Hot Topics in Primary Care 2023 is a resource that explores the newest developments in primary care topics that impact your daily clinical practice.

Click on the link below to access the entire supplement. You can also click on the video panes below to view brief summaries of individual chapters. Titles above the video panes link directly to each article.
 

• A Patient-Centered Approach to Managing IBS-C and CIC
• Acute Pain in Perspective
• Continuous Glucose Monitoring in Practice
• Early Intervention by Family Physicians to Delay Type 1 Diabetes
• Early Life Nutrition and the Developing Brain
• Insomnia Management: A Review and Update
• New Paradigms for CKD Management in Patients With T2D
• Optimized Management of Cardio-Renal-Metabolic (CRM) Conditions in Patients with T2D
• Reducing Cardiopulmonary Risk and Exacerbations in COPD
• Reducing Ischemic Stroke in Diabetes: The Role of GLP-1 RAs
• Use of ICS and Fast-Acting Bronchodilators in Asthma: Past, Present, and Future

This supplement offers the opportunity to earn a total of 4 continuing medical education (CME) credits. Credit is awarded for successful completion of the evaluation after reading the article. The links can be found within the supplement on the first page of each article where CME credits are offered.

Click here to read Hot Topics in Primary Care 2023

This supplement to The Journal of Family Practice was sponsored by the Primary Care Education Consortium and Primary Care Metabolic Group.
Check out these short video segments, which were prepared by the supplement authors and summarize the individual articles.
The title above each video links to the related article.

A Patient-Centered Approach to Managing IBS-C and CIC, Brian E. Lacy, MD, PhD, FACG


Acute Pain in Perspective, Bill McCarberg, MD


Continuous Glucose Monitoring in Practice, Eden M. Miller, DO


Early Intervention by Family Physicians to Delay Type 1 Diabetes, Steven Edelman, MD


Early Life Nutrition and the Developing Brain, Danielle Christifano, PhD; Lara Bennett, MS, RD, LD


Insomnia Management: A Review and Update, David P. Shaha, MD


New Paradigms for CKD Management in Patients With T2D, Joshua J. Neumiller, PharmD, CDCES, FADCES, FASCP; Stephen A. Brunton, MD, FAAFP, CDCES


Optimized Management of Cardio-Renal-Metabolic (CRM) Conditions in Patients with T2D, Jay H. Shubrook, DO; Joshua J. Neumiller, PharmD, CDCES, FADCES, FASCP


Reducing Cardiopulmonary Risk and Exacerbations in COPD, Barbara Yawn, MD, MSc, FAAFP


Reducing Ischemic Stroke in Diabetes: The Role of GLP-1 Ras, John E. Anderson, MD; Javed Butler, MD, MPH, MBA; Andrei V. Alexandrov, MD


Use of ICS and Fast-Acting Bronchodilators in Asthma: Past, Present, and Future, Neil Skolnik, MD; Marissa Norden, DO; Njira Lugogo, MD: Wendy Wright, DNP, ANP-BC, FNP-BC, FAANP, FAAN, FNAP

Hot Topics in Primary Care 2023 is a resource that explores the newest developments in primary care topics that impact your daily clinical practice.

Click on the link below to access the entire supplement. You can also click on the video panes below to view brief summaries of individual chapters. Titles above the video panes link directly to each article.
 

• A Patient-Centered Approach to Managing IBS-C and CIC
• Acute Pain in Perspective
• Continuous Glucose Monitoring in Practice
• Early Intervention by Family Physicians to Delay Type 1 Diabetes
• Early Life Nutrition and the Developing Brain
• Insomnia Management: A Review and Update
• New Paradigms for CKD Management in Patients With T2D
• Optimized Management of Cardio-Renal-Metabolic (CRM) Conditions in Patients with T2D
• Reducing Cardiopulmonary Risk and Exacerbations in COPD
• Reducing Ischemic Stroke in Diabetes: The Role of GLP-1 RAs
• Use of ICS and Fast-Acting Bronchodilators in Asthma: Past, Present, and Future

This supplement offers the opportunity to earn a total of 4 continuing medical education (CME) credits. Credit is awarded for successful completion of the evaluation after reading the article. The links can be found within the supplement on the first page of each article where CME credits are offered.

Click here to read Hot Topics in Primary Care 2023

This supplement to The Journal of Family Practice was sponsored by the Primary Care Education Consortium and Primary Care Metabolic Group.
Check out these short video segments, which were prepared by the supplement authors and summarize the individual articles.
The title above each video links to the related article.

A Patient-Centered Approach to Managing IBS-C and CIC, Brian E. Lacy, MD, PhD, FACG


Acute Pain in Perspective, Bill McCarberg, MD


Continuous Glucose Monitoring in Practice, Eden M. Miller, DO


Early Intervention by Family Physicians to Delay Type 1 Diabetes, Steven Edelman, MD


Early Life Nutrition and the Developing Brain, Danielle Christifano, PhD; Lara Bennett, MS, RD, LD


Insomnia Management: A Review and Update, David P. Shaha, MD


New Paradigms for CKD Management in Patients With T2D, Joshua J. Neumiller, PharmD, CDCES, FADCES, FASCP; Stephen A. Brunton, MD, FAAFP, CDCES


Optimized Management of Cardio-Renal-Metabolic (CRM) Conditions in Patients with T2D, Jay H. Shubrook, DO; Joshua J. Neumiller, PharmD, CDCES, FADCES, FASCP


Reducing Cardiopulmonary Risk and Exacerbations in COPD, Barbara Yawn, MD, MSc, FAAFP


Reducing Ischemic Stroke in Diabetes: The Role of GLP-1 Ras, John E. Anderson, MD; Javed Butler, MD, MPH, MBA; Andrei V. Alexandrov, MD


Use of ICS and Fast-Acting Bronchodilators in Asthma: Past, Present, and Future, Neil Skolnik, MD; Marissa Norden, DO; Njira Lugogo, MD: Wendy Wright, DNP, ANP-BC, FNP-BC, FAANP, FAAN, FNAP

Hot Topics in Primary Care 2023 is a resource that explores the newest developments in primary care topics that impact your daily clinical practice.

Click on the link below to access the entire supplement. You can also click on the video panes below to view brief summaries of individual chapters. Titles above the video panes link directly to each article.
 

• A Patient-Centered Approach to Managing IBS-C and CIC
• Acute Pain in Perspective
• Continuous Glucose Monitoring in Practice
• Early Intervention by Family Physicians to Delay Type 1 Diabetes
• Early Life Nutrition and the Developing Brain
• Insomnia Management: A Review and Update
• New Paradigms for CKD Management in Patients With T2D
• Optimized Management of Cardio-Renal-Metabolic (CRM) Conditions in Patients with T2D
• Reducing Cardiopulmonary Risk and Exacerbations in COPD
• Reducing Ischemic Stroke in Diabetes: The Role of GLP-1 RAs
• Use of ICS and Fast-Acting Bronchodilators in Asthma: Past, Present, and Future

This supplement offers the opportunity to earn a total of 4 continuing medical education (CME) credits. Credit is awarded for successful completion of the evaluation after reading the article. The links can be found within the supplement on the first page of each article where CME credits are offered.

Click here to read Hot Topics in Primary Care 2023

This supplement to The Journal of Family Practice was sponsored by the Primary Care Education Consortium and Primary Care Metabolic Group.
Check out these short video segments, which were prepared by the supplement authors and summarize the individual articles.
The title above each video links to the related article.

A Patient-Centered Approach to Managing IBS-C and CIC, Brian E. Lacy, MD, PhD, FACG


Acute Pain in Perspective, Bill McCarberg, MD


Continuous Glucose Monitoring in Practice, Eden M. Miller, DO


Early Intervention by Family Physicians to Delay Type 1 Diabetes, Steven Edelman, MD


Early Life Nutrition and the Developing Brain, Danielle Christifano, PhD; Lara Bennett, MS, RD, LD


Insomnia Management: A Review and Update, David P. Shaha, MD


New Paradigms for CKD Management in Patients With T2D, Joshua J. Neumiller, PharmD, CDCES, FADCES, FASCP; Stephen A. Brunton, MD, FAAFP, CDCES


Optimized Management of Cardio-Renal-Metabolic (CRM) Conditions in Patients with T2D, Jay H. Shubrook, DO; Joshua J. Neumiller, PharmD, CDCES, FADCES, FASCP


Reducing Cardiopulmonary Risk and Exacerbations in COPD, Barbara Yawn, MD, MSc, FAAFP


Reducing Ischemic Stroke in Diabetes: The Role of GLP-1 Ras, John E. Anderson, MD; Javed Butler, MD, MPH, MBA; Andrei V. Alexandrov, MD


Use of ICS and Fast-Acting Bronchodilators in Asthma: Past, Present, and Future, Neil Skolnik, MD; Marissa Norden, DO; Njira Lugogo, MD: Wendy Wright, DNP, ANP-BC, FNP-BC, FAANP, FAAN, FNAP

To the Editor:

With health care constituting one of the larger segments of the US economy, medical practice is increasingly subject to business considerations.¹ Patients, providers, and organizations are all required to make decisions that reflect choices beyond clinical needs alone. Given the impact of market forces, clinicians often are asked to navigate operational and business decisions. Accordingly, education about the policy and systems that shape care delivery can improve quality and help patients.²

The ability to understand the ecosystem of health care is of utmost importance for medical providers and can be achieved through resident education. Teaching fundamental business concepts enables residents to deliver care that is responsive to the constraints and opportunities encountered by patients and organizations, which ultimately will better prepare them to serve as advocates in alignment with their principal duties as physicians.

Despite the recognizable relationship between business and medicine, training has not yet been standardized to include topics in business education, and clinicians in dermatology are remarkably positioned to benefit because of the variety of practice settings and services they can provide. In dermatology, the diversity of services provided gives rise to complex coding and use of modifiers. Proper utilization of coding and billing is critical to create accurate documentation and receive appropriate reimbursement.³ Furthermore, clinicians in dermatology have to contend with the influence of insurance at many points of care, such as with coverage of pharmaceuticals. Formularies often have wide variability in coverage and are changing as new drugs come to market in the dermatologic space.⁴

The landscape of practice structure also has undergone change with increasing consolidation and mergers. The acquisition of practices by private equity firms has induced changes in practice infrastructure. The impact of changing organizational and managerial influences continues to be a topic of debate, with disparate opinions on how these developments shape standards of physician satisfaction and patient care.⁵

The convergence of these factors points to an important question that is gaining popularity: How will young dermatologists work within the context of all these parameters to best advocate and care for their patients? These questions are garnering more attention and were recently investigated through a survey of participants in a pilot program to evaluate the importance of business education in dermatology residency.

A survey of residency program directors was created by Patrinley and Dewan,⁶ which found that business education during residency was important and additional training should be implemented. Despite the perceived importance of business education, only half of the programs represented by survey respondents offered any structured educational opportunities, revealing a discrepancy between believed importance and practical implementation of business training, which suggests the need to develop a standardized, dermatology-specific curriculum that could be accessed by all residents in training.⁶

We performed a search of the medical literature to identify models of business education in residency programs. Only a few programs were identified, in which courses were predominantly instructed to trainees in primary care–based fields. According to course graduates, the programs were beneficial.^7,8 Programs that had descriptive information about curriculum structure and content were chosen for further investigation and included internal medicine programs at the University of California San Francisco (UCSF) and Columbia University Vagelos College of Physicians and Surgeons (New York, New York). UCSF implemented a Program in Residency Investigation Methods and Epidemiology (PRIME program) to deliver seven 90-minute sessions dedicated to introducing residents to medical economics. Sessions were constructed with the intent of being interactive seminars that took on a variety of forms, including reading-based discussions, case-based analysis, and simulation-based learning.⁷ Columbia University developed a pilot program of week-long didactic sessions that were delivered to third-year internal medicine residents. These seminars featured discussions on health policy and economics, health insurance, technology and cost assessment, legal medicine, public health, community-oriented primary care, and local health department initiatives.⁸ We drew on both courses to build a lecture series focused on the business of dermatology that was delivered to dermatology residents at UMass Chan Medical School (Worcester, Massachusetts). Topic selection also was informed by qualitative input collected via email from recent graduates of the UMass dermatology residency program, focusing on the following areas: the US medical economy and health care costs; billing, coding, and claims processing; quality, relative value units (RVUs), reimbursement, and the merit-based incentive payment system; coverage of pharmaceuticals and teledermatology; and management. Residents were not required to prepare for any of the sessions; they were provided with handouts and slideshow presentations for reference to review at their convenience if desired. Five seminars were virtually conducted by an MD/MBA candidate at the institution (E.H.). They were recorded over the course of an academic year at 1- to 2-month intervals. Each 45-minute session was conducted in a lecture-discussion format and included case examples to help illustrate key principles and stimulate conversation. For example, the lecture on reimbursement incorporated a fee schedule calculation for a shave biopsy, using RVU and geographic pricing cost index (GCPI) multipliers. This demonstrated the variation in Centers for Medicare & Medicaid Services reimbursement in relation to (1) constituents of the RVU calculation (ie, work, practice expense, and malpractice) and (2) practice in a particular location (ie, the GCPI). Following this example, a conversation ensued among participants regarding the factors that drive valuation, with particular interest in variation based on urban vs suburban locations across the United States. Participants also found it of interest to examine the percentage of the valuation dedicated to each constituent and how features such as lesion size informed the final assessment of the charge. Another stylistic choice in developing the model was to include prompts for further consideration prior to transitioning topics in the lectures. For example: when examining the burden of skin disease, the audience was prompted to consider: “What is driving cost escalations, and how will services of the clinical domain meet these evolving needs?” At another point in the introductory lecture, residents were asked: “How do different types of insurance plans impact the management of patients with dermatologic concerns?” These questions were intended to transition residents to the next topic of discussion and highlight take-home points of consideration for medical practice. The project was reviewed by the UMass institutional review board and met criteria for exemption.

Residents who participated in at least 1 lecture (N=10) were surveyed after attendance; there were 7 responses (70% response rate). Residents were asked to rate a series of statements on a scale of 1 (strongly disagree) to 5 (strongly agree) and to provide commentary via an online form. Respondents indicated that the course was enjoyable (average score, 4.00), provided an appropriate level of detail (average score, 4.00), would be beneficial to integrate into a dermatology residency curriculum (average score, 3.86), and informed how they would practice as a clinician (average score, 3.86)(Figure). The respondents agreed that the course met the main goals of this initiative: it helped them develop knowledge about the interface between business and dermatology (4.14) and exposed residents to topics they had not learned about previously (4.71).

Although the course generally was well received, areas for improvement were identified from respondents’ comments, relating to audience engagement and refining the level of detail in the lectures. Recommendations included “less technical jargon and more focus on ‘big picture’ concepts, given audience’s low baseline knowledge”; “more case examples in each module”; and “more diagrams or interactive activities (polls, quizzes, break-out rooms) because the lectures were a bit dense.” This input was taken into consideration when revising the lectures for future use; they were reconstructed to have more case-based examples and prompts to encourage participation.

Resident commentary also demonstrated appreciation for education in this subject material. Statements such as “this is an important topic for future dermatologists” and “thank you so much for taking the time to implement this course” reflected the perceived value of this material during critical academic time. Another resident remarked: “This was great, thanks for putting it together.”

Given the positive experience of the residents and successful implementation of the series, this course was made available to all dermatology trainees on a network server with accompanying written documents. It is planned to be offered on a 3-year cycle in the future and will be updated to reflect inevitable changes in health care.

Although the relationship between business and medicine is increasingly important, teaching business principles has not become standardized or required in medical training. Despite the perception that this content is of value, implementation of programming has lagged behind that recognition, likely due to challenges in designing the curriculum and diffusing content into an already-saturated schedule. A model course that can be replicated in other residency programs would be valuable. We introduced a dermatology-specific lecture series to help prepare trainees for dermatology practice in a variety of clinical settings and train them with the language of business and operations that will equip them to respond to the needs of their patients, their practice, and the medical environment. Findings of this pilot study may not be generalizable to all dermatology residency programs because the sample size was small; the study was conducted at a single institution; and the content was delivered entirely online.

To the Editor:

With health care constituting one of the larger segments of the US economy, medical practice is increasingly subject to business considerations.¹ Patients, providers, and organizations are all required to make decisions that reflect choices beyond clinical needs alone. Given the impact of market forces, clinicians often are asked to navigate operational and business decisions. Accordingly, education about the policy and systems that shape care delivery can improve quality and help patients.²

The ability to understand the ecosystem of health care is of utmost importance for medical providers and can be achieved through resident education. Teaching fundamental business concepts enables residents to deliver care that is responsive to the constraints and opportunities encountered by patients and organizations, which ultimately will better prepare them to serve as advocates in alignment with their principal duties as physicians.

Despite the recognizable relationship between business and medicine, training has not yet been standardized to include topics in business education, and clinicians in dermatology are remarkably positioned to benefit because of the variety of practice settings and services they can provide. In dermatology, the diversity of services provided gives rise to complex coding and use of modifiers. Proper utilization of coding and billing is critical to create accurate documentation and receive appropriate reimbursement.³ Furthermore, clinicians in dermatology have to contend with the influence of insurance at many points of care, such as with coverage of pharmaceuticals. Formularies often have wide variability in coverage and are changing as new drugs come to market in the dermatologic space.⁴

The landscape of practice structure also has undergone change with increasing consolidation and mergers. The acquisition of practices by private equity firms has induced changes in practice infrastructure. The impact of changing organizational and managerial influences continues to be a topic of debate, with disparate opinions on how these developments shape standards of physician satisfaction and patient care.⁵

The convergence of these factors points to an important question that is gaining popularity: How will young dermatologists work within the context of all these parameters to best advocate and care for their patients? These questions are garnering more attention and were recently investigated through a survey of participants in a pilot program to evaluate the importance of business education in dermatology residency.

A survey of residency program directors was created by Patrinley and Dewan,⁶ which found that business education during residency was important and additional training should be implemented. Despite the perceived importance of business education, only half of the programs represented by survey respondents offered any structured educational opportunities, revealing a discrepancy between believed importance and practical implementation of business training, which suggests the need to develop a standardized, dermatology-specific curriculum that could be accessed by all residents in training.⁶

We performed a search of the medical literature to identify models of business education in residency programs. Only a few programs were identified, in which courses were predominantly instructed to trainees in primary care–based fields. According to course graduates, the programs were beneficial.^7,8 Programs that had descriptive information about curriculum structure and content were chosen for further investigation and included internal medicine programs at the University of California San Francisco (UCSF) and Columbia University Vagelos College of Physicians and Surgeons (New York, New York). UCSF implemented a Program in Residency Investigation Methods and Epidemiology (PRIME program) to deliver seven 90-minute sessions dedicated to introducing residents to medical economics. Sessions were constructed with the intent of being interactive seminars that took on a variety of forms, including reading-based discussions, case-based analysis, and simulation-based learning.⁷ Columbia University developed a pilot program of week-long didactic sessions that were delivered to third-year internal medicine residents. These seminars featured discussions on health policy and economics, health insurance, technology and cost assessment, legal medicine, public health, community-oriented primary care, and local health department initiatives.⁸ We drew on both courses to build a lecture series focused on the business of dermatology that was delivered to dermatology residents at UMass Chan Medical School (Worcester, Massachusetts). Topic selection also was informed by qualitative input collected via email from recent graduates of the UMass dermatology residency program, focusing on the following areas: the US medical economy and health care costs; billing, coding, and claims processing; quality, relative value units (RVUs), reimbursement, and the merit-based incentive payment system; coverage of pharmaceuticals and teledermatology; and management. Residents were not required to prepare for any of the sessions; they were provided with handouts and slideshow presentations for reference to review at their convenience if desired. Five seminars were virtually conducted by an MD/MBA candidate at the institution (E.H.). They were recorded over the course of an academic year at 1- to 2-month intervals. Each 45-minute session was conducted in a lecture-discussion format and included case examples to help illustrate key principles and stimulate conversation. For example, the lecture on reimbursement incorporated a fee schedule calculation for a shave biopsy, using RVU and geographic pricing cost index (GCPI) multipliers. This demonstrated the variation in Centers for Medicare & Medicaid Services reimbursement in relation to (1) constituents of the RVU calculation (ie, work, practice expense, and malpractice) and (2) practice in a particular location (ie, the GCPI). Following this example, a conversation ensued among participants regarding the factors that drive valuation, with particular interest in variation based on urban vs suburban locations across the United States. Participants also found it of interest to examine the percentage of the valuation dedicated to each constituent and how features such as lesion size informed the final assessment of the charge. Another stylistic choice in developing the model was to include prompts for further consideration prior to transitioning topics in the lectures. For example: when examining the burden of skin disease, the audience was prompted to consider: “What is driving cost escalations, and how will services of the clinical domain meet these evolving needs?” At another point in the introductory lecture, residents were asked: “How do different types of insurance plans impact the management of patients with dermatologic concerns?” These questions were intended to transition residents to the next topic of discussion and highlight take-home points of consideration for medical practice. The project was reviewed by the UMass institutional review board and met criteria for exemption.

Residents who participated in at least 1 lecture (N=10) were surveyed after attendance; there were 7 responses (70% response rate). Residents were asked to rate a series of statements on a scale of 1 (strongly disagree) to 5 (strongly agree) and to provide commentary via an online form. Respondents indicated that the course was enjoyable (average score, 4.00), provided an appropriate level of detail (average score, 4.00), would be beneficial to integrate into a dermatology residency curriculum (average score, 3.86), and informed how they would practice as a clinician (average score, 3.86)(Figure). The respondents agreed that the course met the main goals of this initiative: it helped them develop knowledge about the interface between business and dermatology (4.14) and exposed residents to topics they had not learned about previously (4.71).

Although the course generally was well received, areas for improvement were identified from respondents’ comments, relating to audience engagement and refining the level of detail in the lectures. Recommendations included “less technical jargon and more focus on ‘big picture’ concepts, given audience’s low baseline knowledge”; “more case examples in each module”; and “more diagrams or interactive activities (polls, quizzes, break-out rooms) because the lectures were a bit dense.” This input was taken into consideration when revising the lectures for future use; they were reconstructed to have more case-based examples and prompts to encourage participation.

Resident commentary also demonstrated appreciation for education in this subject material. Statements such as “this is an important topic for future dermatologists” and “thank you so much for taking the time to implement this course” reflected the perceived value of this material during critical academic time. Another resident remarked: “This was great, thanks for putting it together.”

Given the positive experience of the residents and successful implementation of the series, this course was made available to all dermatology trainees on a network server with accompanying written documents. It is planned to be offered on a 3-year cycle in the future and will be updated to reflect inevitable changes in health care.

Although the relationship between business and medicine is increasingly important, teaching business principles has not become standardized or required in medical training. Despite the perception that this content is of value, implementation of programming has lagged behind that recognition, likely due to challenges in designing the curriculum and diffusing content into an already-saturated schedule. A model course that can be replicated in other residency programs would be valuable. We introduced a dermatology-specific lecture series to help prepare trainees for dermatology practice in a variety of clinical settings and train them with the language of business and operations that will equip them to respond to the needs of their patients, their practice, and the medical environment. Findings of this pilot study may not be generalizable to all dermatology residency programs because the sample size was small; the study was conducted at a single institution; and the content was delivered entirely online.

To the Editor:

With health care constituting one of the larger segments of the US economy, medical practice is increasingly subject to business considerations.¹ Patients, providers, and organizations are all required to make decisions that reflect choices beyond clinical needs alone. Given the impact of market forces, clinicians often are asked to navigate operational and business decisions. Accordingly, education about the policy and systems that shape care delivery can improve quality and help patients.²

The ability to understand the ecosystem of health care is of utmost importance for medical providers and can be achieved through resident education. Teaching fundamental business concepts enables residents to deliver care that is responsive to the constraints and opportunities encountered by patients and organizations, which ultimately will better prepare them to serve as advocates in alignment with their principal duties as physicians.

Despite the recognizable relationship between business and medicine, training has not yet been standardized to include topics in business education, and clinicians in dermatology are remarkably positioned to benefit because of the variety of practice settings and services they can provide. In dermatology, the diversity of services provided gives rise to complex coding and use of modifiers. Proper utilization of coding and billing is critical to create accurate documentation and receive appropriate reimbursement.³ Furthermore, clinicians in dermatology have to contend with the influence of insurance at many points of care, such as with coverage of pharmaceuticals. Formularies often have wide variability in coverage and are changing as new drugs come to market in the dermatologic space.⁴

The landscape of practice structure also has undergone change with increasing consolidation and mergers. The acquisition of practices by private equity firms has induced changes in practice infrastructure. The impact of changing organizational and managerial influences continues to be a topic of debate, with disparate opinions on how these developments shape standards of physician satisfaction and patient care.⁵

The convergence of these factors points to an important question that is gaining popularity: How will young dermatologists work within the context of all these parameters to best advocate and care for their patients? These questions are garnering more attention and were recently investigated through a survey of participants in a pilot program to evaluate the importance of business education in dermatology residency.

A survey of residency program directors was created by Patrinley and Dewan,⁶ which found that business education during residency was important and additional training should be implemented. Despite the perceived importance of business education, only half of the programs represented by survey respondents offered any structured educational opportunities, revealing a discrepancy between believed importance and practical implementation of business training, which suggests the need to develop a standardized, dermatology-specific curriculum that could be accessed by all residents in training.⁶

We performed a search of the medical literature to identify models of business education in residency programs. Only a few programs were identified, in which courses were predominantly instructed to trainees in primary care–based fields. According to course graduates, the programs were beneficial.^7,8 Programs that had descriptive information about curriculum structure and content were chosen for further investigation and included internal medicine programs at the University of California San Francisco (UCSF) and Columbia University Vagelos College of Physicians and Surgeons (New York, New York). UCSF implemented a Program in Residency Investigation Methods and Epidemiology (PRIME program) to deliver seven 90-minute sessions dedicated to introducing residents to medical economics. Sessions were constructed with the intent of being interactive seminars that took on a variety of forms, including reading-based discussions, case-based analysis, and simulation-based learning.⁷ Columbia University developed a pilot program of week-long didactic sessions that were delivered to third-year internal medicine residents. These seminars featured discussions on health policy and economics, health insurance, technology and cost assessment, legal medicine, public health, community-oriented primary care, and local health department initiatives.⁸ We drew on both courses to build a lecture series focused on the business of dermatology that was delivered to dermatology residents at UMass Chan Medical School (Worcester, Massachusetts). Topic selection also was informed by qualitative input collected via email from recent graduates of the UMass dermatology residency program, focusing on the following areas: the US medical economy and health care costs; billing, coding, and claims processing; quality, relative value units (RVUs), reimbursement, and the merit-based incentive payment system; coverage of pharmaceuticals and teledermatology; and management. Residents were not required to prepare for any of the sessions; they were provided with handouts and slideshow presentations for reference to review at their convenience if desired. Five seminars were virtually conducted by an MD/MBA candidate at the institution (E.H.). They were recorded over the course of an academic year at 1- to 2-month intervals. Each 45-minute session was conducted in a lecture-discussion format and included case examples to help illustrate key principles and stimulate conversation. For example, the lecture on reimbursement incorporated a fee schedule calculation for a shave biopsy, using RVU and geographic pricing cost index (GCPI) multipliers. This demonstrated the variation in Centers for Medicare & Medicaid Services reimbursement in relation to (1) constituents of the RVU calculation (ie, work, practice expense, and malpractice) and (2) practice in a particular location (ie, the GCPI). Following this example, a conversation ensued among participants regarding the factors that drive valuation, with particular interest in variation based on urban vs suburban locations across the United States. Participants also found it of interest to examine the percentage of the valuation dedicated to each constituent and how features such as lesion size informed the final assessment of the charge. Another stylistic choice in developing the model was to include prompts for further consideration prior to transitioning topics in the lectures. For example: when examining the burden of skin disease, the audience was prompted to consider: “What is driving cost escalations, and how will services of the clinical domain meet these evolving needs?” At another point in the introductory lecture, residents were asked: “How do different types of insurance plans impact the management of patients with dermatologic concerns?” These questions were intended to transition residents to the next topic of discussion and highlight take-home points of consideration for medical practice. The project was reviewed by the UMass institutional review board and met criteria for exemption.

Residents who participated in at least 1 lecture (N=10) were surveyed after attendance; there were 7 responses (70% response rate). Residents were asked to rate a series of statements on a scale of 1 (strongly disagree) to 5 (strongly agree) and to provide commentary via an online form. Respondents indicated that the course was enjoyable (average score, 4.00), provided an appropriate level of detail (average score, 4.00), would be beneficial to integrate into a dermatology residency curriculum (average score, 3.86), and informed how they would practice as a clinician (average score, 3.86)(Figure). The respondents agreed that the course met the main goals of this initiative: it helped them develop knowledge about the interface between business and dermatology (4.14) and exposed residents to topics they had not learned about previously (4.71).

Although the course generally was well received, areas for improvement were identified from respondents’ comments, relating to audience engagement and refining the level of detail in the lectures. Recommendations included “less technical jargon and more focus on ‘big picture’ concepts, given audience’s low baseline knowledge”; “more case examples in each module”; and “more diagrams or interactive activities (polls, quizzes, break-out rooms) because the lectures were a bit dense.” This input was taken into consideration when revising the lectures for future use; they were reconstructed to have more case-based examples and prompts to encourage participation.

Resident commentary also demonstrated appreciation for education in this subject material. Statements such as “this is an important topic for future dermatologists” and “thank you so much for taking the time to implement this course” reflected the perceived value of this material during critical academic time. Another resident remarked: “This was great, thanks for putting it together.”

Given the positive experience of the residents and successful implementation of the series, this course was made available to all dermatology trainees on a network server with accompanying written documents. It is planned to be offered on a 3-year cycle in the future and will be updated to reflect inevitable changes in health care.

Although the relationship between business and medicine is increasingly important, teaching business principles has not become standardized or required in medical training. Despite the perception that this content is of value, implementation of programming has lagged behind that recognition, likely due to challenges in designing the curriculum and diffusing content into an already-saturated schedule. A model course that can be replicated in other residency programs would be valuable. We introduced a dermatology-specific lecture series to help prepare trainees for dermatology practice in a variety of clinical settings and train them with the language of business and operations that will equip them to respond to the needs of their patients, their practice, and the medical environment. Findings of this pilot study may not be generalizable to all dermatology residency programs because the sample size was small; the study was conducted at a single institution; and the content was delivered entirely online.

Gum disease and tooth loss are linked to hippocampal atrophy and may have a more negative impact on the brain than aging, new research suggests.

Investigators found that in a late middle-aged and older cohort, among patients with mild periodontitis, having fewer teeth was linked to a faster rate of left hippocampal atrophy. For those with severe gum disease, each additional lost tooth was associated with a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“Tooth loss and gum disease, which is inflammation of the tissue around the teeth that can cause shrinkage of the gums and loosening of the teeth, are very common, so evaluating a potential link with dementia is incredibly important,” study investigator Satoshi Yamaguchi, PhD, DDS, of Tohoku University, in Sendai, Japan, said in a release.

“Our study found that these conditions may play a role in the health of the brain area that controls thinking and memory, giving people another reason to take better care of their teeth,” Dr. Yamaguchi noted.

The findings were published online in Neurology.
 

Greater effect than aging

Although previous research suggests that tooth loss and periodontitis are risk factors for Alzheimer’s disease, longitudinal research has not shown a significant correlation between these conditions and hippocampal atrophy.

To clarify this association, the investigators followed 172 men and women (average age, 67 years) who had undergone two MRI brain scans 4 years apart and had had a dental examination. None of the participants had any signs of cognitive decline at baseline.

At study outset, information on cerebrovascular and cardiovascular disease, alcohol consumption, smoking, depression history, and cognitive function was gathered. The Mini Mental State Exam and dental exams were administered at baseline and at 4-year follow-up.

For each participant, the number of teeth was counted, and all participants were assessed for gum disease via periodontal probing depth (PD).

Healthy gums typically measure between 1 and 3 mm in depth. Mild gum disease is signified by measurements of 3-4 mm in several areas. Severe gum disease involves measurements of 5-6 mm and is accompanied by greater bone loss, leading to potential tooth loss.

Multiple regression analysis was performed, with the annual symmetric percentage change (SPC) of hippocampal volume as the dependent variable. The analysis included an interaction term between the number of teeth present (NTP) and mean PD.

Over the 4-year study period, the investigators found that the qualitative interaction between NTP and mean PD was significant for the annual SPC in the left hippocampus.

Among those with mild periodontitis, having fewer teeth correlated with more rapid atrophy of the left hippocampus, such that every tooth lost was equivalent to nearly 1 year of brain aging.

In contrast, having more teeth was associated with a faster rate of left hippocampal atrophy among those with severe periodontitis and was equivalent to 1.3 years of brain aging.

For those with severe gum disease, each additional lost tooth corresponded to a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“This finding indicates that periodontitis may have a greater association with left hippocampal atrophy than the association exhibited by age. Furthermore, in cases of mild periodontitis, fewer teeth may be associated with a subsequent decline in cognitive function,” the investigators write.

The study’s results, they add, highlight the importance of preserving oral health, not just the retaining of teeth. “These findings suggest that retaining teeth with severe gum disease is associated with brain atrophy,” said Dr. Yamaguchi.

“Controlling the progression of gum disease through regular dental visits is crucial, and teeth with severe gum disease may need to be extracted and replaced with appropriate prosthetic devices,” he added.

The researchers note that further studies are needed to confirm these findings.

The study was supported the Japanese Ministry of Education, Culture, Sports, Science, and Technology; Kelo University; Japan Arteriosclerosis Prevention Fund; Japanese Ministry of Health, Labor, and Welfare; Teiko University; Pfizer Japan; Bayer Yakuhin; Chugai Pharmaceutical; Daiichi Sankyo; Astrellas Pharma; Takeda Pharmaceutical; the Health Care Science Institute; the Health Science Center; and the Takeda Science Foundation. The investigators reported no relevant financial relationships.

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

Gum disease and tooth loss are linked to hippocampal atrophy and may have a more negative impact on the brain than aging, new research suggests.

Investigators found that in a late middle-aged and older cohort, among patients with mild periodontitis, having fewer teeth was linked to a faster rate of left hippocampal atrophy. For those with severe gum disease, each additional lost tooth was associated with a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“Tooth loss and gum disease, which is inflammation of the tissue around the teeth that can cause shrinkage of the gums and loosening of the teeth, are very common, so evaluating a potential link with dementia is incredibly important,” study investigator Satoshi Yamaguchi, PhD, DDS, of Tohoku University, in Sendai, Japan, said in a release.

“Our study found that these conditions may play a role in the health of the brain area that controls thinking and memory, giving people another reason to take better care of their teeth,” Dr. Yamaguchi noted.

The findings were published online in Neurology.
 

Greater effect than aging

Although previous research suggests that tooth loss and periodontitis are risk factors for Alzheimer’s disease, longitudinal research has not shown a significant correlation between these conditions and hippocampal atrophy.

To clarify this association, the investigators followed 172 men and women (average age, 67 years) who had undergone two MRI brain scans 4 years apart and had had a dental examination. None of the participants had any signs of cognitive decline at baseline.

At study outset, information on cerebrovascular and cardiovascular disease, alcohol consumption, smoking, depression history, and cognitive function was gathered. The Mini Mental State Exam and dental exams were administered at baseline and at 4-year follow-up.

For each participant, the number of teeth was counted, and all participants were assessed for gum disease via periodontal probing depth (PD).

Healthy gums typically measure between 1 and 3 mm in depth. Mild gum disease is signified by measurements of 3-4 mm in several areas. Severe gum disease involves measurements of 5-6 mm and is accompanied by greater bone loss, leading to potential tooth loss.

Multiple regression analysis was performed, with the annual symmetric percentage change (SPC) of hippocampal volume as the dependent variable. The analysis included an interaction term between the number of teeth present (NTP) and mean PD.

Over the 4-year study period, the investigators found that the qualitative interaction between NTP and mean PD was significant for the annual SPC in the left hippocampus.

Among those with mild periodontitis, having fewer teeth correlated with more rapid atrophy of the left hippocampus, such that every tooth lost was equivalent to nearly 1 year of brain aging.

In contrast, having more teeth was associated with a faster rate of left hippocampal atrophy among those with severe periodontitis and was equivalent to 1.3 years of brain aging.

For those with severe gum disease, each additional lost tooth corresponded to a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“This finding indicates that periodontitis may have a greater association with left hippocampal atrophy than the association exhibited by age. Furthermore, in cases of mild periodontitis, fewer teeth may be associated with a subsequent decline in cognitive function,” the investigators write.

The study’s results, they add, highlight the importance of preserving oral health, not just the retaining of teeth. “These findings suggest that retaining teeth with severe gum disease is associated with brain atrophy,” said Dr. Yamaguchi.

“Controlling the progression of gum disease through regular dental visits is crucial, and teeth with severe gum disease may need to be extracted and replaced with appropriate prosthetic devices,” he added.

The researchers note that further studies are needed to confirm these findings.

The study was supported the Japanese Ministry of Education, Culture, Sports, Science, and Technology; Kelo University; Japan Arteriosclerosis Prevention Fund; Japanese Ministry of Health, Labor, and Welfare; Teiko University; Pfizer Japan; Bayer Yakuhin; Chugai Pharmaceutical; Daiichi Sankyo; Astrellas Pharma; Takeda Pharmaceutical; the Health Care Science Institute; the Health Science Center; and the Takeda Science Foundation. The investigators reported no relevant financial relationships.

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

Gum disease and tooth loss are linked to hippocampal atrophy and may have a more negative impact on the brain than aging, new research suggests.

Investigators found that in a late middle-aged and older cohort, among patients with mild periodontitis, having fewer teeth was linked to a faster rate of left hippocampal atrophy. For those with severe gum disease, each additional lost tooth was associated with a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“Tooth loss and gum disease, which is inflammation of the tissue around the teeth that can cause shrinkage of the gums and loosening of the teeth, are very common, so evaluating a potential link with dementia is incredibly important,” study investigator Satoshi Yamaguchi, PhD, DDS, of Tohoku University, in Sendai, Japan, said in a release.

“Our study found that these conditions may play a role in the health of the brain area that controls thinking and memory, giving people another reason to take better care of their teeth,” Dr. Yamaguchi noted.

The findings were published online in Neurology.
 

Greater effect than aging

Although previous research suggests that tooth loss and periodontitis are risk factors for Alzheimer’s disease, longitudinal research has not shown a significant correlation between these conditions and hippocampal atrophy.

To clarify this association, the investigators followed 172 men and women (average age, 67 years) who had undergone two MRI brain scans 4 years apart and had had a dental examination. None of the participants had any signs of cognitive decline at baseline.

At study outset, information on cerebrovascular and cardiovascular disease, alcohol consumption, smoking, depression history, and cognitive function was gathered. The Mini Mental State Exam and dental exams were administered at baseline and at 4-year follow-up.

For each participant, the number of teeth was counted, and all participants were assessed for gum disease via periodontal probing depth (PD).

Healthy gums typically measure between 1 and 3 mm in depth. Mild gum disease is signified by measurements of 3-4 mm in several areas. Severe gum disease involves measurements of 5-6 mm and is accompanied by greater bone loss, leading to potential tooth loss.

Multiple regression analysis was performed, with the annual symmetric percentage change (SPC) of hippocampal volume as the dependent variable. The analysis included an interaction term between the number of teeth present (NTP) and mean PD.

Over the 4-year study period, the investigators found that the qualitative interaction between NTP and mean PD was significant for the annual SPC in the left hippocampus.

Among those with mild periodontitis, having fewer teeth correlated with more rapid atrophy of the left hippocampus, such that every tooth lost was equivalent to nearly 1 year of brain aging.

In contrast, having more teeth was associated with a faster rate of left hippocampal atrophy among those with severe periodontitis and was equivalent to 1.3 years of brain aging.

For those with severe gum disease, each additional lost tooth corresponded to a faster rate of brain shrinkage, equivalent to 1.3 years of brain aging.

“This finding indicates that periodontitis may have a greater association with left hippocampal atrophy than the association exhibited by age. Furthermore, in cases of mild periodontitis, fewer teeth may be associated with a subsequent decline in cognitive function,” the investigators write.

The study’s results, they add, highlight the importance of preserving oral health, not just the retaining of teeth. “These findings suggest that retaining teeth with severe gum disease is associated with brain atrophy,” said Dr. Yamaguchi.

“Controlling the progression of gum disease through regular dental visits is crucial, and teeth with severe gum disease may need to be extracted and replaced with appropriate prosthetic devices,” he added.

The researchers note that further studies are needed to confirm these findings.

The study was supported the Japanese Ministry of Education, Culture, Sports, Science, and Technology; Kelo University; Japan Arteriosclerosis Prevention Fund; Japanese Ministry of Health, Labor, and Welfare; Teiko University; Pfizer Japan; Bayer Yakuhin; Chugai Pharmaceutical; Daiichi Sankyo; Astrellas Pharma; Takeda Pharmaceutical; the Health Care Science Institute; the Health Science Center; and the Takeda Science Foundation. The investigators reported no relevant financial relationships.

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

The combination of ezetimibe and a moderate-intensity statin after coronary stenting may be safer and more clinically effective than monotherapy with a high-intensity statin, suggests a “real-world” cohort study that is consistent with trial evidence.

In the observational study with more than 273,000 patients who received percutaneous coronary intervention (PCI) with drug-eluting stents (DES), risk for a broad composite clinical primary endpoint fell by one-fourth (P < .001) among those put on the two-drug regimen with a moderate-intensity statin, compared with those getting a high-intensity statin alone.

The dual-agent approach was also associated with a 15% drop in statin discontinuation and a 20% reduced risk for new-onset diabetes requiring medication (P < .001 for both benefits), reported investigators in the Journal of the American College of Cardiology.

The study’s primary endpoint – a composite of cardiovascular (CV) death, myocardial infarction (MI), coronary revascularization, heart failure (HF) hospitalization, or nonfatal stroke at 3 years – replicated that of the randomized RACING trial conducted by many of the same researchers and published about a year ago in The Lancet.

RACING demonstrated that ezetimibe plus a moderate-intensity statin could be as effective as a high-intensity statin in patients with CV disease, “but have fewer side effects and better compliance,” Myeong-Ki Hong, MD, PhD, Severance Hospital, Yonsei University, Seoul, South Korea, said in an interview.

Dr. Hong is senior author on the current observational study based on the CONNECT-DES registry, which compared rosuvastatin 10 mg/day plus ezetimibe 10 mg/day – used in RACING – with rosuvastatin 20 mg/day in a nationwide cohort of 72,050 patients.

“As we know, populations who are enrolled in randomized studies do not sufficiently represent real patients in practice,” he observed, “so we wanted to evaluate the generalizability of the RACING results in daily clinical practice.”

Deepak L. Bhatt, MD, said he likes studies that look at whether clinical trial results “play out in the real world,” as this one did. “They have largely replicated the results of the RACING trial,” suggesting the approach using a moderate-intensity statin “is the way to go,” Dr. Bhatt of Mount Sinai Health System, New York, who was not affiliated with the current report, said in an interview. “In fact, the moderate-intensity combination regimen was actually better in this study.”

He said the observed reduction in new-onset diabetes with the moderate-intensity statin approach is also important. “There is a link between high-dose statins and diabetes. So, if given the choice, if you can get the benefits from a cardiovascular perspective with a lower risk of diabetes, it makes sense to use the combination therapy.”

Dr. Bhatt said he had been using high-intensity statin monotherapy in his high-risk patients, but RACING made him reconsider the value of moderate-dose statin combination therapy. “Going with lower doses of two drugs instead of high doses of one drug minimizes side effects and, in some cases, can even enhance efficacy – so this is not an unreasonable paradigm.”

In the current cohort study of patients prescribed rosuvastatin after DES implantation, 10,794 received rosuvastatin 10 mg/day plus ezetimibe 10 mg/day, and 61,256 were put on rosuvastatin 20 mg/day.

Hazard ratio risk reductions with the dual-agent lipid-lowering therapy approach, compared with high-intensity statin monotherapy, were more favorable for the primary composite clinical endpoint and important secondary events:

• HR, 0.75; 95% confidence interval, 0.70-0.79; P < .001) for CV death, MI, coronary artery revascularization, HF, or stroke at 3 years.
• HR, 0.85; 95% CI, 0.78-0.94; P = .001) for statin discontinuation.
• HR, 0.80; 95% CI, 0.72-0.88; P < .001) for new-onset diabetes requiring medication.

But HRs for rhabdomyolysis, cholecystectomy, or a new cancer diagnosis did not indicate significant differences between the two groups.

“Now that there is evidence to support the favorable clinical outcomes of combination lipid-lowering therapy with moderate-intensity statin plus ezetimibe” for secondary prevention from both RACING and a study reflecting daily clinical practice, Dr. Hong said, “physicians may feel more comfortable with this approach.”

The registry analysis “is remarkable not only for validating the results of the RACING trial in routine clinical practice in a high-risk secondary prevention population, but also for its innovative methodology,” states an accompanying editorial by Ori Ben-Yehuda, MD, Sulpizio Cardiovascular Center, University of California, San Diego.

Use of such a large single-payer database in their study “affords even greater external validity to the findings, complementing the internal validity of the randomized RACING trial,” Dr. Ben-Yehuda writes.

The rationale for combination therapy is strong, but additional data would be helpful, particularly for informing guidelines, he continues. “A pragmatic trial randomizing a broad racial and ethnic group of patients to low-dose statin,” such as a starting dose of 10 mg/day atorvastatin or 5 mg/day rosuvastatin “plus ezetimibe vs. high-intensity statin alone would provide much needed data to help guide lipid-lowering therapy for millions of patients and hopefully increase persistence on therapy.”

The study was supported by the Cardiovascular Research Center, Seoul, South Korea. Dr. Hong and Dr. Ben-Yehuda have disclosed no relevant financial relationships. Dr. Bhatt has previously disclosed grants and/or personal fees from many companies; personal fees from WebMD and other publications or organizations; and having other relationships with Medscape Cardiology and other publications or organizations.

A version of this article appeared on Medscape.com.

The combination of ezetimibe and a moderate-intensity statin after coronary stenting may be safer and more clinically effective than monotherapy with a high-intensity statin, suggests a “real-world” cohort study that is consistent with trial evidence.

In the observational study with more than 273,000 patients who received percutaneous coronary intervention (PCI) with drug-eluting stents (DES), risk for a broad composite clinical primary endpoint fell by one-fourth (P < .001) among those put on the two-drug regimen with a moderate-intensity statin, compared with those getting a high-intensity statin alone.

The dual-agent approach was also associated with a 15% drop in statin discontinuation and a 20% reduced risk for new-onset diabetes requiring medication (P < .001 for both benefits), reported investigators in the Journal of the American College of Cardiology.

The study’s primary endpoint – a composite of cardiovascular (CV) death, myocardial infarction (MI), coronary revascularization, heart failure (HF) hospitalization, or nonfatal stroke at 3 years – replicated that of the randomized RACING trial conducted by many of the same researchers and published about a year ago in The Lancet.

RACING demonstrated that ezetimibe plus a moderate-intensity statin could be as effective as a high-intensity statin in patients with CV disease, “but have fewer side effects and better compliance,” Myeong-Ki Hong, MD, PhD, Severance Hospital, Yonsei University, Seoul, South Korea, said in an interview.

Dr. Hong is senior author on the current observational study based on the CONNECT-DES registry, which compared rosuvastatin 10 mg/day plus ezetimibe 10 mg/day – used in RACING – with rosuvastatin 20 mg/day in a nationwide cohort of 72,050 patients.

“As we know, populations who are enrolled in randomized studies do not sufficiently represent real patients in practice,” he observed, “so we wanted to evaluate the generalizability of the RACING results in daily clinical practice.”

Deepak L. Bhatt, MD, said he likes studies that look at whether clinical trial results “play out in the real world,” as this one did. “They have largely replicated the results of the RACING trial,” suggesting the approach using a moderate-intensity statin “is the way to go,” Dr. Bhatt of Mount Sinai Health System, New York, who was not affiliated with the current report, said in an interview. “In fact, the moderate-intensity combination regimen was actually better in this study.”

He said the observed reduction in new-onset diabetes with the moderate-intensity statin approach is also important. “There is a link between high-dose statins and diabetes. So, if given the choice, if you can get the benefits from a cardiovascular perspective with a lower risk of diabetes, it makes sense to use the combination therapy.”

Dr. Bhatt said he had been using high-intensity statin monotherapy in his high-risk patients, but RACING made him reconsider the value of moderate-dose statin combination therapy. “Going with lower doses of two drugs instead of high doses of one drug minimizes side effects and, in some cases, can even enhance efficacy – so this is not an unreasonable paradigm.”

In the current cohort study of patients prescribed rosuvastatin after DES implantation, 10,794 received rosuvastatin 10 mg/day plus ezetimibe 10 mg/day, and 61,256 were put on rosuvastatin 20 mg/day.

Hazard ratio risk reductions with the dual-agent lipid-lowering therapy approach, compared with high-intensity statin monotherapy, were more favorable for the primary composite clinical endpoint and important secondary events:

• HR, 0.75; 95% confidence interval, 0.70-0.79; P < .001) for CV death, MI, coronary artery revascularization, HF, or stroke at 3 years.
• HR, 0.85; 95% CI, 0.78-0.94; P = .001) for statin discontinuation.
• HR, 0.80; 95% CI, 0.72-0.88; P < .001) for new-onset diabetes requiring medication.

But HRs for rhabdomyolysis, cholecystectomy, or a new cancer diagnosis did not indicate significant differences between the two groups.

“Now that there is evidence to support the favorable clinical outcomes of combination lipid-lowering therapy with moderate-intensity statin plus ezetimibe” for secondary prevention from both RACING and a study reflecting daily clinical practice, Dr. Hong said, “physicians may feel more comfortable with this approach.”

The registry analysis “is remarkable not only for validating the results of the RACING trial in routine clinical practice in a high-risk secondary prevention population, but also for its innovative methodology,” states an accompanying editorial by Ori Ben-Yehuda, MD, Sulpizio Cardiovascular Center, University of California, San Diego.

Use of such a large single-payer database in their study “affords even greater external validity to the findings, complementing the internal validity of the randomized RACING trial,” Dr. Ben-Yehuda writes.

The rationale for combination therapy is strong, but additional data would be helpful, particularly for informing guidelines, he continues. “A pragmatic trial randomizing a broad racial and ethnic group of patients to low-dose statin,” such as a starting dose of 10 mg/day atorvastatin or 5 mg/day rosuvastatin “plus ezetimibe vs. high-intensity statin alone would provide much needed data to help guide lipid-lowering therapy for millions of patients and hopefully increase persistence on therapy.”

The study was supported by the Cardiovascular Research Center, Seoul, South Korea. Dr. Hong and Dr. Ben-Yehuda have disclosed no relevant financial relationships. Dr. Bhatt has previously disclosed grants and/or personal fees from many companies; personal fees from WebMD and other publications or organizations; and having other relationships with Medscape Cardiology and other publications or organizations.

A version of this article appeared on Medscape.com.

The combination of ezetimibe and a moderate-intensity statin after coronary stenting may be safer and more clinically effective than monotherapy with a high-intensity statin, suggests a “real-world” cohort study that is consistent with trial evidence.

In the observational study with more than 273,000 patients who received percutaneous coronary intervention (PCI) with drug-eluting stents (DES), risk for a broad composite clinical primary endpoint fell by one-fourth (P < .001) among those put on the two-drug regimen with a moderate-intensity statin, compared with those getting a high-intensity statin alone.

The dual-agent approach was also associated with a 15% drop in statin discontinuation and a 20% reduced risk for new-onset diabetes requiring medication (P < .001 for both benefits), reported investigators in the Journal of the American College of Cardiology.

The study’s primary endpoint – a composite of cardiovascular (CV) death, myocardial infarction (MI), coronary revascularization, heart failure (HF) hospitalization, or nonfatal stroke at 3 years – replicated that of the randomized RACING trial conducted by many of the same researchers and published about a year ago in The Lancet.

RACING demonstrated that ezetimibe plus a moderate-intensity statin could be as effective as a high-intensity statin in patients with CV disease, “but have fewer side effects and better compliance,” Myeong-Ki Hong, MD, PhD, Severance Hospital, Yonsei University, Seoul, South Korea, said in an interview.

Dr. Hong is senior author on the current observational study based on the CONNECT-DES registry, which compared rosuvastatin 10 mg/day plus ezetimibe 10 mg/day – used in RACING – with rosuvastatin 20 mg/day in a nationwide cohort of 72,050 patients.

“As we know, populations who are enrolled in randomized studies do not sufficiently represent real patients in practice,” he observed, “so we wanted to evaluate the generalizability of the RACING results in daily clinical practice.”

Deepak L. Bhatt, MD, said he likes studies that look at whether clinical trial results “play out in the real world,” as this one did. “They have largely replicated the results of the RACING trial,” suggesting the approach using a moderate-intensity statin “is the way to go,” Dr. Bhatt of Mount Sinai Health System, New York, who was not affiliated with the current report, said in an interview. “In fact, the moderate-intensity combination regimen was actually better in this study.”

He said the observed reduction in new-onset diabetes with the moderate-intensity statin approach is also important. “There is a link between high-dose statins and diabetes. So, if given the choice, if you can get the benefits from a cardiovascular perspective with a lower risk of diabetes, it makes sense to use the combination therapy.”

Dr. Bhatt said he had been using high-intensity statin monotherapy in his high-risk patients, but RACING made him reconsider the value of moderate-dose statin combination therapy. “Going with lower doses of two drugs instead of high doses of one drug minimizes side effects and, in some cases, can even enhance efficacy – so this is not an unreasonable paradigm.”

In the current cohort study of patients prescribed rosuvastatin after DES implantation, 10,794 received rosuvastatin 10 mg/day plus ezetimibe 10 mg/day, and 61,256 were put on rosuvastatin 20 mg/day.

Hazard ratio risk reductions with the dual-agent lipid-lowering therapy approach, compared with high-intensity statin monotherapy, were more favorable for the primary composite clinical endpoint and important secondary events:

• HR, 0.75; 95% confidence interval, 0.70-0.79; P < .001) for CV death, MI, coronary artery revascularization, HF, or stroke at 3 years.
• HR, 0.85; 95% CI, 0.78-0.94; P = .001) for statin discontinuation.
• HR, 0.80; 95% CI, 0.72-0.88; P < .001) for new-onset diabetes requiring medication.

But HRs for rhabdomyolysis, cholecystectomy, or a new cancer diagnosis did not indicate significant differences between the two groups.

“Now that there is evidence to support the favorable clinical outcomes of combination lipid-lowering therapy with moderate-intensity statin plus ezetimibe” for secondary prevention from both RACING and a study reflecting daily clinical practice, Dr. Hong said, “physicians may feel more comfortable with this approach.”

The registry analysis “is remarkable not only for validating the results of the RACING trial in routine clinical practice in a high-risk secondary prevention population, but also for its innovative methodology,” states an accompanying editorial by Ori Ben-Yehuda, MD, Sulpizio Cardiovascular Center, University of California, San Diego.

Use of such a large single-payer database in their study “affords even greater external validity to the findings, complementing the internal validity of the randomized RACING trial,” Dr. Ben-Yehuda writes.

The rationale for combination therapy is strong, but additional data would be helpful, particularly for informing guidelines, he continues. “A pragmatic trial randomizing a broad racial and ethnic group of patients to low-dose statin,” such as a starting dose of 10 mg/day atorvastatin or 5 mg/day rosuvastatin “plus ezetimibe vs. high-intensity statin alone would provide much needed data to help guide lipid-lowering therapy for millions of patients and hopefully increase persistence on therapy.”

The study was supported by the Cardiovascular Research Center, Seoul, South Korea. Dr. Hong and Dr. Ben-Yehuda have disclosed no relevant financial relationships. Dr. Bhatt has previously disclosed grants and/or personal fees from many companies; personal fees from WebMD and other publications or organizations; and having other relationships with Medscape Cardiology and other publications or organizations.

A version of this article appeared on Medscape.com.

In the latest chapter in the U.S. saga of the subcutaneous implantable cardioverter-defibrillator (S-ICD) system (Boston Scientific) – a large postmarket, multicenter registry study – the device performed at least as well as it did in earlier trials, researchers say.

The device met all prespecified safety and efficacy endpoints in a study that enrolled more than 1,600 patients and followed them for about 5 years, they noted in their report on the S-ICD Post-Approval Study (S-ICD-PAS) published online in the Journal of the American College of Cardiology.

The device was 98.4% effective in treating discrete episodes (not part of an arrhythmia storm) of ventricular tachycardia or ventricular fibrillation with shocks, exceeding the prospective performance goal of 94%, the group reported.

The team was “pleasantly surprised” that the device’s safety and efficacy performance “was as good if not better than previous studies,” despite a sicker group of patients, lead author Michael R. Gold, MD, PhD, Medical University of South Carolina, Charleston, said in an interview.

No predictors of initial-shock failure were identified, suggesting the S-ICD should be effective in a broad range of ICD candidates without indications for pacing, Dr. Gold said.

The S-ICD was approved in Europe in 2008 and by the Food and Drug Administration in 2012. Clinical trials have suggested its performance and risk for inappropriate shocks are in line with transvenous-lead systems for most patients with ICD indications who don’t need pacing, while avoiding the sometimes serious risks posed by transvenous leads.

The S-ICD doesn’t have antitachycardia pacing (ATP), an alternative way to stop some arrhythmias and a universal feature of transvenous-lead systems. Its lack of ATP may be partly responsible for the device’s weak uptake in practice, some observers noted.

The S-ICD-PAS study “laudably included centers with variable prior experience with the S-ICD; however, data were not analyzed by center experience,” Jonathan S. Steinberg, MD, and Valentina Kutyifa, MD, PhD, University of Rochester (N.Y.) Medical Center, New York, wrote in an accompanying editorial regarding the report’s potential limitations.

Also of concern, they wrote, is the large proportion of patients who were lost to follow-up; almost 42% left the study before its prospectively defined end.

Still, wrote Dr. Steinberg and Dr. Kutyifa, S-ICD-PAS “provides robust, long-term evidence in favor of S-ICD use in a diverse cohort of younger patients receiving implants for primary or secondary prevention of sudden arrhythmic death.” Further analyses are needed, however, to clarify its performance “in centers with low vs high volume as well as in important clinical subgroups.”

It’s “reassuring to see the phase 4 postapproval study results sort of corroborate what the initial clinical study shows,” Miguel Leal, MD, Emory University, Atlanta, said in an interview.

The study’s significant attrition rate “does not negate the results because the performance curves of the device remained approximately stable over the 5 years,” he said, “suggesting that the patients who were lost [and whose clinical outcomes were not included] may not have made a significant impact when it comes to the final results.”

Although the S-ICD seems unlikely to cause complications related to endovascular occlusions or infection, “it can still cause complications related to the implant technique, particularly a device site erosion or device dislodgement,” said Dr. Leal, who chairs the American Heart Association Council on Clinical Cardiology–Electrocardiography & Arrhythmia Committee.

The S-ICD’s biggest contribution has been “the ability to promote efficacious therapy without a need for penetrating the endovascular space,” he observed. “We need to continue to push the envelope towards developing device-based technologies that spare the endovascular space.”

The study enrolled 1,643 patients at 86 U.S. centers; their mean age was 53 and 32% were women. Of the total, 1637 were implanted with the device, 665 completed the study, 288 died, and 686 left the study before completing follow-up. Of the latter, 102 (6.2% of the total) underwent S-ICD explantation, often because of infection.

In addition to the overall shock efficacy rate of 98.4%, induced-arrhythmia shock efficacy was 98.7%, first-shock efficacy for spontaneous arrhythmias was 92.2%, and the rate for either induced or spontaneous arrhythmia was 94.7%. A mean of 1.1 shocks was needed to terminate the arrhythmias; time to shock delivery averaged 17.5 seconds.

The rate of inappropriate shocks was 6.7% at 1 year and 15.8% at 5 years, notably with no significant differences between patients who had and had not undergone defibrillation threshold testing at implantation.

Of 516 inappropriate-shock episodes in 224 patients, almost 86% resulted from inappropriate sensing. Inappropriate shocks became less frequent with longer implantation times and during the course of the study.

The rate of freedom from type 1 complications, the primary safety endpoint, was 93.4%, besting the 85% performance goal. The rate of freedom from electrode-related complications was 99.3%, compared with the performance goal of 92.5%.

The S-ICD was replaced by a transvenous system because of the need for pacing in 1.6% of the cohort.

Sana M. Al-Khatib, MD, MHS, who chaired a 2017 multisociety guideline for managing ventricular arrhythmias and prevention of sudden death, acknowledged the 5-year safety and effectiveness of the S-ICD but also highlighted the “very high dropout rate.”

Moreover, given the cohort’s average age, “these results cannot be generalized to much older patients, in their 70s and 80s [for example]. More data on the S-ICD in older patients are needed, especially because some of these patients will need pacing, which is not provided by the S-ICD,” Dr. Al-Khatib, Duke University, Durham, N.C., said in an interview.

Longer follow-up of patients with the S-ICD is also needed, she added, and “having an S-ICD that is smaller with longer battery life would be great for my patients.”

The study was sponsored by Boston Scientific. Dr. Gold reported receiving consulting fees from Boston Scientific and Medtronic and participating in clinical trials with Boston Scientific, Medtronic, and Abbott. Dr. Steinberg, Dr. Kutyifa, Dr. Al-Khatib, and Dr. Leal reported no relevant relationships.

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

In the latest chapter in the U.S. saga of the subcutaneous implantable cardioverter-defibrillator (S-ICD) system (Boston Scientific) – a large postmarket, multicenter registry study – the device performed at least as well as it did in earlier trials, researchers say.

The device met all prespecified safety and efficacy endpoints in a study that enrolled more than 1,600 patients and followed them for about 5 years, they noted in their report on the S-ICD Post-Approval Study (S-ICD-PAS) published online in the Journal of the American College of Cardiology.

The device was 98.4% effective in treating discrete episodes (not part of an arrhythmia storm) of ventricular tachycardia or ventricular fibrillation with shocks, exceeding the prospective performance goal of 94%, the group reported.

The team was “pleasantly surprised” that the device’s safety and efficacy performance “was as good if not better than previous studies,” despite a sicker group of patients, lead author Michael R. Gold, MD, PhD, Medical University of South Carolina, Charleston, said in an interview.

No predictors of initial-shock failure were identified, suggesting the S-ICD should be effective in a broad range of ICD candidates without indications for pacing, Dr. Gold said.

The S-ICD was approved in Europe in 2008 and by the Food and Drug Administration in 2012. Clinical trials have suggested its performance and risk for inappropriate shocks are in line with transvenous-lead systems for most patients with ICD indications who don’t need pacing, while avoiding the sometimes serious risks posed by transvenous leads.

The S-ICD doesn’t have antitachycardia pacing (ATP), an alternative way to stop some arrhythmias and a universal feature of transvenous-lead systems. Its lack of ATP may be partly responsible for the device’s weak uptake in practice, some observers noted.

The S-ICD-PAS study “laudably included centers with variable prior experience with the S-ICD; however, data were not analyzed by center experience,” Jonathan S. Steinberg, MD, and Valentina Kutyifa, MD, PhD, University of Rochester (N.Y.) Medical Center, New York, wrote in an accompanying editorial regarding the report’s potential limitations.

Also of concern, they wrote, is the large proportion of patients who were lost to follow-up; almost 42% left the study before its prospectively defined end.

Still, wrote Dr. Steinberg and Dr. Kutyifa, S-ICD-PAS “provides robust, long-term evidence in favor of S-ICD use in a diverse cohort of younger patients receiving implants for primary or secondary prevention of sudden arrhythmic death.” Further analyses are needed, however, to clarify its performance “in centers with low vs high volume as well as in important clinical subgroups.”

It’s “reassuring to see the phase 4 postapproval study results sort of corroborate what the initial clinical study shows,” Miguel Leal, MD, Emory University, Atlanta, said in an interview.

The study’s significant attrition rate “does not negate the results because the performance curves of the device remained approximately stable over the 5 years,” he said, “suggesting that the patients who were lost [and whose clinical outcomes were not included] may not have made a significant impact when it comes to the final results.”

Although the S-ICD seems unlikely to cause complications related to endovascular occlusions or infection, “it can still cause complications related to the implant technique, particularly a device site erosion or device dislodgement,” said Dr. Leal, who chairs the American Heart Association Council on Clinical Cardiology–Electrocardiography & Arrhythmia Committee.

The S-ICD’s biggest contribution has been “the ability to promote efficacious therapy without a need for penetrating the endovascular space,” he observed. “We need to continue to push the envelope towards developing device-based technologies that spare the endovascular space.”

The study enrolled 1,643 patients at 86 U.S. centers; their mean age was 53 and 32% were women. Of the total, 1637 were implanted with the device, 665 completed the study, 288 died, and 686 left the study before completing follow-up. Of the latter, 102 (6.2% of the total) underwent S-ICD explantation, often because of infection.

In addition to the overall shock efficacy rate of 98.4%, induced-arrhythmia shock efficacy was 98.7%, first-shock efficacy for spontaneous arrhythmias was 92.2%, and the rate for either induced or spontaneous arrhythmia was 94.7%. A mean of 1.1 shocks was needed to terminate the arrhythmias; time to shock delivery averaged 17.5 seconds.

The rate of inappropriate shocks was 6.7% at 1 year and 15.8% at 5 years, notably with no significant differences between patients who had and had not undergone defibrillation threshold testing at implantation.

Of 516 inappropriate-shock episodes in 224 patients, almost 86% resulted from inappropriate sensing. Inappropriate shocks became less frequent with longer implantation times and during the course of the study.

The rate of freedom from type 1 complications, the primary safety endpoint, was 93.4%, besting the 85% performance goal. The rate of freedom from electrode-related complications was 99.3%, compared with the performance goal of 92.5%.

The S-ICD was replaced by a transvenous system because of the need for pacing in 1.6% of the cohort.

Sana M. Al-Khatib, MD, MHS, who chaired a 2017 multisociety guideline for managing ventricular arrhythmias and prevention of sudden death, acknowledged the 5-year safety and effectiveness of the S-ICD but also highlighted the “very high dropout rate.”

Moreover, given the cohort’s average age, “these results cannot be generalized to much older patients, in their 70s and 80s [for example]. More data on the S-ICD in older patients are needed, especially because some of these patients will need pacing, which is not provided by the S-ICD,” Dr. Al-Khatib, Duke University, Durham, N.C., said in an interview.

Longer follow-up of patients with the S-ICD is also needed, she added, and “having an S-ICD that is smaller with longer battery life would be great for my patients.”

The study was sponsored by Boston Scientific. Dr. Gold reported receiving consulting fees from Boston Scientific and Medtronic and participating in clinical trials with Boston Scientific, Medtronic, and Abbott. Dr. Steinberg, Dr. Kutyifa, Dr. Al-Khatib, and Dr. Leal reported no relevant relationships.

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

In the latest chapter in the U.S. saga of the subcutaneous implantable cardioverter-defibrillator (S-ICD) system (Boston Scientific) – a large postmarket, multicenter registry study – the device performed at least as well as it did in earlier trials, researchers say.

The device met all prespecified safety and efficacy endpoints in a study that enrolled more than 1,600 patients and followed them for about 5 years, they noted in their report on the S-ICD Post-Approval Study (S-ICD-PAS) published online in the Journal of the American College of Cardiology.

The device was 98.4% effective in treating discrete episodes (not part of an arrhythmia storm) of ventricular tachycardia or ventricular fibrillation with shocks, exceeding the prospective performance goal of 94%, the group reported.

The team was “pleasantly surprised” that the device’s safety and efficacy performance “was as good if not better than previous studies,” despite a sicker group of patients, lead author Michael R. Gold, MD, PhD, Medical University of South Carolina, Charleston, said in an interview.

No predictors of initial-shock failure were identified, suggesting the S-ICD should be effective in a broad range of ICD candidates without indications for pacing, Dr. Gold said.

The S-ICD was approved in Europe in 2008 and by the Food and Drug Administration in 2012. Clinical trials have suggested its performance and risk for inappropriate shocks are in line with transvenous-lead systems for most patients with ICD indications who don’t need pacing, while avoiding the sometimes serious risks posed by transvenous leads.

The S-ICD doesn’t have antitachycardia pacing (ATP), an alternative way to stop some arrhythmias and a universal feature of transvenous-lead systems. Its lack of ATP may be partly responsible for the device’s weak uptake in practice, some observers noted.

The S-ICD-PAS study “laudably included centers with variable prior experience with the S-ICD; however, data were not analyzed by center experience,” Jonathan S. Steinberg, MD, and Valentina Kutyifa, MD, PhD, University of Rochester (N.Y.) Medical Center, New York, wrote in an accompanying editorial regarding the report’s potential limitations.

Also of concern, they wrote, is the large proportion of patients who were lost to follow-up; almost 42% left the study before its prospectively defined end.

Still, wrote Dr. Steinberg and Dr. Kutyifa, S-ICD-PAS “provides robust, long-term evidence in favor of S-ICD use in a diverse cohort of younger patients receiving implants for primary or secondary prevention of sudden arrhythmic death.” Further analyses are needed, however, to clarify its performance “in centers with low vs high volume as well as in important clinical subgroups.”

It’s “reassuring to see the phase 4 postapproval study results sort of corroborate what the initial clinical study shows,” Miguel Leal, MD, Emory University, Atlanta, said in an interview.

The study’s significant attrition rate “does not negate the results because the performance curves of the device remained approximately stable over the 5 years,” he said, “suggesting that the patients who were lost [and whose clinical outcomes were not included] may not have made a significant impact when it comes to the final results.”

Although the S-ICD seems unlikely to cause complications related to endovascular occlusions or infection, “it can still cause complications related to the implant technique, particularly a device site erosion or device dislodgement,” said Dr. Leal, who chairs the American Heart Association Council on Clinical Cardiology–Electrocardiography & Arrhythmia Committee.

The S-ICD’s biggest contribution has been “the ability to promote efficacious therapy without a need for penetrating the endovascular space,” he observed. “We need to continue to push the envelope towards developing device-based technologies that spare the endovascular space.”

The study enrolled 1,643 patients at 86 U.S. centers; their mean age was 53 and 32% were women. Of the total, 1637 were implanted with the device, 665 completed the study, 288 died, and 686 left the study before completing follow-up. Of the latter, 102 (6.2% of the total) underwent S-ICD explantation, often because of infection.

In addition to the overall shock efficacy rate of 98.4%, induced-arrhythmia shock efficacy was 98.7%, first-shock efficacy for spontaneous arrhythmias was 92.2%, and the rate for either induced or spontaneous arrhythmia was 94.7%. A mean of 1.1 shocks was needed to terminate the arrhythmias; time to shock delivery averaged 17.5 seconds.

The rate of inappropriate shocks was 6.7% at 1 year and 15.8% at 5 years, notably with no significant differences between patients who had and had not undergone defibrillation threshold testing at implantation.

Of 516 inappropriate-shock episodes in 224 patients, almost 86% resulted from inappropriate sensing. Inappropriate shocks became less frequent with longer implantation times and during the course of the study.

The rate of freedom from type 1 complications, the primary safety endpoint, was 93.4%, besting the 85% performance goal. The rate of freedom from electrode-related complications was 99.3%, compared with the performance goal of 92.5%.

The S-ICD was replaced by a transvenous system because of the need for pacing in 1.6% of the cohort.

Sana M. Al-Khatib, MD, MHS, who chaired a 2017 multisociety guideline for managing ventricular arrhythmias and prevention of sudden death, acknowledged the 5-year safety and effectiveness of the S-ICD but also highlighted the “very high dropout rate.”

Moreover, given the cohort’s average age, “these results cannot be generalized to much older patients, in their 70s and 80s [for example]. More data on the S-ICD in older patients are needed, especially because some of these patients will need pacing, which is not provided by the S-ICD,” Dr. Al-Khatib, Duke University, Durham, N.C., said in an interview.

Longer follow-up of patients with the S-ICD is also needed, she added, and “having an S-ICD that is smaller with longer battery life would be great for my patients.”

The study was sponsored by Boston Scientific. Dr. Gold reported receiving consulting fees from Boston Scientific and Medtronic and participating in clinical trials with Boston Scientific, Medtronic, and Abbott. Dr. Steinberg, Dr. Kutyifa, Dr. Al-Khatib, and Dr. Leal reported no relevant relationships.

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

New guidelines from the American Association of Clinical Chemistry (AACC) and American Diabetes Association (ADA) address laboratory measures in the diagnosis and management of diabetes.

The document, titled, “Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus,” is primarily aimed at both laboratory professionals and clinicians involved in diabetes care.

The guidance is focused “on the practical aspects of care in order to assist with decisions regarding the use or interpretation of laboratory tests while screening, diagnosing, or monitoring patients with diabetes,” wrote David B. Sacks, MBChB, chief of the clinical chemistry service at the National Institutes of Health (NIH), Bethesda, Md., and coauthors. It was published online in both Clinical Chemistry and Diabetes Care, including the guidelines and executive summary.  

Coauthor M. Sue Kirkman, MD, of the University of North Carolina, Chapel Hill, said in an interview: “One objective of the guidelines is to increase clinicians’ understanding of the strengths and limitations of tests done in a laboratory and also at the point of care, or in daily life, by people with diabetes.”

The evidence-based recommendations, an update of prior versions published in 2011 and 2002, are meant as a supplement to the ADA Standards of Care in Diabetes and do not address aspects of clinical management, she stressed.
 

Addition of advice on CGM

A significant addition since 2011 is detailed information regarding the use of real-time continuous glucose monitoring (CGM), with a “strong” recommendation based on a “high” level of evidence for use in teens and adults with type 1 diabetes who meet certain criteria, and lower-grade advice to use real-time or intermittently scanned CGM in other populations, including children with diabetes, pregnant women with type 1 diabetes, and adults with type 2 diabetes taking insulin.

The document also reminds clinicians to consider test limitations, Dr. Kirkman pointed out.

“We do a lot of testing in screening, diagnosis, and monitoring of diabetes and its complications, yet for many clinicians we think that any result we get – or that a patient gets from home testing – is perfect. We often don’t think about the accuracy or precision of some tests, things that might interfere with the result, intra-individual variation of the test, or how one test may compare to a test of higher accuracy,” she said.

One example is a recommendation to collect blood samples for glucose analysis in tubes containing a rapidly effective inhibitor of glycolysis such as a granulated citrate buffer. If unavailable, the sample tube should be placed immediately into an ice water slurry and centrifuged within 15-30 minutes to remove the cells.

Without those measures, “red cells in blood sitting in the test tube continue to break down glucose, so the concentration of glucose will start to fall very soon. ... How the specimen is handled makes a huge difference in the result,” Dr. Kirkman emphasized.

Another is the recommendation of a confirmatory test when diagnosing diabetes, regardless of the initial test used (A1c, fasting glucose, or oral glucose tolerance test). “There is large intra-individual variation of fasting glucose and even larger for 2-hour glucose on the oral glucose tolerance test. ... This means if you do the test one week and then repeat it the next day or a week later, the results will be quite different. This is a reason why confirmation of an abnormal test is important. Yet many times this isn’t done,” she noted.

Other “strong” recommendations based on “high” evidence levels include:

• Fasting glucose should be measured in venous plasma when used to establish the diagnosis of diabetes, with a diagnostic cutoff of > 7.0 mmol/L (> 126 mg/dL) for diabetes.
• Frequent blood glucose monitoring is recommended for all people with diabetes treated with intensive insulin regimens (with multiple daily injections or insulin pump therapy) and who are not using CGM.
• Routine use of blood glucose monitoring is not recommended for people with type 2 diabetes who are treated with diet and/or oral agents alone.
• Treatment goals should be based on ADA recommendations, i.e., A1c < 7% (< 53 mmol/mol) if it can be achieved without significant hypoglycemia or other adverse treatment effects, with higher targets for special populations.
• Annual testing for albuminuria should begin in pubertal or postpubertal individuals 5 years after diagnosis of type 1 diabetes and at time of diagnosis of type 2 diabetes, regardless of treatment.
• Urine albumin should be measured annually in adults with diabetes using morning spot urine albumin-to-creatinine ratio.

Other guidance in the document pertains to use of ketone testing, genetic markers, autoimmune markers, and C-peptide.

According to Dr. Sacks, “It’s important to measure accurately, but it’s also very important to communicate the relevance to clinicians and to listen to them and share information. ... Patient care is a team effort.”

Dr. Sachs has reported receiving funding from the NIH. Dr. Kirkman has reported no relevant financial relationships.
 

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

New guidelines from the American Association of Clinical Chemistry (AACC) and American Diabetes Association (ADA) address laboratory measures in the diagnosis and management of diabetes.

The document, titled, “Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus,” is primarily aimed at both laboratory professionals and clinicians involved in diabetes care.

The guidance is focused “on the practical aspects of care in order to assist with decisions regarding the use or interpretation of laboratory tests while screening, diagnosing, or monitoring patients with diabetes,” wrote David B. Sacks, MBChB, chief of the clinical chemistry service at the National Institutes of Health (NIH), Bethesda, Md., and coauthors. It was published online in both Clinical Chemistry and Diabetes Care, including the guidelines and executive summary.  

Coauthor M. Sue Kirkman, MD, of the University of North Carolina, Chapel Hill, said in an interview: “One objective of the guidelines is to increase clinicians’ understanding of the strengths and limitations of tests done in a laboratory and also at the point of care, or in daily life, by people with diabetes.”

The evidence-based recommendations, an update of prior versions published in 2011 and 2002, are meant as a supplement to the ADA Standards of Care in Diabetes and do not address aspects of clinical management, she stressed.
 

Addition of advice on CGM

A significant addition since 2011 is detailed information regarding the use of real-time continuous glucose monitoring (CGM), with a “strong” recommendation based on a “high” level of evidence for use in teens and adults with type 1 diabetes who meet certain criteria, and lower-grade advice to use real-time or intermittently scanned CGM in other populations, including children with diabetes, pregnant women with type 1 diabetes, and adults with type 2 diabetes taking insulin.

The document also reminds clinicians to consider test limitations, Dr. Kirkman pointed out.

“We do a lot of testing in screening, diagnosis, and monitoring of diabetes and its complications, yet for many clinicians we think that any result we get – or that a patient gets from home testing – is perfect. We often don’t think about the accuracy or precision of some tests, things that might interfere with the result, intra-individual variation of the test, or how one test may compare to a test of higher accuracy,” she said.

One example is a recommendation to collect blood samples for glucose analysis in tubes containing a rapidly effective inhibitor of glycolysis such as a granulated citrate buffer. If unavailable, the sample tube should be placed immediately into an ice water slurry and centrifuged within 15-30 minutes to remove the cells.

Without those measures, “red cells in blood sitting in the test tube continue to break down glucose, so the concentration of glucose will start to fall very soon. ... How the specimen is handled makes a huge difference in the result,” Dr. Kirkman emphasized.

Another is the recommendation of a confirmatory test when diagnosing diabetes, regardless of the initial test used (A1c, fasting glucose, or oral glucose tolerance test). “There is large intra-individual variation of fasting glucose and even larger for 2-hour glucose on the oral glucose tolerance test. ... This means if you do the test one week and then repeat it the next day or a week later, the results will be quite different. This is a reason why confirmation of an abnormal test is important. Yet many times this isn’t done,” she noted.

Other “strong” recommendations based on “high” evidence levels include:

• Fasting glucose should be measured in venous plasma when used to establish the diagnosis of diabetes, with a diagnostic cutoff of > 7.0 mmol/L (> 126 mg/dL) for diabetes.
• Frequent blood glucose monitoring is recommended for all people with diabetes treated with intensive insulin regimens (with multiple daily injections or insulin pump therapy) and who are not using CGM.
• Routine use of blood glucose monitoring is not recommended for people with type 2 diabetes who are treated with diet and/or oral agents alone.
• Treatment goals should be based on ADA recommendations, i.e., A1c < 7% (< 53 mmol/mol) if it can be achieved without significant hypoglycemia or other adverse treatment effects, with higher targets for special populations.
• Annual testing for albuminuria should begin in pubertal or postpubertal individuals 5 years after diagnosis of type 1 diabetes and at time of diagnosis of type 2 diabetes, regardless of treatment.
• Urine albumin should be measured annually in adults with diabetes using morning spot urine albumin-to-creatinine ratio.

Other guidance in the document pertains to use of ketone testing, genetic markers, autoimmune markers, and C-peptide.

According to Dr. Sacks, “It’s important to measure accurately, but it’s also very important to communicate the relevance to clinicians and to listen to them and share information. ... Patient care is a team effort.”

Dr. Sachs has reported receiving funding from the NIH. Dr. Kirkman has reported no relevant financial relationships.
 

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

New guidelines from the American Association of Clinical Chemistry (AACC) and American Diabetes Association (ADA) address laboratory measures in the diagnosis and management of diabetes.

The document, titled, “Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus,” is primarily aimed at both laboratory professionals and clinicians involved in diabetes care.

The guidance is focused “on the practical aspects of care in order to assist with decisions regarding the use or interpretation of laboratory tests while screening, diagnosing, or monitoring patients with diabetes,” wrote David B. Sacks, MBChB, chief of the clinical chemistry service at the National Institutes of Health (NIH), Bethesda, Md., and coauthors. It was published online in both Clinical Chemistry and Diabetes Care, including the guidelines and executive summary.  

Coauthor M. Sue Kirkman, MD, of the University of North Carolina, Chapel Hill, said in an interview: “One objective of the guidelines is to increase clinicians’ understanding of the strengths and limitations of tests done in a laboratory and also at the point of care, or in daily life, by people with diabetes.”

The evidence-based recommendations, an update of prior versions published in 2011 and 2002, are meant as a supplement to the ADA Standards of Care in Diabetes and do not address aspects of clinical management, she stressed.
 

Addition of advice on CGM

A significant addition since 2011 is detailed information regarding the use of real-time continuous glucose monitoring (CGM), with a “strong” recommendation based on a “high” level of evidence for use in teens and adults with type 1 diabetes who meet certain criteria, and lower-grade advice to use real-time or intermittently scanned CGM in other populations, including children with diabetes, pregnant women with type 1 diabetes, and adults with type 2 diabetes taking insulin.

The document also reminds clinicians to consider test limitations, Dr. Kirkman pointed out.

“We do a lot of testing in screening, diagnosis, and monitoring of diabetes and its complications, yet for many clinicians we think that any result we get – or that a patient gets from home testing – is perfect. We often don’t think about the accuracy or precision of some tests, things that might interfere with the result, intra-individual variation of the test, or how one test may compare to a test of higher accuracy,” she said.

One example is a recommendation to collect blood samples for glucose analysis in tubes containing a rapidly effective inhibitor of glycolysis such as a granulated citrate buffer. If unavailable, the sample tube should be placed immediately into an ice water slurry and centrifuged within 15-30 minutes to remove the cells.

Without those measures, “red cells in blood sitting in the test tube continue to break down glucose, so the concentration of glucose will start to fall very soon. ... How the specimen is handled makes a huge difference in the result,” Dr. Kirkman emphasized.

Another is the recommendation of a confirmatory test when diagnosing diabetes, regardless of the initial test used (A1c, fasting glucose, or oral glucose tolerance test). “There is large intra-individual variation of fasting glucose and even larger for 2-hour glucose on the oral glucose tolerance test. ... This means if you do the test one week and then repeat it the next day or a week later, the results will be quite different. This is a reason why confirmation of an abnormal test is important. Yet many times this isn’t done,” she noted.

Other “strong” recommendations based on “high” evidence levels include:

• Fasting glucose should be measured in venous plasma when used to establish the diagnosis of diabetes, with a diagnostic cutoff of > 7.0 mmol/L (> 126 mg/dL) for diabetes.
• Frequent blood glucose monitoring is recommended for all people with diabetes treated with intensive insulin regimens (with multiple daily injections or insulin pump therapy) and who are not using CGM.
• Routine use of blood glucose monitoring is not recommended for people with type 2 diabetes who are treated with diet and/or oral agents alone.
• Treatment goals should be based on ADA recommendations, i.e., A1c < 7% (< 53 mmol/mol) if it can be achieved without significant hypoglycemia or other adverse treatment effects, with higher targets for special populations.
• Annual testing for albuminuria should begin in pubertal or postpubertal individuals 5 years after diagnosis of type 1 diabetes and at time of diagnosis of type 2 diabetes, regardless of treatment.
• Urine albumin should be measured annually in adults with diabetes using morning spot urine albumin-to-creatinine ratio.

Other guidance in the document pertains to use of ketone testing, genetic markers, autoimmune markers, and C-peptide.

According to Dr. Sacks, “It’s important to measure accurately, but it’s also very important to communicate the relevance to clinicians and to listen to them and share information. ... Patient care is a team effort.”

Dr. Sachs has reported receiving funding from the NIH. Dr. Kirkman has reported no relevant financial relationships.
 

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

Testing children with acute sinusitis symptoms for specific bacteria may dramatically decrease unnecessary antibiotic use, new research suggests.

The study, published in JAMA, found that children with positive nasopharyngeal tests for one or more of Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis had better resolution of symptoms with antibiotics than those without these bacteria.

If antibiotic use was limited to children with H. influenzae or S. pneumoniae in their nasopharynx at the time of diagnosis, antibiotic use would decrease by 53%, according to the study authors.

Sinusitis is common in children, and symptoms are similar with uncomplicated viral upper respiratory infections.

“We have not had a good way to predict which children will benefit from antibiotics,” said Nader Shaikh, MD, MPH, professor of pediatrics and clinical and translational science at the University of Pittsburgh, and the lead study author. “When a child comes in with a sore throat, we test for strep. If the test is positive, we prescribe antibiotics.”

Dr. Shaikh and his colleagues found that the same approach – swabbing the nose and testing for various bacteria – worked for children with sinusitis.

“Children who tested negative for bacteria did not benefit from antibiotics,” Dr. Shaikh said.

In the double-blind clinical trial, Dr. Shaikh and his colleagues randomized 510 children between ages 2 and 11 with acute sinusitis at six academic primary care offices over a 6-year period. Almost two-thirds of participants were between ages 2 and 5, around half were male, and around half were White. All participants had an initial score of nine or higher on the validated Pediatric Rhinosinusitis Symptom Scale (PRSS).

For 10 days, 254 children received oral amoxicillin (90 mg/kg/day) and clavulanate (6.4mg/kg/day) and 256 received placebo.

In children receiving antibiotics, symptoms resolved over a median of 7 days, compared with 9 days for those given placebo (P = .003).

Children without detected nasopharyngeal pathogens did not benefit from antibiotics as much as those with the pathogens, the researchers found. Among those with pathogens, the mean symptom burden score was 1.95 points lower in the group that received antibiotics, compared with the group that received placebo. For those without pathogens, there was a 0.88-point difference between the antibiotic and placebo groups (P = .02).

The researchers also took nasal swabs at the first and final study visits and tested for S. pneumoniae, H. influenzae, and M. catarrhalis. During that time, parents or caregivers used the PRSS to assess their child’s symptoms, and they recorded the nasal discharge color. Nasal discharge color, Dr. Shaikh and colleagues found, was not linked with antibiotic effect.
 

Welcome findings

Pediatricians and primary care providers face a significant clinical dilemma when they consider using antibiotics with upper respiratory tract infections (URTIs), according to John H. Greinwald Jr., MD, professor in the department of pediatrics at Cincinnati Children’s Hospital Medical Center.

“These findings certainly make sense because most respiratory infections in children are viral,” Dr. Greinwald said. “The investigators follow the appropriate clinical guidelines for considering antibiotic use in patients with URTIs, which include URTI symptoms lasting longer than 10 days or symptoms initially getting better, then worsening again day 6 through 10.”

Not only is antibiotic resistance a major public health concern, but the drugs can have side effects such as diarrhea, and their long-term effects on the microbiome are unknown.

“Differentiating who has acute sinusitis from who has a viral infection is difficult for primary care providers,” said Eelam A. Adil, MD, MBA, assistant professor of otolaryngology at Harvard Medical School in Boston.

The findings may help clinicians be more selective with antibiotic prescriptions, according to Jacob G. Eide, MD, a head and neck surgeon at Henry Ford Health in Detroit.

“However, we do not want to deny antibiotics when they are beneficial,” Dr. Eide said. “And the difficulty and costs involved in developing the tests need to be considered.”

Dr. Shaikh and his team are studying ways to bring nasal testing into clinical practice, potentially utilizing commercially available molecular testing and rapid antigen tests that work like COVID-19 at-home tests. They are also exploring if other biomarkers in nasal discharge may indicate the presence of bacteria.

All study authors as well as outside experts reported no relevant financial relationships. The study was supported by the National Institute of Allergy and Infectious Diseases.

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

Testing children with acute sinusitis symptoms for specific bacteria may dramatically decrease unnecessary antibiotic use, new research suggests.

The study, published in JAMA, found that children with positive nasopharyngeal tests for one or more of Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis had better resolution of symptoms with antibiotics than those without these bacteria.

If antibiotic use was limited to children with H. influenzae or S. pneumoniae in their nasopharynx at the time of diagnosis, antibiotic use would decrease by 53%, according to the study authors.

Sinusitis is common in children, and symptoms are similar with uncomplicated viral upper respiratory infections.

“We have not had a good way to predict which children will benefit from antibiotics,” said Nader Shaikh, MD, MPH, professor of pediatrics and clinical and translational science at the University of Pittsburgh, and the lead study author. “When a child comes in with a sore throat, we test for strep. If the test is positive, we prescribe antibiotics.”

Dr. Shaikh and his colleagues found that the same approach – swabbing the nose and testing for various bacteria – worked for children with sinusitis.

“Children who tested negative for bacteria did not benefit from antibiotics,” Dr. Shaikh said.

In the double-blind clinical trial, Dr. Shaikh and his colleagues randomized 510 children between ages 2 and 11 with acute sinusitis at six academic primary care offices over a 6-year period. Almost two-thirds of participants were between ages 2 and 5, around half were male, and around half were White. All participants had an initial score of nine or higher on the validated Pediatric Rhinosinusitis Symptom Scale (PRSS).

For 10 days, 254 children received oral amoxicillin (90 mg/kg/day) and clavulanate (6.4mg/kg/day) and 256 received placebo.

In children receiving antibiotics, symptoms resolved over a median of 7 days, compared with 9 days for those given placebo (P = .003).

Children without detected nasopharyngeal pathogens did not benefit from antibiotics as much as those with the pathogens, the researchers found. Among those with pathogens, the mean symptom burden score was 1.95 points lower in the group that received antibiotics, compared with the group that received placebo. For those without pathogens, there was a 0.88-point difference between the antibiotic and placebo groups (P = .02).

The researchers also took nasal swabs at the first and final study visits and tested for S. pneumoniae, H. influenzae, and M. catarrhalis. During that time, parents or caregivers used the PRSS to assess their child’s symptoms, and they recorded the nasal discharge color. Nasal discharge color, Dr. Shaikh and colleagues found, was not linked with antibiotic effect.
 

Welcome findings

Pediatricians and primary care providers face a significant clinical dilemma when they consider using antibiotics with upper respiratory tract infections (URTIs), according to John H. Greinwald Jr., MD, professor in the department of pediatrics at Cincinnati Children’s Hospital Medical Center.

“These findings certainly make sense because most respiratory infections in children are viral,” Dr. Greinwald said. “The investigators follow the appropriate clinical guidelines for considering antibiotic use in patients with URTIs, which include URTI symptoms lasting longer than 10 days or symptoms initially getting better, then worsening again day 6 through 10.”

Not only is antibiotic resistance a major public health concern, but the drugs can have side effects such as diarrhea, and their long-term effects on the microbiome are unknown.

“Differentiating who has acute sinusitis from who has a viral infection is difficult for primary care providers,” said Eelam A. Adil, MD, MBA, assistant professor of otolaryngology at Harvard Medical School in Boston.

The findings may help clinicians be more selective with antibiotic prescriptions, according to Jacob G. Eide, MD, a head and neck surgeon at Henry Ford Health in Detroit.

“However, we do not want to deny antibiotics when they are beneficial,” Dr. Eide said. “And the difficulty and costs involved in developing the tests need to be considered.”

Dr. Shaikh and his team are studying ways to bring nasal testing into clinical practice, potentially utilizing commercially available molecular testing and rapid antigen tests that work like COVID-19 at-home tests. They are also exploring if other biomarkers in nasal discharge may indicate the presence of bacteria.

All study authors as well as outside experts reported no relevant financial relationships. The study was supported by the National Institute of Allergy and Infectious Diseases.

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

Testing children with acute sinusitis symptoms for specific bacteria may dramatically decrease unnecessary antibiotic use, new research suggests.

The study, published in JAMA, found that children with positive nasopharyngeal tests for one or more of Haemophilus influenzae, Streptococcus pneumoniae, or Moraxella catarrhalis had better resolution of symptoms with antibiotics than those without these bacteria.

If antibiotic use was limited to children with H. influenzae or S. pneumoniae in their nasopharynx at the time of diagnosis, antibiotic use would decrease by 53%, according to the study authors.

Sinusitis is common in children, and symptoms are similar with uncomplicated viral upper respiratory infections.

“We have not had a good way to predict which children will benefit from antibiotics,” said Nader Shaikh, MD, MPH, professor of pediatrics and clinical and translational science at the University of Pittsburgh, and the lead study author. “When a child comes in with a sore throat, we test for strep. If the test is positive, we prescribe antibiotics.”

Dr. Shaikh and his colleagues found that the same approach – swabbing the nose and testing for various bacteria – worked for children with sinusitis.

“Children who tested negative for bacteria did not benefit from antibiotics,” Dr. Shaikh said.

In the double-blind clinical trial, Dr. Shaikh and his colleagues randomized 510 children between ages 2 and 11 with acute sinusitis at six academic primary care offices over a 6-year period. Almost two-thirds of participants were between ages 2 and 5, around half were male, and around half were White. All participants had an initial score of nine or higher on the validated Pediatric Rhinosinusitis Symptom Scale (PRSS).

For 10 days, 254 children received oral amoxicillin (90 mg/kg/day) and clavulanate (6.4mg/kg/day) and 256 received placebo.

In children receiving antibiotics, symptoms resolved over a median of 7 days, compared with 9 days for those given placebo (P = .003).

Children without detected nasopharyngeal pathogens did not benefit from antibiotics as much as those with the pathogens, the researchers found. Among those with pathogens, the mean symptom burden score was 1.95 points lower in the group that received antibiotics, compared with the group that received placebo. For those without pathogens, there was a 0.88-point difference between the antibiotic and placebo groups (P = .02).

The researchers also took nasal swabs at the first and final study visits and tested for S. pneumoniae, H. influenzae, and M. catarrhalis. During that time, parents or caregivers used the PRSS to assess their child’s symptoms, and they recorded the nasal discharge color. Nasal discharge color, Dr. Shaikh and colleagues found, was not linked with antibiotic effect.
 

Welcome findings

Pediatricians and primary care providers face a significant clinical dilemma when they consider using antibiotics with upper respiratory tract infections (URTIs), according to John H. Greinwald Jr., MD, professor in the department of pediatrics at Cincinnati Children’s Hospital Medical Center.

“These findings certainly make sense because most respiratory infections in children are viral,” Dr. Greinwald said. “The investigators follow the appropriate clinical guidelines for considering antibiotic use in patients with URTIs, which include URTI symptoms lasting longer than 10 days or symptoms initially getting better, then worsening again day 6 through 10.”

Not only is antibiotic resistance a major public health concern, but the drugs can have side effects such as diarrhea, and their long-term effects on the microbiome are unknown.

“Differentiating who has acute sinusitis from who has a viral infection is difficult for primary care providers,” said Eelam A. Adil, MD, MBA, assistant professor of otolaryngology at Harvard Medical School in Boston.

The findings may help clinicians be more selective with antibiotic prescriptions, according to Jacob G. Eide, MD, a head and neck surgeon at Henry Ford Health in Detroit.

“However, we do not want to deny antibiotics when they are beneficial,” Dr. Eide said. “And the difficulty and costs involved in developing the tests need to be considered.”

Dr. Shaikh and his team are studying ways to bring nasal testing into clinical practice, potentially utilizing commercially available molecular testing and rapid antigen tests that work like COVID-19 at-home tests. They are also exploring if other biomarkers in nasal discharge may indicate the presence of bacteria.

All study authors as well as outside experts reported no relevant financial relationships. The study was supported by the National Institute of Allergy and Infectious Diseases.

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

To the Editor:

Alopecia areata (AA) is an autoimmune nonscarring hair loss disorder that can present at any age. Patients with AA have a disproportionately high comorbidity burden and low quality of life, often grappling with anxiety, depression, and psychosocial sequelae involving identity, such as reduced self-esteem.^1,2 Although conventional therapies aim to reduce hair loss, none are curative.³ Response to treatment is highly unpredictable, with current data suggesting that up to 50% of patients recover within 1 year while 14% to 25% progress to either alopecia totalis (total scalp hair loss) or alopecia universalis (total body hair loss).⁴ Options for therapeutic intervention remain limited and vary in safety and effectiveness, warranting further research to identify optimal modalities and minimize side effects. Interestingly, scalp rolling has been used as an adjuvant to topical triamcinolone acetonide.^3,5 However, the extent of its effect in combination with other therapies remains unclear. We report 3 pediatric patients with confirmed AA refractory to conventional topical treatment who experienced remarkable scalp hair regrowth after adding biweekly scalp rolling as an adjuvant therapy.

A 7-year-old boy with AA presented with 95% scalp hair loss of 7 months’ duration (Figure 1A)(patient 1). Prior treatments included mometasone solution and clobetasol solution 0.05%. After 3 months of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth after 13 months of treatment (Figure 1B). No pain, bleeding, or other side effects were reported.

An 11-year-old girl with AA presented with 100% hair loss of 7 months’ duration (Figure 2A)(patient 2). Prior treatments included fluocinonide solution and intralesional Kenalog injections. After 4 months of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth after 13 months of treatment (Figure 2B). No pain, bleeding, or other side effects were reported.

A 16-year-old boy with AA presented with 30% hair loss of 4 years’ duration (Figure 3A)(patient 3). Prior treatments included squaric acid and intralesional Kenalog injections. After 2 years of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth at 17 months (Figure 3B). No pain, bleeding, or other side effects were reported.

Scalp rolling—also known as microneedling—provides a multifactorial approach to hair regrowth in patients with AA. The mechanism of action involves both the hair cycle and wound repair pathways by stimulation of the dermal papillae and stem cells.⁶ Scalp rolling has been observed to induce the expression of several hair growth pathway mediators, such as WNT3A, β-catenin, vascular endothelial growth factor, and WNT10B.⁷ Wnt/β-catenin pathway signaling is integral to multiple aspects of the hair regrowth process, including hair morphogenesis, follicle regeneration, and growth of the shaft itself.^8,9 Scalp rolling causes microinjuries to the skin, thereby diverting blood supply to the follicles and stimulating wound regeneration, a process suggested to induce follicle regeneration. This effect is due to increased expression of vascular endothelial growth factor after cutaneous injury, a mediator of both hair growth and cycling as well as wound repair.⁷ Adjuvant scalp rolling creates a synergistic effect by facilitating absorption of topical and intralesional therapies. The physical breakdown of dermal capillary barriers creates microchannels that traverse the stratum corneum, improving the permeability of small-molecule substances and allowing for relatively painless and uniform delivery of combination therapies. A secondary benefit is hypertrophy, which counteracts the atrophy caused by topical steroids via collagen induction.⁷

Additionally, scalp rolling confers minimal risk to the patient, making it safer than conventional pharmacologic therapies such as corticosteroids or Janus kinase (JAK) inhibitors. Although intralesional steroid injections are first-line treatments for limited disease, they can cause pain and skin atrophy.¹⁰ In one cohort of 54 patients, topical steroids were inferior to both oral and intralesional treatment, and oral steroids carried a systemic side-effect profile and worsening of comorbidities including hyperglycemia and hypertension as well as negative effects on bone density.¹¹ Baricitinib, a JAK inhibitor, was the first systemic treatment to gain US Food and Drug Administration approval for severe AA.¹² However, this novel therapeutic confers adverse effects including infection, acne, and hypercholesterolemia, as reported in the BRAVE-AA trials.¹³ More broadly, the US Food and Drug Administration warns of serious long-term risks such as cardiovascular events and malignancy.¹⁴ Given the tremendous potential of JAK inhibitors, further research is warranted to understand both the efficacy of topical formulations as well as the possible role of scalp rolling as its adjuvant.

Finally, scalp rolling is easily accessible and affordable to patients. Scalp rolling devices are readily available and affordable online, and they can be used autonomously at home. This pragmatic option allows patients to take control of their own treatment course and offers a financially feasible alternative to navigating insurance coverage as well as the need for extra office visits for medication refills and monitoring.

We report 3 cases of the use of scalp rolling as an adjuvant to conventional therapy for refractory AA in young patients. Although prospective research is required to establish causality and characterize age-related trends in treatment response, consideration of scalp rolling as an adjuvant to conventional therapy may help to optimize treatment regimens. Given its low risk for side effects and potential benefits, we recommend scalp rolling for patients with refractory AA.

To the Editor:

Alopecia areata (AA) is an autoimmune nonscarring hair loss disorder that can present at any age. Patients with AA have a disproportionately high comorbidity burden and low quality of life, often grappling with anxiety, depression, and psychosocial sequelae involving identity, such as reduced self-esteem.^1,2 Although conventional therapies aim to reduce hair loss, none are curative.³ Response to treatment is highly unpredictable, with current data suggesting that up to 50% of patients recover within 1 year while 14% to 25% progress to either alopecia totalis (total scalp hair loss) or alopecia universalis (total body hair loss).⁴ Options for therapeutic intervention remain limited and vary in safety and effectiveness, warranting further research to identify optimal modalities and minimize side effects. Interestingly, scalp rolling has been used as an adjuvant to topical triamcinolone acetonide.^3,5 However, the extent of its effect in combination with other therapies remains unclear. We report 3 pediatric patients with confirmed AA refractory to conventional topical treatment who experienced remarkable scalp hair regrowth after adding biweekly scalp rolling as an adjuvant therapy.

A 7-year-old boy with AA presented with 95% scalp hair loss of 7 months’ duration (Figure 1A)(patient 1). Prior treatments included mometasone solution and clobetasol solution 0.05%. After 3 months of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth after 13 months of treatment (Figure 1B). No pain, bleeding, or other side effects were reported.

An 11-year-old girl with AA presented with 100% hair loss of 7 months’ duration (Figure 2A)(patient 2). Prior treatments included fluocinonide solution and intralesional Kenalog injections. After 4 months of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth after 13 months of treatment (Figure 2B). No pain, bleeding, or other side effects were reported.

A 16-year-old boy with AA presented with 30% hair loss of 4 years’ duration (Figure 3A)(patient 3). Prior treatments included squaric acid and intralesional Kenalog injections. After 2 years of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth at 17 months (Figure 3B). No pain, bleeding, or other side effects were reported.

Scalp rolling—also known as microneedling—provides a multifactorial approach to hair regrowth in patients with AA. The mechanism of action involves both the hair cycle and wound repair pathways by stimulation of the dermal papillae and stem cells.⁶ Scalp rolling has been observed to induce the expression of several hair growth pathway mediators, such as WNT3A, β-catenin, vascular endothelial growth factor, and WNT10B.⁷ Wnt/β-catenin pathway signaling is integral to multiple aspects of the hair regrowth process, including hair morphogenesis, follicle regeneration, and growth of the shaft itself.^8,9 Scalp rolling causes microinjuries to the skin, thereby diverting blood supply to the follicles and stimulating wound regeneration, a process suggested to induce follicle regeneration. This effect is due to increased expression of vascular endothelial growth factor after cutaneous injury, a mediator of both hair growth and cycling as well as wound repair.⁷ Adjuvant scalp rolling creates a synergistic effect by facilitating absorption of topical and intralesional therapies. The physical breakdown of dermal capillary barriers creates microchannels that traverse the stratum corneum, improving the permeability of small-molecule substances and allowing for relatively painless and uniform delivery of combination therapies. A secondary benefit is hypertrophy, which counteracts the atrophy caused by topical steroids via collagen induction.⁷

Additionally, scalp rolling confers minimal risk to the patient, making it safer than conventional pharmacologic therapies such as corticosteroids or Janus kinase (JAK) inhibitors. Although intralesional steroid injections are first-line treatments for limited disease, they can cause pain and skin atrophy.¹⁰ In one cohort of 54 patients, topical steroids were inferior to both oral and intralesional treatment, and oral steroids carried a systemic side-effect profile and worsening of comorbidities including hyperglycemia and hypertension as well as negative effects on bone density.¹¹ Baricitinib, a JAK inhibitor, was the first systemic treatment to gain US Food and Drug Administration approval for severe AA.¹² However, this novel therapeutic confers adverse effects including infection, acne, and hypercholesterolemia, as reported in the BRAVE-AA trials.¹³ More broadly, the US Food and Drug Administration warns of serious long-term risks such as cardiovascular events and malignancy.¹⁴ Given the tremendous potential of JAK inhibitors, further research is warranted to understand both the efficacy of topical formulations as well as the possible role of scalp rolling as its adjuvant.

Finally, scalp rolling is easily accessible and affordable to patients. Scalp rolling devices are readily available and affordable online, and they can be used autonomously at home. This pragmatic option allows patients to take control of their own treatment course and offers a financially feasible alternative to navigating insurance coverage as well as the need for extra office visits for medication refills and monitoring.

We report 3 cases of the use of scalp rolling as an adjuvant to conventional therapy for refractory AA in young patients. Although prospective research is required to establish causality and characterize age-related trends in treatment response, consideration of scalp rolling as an adjuvant to conventional therapy may help to optimize treatment regimens. Given its low risk for side effects and potential benefits, we recommend scalp rolling for patients with refractory AA.

To the Editor:

Alopecia areata (AA) is an autoimmune nonscarring hair loss disorder that can present at any age. Patients with AA have a disproportionately high comorbidity burden and low quality of life, often grappling with anxiety, depression, and psychosocial sequelae involving identity, such as reduced self-esteem.^1,2 Although conventional therapies aim to reduce hair loss, none are curative.³ Response to treatment is highly unpredictable, with current data suggesting that up to 50% of patients recover within 1 year while 14% to 25% progress to either alopecia totalis (total scalp hair loss) or alopecia universalis (total body hair loss).⁴ Options for therapeutic intervention remain limited and vary in safety and effectiveness, warranting further research to identify optimal modalities and minimize side effects. Interestingly, scalp rolling has been used as an adjuvant to topical triamcinolone acetonide.^3,5 However, the extent of its effect in combination with other therapies remains unclear. We report 3 pediatric patients with confirmed AA refractory to conventional topical treatment who experienced remarkable scalp hair regrowth after adding biweekly scalp rolling as an adjuvant therapy.

A 7-year-old boy with AA presented with 95% scalp hair loss of 7 months’ duration (Figure 1A)(patient 1). Prior treatments included mometasone solution and clobetasol solution 0.05%. After 3 months of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth after 13 months of treatment (Figure 1B). No pain, bleeding, or other side effects were reported.

An 11-year-old girl with AA presented with 100% hair loss of 7 months’ duration (Figure 2A)(patient 2). Prior treatments included fluocinonide solution and intralesional Kenalog injections. After 4 months of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth after 13 months of treatment (Figure 2B). No pain, bleeding, or other side effects were reported.

A 16-year-old boy with AA presented with 30% hair loss of 4 years’ duration (Figure 3A)(patient 3). Prior treatments included squaric acid and intralesional Kenalog injections. After 2 years of conventional topical therapy, twice-weekly scalp rolling with a 0.25-mm scalp roller of their choosing was added to the regimen, with clobetasol solution 0.05% and minoxidil foam 5% applied immediately after each scalp rolling session. The patient experienced 95% scalp hair regrowth at 17 months (Figure 3B). No pain, bleeding, or other side effects were reported.

Scalp rolling—also known as microneedling—provides a multifactorial approach to hair regrowth in patients with AA. The mechanism of action involves both the hair cycle and wound repair pathways by stimulation of the dermal papillae and stem cells.⁶ Scalp rolling has been observed to induce the expression of several hair growth pathway mediators, such as WNT3A, β-catenin, vascular endothelial growth factor, and WNT10B.⁷ Wnt/β-catenin pathway signaling is integral to multiple aspects of the hair regrowth process, including hair morphogenesis, follicle regeneration, and growth of the shaft itself.^8,9 Scalp rolling causes microinjuries to the skin, thereby diverting blood supply to the follicles and stimulating wound regeneration, a process suggested to induce follicle regeneration. This effect is due to increased expression of vascular endothelial growth factor after cutaneous injury, a mediator of both hair growth and cycling as well as wound repair.⁷ Adjuvant scalp rolling creates a synergistic effect by facilitating absorption of topical and intralesional therapies. The physical breakdown of dermal capillary barriers creates microchannels that traverse the stratum corneum, improving the permeability of small-molecule substances and allowing for relatively painless and uniform delivery of combination therapies. A secondary benefit is hypertrophy, which counteracts the atrophy caused by topical steroids via collagen induction.⁷

Additionally, scalp rolling confers minimal risk to the patient, making it safer than conventional pharmacologic therapies such as corticosteroids or Janus kinase (JAK) inhibitors. Although intralesional steroid injections are first-line treatments for limited disease, they can cause pain and skin atrophy.¹⁰ In one cohort of 54 patients, topical steroids were inferior to both oral and intralesional treatment, and oral steroids carried a systemic side-effect profile and worsening of comorbidities including hyperglycemia and hypertension as well as negative effects on bone density.¹¹ Baricitinib, a JAK inhibitor, was the first systemic treatment to gain US Food and Drug Administration approval for severe AA.¹² However, this novel therapeutic confers adverse effects including infection, acne, and hypercholesterolemia, as reported in the BRAVE-AA trials.¹³ More broadly, the US Food and Drug Administration warns of serious long-term risks such as cardiovascular events and malignancy.¹⁴ Given the tremendous potential of JAK inhibitors, further research is warranted to understand both the efficacy of topical formulations as well as the possible role of scalp rolling as its adjuvant.

Finally, scalp rolling is easily accessible and affordable to patients. Scalp rolling devices are readily available and affordable online, and they can be used autonomously at home. This pragmatic option allows patients to take control of their own treatment course and offers a financially feasible alternative to navigating insurance coverage as well as the need for extra office visits for medication refills and monitoring.

We report 3 cases of the use of scalp rolling as an adjuvant to conventional therapy for refractory AA in young patients. Although prospective research is required to establish causality and characterize age-related trends in treatment response, consideration of scalp rolling as an adjuvant to conventional therapy may help to optimize treatment regimens. Given its low risk for side effects and potential benefits, we recommend scalp rolling for patients with refractory AA.

To the Editor:

Cryptococcus neoformans is an opportunistic fungus with a predilection for immunocompromised hosts, including solid organ transplant recipients (SOTRs). However, the rapid emergence of diffuse panniculitis only upon the start of therapy for extracutaneous disease is a rare phenomenon. We report the case of a liver transplant recipient who developed a paradoxical inflammatory reaction after initiating liposomal amphotericin B therapy for disseminated C neoformans, which manifested as progressive indurated plaques histologically consistent with cryptococcal panniculitis.

A 44-year-old man who received an orthotopic liver transplant 12 months prior and was on prednisone (20 mg daily) and tacrolimus (7 mg total daily) was admitted for multifocal pneumonia complicated by septic shock. Blood and respiratory cultures grew C neoformans, and lumbar puncture evaluation of cerebrospinal fluid revealed the presence of Cryptococcus antigen in 1:40 titers. Liposomal amphotericin B 5 mg/kg intravenous daily and fluconazole 400 mg intravenous daily were administered starting on the fourth day of admission; maintenance tacrolimus and steroids were stopped. Within 36 hours of treatment initiation, an erythematous papular rash was noted on the extremities, which initially was deemed an infusion reaction. Over the next 6 days, the rash became progressively confluent and hyperpigmented. A dermatologist was consulted on the fifteenth day of admission.

Physical examination by dermatology revealed diffuse, hyperpigmented to erythematous macules on the torso, back, arms, and legs that coalesced into dusky indurated plaques along the thighs, right side of the flank, and right upper arm (Figure 1). Laboratory analysis revealed thrombocytopenia but was otherwise unremarkable. Histoplasma antigen and Coccidioides IgG and IgM enzyme immunoassays were negative, as were cytomegalovirus, HIV, and rapid plasma reagin test results. Blood culture testing was repeated, and the findings were negative.

The emergence of the rash after amphotericin initiation prompted concern that the cause was due to a drug reaction rather than cutaneous involvement of cryptococcal infection. Punch biopsies were obtained from the thigh plaque. Hematoxylin and eosin and Grocott-Gomori methenamine-silver stains revealed cryptococcal organisms in the dermis and subcutaneous fat (Figure 2). Bacterial, acid-fast bacillus, and fungal cultures showed no growth.

The patient was diagnosed with cryptococcal panniculitis. Induction therapy with liposomal amphotericin B 5 mg/kg daily and flucytosine 25 mg/kg twice daily was pursued. During the treatment, cutaneous involvement evolved into superficial desquamation. The patient ultimately died from shock secondary to persistent cryptococcal fungemia.

Cryptococcus neoformans is an opportunistic fungal infection that represents a notable hazard to SOTR, inflicting 1.5% to 2.8% of this population and carrying a 19% to 42% mortality rate.^1,2 This infection occurs at a median of 1.6 to 2.3 years after transplantation,^1,3 though liver transplant recipients and those with immune reconstitution inflammatory syndrome (IRIS)–like complications may present sooner (8.8 and 10.5 months, respectively).⁴ Cutaneous involvement comprises 17% to 21% of cases and is associated with extensive dissemination, including the central nervous system, lung, and bloodstream (61.5%, 23.1%, and 38.5%, respectively).^1-3 When Cryptococcus infects the skin, it classically manifests as multiple nodules, umbilicated papules, ulcers, or cellulitis.³ Involvement of subcutaneous adipose tissue is uncommon and primarily is observed at initial presentation alongside disseminated disease.^5-8 Our case is unique because cutaneous involvement was absent until treatment initiation.

Similar patterns of worsened or unmasked disease following treatment initiation have been observed in SOTRs with extracutaneous cryptococcus and were attributed to IRIS-like phenomena that generate a hyperactive inflammatory response to infection.^4,9 Common immunosuppressive regimens, particularly tacrolimus, depress helper T cell (T_H1) cytokine release and promote a T_H2-dominant, anti-inflammatory state.¹⁰ In cryptococcosis, the fungus itself may stimulate a comparable cytokine milieu to promote immunologic evasion and dissemination. Cryptococcal IRIS-like responses in SOTRs are precipitated by rapid reduction or withdrawal of calcineurin inhibitors and corticosteroids, in combination with the inherent mitogenicity of the C neoformans polysaccharide capsule and antifungal agents.¹⁰ In our patient, cryptococcal yeasts may have invaded subcutaneous tissues when he became fungemic but remained subclinical due to minimal inflammatory recruitment. As treatment began and immunosuppressants diminished, fungal recognition and massive cytokine release resulted in frank panniculitis via precipitous immune dysregulation.

First-line therapy of cryptococcosis entails the use of liposomal amphotericin B and flucytosine for induction, followed by fluconazole for consolidation and maintenance. Use of corticosteroids is atypical to the antifungal regimen; however, a role for them has been suggested in severe IRIS involving individuals who are HIV positive, such as those with lesions demonstrating mass effect.¹¹ Rare case reports have described their utility as adjunctive therapies against cryptococcus in SOTRs when treatment with antifungal agents alone failed.¹² Given the paucity of prospective trials to support corticosteroid use in SOTRs as well as the worse global outcomes in cases of cryptococcal meningitis,¹³ therapeutic corticosteroids were not administered in our patient.

Although our case represents a rare event, cutaneous cryptococcosis and IRIS-like phenomena are clinically relevant complications in immunocompromised patients. In particular, they should be promptly considered in SOTRs receiving maintenance immunosuppressants who demonstrate symptom aggravation despite negative microbial culture results and uninterrupted antifungal therapy.

To the Editor:

Cryptococcus neoformans is an opportunistic fungus with a predilection for immunocompromised hosts, including solid organ transplant recipients (SOTRs). However, the rapid emergence of diffuse panniculitis only upon the start of therapy for extracutaneous disease is a rare phenomenon. We report the case of a liver transplant recipient who developed a paradoxical inflammatory reaction after initiating liposomal amphotericin B therapy for disseminated C neoformans, which manifested as progressive indurated plaques histologically consistent with cryptococcal panniculitis.

A 44-year-old man who received an orthotopic liver transplant 12 months prior and was on prednisone (20 mg daily) and tacrolimus (7 mg total daily) was admitted for multifocal pneumonia complicated by septic shock. Blood and respiratory cultures grew C neoformans, and lumbar puncture evaluation of cerebrospinal fluid revealed the presence of Cryptococcus antigen in 1:40 titers. Liposomal amphotericin B 5 mg/kg intravenous daily and fluconazole 400 mg intravenous daily were administered starting on the fourth day of admission; maintenance tacrolimus and steroids were stopped. Within 36 hours of treatment initiation, an erythematous papular rash was noted on the extremities, which initially was deemed an infusion reaction. Over the next 6 days, the rash became progressively confluent and hyperpigmented. A dermatologist was consulted on the fifteenth day of admission.

Physical examination by dermatology revealed diffuse, hyperpigmented to erythematous macules on the torso, back, arms, and legs that coalesced into dusky indurated plaques along the thighs, right side of the flank, and right upper arm (Figure 1). Laboratory analysis revealed thrombocytopenia but was otherwise unremarkable. Histoplasma antigen and Coccidioides IgG and IgM enzyme immunoassays were negative, as were cytomegalovirus, HIV, and rapid plasma reagin test results. Blood culture testing was repeated, and the findings were negative.

The emergence of the rash after amphotericin initiation prompted concern that the cause was due to a drug reaction rather than cutaneous involvement of cryptococcal infection. Punch biopsies were obtained from the thigh plaque. Hematoxylin and eosin and Grocott-Gomori methenamine-silver stains revealed cryptococcal organisms in the dermis and subcutaneous fat (Figure 2). Bacterial, acid-fast bacillus, and fungal cultures showed no growth.

The patient was diagnosed with cryptococcal panniculitis. Induction therapy with liposomal amphotericin B 5 mg/kg daily and flucytosine 25 mg/kg twice daily was pursued. During the treatment, cutaneous involvement evolved into superficial desquamation. The patient ultimately died from shock secondary to persistent cryptococcal fungemia.

Cryptococcus neoformans is an opportunistic fungal infection that represents a notable hazard to SOTR, inflicting 1.5% to 2.8% of this population and carrying a 19% to 42% mortality rate.^1,2 This infection occurs at a median of 1.6 to 2.3 years after transplantation,^1,3 though liver transplant recipients and those with immune reconstitution inflammatory syndrome (IRIS)–like complications may present sooner (8.8 and 10.5 months, respectively).⁴ Cutaneous involvement comprises 17% to 21% of cases and is associated with extensive dissemination, including the central nervous system, lung, and bloodstream (61.5%, 23.1%, and 38.5%, respectively).^1-3 When Cryptococcus infects the skin, it classically manifests as multiple nodules, umbilicated papules, ulcers, or cellulitis.³ Involvement of subcutaneous adipose tissue is uncommon and primarily is observed at initial presentation alongside disseminated disease.^5-8 Our case is unique because cutaneous involvement was absent until treatment initiation.

Similar patterns of worsened or unmasked disease following treatment initiation have been observed in SOTRs with extracutaneous cryptococcus and were attributed to IRIS-like phenomena that generate a hyperactive inflammatory response to infection.^4,9 Common immunosuppressive regimens, particularly tacrolimus, depress helper T cell (T_H1) cytokine release and promote a T_H2-dominant, anti-inflammatory state.¹⁰ In cryptococcosis, the fungus itself may stimulate a comparable cytokine milieu to promote immunologic evasion and dissemination. Cryptococcal IRIS-like responses in SOTRs are precipitated by rapid reduction or withdrawal of calcineurin inhibitors and corticosteroids, in combination with the inherent mitogenicity of the C neoformans polysaccharide capsule and antifungal agents.¹⁰ In our patient, cryptococcal yeasts may have invaded subcutaneous tissues when he became fungemic but remained subclinical due to minimal inflammatory recruitment. As treatment began and immunosuppressants diminished, fungal recognition and massive cytokine release resulted in frank panniculitis via precipitous immune dysregulation.

First-line therapy of cryptococcosis entails the use of liposomal amphotericin B and flucytosine for induction, followed by fluconazole for consolidation and maintenance. Use of corticosteroids is atypical to the antifungal regimen; however, a role for them has been suggested in severe IRIS involving individuals who are HIV positive, such as those with lesions demonstrating mass effect.¹¹ Rare case reports have described their utility as adjunctive therapies against cryptococcus in SOTRs when treatment with antifungal agents alone failed.¹² Given the paucity of prospective trials to support corticosteroid use in SOTRs as well as the worse global outcomes in cases of cryptococcal meningitis,¹³ therapeutic corticosteroids were not administered in our patient.

Although our case represents a rare event, cutaneous cryptococcosis and IRIS-like phenomena are clinically relevant complications in immunocompromised patients. In particular, they should be promptly considered in SOTRs receiving maintenance immunosuppressants who demonstrate symptom aggravation despite negative microbial culture results and uninterrupted antifungal therapy.

To the Editor:

Cryptococcus neoformans is an opportunistic fungus with a predilection for immunocompromised hosts, including solid organ transplant recipients (SOTRs). However, the rapid emergence of diffuse panniculitis only upon the start of therapy for extracutaneous disease is a rare phenomenon. We report the case of a liver transplant recipient who developed a paradoxical inflammatory reaction after initiating liposomal amphotericin B therapy for disseminated C neoformans, which manifested as progressive indurated plaques histologically consistent with cryptococcal panniculitis.

A 44-year-old man who received an orthotopic liver transplant 12 months prior and was on prednisone (20 mg daily) and tacrolimus (7 mg total daily) was admitted for multifocal pneumonia complicated by septic shock. Blood and respiratory cultures grew C neoformans, and lumbar puncture evaluation of cerebrospinal fluid revealed the presence of Cryptococcus antigen in 1:40 titers. Liposomal amphotericin B 5 mg/kg intravenous daily and fluconazole 400 mg intravenous daily were administered starting on the fourth day of admission; maintenance tacrolimus and steroids were stopped. Within 36 hours of treatment initiation, an erythematous papular rash was noted on the extremities, which initially was deemed an infusion reaction. Over the next 6 days, the rash became progressively confluent and hyperpigmented. A dermatologist was consulted on the fifteenth day of admission.

Physical examination by dermatology revealed diffuse, hyperpigmented to erythematous macules on the torso, back, arms, and legs that coalesced into dusky indurated plaques along the thighs, right side of the flank, and right upper arm (Figure 1). Laboratory analysis revealed thrombocytopenia but was otherwise unremarkable. Histoplasma antigen and Coccidioides IgG and IgM enzyme immunoassays were negative, as were cytomegalovirus, HIV, and rapid plasma reagin test results. Blood culture testing was repeated, and the findings were negative.

The emergence of the rash after amphotericin initiation prompted concern that the cause was due to a drug reaction rather than cutaneous involvement of cryptococcal infection. Punch biopsies were obtained from the thigh plaque. Hematoxylin and eosin and Grocott-Gomori methenamine-silver stains revealed cryptococcal organisms in the dermis and subcutaneous fat (Figure 2). Bacterial, acid-fast bacillus, and fungal cultures showed no growth.

The patient was diagnosed with cryptococcal panniculitis. Induction therapy with liposomal amphotericin B 5 mg/kg daily and flucytosine 25 mg/kg twice daily was pursued. During the treatment, cutaneous involvement evolved into superficial desquamation. The patient ultimately died from shock secondary to persistent cryptococcal fungemia.

Cryptococcus neoformans is an opportunistic fungal infection that represents a notable hazard to SOTR, inflicting 1.5% to 2.8% of this population and carrying a 19% to 42% mortality rate.^1,2 This infection occurs at a median of 1.6 to 2.3 years after transplantation,^1,3 though liver transplant recipients and those with immune reconstitution inflammatory syndrome (IRIS)–like complications may present sooner (8.8 and 10.5 months, respectively).⁴ Cutaneous involvement comprises 17% to 21% of cases and is associated with extensive dissemination, including the central nervous system, lung, and bloodstream (61.5%, 23.1%, and 38.5%, respectively).^1-3 When Cryptococcus infects the skin, it classically manifests as multiple nodules, umbilicated papules, ulcers, or cellulitis.³ Involvement of subcutaneous adipose tissue is uncommon and primarily is observed at initial presentation alongside disseminated disease.^5-8 Our case is unique because cutaneous involvement was absent until treatment initiation.

Similar patterns of worsened or unmasked disease following treatment initiation have been observed in SOTRs with extracutaneous cryptococcus and were attributed to IRIS-like phenomena that generate a hyperactive inflammatory response to infection.^4,9 Common immunosuppressive regimens, particularly tacrolimus, depress helper T cell (T_H1) cytokine release and promote a T_H2-dominant, anti-inflammatory state.¹⁰ In cryptococcosis, the fungus itself may stimulate a comparable cytokine milieu to promote immunologic evasion and dissemination. Cryptococcal IRIS-like responses in SOTRs are precipitated by rapid reduction or withdrawal of calcineurin inhibitors and corticosteroids, in combination with the inherent mitogenicity of the C neoformans polysaccharide capsule and antifungal agents.¹⁰ In our patient, cryptococcal yeasts may have invaded subcutaneous tissues when he became fungemic but remained subclinical due to minimal inflammatory recruitment. As treatment began and immunosuppressants diminished, fungal recognition and massive cytokine release resulted in frank panniculitis via precipitous immune dysregulation.

First-line therapy of cryptococcosis entails the use of liposomal amphotericin B and flucytosine for induction, followed by fluconazole for consolidation and maintenance. Use of corticosteroids is atypical to the antifungal regimen; however, a role for them has been suggested in severe IRIS involving individuals who are HIV positive, such as those with lesions demonstrating mass effect.¹¹ Rare case reports have described their utility as adjunctive therapies against cryptococcus in SOTRs when treatment with antifungal agents alone failed.¹² Given the paucity of prospective trials to support corticosteroid use in SOTRs as well as the worse global outcomes in cases of cryptococcal meningitis,¹³ therapeutic corticosteroids were not administered in our patient.

Although our case represents a rare event, cutaneous cryptococcosis and IRIS-like phenomena are clinically relevant complications in immunocompromised patients. In particular, they should be promptly considered in SOTRs receiving maintenance immunosuppressants who demonstrate symptom aggravation despite negative microbial culture results and uninterrupted antifungal therapy.

Investigators have found a correlation between vitamin D deficiency and psoriasis severity, suggesting that some people who increase their intake of the vitamin could better control this skin condition that affects up to 8 million people in the United States alone. 

Brown University researchers studied almost 500 psoriasis cases taken from the National Health and Nutrition Examination Survey (NHANES), the scientists told attendees at the conference of the American Society for Nutrition. They compared the peoples’ reports on how much of their body surface was affected by psoriasis to vitamin D levels collected in blood samples.

“After adjusting for lifestyle factors such as smoking, the analysis showed that lower vitamin D levels and vitamin D deficiency were significantly associated with greater psoriasis severity,” the ASN said in a news release. “The researchers also found that patients with the least amount of body surface affected by psoriasis had the highest average vitamin D levels while those with the greatest affected area had the lowest average levels of vitamin D.”

The researchers said that people with psoriasis might improve their condition by getting more vitamin D in their diet and through supplements.

“Topical synthetic vitamin D creams are emerging as new therapies for psoriasis, but these usually require a doctor’s prescription,” said researcher Rachel K. Lim, an MD candidate at Brown University, Providence, R.I. “Our results suggest that a vitamin D–rich diet or oral vitamin D supplementation may also provide some benefit to psoriasis patients.”

The researchers said that vitamin D toxicity is rare but that people should consult with their medical caregivers before they start taking supplements.

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

Investigators have found a correlation between vitamin D deficiency and psoriasis severity, suggesting that some people who increase their intake of the vitamin could better control this skin condition that affects up to 8 million people in the United States alone. 

Brown University researchers studied almost 500 psoriasis cases taken from the National Health and Nutrition Examination Survey (NHANES), the scientists told attendees at the conference of the American Society for Nutrition. They compared the peoples’ reports on how much of their body surface was affected by psoriasis to vitamin D levels collected in blood samples.

“After adjusting for lifestyle factors such as smoking, the analysis showed that lower vitamin D levels and vitamin D deficiency were significantly associated with greater psoriasis severity,” the ASN said in a news release. “The researchers also found that patients with the least amount of body surface affected by psoriasis had the highest average vitamin D levels while those with the greatest affected area had the lowest average levels of vitamin D.”

The researchers said that people with psoriasis might improve their condition by getting more vitamin D in their diet and through supplements.

“Topical synthetic vitamin D creams are emerging as new therapies for psoriasis, but these usually require a doctor’s prescription,” said researcher Rachel K. Lim, an MD candidate at Brown University, Providence, R.I. “Our results suggest that a vitamin D–rich diet or oral vitamin D supplementation may also provide some benefit to psoriasis patients.”

The researchers said that vitamin D toxicity is rare but that people should consult with their medical caregivers before they start taking supplements.

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

Investigators have found a correlation between vitamin D deficiency and psoriasis severity, suggesting that some people who increase their intake of the vitamin could better control this skin condition that affects up to 8 million people in the United States alone. 

Brown University researchers studied almost 500 psoriasis cases taken from the National Health and Nutrition Examination Survey (NHANES), the scientists told attendees at the conference of the American Society for Nutrition. They compared the peoples’ reports on how much of their body surface was affected by psoriasis to vitamin D levels collected in blood samples.

“After adjusting for lifestyle factors such as smoking, the analysis showed that lower vitamin D levels and vitamin D deficiency were significantly associated with greater psoriasis severity,” the ASN said in a news release. “The researchers also found that patients with the least amount of body surface affected by psoriasis had the highest average vitamin D levels while those with the greatest affected area had the lowest average levels of vitamin D.”

The researchers said that people with psoriasis might improve their condition by getting more vitamin D in their diet and through supplements.

“Topical synthetic vitamin D creams are emerging as new therapies for psoriasis, but these usually require a doctor’s prescription,” said researcher Rachel K. Lim, an MD candidate at Brown University, Providence, R.I. “Our results suggest that a vitamin D–rich diet or oral vitamin D supplementation may also provide some benefit to psoriasis patients.”

The researchers said that vitamin D toxicity is rare but that people should consult with their medical caregivers before they start taking supplements.

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