported cases have shown diminished keratin 9, keratin 2e, and connexin 26 expression, which normally are abundant in the acral epidermis. Abnormal expression of antigens associated with epidermal proliferation and differentiation also have been reported,³ suggesting that there is an altered regulation of the cutaneous desquamation process.

Histologically, circumscribed palmar hypokeratosis is characterized by an abrupt reduction in the stratum corneum (Figure), forming a step between the lesion and the perilesional normal skin.^2,3 The clinical appearance of erythema is due to visualization of dermal blood circulation in the area of corneal thinning and is not a result of vasodilation. The dermis is uninvolved, and inflammation is absent. The differential diagnosis includes psoriasis, Bowen disease, porokeratosis, and dermatophytosis.³

Circumscribed palmar hypokeratosis is a chronic condition, and there are no known reports of development of malignancy. Treatment is not required but may include cryotherapy; topical therapy with corticosteroids, retinoids, urea, and calcipotriene; and photodynamic therapy. Circumscribed hypokeratosis should be included in the differential diagnosis of palmar lesions.

The Diagnosis: Circumscribed Palmar Hypokeratosis

Circumscribed palmar hypokeratosis is a rare, benign, acquired dermatosis that was first described by Pérez et al¹ in 2002 and is characterized by annular plaques with an atrophic center and hyperkeratotic edges. Classically, the lesions present on the thenar and hypothenar eminences of the palms.² The condition predominantly affects women (4:1 ratio), with a mean age of onset of 65 years.³

Although the pathogenesis of circumscribed palmar hypokeratosis is unknown, local trauma generally is considered to be the causative factor. Other hypotheses include human papillomaviruses 4 and 6 infection and primary abnormal keratinization in the epidermis.³ Immunohistochemical studies have demonstrated increased expression of keratin 16 and Ki-67 in cutaneous lesions, which is postulated to be responsible for keratinocyte fragility associated with epidermal hyperproliferation. Other reported cases have shown diminished keratin 9, keratin 2e, and connexin 26 expression, which normally are abundant in the acral epidermis. Abnormal expression of antigens associated with epidermal proliferation and differentiation also have been reported,³ suggesting that there is an altered regulation of the cutaneous desquamation process.

Histologically, circumscribed palmar hypokeratosis is characterized by an abrupt reduction in the stratum corneum (Figure), forming a step between the lesion and the perilesional normal skin.^2,3 The clinical appearance of erythema is due to visualization of dermal blood circulation in the area of corneal thinning and is not a result of vasodilation. The dermis is uninvolved, and inflammation is absent. The differential diagnosis includes psoriasis, Bowen disease, porokeratosis, and dermatophytosis.³

Circumscribed palmar hypokeratosis is a chronic condition, and there are no known reports of development of malignancy. Treatment is not required but may include cryotherapy; topical therapy with corticosteroids, retinoids, urea, and calcipotriene; and photodynamic therapy. Circumscribed hypokeratosis should be included in the differential diagnosis of palmar lesions.

ORLANDO – Intensified multifactorial treatment proved cost effective over time in type 2 diabetes patients in the practice-changing Steno-2 study, according to 21-year follow-up data from the randomized Danish study.

Cumulative direct health care costs from the start of the trial in 1993 through 2014 were about $13 million in 24 patients in the intensive treatment group who were available for follow-up, and about $12.3 million in 42 patients in the conventional treatment group. The difference in costs between the groups was not statistically significant, Joachim Gaede reported at the annual scientific sessions of the American Diabetes Association.

Costs per patient-year during 1996-2014, however, were significantly lower in the intensive treatment group ($9,648 vs. $10, 681, respectively), said Mr. Gaede, a graduate student in the medicine program at the University of Copenhagen.

Furthermore, patients in the intensified treatment group lived a median of 7.9 years longer than did those who were in the conventional treatment group, suggesting that while costs might be higher early on, investing in early intensified treatment of all known modifiable risk factors in high-risk patients will prolong life and still save money over time thanks to reduced complication-related costs, he noted.

Steno-2 was an open, parallel group study initiated in 1993 to compare conventional multifactorial treatment of type 2 diabetes mellitus (T2DM) with an intensified approach over an 8-year period. Enrollment included 160 patients with high-risk type 2 diabetes. After the primary composite cardiovascular endpoint was assessed, the trial continued as an observational study, with all patients given the intensified, multifactorial treatment that consisted of lifestyle measures and medications targeting hyperglycemia, hypertension, hypercholesterolemia, and hypercoagulation.

Reports from the study over the years led to changes in treatment guidelines to promote more intensive multifactorial treatment, Mr. Gaede said. For example, the initial results reported in 1999 showed a 50% relative risk reduction in kidney, eye, and nerve complications after 4 years with intensive versus conventional treatment; a 2003 report showed a 53% relative risk reduction in MI, stroke, and amputation after 8 years; and a 2008 report demonstrated a 46% relative risk reduction in death after 13 years. Finally, in 2016 a 7.9-year gain in lifespan after 21 years with intensive versus conventional treatment was reported.

In this video interview, Mr. Gaede, junior lead study author, discusses the Steno-2 study findings and the current cost analysis data.

“The bottom line is that ... you can actually, as a patient, be treated at a specialized diabetes clinic ... and, in the long run, it doesn’t cost you anything” more, he said, explaining that the up-front costs of intensive treatment are offset by the money saved because of the reduced complications over time.

Mr. Gaede reported having no disclosures.

[email protected]

SOURCE: Gaede J et al. ADA 2018, Abstract 162-OR.

ORLANDO – Intensified multifactorial treatment proved cost effective over time in type 2 diabetes patients in the practice-changing Steno-2 study, according to 21-year follow-up data from the randomized Danish study.

Cumulative direct health care costs from the start of the trial in 1993 through 2014 were about $13 million in 24 patients in the intensive treatment group who were available for follow-up, and about $12.3 million in 42 patients in the conventional treatment group. The difference in costs between the groups was not statistically significant, Joachim Gaede reported at the annual scientific sessions of the American Diabetes Association.

Costs per patient-year during 1996-2014, however, were significantly lower in the intensive treatment group ($9,648 vs. $10, 681, respectively), said Mr. Gaede, a graduate student in the medicine program at the University of Copenhagen.

Furthermore, patients in the intensified treatment group lived a median of 7.9 years longer than did those who were in the conventional treatment group, suggesting that while costs might be higher early on, investing in early intensified treatment of all known modifiable risk factors in high-risk patients will prolong life and still save money over time thanks to reduced complication-related costs, he noted.

Steno-2 was an open, parallel group study initiated in 1993 to compare conventional multifactorial treatment of type 2 diabetes mellitus (T2DM) with an intensified approach over an 8-year period. Enrollment included 160 patients with high-risk type 2 diabetes. After the primary composite cardiovascular endpoint was assessed, the trial continued as an observational study, with all patients given the intensified, multifactorial treatment that consisted of lifestyle measures and medications targeting hyperglycemia, hypertension, hypercholesterolemia, and hypercoagulation.

Reports from the study over the years led to changes in treatment guidelines to promote more intensive multifactorial treatment, Mr. Gaede said. For example, the initial results reported in 1999 showed a 50% relative risk reduction in kidney, eye, and nerve complications after 4 years with intensive versus conventional treatment; a 2003 report showed a 53% relative risk reduction in MI, stroke, and amputation after 8 years; and a 2008 report demonstrated a 46% relative risk reduction in death after 13 years. Finally, in 2016 a 7.9-year gain in lifespan after 21 years with intensive versus conventional treatment was reported.

In this video interview, Mr. Gaede, junior lead study author, discusses the Steno-2 study findings and the current cost analysis data.

“The bottom line is that ... you can actually, as a patient, be treated at a specialized diabetes clinic ... and, in the long run, it doesn’t cost you anything” more, he said, explaining that the up-front costs of intensive treatment are offset by the money saved because of the reduced complications over time.

Mr. Gaede reported having no disclosures.

[email protected]

SOURCE: Gaede J et al. ADA 2018, Abstract 162-OR.

ORLANDO – Intensified multifactorial treatment proved cost effective over time in type 2 diabetes patients in the practice-changing Steno-2 study, according to 21-year follow-up data from the randomized Danish study.

Cumulative direct health care costs from the start of the trial in 1993 through 2014 were about $13 million in 24 patients in the intensive treatment group who were available for follow-up, and about $12.3 million in 42 patients in the conventional treatment group. The difference in costs between the groups was not statistically significant, Joachim Gaede reported at the annual scientific sessions of the American Diabetes Association.

Costs per patient-year during 1996-2014, however, were significantly lower in the intensive treatment group ($9,648 vs. $10, 681, respectively), said Mr. Gaede, a graduate student in the medicine program at the University of Copenhagen.

Furthermore, patients in the intensified treatment group lived a median of 7.9 years longer than did those who were in the conventional treatment group, suggesting that while costs might be higher early on, investing in early intensified treatment of all known modifiable risk factors in high-risk patients will prolong life and still save money over time thanks to reduced complication-related costs, he noted.

Steno-2 was an open, parallel group study initiated in 1993 to compare conventional multifactorial treatment of type 2 diabetes mellitus (T2DM) with an intensified approach over an 8-year period. Enrollment included 160 patients with high-risk type 2 diabetes. After the primary composite cardiovascular endpoint was assessed, the trial continued as an observational study, with all patients given the intensified, multifactorial treatment that consisted of lifestyle measures and medications targeting hyperglycemia, hypertension, hypercholesterolemia, and hypercoagulation.

Reports from the study over the years led to changes in treatment guidelines to promote more intensive multifactorial treatment, Mr. Gaede said. For example, the initial results reported in 1999 showed a 50% relative risk reduction in kidney, eye, and nerve complications after 4 years with intensive versus conventional treatment; a 2003 report showed a 53% relative risk reduction in MI, stroke, and amputation after 8 years; and a 2008 report demonstrated a 46% relative risk reduction in death after 13 years. Finally, in 2016 a 7.9-year gain in lifespan after 21 years with intensive versus conventional treatment was reported.

In this video interview, Mr. Gaede, junior lead study author, discusses the Steno-2 study findings and the current cost analysis data.

“The bottom line is that ... you can actually, as a patient, be treated at a specialized diabetes clinic ... and, in the long run, it doesn’t cost you anything” more, he said, explaining that the up-front costs of intensive treatment are offset by the money saved because of the reduced complications over time.

Mr. Gaede reported having no disclosures.

[email protected]

SOURCE: Gaede J et al. ADA 2018, Abstract 162-OR.

PARIS – Interventional cardiologists are hopeful that a new generation of investigational coronary stents designed specifically for use in diabetes patients will improve upon the relatively poor current outcomes of percutaneous coronary intervention in that population.

The operative word here is “abluminal.” Both of the novel drug-eluting stents featured at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions position their antirestenosis drugs abluminally: that is, aimed toward the vessel wall surface, not the lumen.

“The hypothesis is that providing more drug and better drug delivery per square millimeter at the vessel wall will result in possible reduction of diffuse restenosis in diabetics,” explained Luca Testa, MD, PhD, head of the coronary revascularization unit at San Donato Hospital in Milan.

There is a major unmet need for improved stent technology that addresses the special needs of diabetes patients, who tend to have more diffuse and rapidly progressive coronary artery disease (CAD) with longer lesions. Target lesion revascularization rates at 5 years of follow-up in diabetes patients with current generation drug-eluting stents (DES) remain high, at 20% or more. And diabetes patients are roughly 3.5-fold more likely to have nonfocal, diffuse coronary lesions than are nondiabetic patients with CAD, the cardiologist noted.

Bruce Jancin/MDedge News

[email protected]

PARIS – Interventional cardiologists are hopeful that a new generation of investigational coronary stents designed specifically for use in diabetes patients will improve upon the relatively poor current outcomes of percutaneous coronary intervention in that population.

The operative word here is “abluminal.” Both of the novel drug-eluting stents featured at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions position their antirestenosis drugs abluminally: that is, aimed toward the vessel wall surface, not the lumen.

“The hypothesis is that providing more drug and better drug delivery per square millimeter at the vessel wall will result in possible reduction of diffuse restenosis in diabetics,” explained Luca Testa, MD, PhD, head of the coronary revascularization unit at San Donato Hospital in Milan.

There is a major unmet need for improved stent technology that addresses the special needs of diabetes patients, who tend to have more diffuse and rapidly progressive coronary artery disease (CAD) with longer lesions. Target lesion revascularization rates at 5 years of follow-up in diabetes patients with current generation drug-eluting stents (DES) remain high, at 20% or more. And diabetes patients are roughly 3.5-fold more likely to have nonfocal, diffuse coronary lesions than are nondiabetic patients with CAD, the cardiologist noted.

Bruce Jancin/MDedge News

[email protected]

PARIS – Interventional cardiologists are hopeful that a new generation of investigational coronary stents designed specifically for use in diabetes patients will improve upon the relatively poor current outcomes of percutaneous coronary intervention in that population.

The operative word here is “abluminal.” Both of the novel drug-eluting stents featured at the annual meeting of the European Association of Percutaneous Cardiovascular Interventions position their antirestenosis drugs abluminally: that is, aimed toward the vessel wall surface, not the lumen.

“The hypothesis is that providing more drug and better drug delivery per square millimeter at the vessel wall will result in possible reduction of diffuse restenosis in diabetics,” explained Luca Testa, MD, PhD, head of the coronary revascularization unit at San Donato Hospital in Milan.

There is a major unmet need for improved stent technology that addresses the special needs of diabetes patients, who tend to have more diffuse and rapidly progressive coronary artery disease (CAD) with longer lesions. Target lesion revascularization rates at 5 years of follow-up in diabetes patients with current generation drug-eluting stents (DES) remain high, at 20% or more. And diabetes patients are roughly 3.5-fold more likely to have nonfocal, diffuse coronary lesions than are nondiabetic patients with CAD, the cardiologist noted.

Bruce Jancin/MDedge News

[email protected]

What will be the role of humans in the future health system?

At first blush, this is a peculiar question. Health care is all about humans. How could one doubt their presence or role? It is working with and for people that attracted many to this profession.

On the cusp of a significant health system reformulation, it is the very question that hospitalists now must ponder. Just as ATMs replaced bank cashiers, online shopping replaced retail stores, and autonomous cars will soon replace drivers, the human landscape of health care is about to change. What pressures will force the changes?

Hospitalist insight needed

What is the role of hospitalist leaders in this shifting equation? Hospitalists already can claim significant credit for introducing major changes in the landscape of hospital care in this country, with all the concomitant improvements in the efficiencies and quality of more integrated service delivery. Can you also guide the system in strategically selecting where and how technology can best be applied to automate and reconfigure service delivery?

The most important questions are: What is it that humans in health care uniquely do that cannot otherwise be accomplished? Are we able to hold onto the humane sides of health care, even as we seek to introduce cost-saving efficiencies?

Top of mind come the most personal sides of health service delivery: touch, empathy, understanding, and care itself. Next come human analysis, understanding, and translation. And beyond that, leadership, direction, and the vision to craft a health care system that meets our societal expectations – not just for the wealthy who cannot afford it – but for everyone.

It would be easy to dismiss this conversation. Society never decided whether those bank tellers, travel agents, or journalists were critical to our functioning. Along these same lines, you and your patients are more than mere algorithms.

As I often share in my leadership seminars, one key function of leaders is to identify and ask the right questions and to be at the decision-making table. What are those questions?

As a hospitalist leader, which part of your work and your activities could be eased by automation? Where might technology ease pressures and enhance your interactions with patients? How do we improve the efficiencies and effectiveness of health service delivery while we preserve the very human qualities that are fundamental to its values? No patient wants to speak to a physician who stares at a computer screen without eye contact, reassurance, or genuine interest. We can do better than that.

Business stakeholders in the system – and clearly, they are positioning and are powerful – will hold great sway on the contours of our future health care system. They could see humans – with all their costs, imperfections, and distractions – as replaceable.

Know that as you lead and pose your questions, there are people interested in listening. Certainly, the tech industry is looking for opportunities to generate broad market appeal. Similarly, health system decision makers looking to enhance how the system functions likewise seek guidance on what could – and could not – work. And who knows: Those decision makers could very well be you.

This is a conversation the country deserves. There is nothing more intimate, more personally important, and more professionally satisfying than the genuine person-to-person quality of what we do in health care. What we arrive at in the end should be achieved by intent, not by accident.
 

Dr. Marcus is coauthor of “Renegotiating Health Care: Resolving Conflict to Build Collaboration,” 2nd ed. (San Francisco: Jossey-Bass Publishers, 2011) and is director of the program for health care negotiation and conflict resolution, Harvard T.H. Chan School of Public Health, Boston. Dr. Marcus teaches regularly in the SHM Leadership Academy. He can be reached at [email protected].

What will be the role of humans in the future health system?

At first blush, this is a peculiar question. Health care is all about humans. How could one doubt their presence or role? It is working with and for people that attracted many to this profession.

On the cusp of a significant health system reformulation, it is the very question that hospitalists now must ponder. Just as ATMs replaced bank cashiers, online shopping replaced retail stores, and autonomous cars will soon replace drivers, the human landscape of health care is about to change. What pressures will force the changes?

Hospitalist insight needed

What is the role of hospitalist leaders in this shifting equation? Hospitalists already can claim significant credit for introducing major changes in the landscape of hospital care in this country, with all the concomitant improvements in the efficiencies and quality of more integrated service delivery. Can you also guide the system in strategically selecting where and how technology can best be applied to automate and reconfigure service delivery?

The most important questions are: What is it that humans in health care uniquely do that cannot otherwise be accomplished? Are we able to hold onto the humane sides of health care, even as we seek to introduce cost-saving efficiencies?

Top of mind come the most personal sides of health service delivery: touch, empathy, understanding, and care itself. Next come human analysis, understanding, and translation. And beyond that, leadership, direction, and the vision to craft a health care system that meets our societal expectations – not just for the wealthy who cannot afford it – but for everyone.

It would be easy to dismiss this conversation. Society never decided whether those bank tellers, travel agents, or journalists were critical to our functioning. Along these same lines, you and your patients are more than mere algorithms.

As I often share in my leadership seminars, one key function of leaders is to identify and ask the right questions and to be at the decision-making table. What are those questions?

As a hospitalist leader, which part of your work and your activities could be eased by automation? Where might technology ease pressures and enhance your interactions with patients? How do we improve the efficiencies and effectiveness of health service delivery while we preserve the very human qualities that are fundamental to its values? No patient wants to speak to a physician who stares at a computer screen without eye contact, reassurance, or genuine interest. We can do better than that.

Business stakeholders in the system – and clearly, they are positioning and are powerful – will hold great sway on the contours of our future health care system. They could see humans – with all their costs, imperfections, and distractions – as replaceable.

Know that as you lead and pose your questions, there are people interested in listening. Certainly, the tech industry is looking for opportunities to generate broad market appeal. Similarly, health system decision makers looking to enhance how the system functions likewise seek guidance on what could – and could not – work. And who knows: Those decision makers could very well be you.

This is a conversation the country deserves. There is nothing more intimate, more personally important, and more professionally satisfying than the genuine person-to-person quality of what we do in health care. What we arrive at in the end should be achieved by intent, not by accident.
 

Dr. Marcus is coauthor of “Renegotiating Health Care: Resolving Conflict to Build Collaboration,” 2nd ed. (San Francisco: Jossey-Bass Publishers, 2011) and is director of the program for health care negotiation and conflict resolution, Harvard T.H. Chan School of Public Health, Boston. Dr. Marcus teaches regularly in the SHM Leadership Academy. He can be reached at [email protected].

What will be the role of humans in the future health system?

At first blush, this is a peculiar question. Health care is all about humans. How could one doubt their presence or role? It is working with and for people that attracted many to this profession.

On the cusp of a significant health system reformulation, it is the very question that hospitalists now must ponder. Just as ATMs replaced bank cashiers, online shopping replaced retail stores, and autonomous cars will soon replace drivers, the human landscape of health care is about to change. What pressures will force the changes?

Hospitalist insight needed

What is the role of hospitalist leaders in this shifting equation? Hospitalists already can claim significant credit for introducing major changes in the landscape of hospital care in this country, with all the concomitant improvements in the efficiencies and quality of more integrated service delivery. Can you also guide the system in strategically selecting where and how technology can best be applied to automate and reconfigure service delivery?

The most important questions are: What is it that humans in health care uniquely do that cannot otherwise be accomplished? Are we able to hold onto the humane sides of health care, even as we seek to introduce cost-saving efficiencies?

Top of mind come the most personal sides of health service delivery: touch, empathy, understanding, and care itself. Next come human analysis, understanding, and translation. And beyond that, leadership, direction, and the vision to craft a health care system that meets our societal expectations – not just for the wealthy who cannot afford it – but for everyone.

It would be easy to dismiss this conversation. Society never decided whether those bank tellers, travel agents, or journalists were critical to our functioning. Along these same lines, you and your patients are more than mere algorithms.

As I often share in my leadership seminars, one key function of leaders is to identify and ask the right questions and to be at the decision-making table. What are those questions?

As a hospitalist leader, which part of your work and your activities could be eased by automation? Where might technology ease pressures and enhance your interactions with patients? How do we improve the efficiencies and effectiveness of health service delivery while we preserve the very human qualities that are fundamental to its values? No patient wants to speak to a physician who stares at a computer screen without eye contact, reassurance, or genuine interest. We can do better than that.

Business stakeholders in the system – and clearly, they are positioning and are powerful – will hold great sway on the contours of our future health care system. They could see humans – with all their costs, imperfections, and distractions – as replaceable.

Know that as you lead and pose your questions, there are people interested in listening. Certainly, the tech industry is looking for opportunities to generate broad market appeal. Similarly, health system decision makers looking to enhance how the system functions likewise seek guidance on what could – and could not – work. And who knows: Those decision makers could very well be you.

This is a conversation the country deserves. There is nothing more intimate, more personally important, and more professionally satisfying than the genuine person-to-person quality of what we do in health care. What we arrive at in the end should be achieved by intent, not by accident.
 

Dr. Marcus is coauthor of “Renegotiating Health Care: Resolving Conflict to Build Collaboration,” 2nd ed. (San Francisco: Jossey-Bass Publishers, 2011) and is director of the program for health care negotiation and conflict resolution, Harvard T.H. Chan School of Public Health, Boston. Dr. Marcus teaches regularly in the SHM Leadership Academy. He can be reached at [email protected].

The authors would like to make the following corrections to their manuscript, Cardiac Troponins in Low-Risk Pulmonary Embolism Patients: A Systematic Review and Meta-Analysis (doi: 10.12788/jhm.2961), published online first April 25, 2018 (all corrections in bold):

• The last sentence of the results section in the abstract should read: The pooled likelihood ratios (LRs) for all-cause mortality were positive LR 2.04 [95% CI, 1.53 to 2.72] and negative LR 0.72 [95% CI, 0.37 to 1.40].  
• In the "All studies pooled" of the last row of Table 2, Tn+ is corrected to 463. See revised table below.
• On page E5, the first paragraph in the "Outcomes of Studies with Corresponding Troponin+ and Troponin-" section beginning with the fifth sentence should read as follows):

"In the pooled data, 463 (67%) patients tested negative for troponin and 228 (33%) tested positive. The overall mortality (from sensitivity analysis) including in-hospital, 30-day, and 90-day mortalities was 1.2%. The NPVs for all individual studies and the overall NPV are 1 or approximately 1. The overall PPVs and by study were low, ranging from 0 to 0.60. The PLRs and NLRs were not estimated for an outcome within an individual study if none of the patients experienced the outcome. When outcomes were only observed among troponin-negative patients, such as in the study of Moore (2009) who used 30-day all-cause mortality, the PLR had a value of zero. When outcomes were only observed among troponin-positive patients, as for 30-day all-cause mortality in the Hakemi9(2015), Lauque10 (2014), and Lankeit16 (2011) studies, the NLR had a value of zero. For zero cells, a continuity correction of 0.5 was applied. The pooled likelihood ratios (LRs) for all-cause mortality were positive LR 2.04 [95% CI, 1.53 to 2.72] and negative LR 0.72 [95% CI, 0.37 to 1.40]. The OR for all-cause mortality was 4.79 [95% CI 1.11 to 20.68, P = .0357].

The authors would like to make the following corrections to their manuscript, Cardiac Troponins in Low-Risk Pulmonary Embolism Patients: A Systematic Review and Meta-Analysis (doi: 10.12788/jhm.2961), published online first April 25, 2018 (all corrections in bold):

• The last sentence of the results section in the abstract should read: The pooled likelihood ratios (LRs) for all-cause mortality were positive LR 2.04 [95% CI, 1.53 to 2.72] and negative LR 0.72 [95% CI, 0.37 to 1.40].  
• In the "All studies pooled" of the last row of Table 2, Tn+ is corrected to 463. See revised table below.
• On page E5, the first paragraph in the "Outcomes of Studies with Corresponding Troponin+ and Troponin-" section beginning with the fifth sentence should read as follows):

"In the pooled data, 463 (67%) patients tested negative for troponin and 228 (33%) tested positive. The overall mortality (from sensitivity analysis) including in-hospital, 30-day, and 90-day mortalities was 1.2%. The NPVs for all individual studies and the overall NPV are 1 or approximately 1. The overall PPVs and by study were low, ranging from 0 to 0.60. The PLRs and NLRs were not estimated for an outcome within an individual study if none of the patients experienced the outcome. When outcomes were only observed among troponin-negative patients, such as in the study of Moore (2009) who used 30-day all-cause mortality, the PLR had a value of zero. When outcomes were only observed among troponin-positive patients, as for 30-day all-cause mortality in the Hakemi9(2015), Lauque10 (2014), and Lankeit16 (2011) studies, the NLR had a value of zero. For zero cells, a continuity correction of 0.5 was applied. The pooled likelihood ratios (LRs) for all-cause mortality were positive LR 2.04 [95% CI, 1.53 to 2.72] and negative LR 0.72 [95% CI, 0.37 to 1.40]. The OR for all-cause mortality was 4.79 [95% CI 1.11 to 20.68, P = .0357].

The authors would like to make the following corrections to their manuscript, Cardiac Troponins in Low-Risk Pulmonary Embolism Patients: A Systematic Review and Meta-Analysis (doi: 10.12788/jhm.2961), published online first April 25, 2018 (all corrections in bold):

• The last sentence of the results section in the abstract should read: The pooled likelihood ratios (LRs) for all-cause mortality were positive LR 2.04 [95% CI, 1.53 to 2.72] and negative LR 0.72 [95% CI, 0.37 to 1.40].  
• In the "All studies pooled" of the last row of Table 2, Tn+ is corrected to 463. See revised table below.
• On page E5, the first paragraph in the "Outcomes of Studies with Corresponding Troponin+ and Troponin-" section beginning with the fifth sentence should read as follows):

"In the pooled data, 463 (67%) patients tested negative for troponin and 228 (33%) tested positive. The overall mortality (from sensitivity analysis) including in-hospital, 30-day, and 90-day mortalities was 1.2%. The NPVs for all individual studies and the overall NPV are 1 or approximately 1. The overall PPVs and by study were low, ranging from 0 to 0.60. The PLRs and NLRs were not estimated for an outcome within an individual study if none of the patients experienced the outcome. When outcomes were only observed among troponin-negative patients, such as in the study of Moore (2009) who used 30-day all-cause mortality, the PLR had a value of zero. When outcomes were only observed among troponin-positive patients, as for 30-day all-cause mortality in the Hakemi9(2015), Lauque10 (2014), and Lankeit16 (2011) studies, the NLR had a value of zero. For zero cells, a continuity correction of 0.5 was applied. The pooled likelihood ratios (LRs) for all-cause mortality were positive LR 2.04 [95% CI, 1.53 to 2.72] and negative LR 0.72 [95% CI, 0.37 to 1.40]. The OR for all-cause mortality was 4.79 [95% CI 1.11 to 20.68, P = .0357].

AMSTERDAM – Ultrasound of the salivary glands is a readily available and inexpensive tool for the diagnosis of Sjögren’s syndrome, according to a study that evaluated this test in relation to the recent American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria.

In a video interview, Esther-Jellina Mossel reported that the sensitivity and specificity of a Sjögren’s syndrome diagnosis is essentially unchanged when ultrasound replaces a positive ocular staining score, the Schirmer test, or an unstimulated whole saliva flow test, without reducing diagnostic accuracy.

The sensitivity of the diagnosis is reduced only if ultrasound is used to replace either of the two remaining ACR/EULAR criteria, which are a labial gland biopsy or an anti-SSA antibody test. In relation to the three criteria that it can replace without loss of diagnostic accuracy, ultrasound might have advantages.

“People who don’t have access to an ophthalmologist performing an ocular staining score, for instance, could use an ultrasound of the salivary glands instead of the ocular staining score and still make a diagnosis,” said Ms. Mossel, a PhD student in the department of rheumatology at the University of Groningen (the Netherlands).

Ultrasound, which is commonly used to evaluate joints of patients with inflammatory diseases, is available in the offices of most rheumatologists, according to Ms. Mossel. She estimated that the evaluation of the salivary glands, which reveals characteristic hypoechogenic areas when Sjögren’s syndrome is present, takes about 10 minutes.

At Ms. Mossel’s center, ultrasound has already become a standard tool for the diagnosis of Sjögren’s syndrome. She said that other centers have also found this imaging tool to be accurate and useful for Sjögren’s syndrome diagnosis.

Based on the experience at the University of Groningen, Ms. Mossel believes that ultrasound will eventually be widely adopted for Sjögren’s syndrome diagnosis. Indeed, she expects that this strategy is likely to be added to the ACR/EULAR diagnostic criteria when its accuracy becomes more generally recognized.

AMSTERDAM – Ultrasound of the salivary glands is a readily available and inexpensive tool for the diagnosis of Sjögren’s syndrome, according to a study that evaluated this test in relation to the recent American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria.

In a video interview, Esther-Jellina Mossel reported that the sensitivity and specificity of a Sjögren’s syndrome diagnosis is essentially unchanged when ultrasound replaces a positive ocular staining score, the Schirmer test, or an unstimulated whole saliva flow test, without reducing diagnostic accuracy.

The sensitivity of the diagnosis is reduced only if ultrasound is used to replace either of the two remaining ACR/EULAR criteria, which are a labial gland biopsy or an anti-SSA antibody test. In relation to the three criteria that it can replace without loss of diagnostic accuracy, ultrasound might have advantages.

“People who don’t have access to an ophthalmologist performing an ocular staining score, for instance, could use an ultrasound of the salivary glands instead of the ocular staining score and still make a diagnosis,” said Ms. Mossel, a PhD student in the department of rheumatology at the University of Groningen (the Netherlands).

Ultrasound, which is commonly used to evaluate joints of patients with inflammatory diseases, is available in the offices of most rheumatologists, according to Ms. Mossel. She estimated that the evaluation of the salivary glands, which reveals characteristic hypoechogenic areas when Sjögren’s syndrome is present, takes about 10 minutes.

At Ms. Mossel’s center, ultrasound has already become a standard tool for the diagnosis of Sjögren’s syndrome. She said that other centers have also found this imaging tool to be accurate and useful for Sjögren’s syndrome diagnosis.

Based on the experience at the University of Groningen, Ms. Mossel believes that ultrasound will eventually be widely adopted for Sjögren’s syndrome diagnosis. Indeed, she expects that this strategy is likely to be added to the ACR/EULAR diagnostic criteria when its accuracy becomes more generally recognized.

AMSTERDAM – Ultrasound of the salivary glands is a readily available and inexpensive tool for the diagnosis of Sjögren’s syndrome, according to a study that evaluated this test in relation to the recent American College of Rheumatology and European League Against Rheumatism (ACR/EULAR) classification criteria.

In a video interview, Esther-Jellina Mossel reported that the sensitivity and specificity of a Sjögren’s syndrome diagnosis is essentially unchanged when ultrasound replaces a positive ocular staining score, the Schirmer test, or an unstimulated whole saliva flow test, without reducing diagnostic accuracy.

The sensitivity of the diagnosis is reduced only if ultrasound is used to replace either of the two remaining ACR/EULAR criteria, which are a labial gland biopsy or an anti-SSA antibody test. In relation to the three criteria that it can replace without loss of diagnostic accuracy, ultrasound might have advantages.

“People who don’t have access to an ophthalmologist performing an ocular staining score, for instance, could use an ultrasound of the salivary glands instead of the ocular staining score and still make a diagnosis,” said Ms. Mossel, a PhD student in the department of rheumatology at the University of Groningen (the Netherlands).

Ultrasound, which is commonly used to evaluate joints of patients with inflammatory diseases, is available in the offices of most rheumatologists, according to Ms. Mossel. She estimated that the evaluation of the salivary glands, which reveals characteristic hypoechogenic areas when Sjögren’s syndrome is present, takes about 10 minutes.

At Ms. Mossel’s center, ultrasound has already become a standard tool for the diagnosis of Sjögren’s syndrome. She said that other centers have also found this imaging tool to be accurate and useful for Sjögren’s syndrome diagnosis.

Based on the experience at the University of Groningen, Ms. Mossel believes that ultrasound will eventually be widely adopted for Sjögren’s syndrome diagnosis. Indeed, she expects that this strategy is likely to be added to the ACR/EULAR diagnostic criteria when its accuracy becomes more generally recognized.

The Food and Drug Administration has approved cannabidiol oral solution (Epidiolex, GW Pharmaceuticals) for the treatment of two rare pediatric seizure disorders.

The approval, the first for a marijuana-derived pharmaceutical product, falls in line with the unanimous recommendation of an FDA advisory panel to approve cannabidiol oral solution (CBD-OS) for the treatment of Lennox-Gastaut syndrome and Dravet syndrome in patients 2 years of age and older.

“This product approval demonstrates that advancing sound scientific research to investigate ingredients derived from marijuana can lead to important therapies. This new treatment provides new options for patients,” said FDA Commissioner Scott Gottlieb, MD, in a statement.

However, he cautioned, “This is an important medical advance. But it’s also important to note that this is not an approval of marijuana or all of its components. This is the approval of one specific CBD medication for a specific use. And it was based on well-controlled clinical trials evaluating the use of this compound in the treatment of a specific condition.”

The FDA Peripheral and Central Nervous System Drugs Advisory Committee’s earlier positive recommendation was based on three randomized, double-blind, placebo-controlled clinical trials. These trials showed a 50% reduction of drop seizure frequency in 40%-44% of patients with Lennox-Gastaut syndrome, and a 39% decrease in convulsive seizure frequency for trial participants with Dravet Syndrome. A total of 516 patients with one of the two seizure disorders participated in the clinical trials.

“In addition to another important treatment option for Lennox-Gastaut patients, this first-ever approval of a drug specifically for Dravet patients will provide a significant and needed improvement in the therapeutic approach to caring for people with this condition,” said Billy Dunn, MD, director of the Division of Neurology Products in the FDA Center for Drug Evaluation and Research, in a statement.

After reviewing information provided by the drug’s sponsor and the FDA, the advisory committee judged that CBD-OS, derived from a non-psychoactive chemical found in marijuana, was very unlikely to have potential for abuse.

Sedation, sleepiness, and lethargy were among the most frequently reported adverse events for the patients taking CBD-OS. In data pooled from the clinical trials, 16.3% of patients taking CBD-OS at the higher dose of 20 mg/kg/day had liver transaminase elevations above three times the upper limit of normal; this level of transaminase elevation was seen in 0.9% of patients taking placebo.

A patient medication guide detailing risks and how the drug should be used will accompany CBD-OS when it is dispensed, according to the FDA approval.

In his statement, Dr. Gottlieb put the approval in the context of the FDA’s broader efforts to encourage a strong clinical development program for marijuana-derived drugs that does not compromise standards for ensuring safety and efficacy of drugs approved by the agency. He also noted that ongoing efforts to support high quality research into marijuana-based therapies involve other federal agencies, including the National Institute on Drug Abuse and the Drug Enforcement Administration.

The FDA’s actions against companies distributing unapproved products that contain cannabidiol and making unproven marketing claims will continue, said Dr. Gottlieb. Still, “Today’s approval demonstrates our commitment to the scientific process and working with product developers to bring marijuana-based products to market,” he said.
 

[email protected]

The Food and Drug Administration has approved cannabidiol oral solution (Epidiolex, GW Pharmaceuticals) for the treatment of two rare pediatric seizure disorders.

The approval, the first for a marijuana-derived pharmaceutical product, falls in line with the unanimous recommendation of an FDA advisory panel to approve cannabidiol oral solution (CBD-OS) for the treatment of Lennox-Gastaut syndrome and Dravet syndrome in patients 2 years of age and older.

“This product approval demonstrates that advancing sound scientific research to investigate ingredients derived from marijuana can lead to important therapies. This new treatment provides new options for patients,” said FDA Commissioner Scott Gottlieb, MD, in a statement.

However, he cautioned, “This is an important medical advance. But it’s also important to note that this is not an approval of marijuana or all of its components. This is the approval of one specific CBD medication for a specific use. And it was based on well-controlled clinical trials evaluating the use of this compound in the treatment of a specific condition.”

The FDA Peripheral and Central Nervous System Drugs Advisory Committee’s earlier positive recommendation was based on three randomized, double-blind, placebo-controlled clinical trials. These trials showed a 50% reduction of drop seizure frequency in 40%-44% of patients with Lennox-Gastaut syndrome, and a 39% decrease in convulsive seizure frequency for trial participants with Dravet Syndrome. A total of 516 patients with one of the two seizure disorders participated in the clinical trials.

“In addition to another important treatment option for Lennox-Gastaut patients, this first-ever approval of a drug specifically for Dravet patients will provide a significant and needed improvement in the therapeutic approach to caring for people with this condition,” said Billy Dunn, MD, director of the Division of Neurology Products in the FDA Center for Drug Evaluation and Research, in a statement.

After reviewing information provided by the drug’s sponsor and the FDA, the advisory committee judged that CBD-OS, derived from a non-psychoactive chemical found in marijuana, was very unlikely to have potential for abuse.

Sedation, sleepiness, and lethargy were among the most frequently reported adverse events for the patients taking CBD-OS. In data pooled from the clinical trials, 16.3% of patients taking CBD-OS at the higher dose of 20 mg/kg/day had liver transaminase elevations above three times the upper limit of normal; this level of transaminase elevation was seen in 0.9% of patients taking placebo.

A patient medication guide detailing risks and how the drug should be used will accompany CBD-OS when it is dispensed, according to the FDA approval.

In his statement, Dr. Gottlieb put the approval in the context of the FDA’s broader efforts to encourage a strong clinical development program for marijuana-derived drugs that does not compromise standards for ensuring safety and efficacy of drugs approved by the agency. He also noted that ongoing efforts to support high quality research into marijuana-based therapies involve other federal agencies, including the National Institute on Drug Abuse and the Drug Enforcement Administration.

The FDA’s actions against companies distributing unapproved products that contain cannabidiol and making unproven marketing claims will continue, said Dr. Gottlieb. Still, “Today’s approval demonstrates our commitment to the scientific process and working with product developers to bring marijuana-based products to market,” he said.
 

[email protected]

The Food and Drug Administration has approved cannabidiol oral solution (Epidiolex, GW Pharmaceuticals) for the treatment of two rare pediatric seizure disorders.

The approval, the first for a marijuana-derived pharmaceutical product, falls in line with the unanimous recommendation of an FDA advisory panel to approve cannabidiol oral solution (CBD-OS) for the treatment of Lennox-Gastaut syndrome and Dravet syndrome in patients 2 years of age and older.

“This product approval demonstrates that advancing sound scientific research to investigate ingredients derived from marijuana can lead to important therapies. This new treatment provides new options for patients,” said FDA Commissioner Scott Gottlieb, MD, in a statement.

However, he cautioned, “This is an important medical advance. But it’s also important to note that this is not an approval of marijuana or all of its components. This is the approval of one specific CBD medication for a specific use. And it was based on well-controlled clinical trials evaluating the use of this compound in the treatment of a specific condition.”

The FDA Peripheral and Central Nervous System Drugs Advisory Committee’s earlier positive recommendation was based on three randomized, double-blind, placebo-controlled clinical trials. These trials showed a 50% reduction of drop seizure frequency in 40%-44% of patients with Lennox-Gastaut syndrome, and a 39% decrease in convulsive seizure frequency for trial participants with Dravet Syndrome. A total of 516 patients with one of the two seizure disorders participated in the clinical trials.

“In addition to another important treatment option for Lennox-Gastaut patients, this first-ever approval of a drug specifically for Dravet patients will provide a significant and needed improvement in the therapeutic approach to caring for people with this condition,” said Billy Dunn, MD, director of the Division of Neurology Products in the FDA Center for Drug Evaluation and Research, in a statement.

After reviewing information provided by the drug’s sponsor and the FDA, the advisory committee judged that CBD-OS, derived from a non-psychoactive chemical found in marijuana, was very unlikely to have potential for abuse.

Sedation, sleepiness, and lethargy were among the most frequently reported adverse events for the patients taking CBD-OS. In data pooled from the clinical trials, 16.3% of patients taking CBD-OS at the higher dose of 20 mg/kg/day had liver transaminase elevations above three times the upper limit of normal; this level of transaminase elevation was seen in 0.9% of patients taking placebo.

A patient medication guide detailing risks and how the drug should be used will accompany CBD-OS when it is dispensed, according to the FDA approval.

In his statement, Dr. Gottlieb put the approval in the context of the FDA’s broader efforts to encourage a strong clinical development program for marijuana-derived drugs that does not compromise standards for ensuring safety and efficacy of drugs approved by the agency. He also noted that ongoing efforts to support high quality research into marijuana-based therapies involve other federal agencies, including the National Institute on Drug Abuse and the Drug Enforcement Administration.

The FDA’s actions against companies distributing unapproved products that contain cannabidiol and making unproven marketing claims will continue, said Dr. Gottlieb. Still, “Today’s approval demonstrates our commitment to the scientific process and working with product developers to bring marijuana-based products to market,” he said.
 

[email protected]

Clomiphene citrate significantly improved markers of polycystic ovarian syndrome (PCOS) and improved ovulation and pregnancy outcomes in women with PCOS, according to data from 72 women.

Nitric oxide (NO), interleukin-10 (IL-10), and matrix metalloproteinase–9 (MMP-9) “are known to be involved in the pathogenesis as well as the complications of PCOS,” wrote Angel Mercy Sylus, MD, of the Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India, and colleagues.

Clomiphene citrate is used to treat infertility, including infertile women with PCOS, but its mechanism of action remains unclear, the researchers wrote.

In a study published in the European Journal of Obstetrics & Gynecology and Reproductive Biology, the researchers enrolled 72 women with PCOS. The women received 50 mg of oral clomiphene citrate daily on days 3-7 of their cycles to induce ovulation. Levels of NO, IL-10, and MMP-9 were measured at baseline and after 3 weeks. The average age of the women was 25 years, and the average body mass index was 26.4 kg/m².

After the participants took clomiphene citrate, their levels of NO and IL-10 were significantly higher, compared with baseline (P = .03 and P less than .001, respectively), and MMP-9 levels were significantly lower, compared with baseline (P less than .001).

The ovulation rate in the study population was 52.8%, and the clinical pregnancy rate was 19.4%. Levels of MMP-9 were significantly reduced (P less than .001) in the ovulatory group, compared with the nonovulatory group, the researchers noted. “Although the mechanism through which CC [clomiphene citrate] reduces MMP-9 and increases IL-10 is not clear, our findings indicate that CC therapy improves ovulation by reducing inflammation and reducing MMP-9 levels,” they wrote.

The findings were limited by several factors, mainly by the timing of the 4-week assessment of NO, IL-10, and MPP-9 for ethical reasons, the researchers wrote. They did not get study approval to conduct a separate blood collection. In addition, the study did not measure the effect of increasing doses of clomiphene citrate.

However, the results have suggested that clomiphene citrate can help promote ovulation and pregnancy for infertile women with PCOS, and further studies are needed to assess the mechanism of action and the effect of higher doses on NO, IL-10, and MPP-9, the researchers wrote.

The study was supported by a grant from the Jawaharlal Institute of Postgraduate Medical Education and Research intramural fund. The researchers had no financial conflicts to disclose.
 

SOURCE: Sylus AM et al. Eur J Obstet Gynecol Reprod Biol. 2018 Sept; 228:27-31.

Clomiphene citrate significantly improved markers of polycystic ovarian syndrome (PCOS) and improved ovulation and pregnancy outcomes in women with PCOS, according to data from 72 women.

Nitric oxide (NO), interleukin-10 (IL-10), and matrix metalloproteinase–9 (MMP-9) “are known to be involved in the pathogenesis as well as the complications of PCOS,” wrote Angel Mercy Sylus, MD, of the Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India, and colleagues.

Clomiphene citrate is used to treat infertility, including infertile women with PCOS, but its mechanism of action remains unclear, the researchers wrote.

In a study published in the European Journal of Obstetrics & Gynecology and Reproductive Biology, the researchers enrolled 72 women with PCOS. The women received 50 mg of oral clomiphene citrate daily on days 3-7 of their cycles to induce ovulation. Levels of NO, IL-10, and MMP-9 were measured at baseline and after 3 weeks. The average age of the women was 25 years, and the average body mass index was 26.4 kg/m².

After the participants took clomiphene citrate, their levels of NO and IL-10 were significantly higher, compared with baseline (P = .03 and P less than .001, respectively), and MMP-9 levels were significantly lower, compared with baseline (P less than .001).

The ovulation rate in the study population was 52.8%, and the clinical pregnancy rate was 19.4%. Levels of MMP-9 were significantly reduced (P less than .001) in the ovulatory group, compared with the nonovulatory group, the researchers noted. “Although the mechanism through which CC [clomiphene citrate] reduces MMP-9 and increases IL-10 is not clear, our findings indicate that CC therapy improves ovulation by reducing inflammation and reducing MMP-9 levels,” they wrote.

The findings were limited by several factors, mainly by the timing of the 4-week assessment of NO, IL-10, and MPP-9 for ethical reasons, the researchers wrote. They did not get study approval to conduct a separate blood collection. In addition, the study did not measure the effect of increasing doses of clomiphene citrate.

However, the results have suggested that clomiphene citrate can help promote ovulation and pregnancy for infertile women with PCOS, and further studies are needed to assess the mechanism of action and the effect of higher doses on NO, IL-10, and MPP-9, the researchers wrote.

The study was supported by a grant from the Jawaharlal Institute of Postgraduate Medical Education and Research intramural fund. The researchers had no financial conflicts to disclose.
 

SOURCE: Sylus AM et al. Eur J Obstet Gynecol Reprod Biol. 2018 Sept; 228:27-31.

Clomiphene citrate significantly improved markers of polycystic ovarian syndrome (PCOS) and improved ovulation and pregnancy outcomes in women with PCOS, according to data from 72 women.

Nitric oxide (NO), interleukin-10 (IL-10), and matrix metalloproteinase–9 (MMP-9) “are known to be involved in the pathogenesis as well as the complications of PCOS,” wrote Angel Mercy Sylus, MD, of the Jawaharlal Institute of Postgraduate Medical Education & Research, Puducherry, India, and colleagues.

Clomiphene citrate is used to treat infertility, including infertile women with PCOS, but its mechanism of action remains unclear, the researchers wrote.

In a study published in the European Journal of Obstetrics & Gynecology and Reproductive Biology, the researchers enrolled 72 women with PCOS. The women received 50 mg of oral clomiphene citrate daily on days 3-7 of their cycles to induce ovulation. Levels of NO, IL-10, and MMP-9 were measured at baseline and after 3 weeks. The average age of the women was 25 years, and the average body mass index was 26.4 kg/m².

After the participants took clomiphene citrate, their levels of NO and IL-10 were significantly higher, compared with baseline (P = .03 and P less than .001, respectively), and MMP-9 levels were significantly lower, compared with baseline (P less than .001).

The ovulation rate in the study population was 52.8%, and the clinical pregnancy rate was 19.4%. Levels of MMP-9 were significantly reduced (P less than .001) in the ovulatory group, compared with the nonovulatory group, the researchers noted. “Although the mechanism through which CC [clomiphene citrate] reduces MMP-9 and increases IL-10 is not clear, our findings indicate that CC therapy improves ovulation by reducing inflammation and reducing MMP-9 levels,” they wrote.

The findings were limited by several factors, mainly by the timing of the 4-week assessment of NO, IL-10, and MPP-9 for ethical reasons, the researchers wrote. They did not get study approval to conduct a separate blood collection. In addition, the study did not measure the effect of increasing doses of clomiphene citrate.

However, the results have suggested that clomiphene citrate can help promote ovulation and pregnancy for infertile women with PCOS, and further studies are needed to assess the mechanism of action and the effect of higher doses on NO, IL-10, and MPP-9, the researchers wrote.

The study was supported by a grant from the Jawaharlal Institute of Postgraduate Medical Education and Research intramural fund. The researchers had no financial conflicts to disclose.
 

SOURCE: Sylus AM et al. Eur J Obstet Gynecol Reprod Biol. 2018 Sept; 228:27-31.

AMSTERDAM – Phase 2 data with the IL-23 inhibitor risankizumab at week 24 were even more impressive than the week 16 data, showing that without any further dosing after week 16, all doses provided protection against radiographic progression relative to placebo at 24 weeks, according to data presented at the European Congress of Rheumatology.

In a video interview, first author Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle, explained that it is not only the high rates of response to risankizumab but also the prolonged response that are attracting attention.

Risankizumab is among several monoclonal antibodies developed to target the p19 subunit of the proinflammatory cytokine IL-23. These drugs have already shown a high degree of efficacy for psoriasis, according to Dr. Mease. However, the new data with risankizumab confirm prolonged responses against a broad range of additional clinical targets specific to psoriatic arthritis, including bone destruction and enthesitis.

A prolonged response in patients treated with a single, relatively low dose of risankizumab is one of the intriguing findings. While three of the four active treatments arms received multiple infusions of 150 mg, the single-dose arm received only 75 mg of risankizumab once at baseline. At 16 weeks and 24 weeks, all arms, including the single-dose arm, met the primary endpoint of superiority to placebo for ACR20. At week 24, the single infusion of 75 mg was also providing significant benefit for several secondary endpoints, including radiographic progression.

However, the higher, more frequent doses did show greater efficacy overall. For example, patients in the arm with the most frequent dosing of risankizumab (every 4 weeks) and no dosing after week 16 continued to show significant improvement in enthesitis. A less frequent schedule of 150 mg risankizumab and the arm receiving a single dose of 75 mg risankizumab were not associated with a significant advantage over placebo for this endpoint.

Still, the prolonged responses at week 24 suggest that it may be possible to administer risankizumab at intervals that are less frequent than many other biologics.

So far, there “is nothing remarkable about safety,” Dr. Mease explained. A higher rate of infection relative to placebo was a treatment-emergent side effect in this study, but Dr. Mease said the drug is well tolerated.

Risankizumab is poised for evaluation in a phase 3 trial for psoriatic arthritis, and Dr. Mease was optimistic about its potential role, predicting that this, as well as other anti-IL23 p19 monoclonal antibodies, is likely to be an “important addition to our armamentarium.”

AbbVie and Boehringer Ingelheim funded the risankizumab study. Dr. Mease has received grant/research support from AbbVie and many other pharmaceutical companies. He also is a consultant to them and is on their speakers bureaus.

SOURCE: Mease P et al. Ann Rheum Dis. 2018;77(Suppl 2):200-1. Abstract OP0307

AMSTERDAM – Phase 2 data with the IL-23 inhibitor risankizumab at week 24 were even more impressive than the week 16 data, showing that without any further dosing after week 16, all doses provided protection against radiographic progression relative to placebo at 24 weeks, according to data presented at the European Congress of Rheumatology.

In a video interview, first author Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle, explained that it is not only the high rates of response to risankizumab but also the prolonged response that are attracting attention.

Risankizumab is among several monoclonal antibodies developed to target the p19 subunit of the proinflammatory cytokine IL-23. These drugs have already shown a high degree of efficacy for psoriasis, according to Dr. Mease. However, the new data with risankizumab confirm prolonged responses against a broad range of additional clinical targets specific to psoriatic arthritis, including bone destruction and enthesitis.

A prolonged response in patients treated with a single, relatively low dose of risankizumab is one of the intriguing findings. While three of the four active treatments arms received multiple infusions of 150 mg, the single-dose arm received only 75 mg of risankizumab once at baseline. At 16 weeks and 24 weeks, all arms, including the single-dose arm, met the primary endpoint of superiority to placebo for ACR20. At week 24, the single infusion of 75 mg was also providing significant benefit for several secondary endpoints, including radiographic progression.

However, the higher, more frequent doses did show greater efficacy overall. For example, patients in the arm with the most frequent dosing of risankizumab (every 4 weeks) and no dosing after week 16 continued to show significant improvement in enthesitis. A less frequent schedule of 150 mg risankizumab and the arm receiving a single dose of 75 mg risankizumab were not associated with a significant advantage over placebo for this endpoint.

Still, the prolonged responses at week 24 suggest that it may be possible to administer risankizumab at intervals that are less frequent than many other biologics.

So far, there “is nothing remarkable about safety,” Dr. Mease explained. A higher rate of infection relative to placebo was a treatment-emergent side effect in this study, but Dr. Mease said the drug is well tolerated.

Risankizumab is poised for evaluation in a phase 3 trial for psoriatic arthritis, and Dr. Mease was optimistic about its potential role, predicting that this, as well as other anti-IL23 p19 monoclonal antibodies, is likely to be an “important addition to our armamentarium.”

AbbVie and Boehringer Ingelheim funded the risankizumab study. Dr. Mease has received grant/research support from AbbVie and many other pharmaceutical companies. He also is a consultant to them and is on their speakers bureaus.

SOURCE: Mease P et al. Ann Rheum Dis. 2018;77(Suppl 2):200-1. Abstract OP0307

AMSTERDAM – Phase 2 data with the IL-23 inhibitor risankizumab at week 24 were even more impressive than the week 16 data, showing that without any further dosing after week 16, all doses provided protection against radiographic progression relative to placebo at 24 weeks, according to data presented at the European Congress of Rheumatology.

In a video interview, first author Philip J. Mease, MD, a rheumatologist at Swedish Medical Center in Seattle, explained that it is not only the high rates of response to risankizumab but also the prolonged response that are attracting attention.

Risankizumab is among several monoclonal antibodies developed to target the p19 subunit of the proinflammatory cytokine IL-23. These drugs have already shown a high degree of efficacy for psoriasis, according to Dr. Mease. However, the new data with risankizumab confirm prolonged responses against a broad range of additional clinical targets specific to psoriatic arthritis, including bone destruction and enthesitis.

A prolonged response in patients treated with a single, relatively low dose of risankizumab is one of the intriguing findings. While three of the four active treatments arms received multiple infusions of 150 mg, the single-dose arm received only 75 mg of risankizumab once at baseline. At 16 weeks and 24 weeks, all arms, including the single-dose arm, met the primary endpoint of superiority to placebo for ACR20. At week 24, the single infusion of 75 mg was also providing significant benefit for several secondary endpoints, including radiographic progression.

However, the higher, more frequent doses did show greater efficacy overall. For example, patients in the arm with the most frequent dosing of risankizumab (every 4 weeks) and no dosing after week 16 continued to show significant improvement in enthesitis. A less frequent schedule of 150 mg risankizumab and the arm receiving a single dose of 75 mg risankizumab were not associated with a significant advantage over placebo for this endpoint.

Still, the prolonged responses at week 24 suggest that it may be possible to administer risankizumab at intervals that are less frequent than many other biologics.

So far, there “is nothing remarkable about safety,” Dr. Mease explained. A higher rate of infection relative to placebo was a treatment-emergent side effect in this study, but Dr. Mease said the drug is well tolerated.

Risankizumab is poised for evaluation in a phase 3 trial for psoriatic arthritis, and Dr. Mease was optimistic about its potential role, predicting that this, as well as other anti-IL23 p19 monoclonal antibodies, is likely to be an “important addition to our armamentarium.”

AbbVie and Boehringer Ingelheim funded the risankizumab study. Dr. Mease has received grant/research support from AbbVie and many other pharmaceutical companies. He also is a consultant to them and is on their speakers bureaus.

SOURCE: Mease P et al. Ann Rheum Dis. 2018;77(Suppl 2):200-1. Abstract OP0307

ORLANDO – The proportion of diabetes patients enrolled in high-deductible health plans jumped from 10% in 2005 to about 50% in 2014, according to a review of insurance data for 63 million Americans under age 65 years.

Diabetes patients often don’t have a choice. To cut costs, high-deductible plans are increasingly the only ones employers offer.

While that may be adequate for healthy people, it’s quite another issue for people with chronic conditions, especially ones with low income. Out-of-pocket expenses can be thousands of dollars more than with traditional health plans, and the extra costs aren’t always offset by lower premiums.

The trend is concerning, said senior investigator J. Frank Wharam, MB, MPH, an associate professor of population medicine at Harvard Medical School, Boston. He explained the problem, and what’s being done about it, in an interview at the annual scientific sessions of the American Diabetes Association.

[email protected]

SOURCE: Garabedian LF et al. ADA 2018. Abstract 175-OR.


 

ORLANDO – The proportion of diabetes patients enrolled in high-deductible health plans jumped from 10% in 2005 to about 50% in 2014, according to a review of insurance data for 63 million Americans under age 65 years.

Diabetes patients often don’t have a choice. To cut costs, high-deductible plans are increasingly the only ones employers offer.

While that may be adequate for healthy people, it’s quite another issue for people with chronic conditions, especially ones with low income. Out-of-pocket expenses can be thousands of dollars more than with traditional health plans, and the extra costs aren’t always offset by lower premiums.

The trend is concerning, said senior investigator J. Frank Wharam, MB, MPH, an associate professor of population medicine at Harvard Medical School, Boston. He explained the problem, and what’s being done about it, in an interview at the annual scientific sessions of the American Diabetes Association.

[email protected]

SOURCE: Garabedian LF et al. ADA 2018. Abstract 175-OR.


 

ORLANDO – The proportion of diabetes patients enrolled in high-deductible health plans jumped from 10% in 2005 to about 50% in 2014, according to a review of insurance data for 63 million Americans under age 65 years.

Diabetes patients often don’t have a choice. To cut costs, high-deductible plans are increasingly the only ones employers offer.

While that may be adequate for healthy people, it’s quite another issue for people with chronic conditions, especially ones with low income. Out-of-pocket expenses can be thousands of dollars more than with traditional health plans, and the extra costs aren’t always offset by lower premiums.

The trend is concerning, said senior investigator J. Frank Wharam, MB, MPH, an associate professor of population medicine at Harvard Medical School, Boston. He explained the problem, and what’s being done about it, in an interview at the annual scientific sessions of the American Diabetes Association.

[email protected]

SOURCE: Garabedian LF et al. ADA 2018. Abstract 175-OR.