On the top left of my desktop is an electronic sticky note entitled, “Apply in Future.” This was where the AGA editorial fellowship was listed when I first started GI fellowship. My interest in the behind-the-scenes of scientific publishing developed early. I wanted to learn not only about the decision-making by the editorial board but also other aspects that impact the process from submission to publication. While waiting for my opportunity to apply, I became a reviewer for several journals and then an associate editor of ACG Case Reports Journal, which gave me some insight.

I applied to the editorial fellowship as a second-year fellow, to start as a third-year fellow. I figured this would give me several chances to apply again if I was not selected! I started off by talking to my program director to ensure that I would have enough time, given other responsibilities. The application consisted of a cover letter, where I expressed why I was interested, particularly focusing on my passion for research and my experience with scientific publishing, a letter of recommendation, and a CV. I was ecstatic when I was selected for the AGA editorial fellowship for Clinical Gastroenterology and Hepatology (CGH), whose editorial board’s mission best aligned with my interests.

Dr. Jonathan Buscaglia was the editorial fellows’ mentor for CGH – he met with us and provided an outline of the year. For the first 6 months, I was a reviewer for submitted manuscripts within my topic of interest – pancreaticobiliary diseases and advanced endoscopy and technology. Dr. Buscaglia gave me feedback on my reviews to improve my critical assessment of study designs and interpreted results. After 6 months as a reviewer, I took on the role of an associate editor. I selected reviewers, evaluated the reviews, and made the decision to accept or reject a manuscript. I presented my assigned manuscript at the weekly board of editors meeting, which was one of the biggest learning experiences. Leading researchers from all over the world gathered at a virtual table and discussed whether each study would have clinical impact on the medical community. Each editor contributed a unique perspective that facilitated a robust and thoughtful discussion of each manuscript brought to the table. I was in awe each week.

What I have learned so far during my year as an AGA editorial fellow with CGH has shaped my approach to personal research and will continue to do so as I develop my research career. It has greatly improved my assessment of the literature and I hope to continue to be involved in the critical review process, especially as a reviewer in my early career, and eventually, a part of an editorial board for a journal that truly impacts clinical medicine, such as Clinical Gastroenterology and Hepatology.
 

Dr. Trieu is a gastroenterology and hepatology fellow at Loyola University Medical Center, Maywood, Ill. She has no conflicts of interest to disclose.

On the top left of my desktop is an electronic sticky note entitled, “Apply in Future.” This was where the AGA editorial fellowship was listed when I first started GI fellowship. My interest in the behind-the-scenes of scientific publishing developed early. I wanted to learn not only about the decision-making by the editorial board but also other aspects that impact the process from submission to publication. While waiting for my opportunity to apply, I became a reviewer for several journals and then an associate editor of ACG Case Reports Journal, which gave me some insight.

I applied to the editorial fellowship as a second-year fellow, to start as a third-year fellow. I figured this would give me several chances to apply again if I was not selected! I started off by talking to my program director to ensure that I would have enough time, given other responsibilities. The application consisted of a cover letter, where I expressed why I was interested, particularly focusing on my passion for research and my experience with scientific publishing, a letter of recommendation, and a CV. I was ecstatic when I was selected for the AGA editorial fellowship for Clinical Gastroenterology and Hepatology (CGH), whose editorial board’s mission best aligned with my interests.

Dr. Jonathan Buscaglia was the editorial fellows’ mentor for CGH – he met with us and provided an outline of the year. For the first 6 months, I was a reviewer for submitted manuscripts within my topic of interest – pancreaticobiliary diseases and advanced endoscopy and technology. Dr. Buscaglia gave me feedback on my reviews to improve my critical assessment of study designs and interpreted results. After 6 months as a reviewer, I took on the role of an associate editor. I selected reviewers, evaluated the reviews, and made the decision to accept or reject a manuscript. I presented my assigned manuscript at the weekly board of editors meeting, which was one of the biggest learning experiences. Leading researchers from all over the world gathered at a virtual table and discussed whether each study would have clinical impact on the medical community. Each editor contributed a unique perspective that facilitated a robust and thoughtful discussion of each manuscript brought to the table. I was in awe each week.

What I have learned so far during my year as an AGA editorial fellow with CGH has shaped my approach to personal research and will continue to do so as I develop my research career. It has greatly improved my assessment of the literature and I hope to continue to be involved in the critical review process, especially as a reviewer in my early career, and eventually, a part of an editorial board for a journal that truly impacts clinical medicine, such as Clinical Gastroenterology and Hepatology.
 

Dr. Trieu is a gastroenterology and hepatology fellow at Loyola University Medical Center, Maywood, Ill. She has no conflicts of interest to disclose.

On the top left of my desktop is an electronic sticky note entitled, “Apply in Future.” This was where the AGA editorial fellowship was listed when I first started GI fellowship. My interest in the behind-the-scenes of scientific publishing developed early. I wanted to learn not only about the decision-making by the editorial board but also other aspects that impact the process from submission to publication. While waiting for my opportunity to apply, I became a reviewer for several journals and then an associate editor of ACG Case Reports Journal, which gave me some insight.

I applied to the editorial fellowship as a second-year fellow, to start as a third-year fellow. I figured this would give me several chances to apply again if I was not selected! I started off by talking to my program director to ensure that I would have enough time, given other responsibilities. The application consisted of a cover letter, where I expressed why I was interested, particularly focusing on my passion for research and my experience with scientific publishing, a letter of recommendation, and a CV. I was ecstatic when I was selected for the AGA editorial fellowship for Clinical Gastroenterology and Hepatology (CGH), whose editorial board’s mission best aligned with my interests.

Dr. Jonathan Buscaglia was the editorial fellows’ mentor for CGH – he met with us and provided an outline of the year. For the first 6 months, I was a reviewer for submitted manuscripts within my topic of interest – pancreaticobiliary diseases and advanced endoscopy and technology. Dr. Buscaglia gave me feedback on my reviews to improve my critical assessment of study designs and interpreted results. After 6 months as a reviewer, I took on the role of an associate editor. I selected reviewers, evaluated the reviews, and made the decision to accept or reject a manuscript. I presented my assigned manuscript at the weekly board of editors meeting, which was one of the biggest learning experiences. Leading researchers from all over the world gathered at a virtual table and discussed whether each study would have clinical impact on the medical community. Each editor contributed a unique perspective that facilitated a robust and thoughtful discussion of each manuscript brought to the table. I was in awe each week.

What I have learned so far during my year as an AGA editorial fellow with CGH has shaped my approach to personal research and will continue to do so as I develop my research career. It has greatly improved my assessment of the literature and I hope to continue to be involved in the critical review process, especially as a reviewer in my early career, and eventually, a part of an editorial board for a journal that truly impacts clinical medicine, such as Clinical Gastroenterology and Hepatology.
 

Dr. Trieu is a gastroenterology and hepatology fellow at Loyola University Medical Center, Maywood, Ill. She has no conflicts of interest to disclose.

Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.  

Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”

This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.

It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.

The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.

A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
 

Use of CGM devices in hospital

The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).

“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.

Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.

However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.

That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”

On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.

The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).

To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”

“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”

The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.

Nine key recommendations

Dr. Korytkowski identified nine key recommendations:

• CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
• Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
• Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
• Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
• Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
• Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
• Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
• Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
• Correctional insulin – “otherwise known as sliding-scale insulin” –  can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
• Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission. 

The guideline writers’ hopes

“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.

The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”

Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.” 

Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.

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

Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.  

Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”

This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.

It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.

The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.

A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
 

Use of CGM devices in hospital

The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).

“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.

Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.

However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.

That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”

On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.

The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).

To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”

“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”

The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.

Nine key recommendations

Dr. Korytkowski identified nine key recommendations:

• CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
• Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
• Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
• Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
• Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
• Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
• Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
• Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
• Correctional insulin – “otherwise known as sliding-scale insulin” –  can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
• Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission. 

The guideline writers’ hopes

“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.

The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”

Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.” 

Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.

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

Goal-directed glycemic management – which may include new technologies for glucose monitoring – for non–critically ill hospitalized patients who have diabetes or newly recognized hyperglycemia can improve outcomes, according to a new practice guideline from the Endocrine Society.  

Even though roughly 35% of hospitalized patients have diabetes or newly discovered hyperglycemia, there is “wide variability in glycemic management in clinical practice,” writing panel chair Mary Korytkowski, MD, from the University of Pittsburgh, said at the annual meeting of the Endocrine Society. “These patients get admitted to every patient service in the hospital, meaning that every clinical service will encounter this group of patients, and their glycemic management can have a major effect on their outcomes. Both short term and long term.”

This guideline provides strategies “to achieve previously recommended glycemic goals while also reducing the risk for hypoglycemia, and this includes inpatient use of insulin pump therapy or continuous glucose monitoring [CGM] devices, among others,” she said.

It also includes “recommendations for preoperative glycemic goals as well as when the use of correctional insulin – well known as sliding scale insulin – may be appropriate” and when it is not.

The document, which replaces a 2012 guideline, was published online in the Journal of Clinical Endocrinology & Metabolism.

A multidisciplinary panel developed the document over the last 3 years to answer 10 clinical practice questions related to management of non–critically ill hospitalized patients with diabetes or newly discovered hyperglycemia.
 

Use of CGM devices in hospital

The first recommendation is: “In adults with insulin-treated diabetes hospitalized for noncritical illness who are at high risk of hypoglycemia, we suggest the use of real-time [CGM] with confirmatory bedside point-of-care blood glucose monitoring for adjustments in insulin dosing rather than point-of-care blood glucose rather than testing alone in hospital settings where resources and training are available.” (Conditional recommendation. Low certainty of evidence).

“We were actually very careful in terms of looking at the data” for use of CGMs, Dr. Korytkowski said in an interview.

Although CGMs are approved by the Food and Drug Administration in the outpatient setting, and that’s becoming the standard of care there, they are not yet approved for in-hospital use.

However, the FDA granted an emergency allowance for use of CGMs in hospitals during the COVID-19 pandemic.

That was “when everyone was scrambling for what to do,” Dr. Korytkowski noted. “There was a shortage of personal protective equipment and a real interest in trying to limit the amount of exposure of healthcare personnel in some of these really critically ill patients for whom intravenous insulin therapy was used to control their glucose level.”

On March 1, the FDA granted Breakthrough Devices Designation for Dexcom CGM use in the hospital setting.

The new guideline suggests CGM be used to detect trends in glycemic management, with insulin dosing decisions made with point-of-care glucose measure (the standard of care).

To implement CGM for glycemic management in hospitals, Dr. Korytkowski said, would require “extensive staff and nursing education to have people with expertise available to provide support to nursing personnel who are both placing these devices, changing these devices, looking at trends, and then knowing when to remove them for certain procedures such as MRI or radiologic procedures.”

“We know that not all hospitals may be readily available to use these devices,” she said. “It is an area of active research. But the use of these devices during the pandemic, in both critical care and non–critical care setting has really provided us with a lot of information that was used to formulate this suggestion in the guideline.”

The document addresses the following areas: CGM, continuous subcutaneous insulin infusion pump therapy, inpatient diabetes education, prespecified preoperative glycemic targets, use of neutral protamine Hagedorn insulin for glucocorticoid or enteral nutrition-associated hyperglycemia, noninsulin therapies, preoperative carbohydrate-containing oral fluids, carbohydrate counting for prandial (mealtime) insulin dosing, and correctional and scheduled (basal or basal bolus) insulin therapies.

Nine key recommendations

Dr. Korytkowski identified nine key recommendations:

• CGM systems can help guide glycemic management with reduced risk for hypoglycemia.
• Patients experiencing glucocorticoid- or enteral nutrition–associated hyperglycemia require scheduled insulin therapy to address anticipated glucose excursions.
• Selected patients using insulin pump therapy prior to a hospital admission can continue to use these devices in the hospital if they have the mental and physical capacity to do so with knowledgeable hospital personnel.
• Diabetes self-management education provided to hospitalized patients can promote improved glycemic control following discharge with reductions in the risk for hospital readmission. “We know that is recommended for patients in the outpatient setting but often they do not get this,” she said. “We were able to observe that this can also impact long-term outcomes “
• Patients with diabetes scheduled for elective surgery may have improved postoperative outcomes when preoperative hemoglobin A1c is 8% or less and preoperative blood glucose is less than 180 mg/dL. “This recommendation answers the question: ‘Where should glycemic goals be for people who are undergoing surgery?’ ”
• Providing preoperative carbohydrate-containing beverages to patients with known diabetes is not recommended.
• Patients with newly recognized hyperglycemia or well-managed diabetes on noninsulin therapy may be treated with correctional insulin alone as initial therapy at hospital admission.
• Some noninsulin diabetes therapies can be used in combination with correction insulin for patients with type 2 diabetes who have mild hyperglycemia.
• Correctional insulin – “otherwise known as sliding-scale insulin” –  can be used as initial therapy for patients with newly recognized hyperglycemia or type 2 diabetes treated with noninsulin therapy prior to hospital admission.
• Scheduled insulin therapy is preferred for patients experiencing persistent blood glucose values greater than 180 mg/dL and is recommended for patients using insulin therapy prior to admission. 

The guideline writers’ hopes

“We hope that this guideline will resolve debates” about appropriate preoperative glycemic management and when sliding-scale insulin can be used and should not be used, said Dr. Korytkowski.

The authors also hope that “it will stimulate research funding for this very important aspect of diabetes care, and that hospitals will recognize the importance of having access to knowledgeable diabetes care and education specialists who can provide staff education regarding inpatient glycemic management, provide oversight for patients using insulin pump therapy or CGM devices, and empower hospital nurses to provide diabetes [self-management] education prior to patient discharge.”

Claire Pegg, the patient representative on the panel, hopes “that this guideline serves as the beginning of a conversation that will allow inpatient caregivers to provide individualized care to patients – some of whom may be self-sufficient with their glycemic management and others who need additional assistance.” 

Development of the guideline was funded by the Endocrine Society. Dr. Korytkowski has reported no relevant financial disclosures.

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

Depression, self-harm, and suicide among people with type 1 and type 2 diabetes are “underappreciated” among health care practitioners, according to Katharine Barnard-Kelly, PhD, who founded the Reducing Suicide Rates Among Individuals With Diabetes (RESCUE) advocacy group in 2021.

“We have the most advanced technology to achieve glycemic control, but the mental burden remains underappreciated,” she said at a symposium with other speakers from RESCUE during the annual scientific sessions of the American Diabetes Association.

Notably, suicide and self-harm are “all too common” among young adults with type 1 diabetes who are receiving insulin, said Dr. Barnard-Kelly, a psychologist and visiting professor at Southern Health NHS Foundation Trust, Southampton, United Kingdom. And insulin under- or overdosing is the most common method of self-harm.  

However, “with a multipronged approach to awareness, education, and identification, we have the opportunity to intervene on the link between suicide and diabetes,” she said, noting that the aim is to “raise awareness and arm [doctors and others] with messages that can ultimately save a young person’s life if adopted in clinical practice and through mental health screenings.”

The rationale behind the RESCUE initiative is also described in a brief report published in Diabetes Technology & Therapeutics.
 

Six key messages

RESCUE now has “approximately 30 members across academia, clinical practice, industry, advocacy, government, regulatory bodies [including the U.S. Food and Drug Administration], and people with diabetes from several countries,” Dr. Barnard-Kelly told this news organization.

She identified six key messages from the symposium:

• “Suicide prevalence is considerably higher among people with diabetes than the general population.
• Talking about suicide does not increase an individual’s risk of suicide.
• Current screening tools for depression and suicide are not sufficiently sensitive to be effective among people with diabetes.
• Identification of suicidal acts among people with diabetes is extremely difficult.
• For every suicide, the World Health Organization reports there are 20 suicide attempts.
• Health care providers often underestimate the prevalence of suicidality among their patient population and feel ill-equipped to initiate conversations with their patients about suicide.”

Dr. Barnard-Kelly also presented some sobering statistics that highlight the need for increased awareness.

A study  reported that, of 160 cases of insulin overdose, 90% were suicides.

Adolescents and young adults with type 2 diabetes are 61% more likely to report suicidal thoughts than those without diabetes.

The risk of depression is two- to three-times higher in people with diabetes. According to another study, 7% of deaths in individuals with type 1 diabetes are estimated to be from suicide.

Survey about screening for depression, suicide risk in diabetes

During the symposium, Daniel R. Chernavvsky, MD, reported results from a small online survey of health care professionals who treat patients with type 1 or type 2 diabetes, which identified their concerns about screening for depression and assessing suicide risk in patients with diabetes.

Respondents were mainly from the United States (103) but were also from the United Kingdom (18), Slovenia, and the Netherlands (5), said Dr. Chernavvsky, who is senior director of medical affairs at Dexcom, Charlottesville, Va.

They included 59 doctors, 21 nurses,17 diabetes educators, 15 psychologists, seven dieticians, four social workers, and six “other” health care professionals, with a mean age of 46 (range, 25-72 years old) who had been working on average 14 years (range, 0.5-45 years).

Close to three-quarters (72%) reported that at least one of their patients had attempted suicide. The most common self-harm behaviors in their patients were insulin omission or a too large insulin bolus, and less often, binge eating.

Almost all respondents (95%) believed that routine visits to the diabetes clinic were appropriate times to discuss depression, self-injury, and suicidal ideation – at every visit (42% of respondents) or some visits (52%).

Only 30% were comfortable asking patients about self-harm or suicide.

Psychologists and social workers were very comfortable, but others were less comfortable or not comfortable at all.  

Many respondents expressed concerns such as, “What do I do?” “Would I make the problem worse?” “Would I give the patient the idea?” Some reported they had “limited resources” or it “feels invasive.”

They identified a need for “a better understanding of what [they could] do to support and care for patients,” and “more knowledge about how to deal with [patients’] answers” to screening questionnaires.
 

Screening for psychological morbidities in diabetes

Guidelines from the ADA and the International Society for Pediatric and Adolescent Diabetes recommend routine screening of patients with diabetes for psychological morbidities, including depression, said Shideh Majidi, MD.  

Depression is associated with higher A1c, noted Dr. Majidi, who is associate director, childhood and adolescent diabetes program at Children’s National Hospital, Washington, D.C.

She identified the following topics that need to be addressed when considering implementing a program for depression screening and suicide risk assessment in a diabetes clinic:

• Conducting screening: Which screening questionnaire will you use? Who will do it? Where? How often?
• Scoring screening questionnaires: Who will do it?
• Depression screening discussion: Who will do it? How will the person be notified of the score?
• Suicide risk assessment: Who will conduct it? What is the process to get someone to the emergency department?
• Resources/referral: Who will initiate and follow-up? 

Next steps

The RESCUE advocacy group is preparing educational and support materials for health care professionals who treat patients with diabetes, as well as other materials for patients themselves.

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

Depression, self-harm, and suicide among people with type 1 and type 2 diabetes are “underappreciated” among health care practitioners, according to Katharine Barnard-Kelly, PhD, who founded the Reducing Suicide Rates Among Individuals With Diabetes (RESCUE) advocacy group in 2021.

“We have the most advanced technology to achieve glycemic control, but the mental burden remains underappreciated,” she said at a symposium with other speakers from RESCUE during the annual scientific sessions of the American Diabetes Association.

Notably, suicide and self-harm are “all too common” among young adults with type 1 diabetes who are receiving insulin, said Dr. Barnard-Kelly, a psychologist and visiting professor at Southern Health NHS Foundation Trust, Southampton, United Kingdom. And insulin under- or overdosing is the most common method of self-harm.  

However, “with a multipronged approach to awareness, education, and identification, we have the opportunity to intervene on the link between suicide and diabetes,” she said, noting that the aim is to “raise awareness and arm [doctors and others] with messages that can ultimately save a young person’s life if adopted in clinical practice and through mental health screenings.”

The rationale behind the RESCUE initiative is also described in a brief report published in Diabetes Technology & Therapeutics.
 

Six key messages

RESCUE now has “approximately 30 members across academia, clinical practice, industry, advocacy, government, regulatory bodies [including the U.S. Food and Drug Administration], and people with diabetes from several countries,” Dr. Barnard-Kelly told this news organization.

She identified six key messages from the symposium:

• “Suicide prevalence is considerably higher among people with diabetes than the general population.
• Talking about suicide does not increase an individual’s risk of suicide.
• Current screening tools for depression and suicide are not sufficiently sensitive to be effective among people with diabetes.
• Identification of suicidal acts among people with diabetes is extremely difficult.
• For every suicide, the World Health Organization reports there are 20 suicide attempts.
• Health care providers often underestimate the prevalence of suicidality among their patient population and feel ill-equipped to initiate conversations with their patients about suicide.”

Dr. Barnard-Kelly also presented some sobering statistics that highlight the need for increased awareness.

A study  reported that, of 160 cases of insulin overdose, 90% were suicides.

Adolescents and young adults with type 2 diabetes are 61% more likely to report suicidal thoughts than those without diabetes.

The risk of depression is two- to three-times higher in people with diabetes. According to another study, 7% of deaths in individuals with type 1 diabetes are estimated to be from suicide.

Survey about screening for depression, suicide risk in diabetes

During the symposium, Daniel R. Chernavvsky, MD, reported results from a small online survey of health care professionals who treat patients with type 1 or type 2 diabetes, which identified their concerns about screening for depression and assessing suicide risk in patients with diabetes.

Respondents were mainly from the United States (103) but were also from the United Kingdom (18), Slovenia, and the Netherlands (5), said Dr. Chernavvsky, who is senior director of medical affairs at Dexcom, Charlottesville, Va.

They included 59 doctors, 21 nurses,17 diabetes educators, 15 psychologists, seven dieticians, four social workers, and six “other” health care professionals, with a mean age of 46 (range, 25-72 years old) who had been working on average 14 years (range, 0.5-45 years).

Close to three-quarters (72%) reported that at least one of their patients had attempted suicide. The most common self-harm behaviors in their patients were insulin omission or a too large insulin bolus, and less often, binge eating.

Almost all respondents (95%) believed that routine visits to the diabetes clinic were appropriate times to discuss depression, self-injury, and suicidal ideation – at every visit (42% of respondents) or some visits (52%).

Only 30% were comfortable asking patients about self-harm or suicide.

Psychologists and social workers were very comfortable, but others were less comfortable or not comfortable at all.  

Many respondents expressed concerns such as, “What do I do?” “Would I make the problem worse?” “Would I give the patient the idea?” Some reported they had “limited resources” or it “feels invasive.”

They identified a need for “a better understanding of what [they could] do to support and care for patients,” and “more knowledge about how to deal with [patients’] answers” to screening questionnaires.
 

Screening for psychological morbidities in diabetes

Guidelines from the ADA and the International Society for Pediatric and Adolescent Diabetes recommend routine screening of patients with diabetes for psychological morbidities, including depression, said Shideh Majidi, MD.  

Depression is associated with higher A1c, noted Dr. Majidi, who is associate director, childhood and adolescent diabetes program at Children’s National Hospital, Washington, D.C.

She identified the following topics that need to be addressed when considering implementing a program for depression screening and suicide risk assessment in a diabetes clinic:

• Conducting screening: Which screening questionnaire will you use? Who will do it? Where? How often?
• Scoring screening questionnaires: Who will do it?
• Depression screening discussion: Who will do it? How will the person be notified of the score?
• Suicide risk assessment: Who will conduct it? What is the process to get someone to the emergency department?
• Resources/referral: Who will initiate and follow-up? 

Next steps

The RESCUE advocacy group is preparing educational and support materials for health care professionals who treat patients with diabetes, as well as other materials for patients themselves.

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

Depression, self-harm, and suicide among people with type 1 and type 2 diabetes are “underappreciated” among health care practitioners, according to Katharine Barnard-Kelly, PhD, who founded the Reducing Suicide Rates Among Individuals With Diabetes (RESCUE) advocacy group in 2021.

“We have the most advanced technology to achieve glycemic control, but the mental burden remains underappreciated,” she said at a symposium with other speakers from RESCUE during the annual scientific sessions of the American Diabetes Association.

Notably, suicide and self-harm are “all too common” among young adults with type 1 diabetes who are receiving insulin, said Dr. Barnard-Kelly, a psychologist and visiting professor at Southern Health NHS Foundation Trust, Southampton, United Kingdom. And insulin under- or overdosing is the most common method of self-harm.  

However, “with a multipronged approach to awareness, education, and identification, we have the opportunity to intervene on the link between suicide and diabetes,” she said, noting that the aim is to “raise awareness and arm [doctors and others] with messages that can ultimately save a young person’s life if adopted in clinical practice and through mental health screenings.”

The rationale behind the RESCUE initiative is also described in a brief report published in Diabetes Technology & Therapeutics.
 

Six key messages

RESCUE now has “approximately 30 members across academia, clinical practice, industry, advocacy, government, regulatory bodies [including the U.S. Food and Drug Administration], and people with diabetes from several countries,” Dr. Barnard-Kelly told this news organization.

She identified six key messages from the symposium:

• “Suicide prevalence is considerably higher among people with diabetes than the general population.
• Talking about suicide does not increase an individual’s risk of suicide.
• Current screening tools for depression and suicide are not sufficiently sensitive to be effective among people with diabetes.
• Identification of suicidal acts among people with diabetes is extremely difficult.
• For every suicide, the World Health Organization reports there are 20 suicide attempts.
• Health care providers often underestimate the prevalence of suicidality among their patient population and feel ill-equipped to initiate conversations with their patients about suicide.”

Dr. Barnard-Kelly also presented some sobering statistics that highlight the need for increased awareness.

A study  reported that, of 160 cases of insulin overdose, 90% were suicides.

Adolescents and young adults with type 2 diabetes are 61% more likely to report suicidal thoughts than those without diabetes.

The risk of depression is two- to three-times higher in people with diabetes. According to another study, 7% of deaths in individuals with type 1 diabetes are estimated to be from suicide.

Survey about screening for depression, suicide risk in diabetes

During the symposium, Daniel R. Chernavvsky, MD, reported results from a small online survey of health care professionals who treat patients with type 1 or type 2 diabetes, which identified their concerns about screening for depression and assessing suicide risk in patients with diabetes.

Respondents were mainly from the United States (103) but were also from the United Kingdom (18), Slovenia, and the Netherlands (5), said Dr. Chernavvsky, who is senior director of medical affairs at Dexcom, Charlottesville, Va.

They included 59 doctors, 21 nurses,17 diabetes educators, 15 psychologists, seven dieticians, four social workers, and six “other” health care professionals, with a mean age of 46 (range, 25-72 years old) who had been working on average 14 years (range, 0.5-45 years).

Close to three-quarters (72%) reported that at least one of their patients had attempted suicide. The most common self-harm behaviors in their patients were insulin omission or a too large insulin bolus, and less often, binge eating.

Almost all respondents (95%) believed that routine visits to the diabetes clinic were appropriate times to discuss depression, self-injury, and suicidal ideation – at every visit (42% of respondents) or some visits (52%).

Only 30% were comfortable asking patients about self-harm or suicide.

Psychologists and social workers were very comfortable, but others were less comfortable or not comfortable at all.  

Many respondents expressed concerns such as, “What do I do?” “Would I make the problem worse?” “Would I give the patient the idea?” Some reported they had “limited resources” or it “feels invasive.”

They identified a need for “a better understanding of what [they could] do to support and care for patients,” and “more knowledge about how to deal with [patients’] answers” to screening questionnaires.
 

Screening for psychological morbidities in diabetes

Guidelines from the ADA and the International Society for Pediatric and Adolescent Diabetes recommend routine screening of patients with diabetes for psychological morbidities, including depression, said Shideh Majidi, MD.  

Depression is associated with higher A1c, noted Dr. Majidi, who is associate director, childhood and adolescent diabetes program at Children’s National Hospital, Washington, D.C.

She identified the following topics that need to be addressed when considering implementing a program for depression screening and suicide risk assessment in a diabetes clinic:

• Conducting screening: Which screening questionnaire will you use? Who will do it? Where? How often?
• Scoring screening questionnaires: Who will do it?
• Depression screening discussion: Who will do it? How will the person be notified of the score?
• Suicide risk assessment: Who will conduct it? What is the process to get someone to the emergency department?
• Resources/referral: Who will initiate and follow-up? 

Next steps

The RESCUE advocacy group is preparing educational and support materials for health care professionals who treat patients with diabetes, as well as other materials for patients themselves.

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

For many years, COPD has remained one of the top four leading causes of death in the United States according to CDC data. Around the world, it is responsible for about 3 million deaths annually. It is estimated that 16 million Americans are now diagnosed with COPD. However, it is commonly agreed by experts that it is widely underdiagnosed and there may be millions more suffering from this disease.

The direct costs of COPD are around $49 billion a year in direct costs, with billions more in indirect costs. Around the globe, COPD is one of the top three causes of death, with 90% of deaths happening in low- and middle-income countries. The burden of COPD is expected to grow over time because of the aging population and continued exposure to COPD risk factors.

The Global Initiative for Chronic Obstructive Lung Disease report (or GOLD) is revised every year, translated into many languages, and used by health care workers globally. It was started in 1998, and its aim was to produce guidelines based on the best scientific evidence available that was nonbiased to be used for assessment, diagnosis, and treatment of patients with COPD. The first report was issued in 2001. The method of producing the GOLD report was to do a search of PubMed for evidence-based, peer-reviewed studies. Those not captured by this method could be submitted for review. The science committee then meets twice a year and reviews each publication, eventually agreeing on a set of guidelines/updates.
 

2022 GOLD Report

For the 2022 GOLD report, 160 new references were added. Overall, the GOLD report is five chapters (more than 150 pages) giving in-depth guidance for the diagnosis, prevention, management, and treatment of patients with stable COPD, COPD exacerbations, and hospitalized patients.

The report suggests that COPD is being underdiagnosed. It’s important for primary care doctors to understand the new guidelines, because they are the clinicians who are most likely to be diagnosing and treating patients with COPD.

Family physicians and internists will be seeing more and more cases as the population ages, and we need to do a better job of recognizing patients who have COPD. If possible, we should try to have spirometry available in our practices. Like any other disease, we know prevention works best so primary care physicians also need to be looking for risk factors, such as smoking history, and help patients try to reduce them if possible. Below is more explanation of the latest guidelines.

For most of us, when we learned about COPD as a disease, the terms “chronic bronchitis” and “emphysema” were emphasized. These words are no longer used as synonymous for COPD.

The disease is now described as involving chronic limitation in airflow that results from a combination of small airway disease and parenchymal destruction (emphysema). The rates of each vary from person to person and progress at different rates. Key factors that contribute to COPD disease burden include chronic inflammation, narrowing of small airways, loss of alveolar attachments, loss of elastic recoil, and mucociliary dysfunction, according to the 2022 GOLD report.

Respiratory symptoms may precede the onset of airflow limitation. COPD should be considered in any patient with dyspnea, chronic cough or sputum production, a history of recurrent lower respiratory tract infections, and risk factors for the disease.

The biggest risk factor for COPD is smoking. Other risk factors include occupational exposure, e-cigarette use, pollution, genetic factors, and comorbid conditions. Symptoms of the disease can include chest tightness, wheezing, and fatigue.

To make a diagnosis of COPD, spirometry is required, the latest GOLD report says. A postbronchodilator FEV₁/FVC less than 0.70 confirms persistent airflow limitation and hence COPD. This value is used in clinical trials and forms the basis of what most treatment guidelines are derived from. It would be beneficial for any physician treating COPD patients to have easy access to spirometry. It provides the most reproducible and objective measurement of airflow limitation. Also, it was found that assessing the degree of reversibility of airflow limitation to decide therapeutic decisions is no longer recommended and thus, asking the patient to stop inhaled medications beforehand is unnecessary. To access the impact COPD has on a patient’s life beyond dyspnea, the guidelines recommend doing a disease-specific health questionnaire, such as the COPD Assessment Test (CAT).

Along with patient symptoms and history of exacerbations, spirometry is crucial for the diagnosis, prognosis, and therapeutic decisions in COPD patients, according to the GOLD guidance. The best predictor of frequent exacerbations, however, is a history of previous exacerbations. In cases where there is a discrepancy between airflow limitation and symptoms, additional testing should be considered. Alpha-1 antitrypsin deficiency (AATD) screening should be considered in younger patients (under 45 years) with perilobular emphysema, and those in areas of high AATD prevalence. Chest x-rays are not recommended in diagnosing COPD but can be helpful if other comorbidities are present. CT scan is not routinely recommended but should be used only for the detection of bronchiectasis, if the patient meets the criteria for lung cancer screening, if surgery is necessary, or if other diseases may need to be evaluated.

Pulse oximetry can be helpful in accessing degree of severity, respiratory failure, and right heart failure. Walking tests can be helpful for evaluating disability and mortality risk. Other tests that have been used but are not routinely recommended include plethysmography and diffusing capacity of the lungs for carbon monoxide.

Composite scores can identify patients who are at increased risk of mortality. One such score is the BODE (Body mass, Obstruction, Dyspnea, and Exercise) method. Biomarkers are being investigated, but data are still not available to recommend their routine use.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

For many years, COPD has remained one of the top four leading causes of death in the United States according to CDC data. Around the world, it is responsible for about 3 million deaths annually. It is estimated that 16 million Americans are now diagnosed with COPD. However, it is commonly agreed by experts that it is widely underdiagnosed and there may be millions more suffering from this disease.

The direct costs of COPD are around $49 billion a year in direct costs, with billions more in indirect costs. Around the globe, COPD is one of the top three causes of death, with 90% of deaths happening in low- and middle-income countries. The burden of COPD is expected to grow over time because of the aging population and continued exposure to COPD risk factors.

The Global Initiative for Chronic Obstructive Lung Disease report (or GOLD) is revised every year, translated into many languages, and used by health care workers globally. It was started in 1998, and its aim was to produce guidelines based on the best scientific evidence available that was nonbiased to be used for assessment, diagnosis, and treatment of patients with COPD. The first report was issued in 2001. The method of producing the GOLD report was to do a search of PubMed for evidence-based, peer-reviewed studies. Those not captured by this method could be submitted for review. The science committee then meets twice a year and reviews each publication, eventually agreeing on a set of guidelines/updates.
 

2022 GOLD Report

For the 2022 GOLD report, 160 new references were added. Overall, the GOLD report is five chapters (more than 150 pages) giving in-depth guidance for the diagnosis, prevention, management, and treatment of patients with stable COPD, COPD exacerbations, and hospitalized patients.

The report suggests that COPD is being underdiagnosed. It’s important for primary care doctors to understand the new guidelines, because they are the clinicians who are most likely to be diagnosing and treating patients with COPD.

Family physicians and internists will be seeing more and more cases as the population ages, and we need to do a better job of recognizing patients who have COPD. If possible, we should try to have spirometry available in our practices. Like any other disease, we know prevention works best so primary care physicians also need to be looking for risk factors, such as smoking history, and help patients try to reduce them if possible. Below is more explanation of the latest guidelines.

For most of us, when we learned about COPD as a disease, the terms “chronic bronchitis” and “emphysema” were emphasized. These words are no longer used as synonymous for COPD.

The disease is now described as involving chronic limitation in airflow that results from a combination of small airway disease and parenchymal destruction (emphysema). The rates of each vary from person to person and progress at different rates. Key factors that contribute to COPD disease burden include chronic inflammation, narrowing of small airways, loss of alveolar attachments, loss of elastic recoil, and mucociliary dysfunction, according to the 2022 GOLD report.

Respiratory symptoms may precede the onset of airflow limitation. COPD should be considered in any patient with dyspnea, chronic cough or sputum production, a history of recurrent lower respiratory tract infections, and risk factors for the disease.

The biggest risk factor for COPD is smoking. Other risk factors include occupational exposure, e-cigarette use, pollution, genetic factors, and comorbid conditions. Symptoms of the disease can include chest tightness, wheezing, and fatigue.

To make a diagnosis of COPD, spirometry is required, the latest GOLD report says. A postbronchodilator FEV₁/FVC less than 0.70 confirms persistent airflow limitation and hence COPD. This value is used in clinical trials and forms the basis of what most treatment guidelines are derived from. It would be beneficial for any physician treating COPD patients to have easy access to spirometry. It provides the most reproducible and objective measurement of airflow limitation. Also, it was found that assessing the degree of reversibility of airflow limitation to decide therapeutic decisions is no longer recommended and thus, asking the patient to stop inhaled medications beforehand is unnecessary. To access the impact COPD has on a patient’s life beyond dyspnea, the guidelines recommend doing a disease-specific health questionnaire, such as the COPD Assessment Test (CAT).

Along with patient symptoms and history of exacerbations, spirometry is crucial for the diagnosis, prognosis, and therapeutic decisions in COPD patients, according to the GOLD guidance. The best predictor of frequent exacerbations, however, is a history of previous exacerbations. In cases where there is a discrepancy between airflow limitation and symptoms, additional testing should be considered. Alpha-1 antitrypsin deficiency (AATD) screening should be considered in younger patients (under 45 years) with perilobular emphysema, and those in areas of high AATD prevalence. Chest x-rays are not recommended in diagnosing COPD but can be helpful if other comorbidities are present. CT scan is not routinely recommended but should be used only for the detection of bronchiectasis, if the patient meets the criteria for lung cancer screening, if surgery is necessary, or if other diseases may need to be evaluated.

Pulse oximetry can be helpful in accessing degree of severity, respiratory failure, and right heart failure. Walking tests can be helpful for evaluating disability and mortality risk. Other tests that have been used but are not routinely recommended include plethysmography and diffusing capacity of the lungs for carbon monoxide.

Composite scores can identify patients who are at increased risk of mortality. One such score is the BODE (Body mass, Obstruction, Dyspnea, and Exercise) method. Biomarkers are being investigated, but data are still not available to recommend their routine use.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

For many years, COPD has remained one of the top four leading causes of death in the United States according to CDC data. Around the world, it is responsible for about 3 million deaths annually. It is estimated that 16 million Americans are now diagnosed with COPD. However, it is commonly agreed by experts that it is widely underdiagnosed and there may be millions more suffering from this disease.

The direct costs of COPD are around $49 billion a year in direct costs, with billions more in indirect costs. Around the globe, COPD is one of the top three causes of death, with 90% of deaths happening in low- and middle-income countries. The burden of COPD is expected to grow over time because of the aging population and continued exposure to COPD risk factors.

The Global Initiative for Chronic Obstructive Lung Disease report (or GOLD) is revised every year, translated into many languages, and used by health care workers globally. It was started in 1998, and its aim was to produce guidelines based on the best scientific evidence available that was nonbiased to be used for assessment, diagnosis, and treatment of patients with COPD. The first report was issued in 2001. The method of producing the GOLD report was to do a search of PubMed for evidence-based, peer-reviewed studies. Those not captured by this method could be submitted for review. The science committee then meets twice a year and reviews each publication, eventually agreeing on a set of guidelines/updates.
 

2022 GOLD Report

For the 2022 GOLD report, 160 new references were added. Overall, the GOLD report is five chapters (more than 150 pages) giving in-depth guidance for the diagnosis, prevention, management, and treatment of patients with stable COPD, COPD exacerbations, and hospitalized patients.

The report suggests that COPD is being underdiagnosed. It’s important for primary care doctors to understand the new guidelines, because they are the clinicians who are most likely to be diagnosing and treating patients with COPD.

Family physicians and internists will be seeing more and more cases as the population ages, and we need to do a better job of recognizing patients who have COPD. If possible, we should try to have spirometry available in our practices. Like any other disease, we know prevention works best so primary care physicians also need to be looking for risk factors, such as smoking history, and help patients try to reduce them if possible. Below is more explanation of the latest guidelines.

For most of us, when we learned about COPD as a disease, the terms “chronic bronchitis” and “emphysema” were emphasized. These words are no longer used as synonymous for COPD.

The disease is now described as involving chronic limitation in airflow that results from a combination of small airway disease and parenchymal destruction (emphysema). The rates of each vary from person to person and progress at different rates. Key factors that contribute to COPD disease burden include chronic inflammation, narrowing of small airways, loss of alveolar attachments, loss of elastic recoil, and mucociliary dysfunction, according to the 2022 GOLD report.

Respiratory symptoms may precede the onset of airflow limitation. COPD should be considered in any patient with dyspnea, chronic cough or sputum production, a history of recurrent lower respiratory tract infections, and risk factors for the disease.

The biggest risk factor for COPD is smoking. Other risk factors include occupational exposure, e-cigarette use, pollution, genetic factors, and comorbid conditions. Symptoms of the disease can include chest tightness, wheezing, and fatigue.

To make a diagnosis of COPD, spirometry is required, the latest GOLD report says. A postbronchodilator FEV₁/FVC less than 0.70 confirms persistent airflow limitation and hence COPD. This value is used in clinical trials and forms the basis of what most treatment guidelines are derived from. It would be beneficial for any physician treating COPD patients to have easy access to spirometry. It provides the most reproducible and objective measurement of airflow limitation. Also, it was found that assessing the degree of reversibility of airflow limitation to decide therapeutic decisions is no longer recommended and thus, asking the patient to stop inhaled medications beforehand is unnecessary. To access the impact COPD has on a patient’s life beyond dyspnea, the guidelines recommend doing a disease-specific health questionnaire, such as the COPD Assessment Test (CAT).

Along with patient symptoms and history of exacerbations, spirometry is crucial for the diagnosis, prognosis, and therapeutic decisions in COPD patients, according to the GOLD guidance. The best predictor of frequent exacerbations, however, is a history of previous exacerbations. In cases where there is a discrepancy between airflow limitation and symptoms, additional testing should be considered. Alpha-1 antitrypsin deficiency (AATD) screening should be considered in younger patients (under 45 years) with perilobular emphysema, and those in areas of high AATD prevalence. Chest x-rays are not recommended in diagnosing COPD but can be helpful if other comorbidities are present. CT scan is not routinely recommended but should be used only for the detection of bronchiectasis, if the patient meets the criteria for lung cancer screening, if surgery is necessary, or if other diseases may need to be evaluated.

Pulse oximetry can be helpful in accessing degree of severity, respiratory failure, and right heart failure. Walking tests can be helpful for evaluating disability and mortality risk. Other tests that have been used but are not routinely recommended include plethysmography and diffusing capacity of the lungs for carbon monoxide.

Composite scores can identify patients who are at increased risk of mortality. One such score is the BODE (Body mass, Obstruction, Dyspnea, and Exercise) method. Biomarkers are being investigated, but data are still not available to recommend their routine use.
 

Dr. Girgis practices family medicine in South River, N.J., and is a clinical assistant professor of family medicine at Robert Wood Johnson Medical School, New Brunswick, N.J. You can contact her at [email protected].

THE CASE

A 62-year-old postmenopausal woman presented to the clinic as a new patient for her annual physical examination. She reported a 9-year history of symptoms including dysuria, post-void dribbling, dyspareunia, and urinary incontinence on review of systems. Her physical examination revealed an anterior vaginal wall bulge (FIGURE). Results of a urinalysis were negative. The patient was referred to Urology for further evaluation.

THE DIAGNOSIS

A pelvic magnetic resonance imaging (MRI) scan revealed a large periurethral diverticulum with a horseshoe shape.

DISCUSSION

Urethral diverticulum is a permanent sac-like cavity projecting into the periurethral fascia arising from the posterior urethral lumen.¹ It is a rare condition that affects fewer than 20 per 1 million women per year.² Urethral diverticulum can range from 1 cm to 8 cm in diameter and is located in the mid or distal urethra.^1,3

Women are more likely than men to develop urethral diverticulum, and it can manifest at any age, usually in the third through seventh decade.^4,5 It was once thought to be more common in Black women, although the literature does not support this.⁶ Black women are 3 times more likely to be operated on than White women to treat urethral diverticula.⁷

Unknown origin. Most cases of urethral diverticulum are acquired; the etiology is uncertain.^8,9 The assumption is that urethral diverticulum occurs as a result of repeated infection of the periurethral glands with subsequent obstruction, abscess formation, and chronic inflammation.^1,2,4 Childbirth trauma, iatrogenic causes, and urethral instrumentation have also been implicated.^3,4 In rare cases of congenital urethral diverticula, the diverticula are thought to be remnants of Gartner duct cysts, and yet, incidence in the pediatric population is low.⁸

Diagnosis is confirmed through physical exam and imaging

The urethral diverticulum manifests anteriorly and palpation of the anterior vaginal wall may reveal a painful mass.¹⁰ A split-speculum is used for careful inspection and palpation of the anterior vaginal wall.⁹ If the diverticulum is found to be firm on palpation, or there is bloody urethral drainage, malignancy (although rare) must be ruled out.^4,5 Refer such patients to a urologist or urogynecologist.

The MRI, with or without endoluminal coil, is considered the gold standard in diagnosing urethral diverticulum.

Radiologic imaging (eg, ultrasound, voiding cystourethrography [VCUG], and MRI) is useful in detecting the size, location, and extent of the diverticulum, revealing the relationship to surrounding tissues, and providing insights for appropriate surgical management.^3,4,9 Ultrasound, which is usually readily available, noninvasive, and less expensive, can be considered for initial screening of suspected urethral diverticulum.^3,11 A postvoid MRI is recommended when a urethral diverticulum is highly suspected.^11,12 The MRI, with or without endoluminal coil, is considered the gold standard; it is a favorable complement to the work-up and offers the most diagnostic value.^3,4 According to a single-institution study, the MRI was 100% sensitive and specific in diagnosing urethral diverticulum.¹² However, the limitation of the MRI lies in its cost and lack of availability in some countries.¹³

Continue to: Nonspecific symptoms may lead to misdiagnosis

Nonspecific symptoms may lead to misdiagnosis. The symptoms associated with urethral diverticulum are diverse and linked to several differential diagnoses (TABLE).^3,4,12 The most common signs and symptoms are pelvic pain, urethral mass, dyspareunia, dysuria, urinary incontinence, and post-void dribbling—all of which are considered nonspecific.^3,10,11 These nonspecific symptoms (or even an absence of symptoms), along with a physician’s lack of familiarity with urethral diverticulum, can result in a misdiagnosis or even a delayed diagnosis (up to 5.2 years).^3,10

Managing symptoms vs preventing recurrence

Conservative management with antibiotics, anticholinergics, and/or observation is acceptable for patients with mild symptoms and those who are pregnant or who have a current infection or serious comorbidities that preclude surgery.^3,9 Complete excision of the urethral diverticulum with reconstruction is considered the most effective surgical management for symptom relief and recurrence prevention.^3,4,11,14

Our patient underwent a successful transvaginal suburethral diverticulectomy.

THE TAKEAWAY

The diagnosis of female urethral diverticulum is often delayed or misdiagnosed because symptoms are diverse and nonspecific. One should have a high degree of suspicion for urethral diverticulum in patients with dysuria, dyspareunia, pelvic pain, urinary incontinence, and irritative voiding symptoms who are not responding to conservative management. Ultrasound is an appropriate first-line imaging modality. However, a pelvic MRI is the most sensitive and specific in diagnosing urethral diverticulum.¹²

CORRESPONDENCE
Folashade Omole, MD, FAAFP, 720 Westview Drive, Atlanta, GA 30310; [email protected]

THE CASE

A 62-year-old postmenopausal woman presented to the clinic as a new patient for her annual physical examination. She reported a 9-year history of symptoms including dysuria, post-void dribbling, dyspareunia, and urinary incontinence on review of systems. Her physical examination revealed an anterior vaginal wall bulge (FIGURE). Results of a urinalysis were negative. The patient was referred to Urology for further evaluation.

THE DIAGNOSIS

A pelvic magnetic resonance imaging (MRI) scan revealed a large periurethral diverticulum with a horseshoe shape.

DISCUSSION

Urethral diverticulum is a permanent sac-like cavity projecting into the periurethral fascia arising from the posterior urethral lumen.¹ It is a rare condition that affects fewer than 20 per 1 million women per year.² Urethral diverticulum can range from 1 cm to 8 cm in diameter and is located in the mid or distal urethra.^1,3

Women are more likely than men to develop urethral diverticulum, and it can manifest at any age, usually in the third through seventh decade.^4,5 It was once thought to be more common in Black women, although the literature does not support this.⁶ Black women are 3 times more likely to be operated on than White women to treat urethral diverticula.⁷

Unknown origin. Most cases of urethral diverticulum are acquired; the etiology is uncertain.^8,9 The assumption is that urethral diverticulum occurs as a result of repeated infection of the periurethral glands with subsequent obstruction, abscess formation, and chronic inflammation.^1,2,4 Childbirth trauma, iatrogenic causes, and urethral instrumentation have also been implicated.^3,4 In rare cases of congenital urethral diverticula, the diverticula are thought to be remnants of Gartner duct cysts, and yet, incidence in the pediatric population is low.⁸

Diagnosis is confirmed through physical exam and imaging

The urethral diverticulum manifests anteriorly and palpation of the anterior vaginal wall may reveal a painful mass.¹⁰ A split-speculum is used for careful inspection and palpation of the anterior vaginal wall.⁹ If the diverticulum is found to be firm on palpation, or there is bloody urethral drainage, malignancy (although rare) must be ruled out.^4,5 Refer such patients to a urologist or urogynecologist.

The MRI, with or without endoluminal coil, is considered the gold standard in diagnosing urethral diverticulum.

Radiologic imaging (eg, ultrasound, voiding cystourethrography [VCUG], and MRI) is useful in detecting the size, location, and extent of the diverticulum, revealing the relationship to surrounding tissues, and providing insights for appropriate surgical management.^3,4,9 Ultrasound, which is usually readily available, noninvasive, and less expensive, can be considered for initial screening of suspected urethral diverticulum.^3,11 A postvoid MRI is recommended when a urethral diverticulum is highly suspected.^11,12 The MRI, with or without endoluminal coil, is considered the gold standard; it is a favorable complement to the work-up and offers the most diagnostic value.^3,4 According to a single-institution study, the MRI was 100% sensitive and specific in diagnosing urethral diverticulum.¹² However, the limitation of the MRI lies in its cost and lack of availability in some countries.¹³

Continue to: Nonspecific symptoms may lead to misdiagnosis

Nonspecific symptoms may lead to misdiagnosis. The symptoms associated with urethral diverticulum are diverse and linked to several differential diagnoses (TABLE).^3,4,12 The most common signs and symptoms are pelvic pain, urethral mass, dyspareunia, dysuria, urinary incontinence, and post-void dribbling—all of which are considered nonspecific.^3,10,11 These nonspecific symptoms (or even an absence of symptoms), along with a physician’s lack of familiarity with urethral diverticulum, can result in a misdiagnosis or even a delayed diagnosis (up to 5.2 years).^3,10

Managing symptoms vs preventing recurrence

Conservative management with antibiotics, anticholinergics, and/or observation is acceptable for patients with mild symptoms and those who are pregnant or who have a current infection or serious comorbidities that preclude surgery.^3,9 Complete excision of the urethral diverticulum with reconstruction is considered the most effective surgical management for symptom relief and recurrence prevention.^3,4,11,14

Our patient underwent a successful transvaginal suburethral diverticulectomy.

THE TAKEAWAY

The diagnosis of female urethral diverticulum is often delayed or misdiagnosed because symptoms are diverse and nonspecific. One should have a high degree of suspicion for urethral diverticulum in patients with dysuria, dyspareunia, pelvic pain, urinary incontinence, and irritative voiding symptoms who are not responding to conservative management. Ultrasound is an appropriate first-line imaging modality. However, a pelvic MRI is the most sensitive and specific in diagnosing urethral diverticulum.¹²

CORRESPONDENCE
Folashade Omole, MD, FAAFP, 720 Westview Drive, Atlanta, GA 30310; [email protected]

THE CASE

A 62-year-old postmenopausal woman presented to the clinic as a new patient for her annual physical examination. She reported a 9-year history of symptoms including dysuria, post-void dribbling, dyspareunia, and urinary incontinence on review of systems. Her physical examination revealed an anterior vaginal wall bulge (FIGURE). Results of a urinalysis were negative. The patient was referred to Urology for further evaluation.

THE DIAGNOSIS

A pelvic magnetic resonance imaging (MRI) scan revealed a large periurethral diverticulum with a horseshoe shape.

DISCUSSION

Urethral diverticulum is a permanent sac-like cavity projecting into the periurethral fascia arising from the posterior urethral lumen.¹ It is a rare condition that affects fewer than 20 per 1 million women per year.² Urethral diverticulum can range from 1 cm to 8 cm in diameter and is located in the mid or distal urethra.^1,3

Women are more likely than men to develop urethral diverticulum, and it can manifest at any age, usually in the third through seventh decade.^4,5 It was once thought to be more common in Black women, although the literature does not support this.⁶ Black women are 3 times more likely to be operated on than White women to treat urethral diverticula.⁷

Unknown origin. Most cases of urethral diverticulum are acquired; the etiology is uncertain.^8,9 The assumption is that urethral diverticulum occurs as a result of repeated infection of the periurethral glands with subsequent obstruction, abscess formation, and chronic inflammation.^1,2,4 Childbirth trauma, iatrogenic causes, and urethral instrumentation have also been implicated.^3,4 In rare cases of congenital urethral diverticula, the diverticula are thought to be remnants of Gartner duct cysts, and yet, incidence in the pediatric population is low.⁸

Diagnosis is confirmed through physical exam and imaging

The urethral diverticulum manifests anteriorly and palpation of the anterior vaginal wall may reveal a painful mass.¹⁰ A split-speculum is used for careful inspection and palpation of the anterior vaginal wall.⁹ If the diverticulum is found to be firm on palpation, or there is bloody urethral drainage, malignancy (although rare) must be ruled out.^4,5 Refer such patients to a urologist or urogynecologist.

The MRI, with or without endoluminal coil, is considered the gold standard in diagnosing urethral diverticulum.

Radiologic imaging (eg, ultrasound, voiding cystourethrography [VCUG], and MRI) is useful in detecting the size, location, and extent of the diverticulum, revealing the relationship to surrounding tissues, and providing insights for appropriate surgical management.^3,4,9 Ultrasound, which is usually readily available, noninvasive, and less expensive, can be considered for initial screening of suspected urethral diverticulum.^3,11 A postvoid MRI is recommended when a urethral diverticulum is highly suspected.^11,12 The MRI, with or without endoluminal coil, is considered the gold standard; it is a favorable complement to the work-up and offers the most diagnostic value.^3,4 According to a single-institution study, the MRI was 100% sensitive and specific in diagnosing urethral diverticulum.¹² However, the limitation of the MRI lies in its cost and lack of availability in some countries.¹³

Continue to: Nonspecific symptoms may lead to misdiagnosis

Nonspecific symptoms may lead to misdiagnosis. The symptoms associated with urethral diverticulum are diverse and linked to several differential diagnoses (TABLE).^3,4,12 The most common signs and symptoms are pelvic pain, urethral mass, dyspareunia, dysuria, urinary incontinence, and post-void dribbling—all of which are considered nonspecific.^3,10,11 These nonspecific symptoms (or even an absence of symptoms), along with a physician’s lack of familiarity with urethral diverticulum, can result in a misdiagnosis or even a delayed diagnosis (up to 5.2 years).^3,10

Managing symptoms vs preventing recurrence

Conservative management with antibiotics, anticholinergics, and/or observation is acceptable for patients with mild symptoms and those who are pregnant or who have a current infection or serious comorbidities that preclude surgery.^3,9 Complete excision of the urethral diverticulum with reconstruction is considered the most effective surgical management for symptom relief and recurrence prevention.^3,4,11,14

Our patient underwent a successful transvaginal suburethral diverticulectomy.

THE TAKEAWAY

The diagnosis of female urethral diverticulum is often delayed or misdiagnosed because symptoms are diverse and nonspecific. One should have a high degree of suspicion for urethral diverticulum in patients with dysuria, dyspareunia, pelvic pain, urinary incontinence, and irritative voiding symptoms who are not responding to conservative management. Ultrasound is an appropriate first-line imaging modality. However, a pelvic MRI is the most sensitive and specific in diagnosing urethral diverticulum.¹²

CORRESPONDENCE
Folashade Omole, MD, FAAFP, 720 Westview Drive, Atlanta, GA 30310; [email protected]

AN 8-YEAR-OLD BOY was evaluated by his family physician for a widespread rash that had first appeared on his arms 4 months earlier. Physical examination revealed 1- to 2-mm hypopigmented, smooth, and dome-shaped papules in clusters and linear arrays on the child’s back, shoulders, and extensor surfaces of both arms (FIGURE). There was no tenderness to palpation of the affected areas, but the patient complained of pruritus. Otherwise, he was in good health.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

This clinical manifestation of multiple, hypopigmented, pinhead-sized papules is most consistent with the diagnosis of lichen nitidus. The linear appearance of the micropapules at sites of trauma or skin pressure (known as the Koebner phenomenon) is a valuable clue in the diagnosis of this skin disorder. In this case, it was most likely the result of the child scratching his skin.

A rare and chronic inflammatory skin condition, lichen nitidus is characterized by numerous small, skin-colored papules that are often arranged in clusters on the upper extremities, the genitalia, and the anterior trunk.¹ The papules are less likely to occur on the face, lower extremities, palms, and soles. Oral mucosal and nail involvement are rare. The condition is usually asymptomatic but can sometimes be associated with pruritus.

Most patients experience spontaneous resolution of lesions within several years; treatment is primarily for symptomatic or cosmetic purposes.

Lichen nitidus occurs more frequently in children or young adults and has a female predominance.¹ It does not exhibit a predilection of any race.² The etiology and pathogenesis of lichen nitidus remain unclear. Genetic factors have been proposed as a potential cause; it has also been reported to be associated with Down syndrome.³

Making the Dx with dermoscopy, skin biopsy

Dermoscopy is a useful technique for diagnosing lichen nitidus. Dermoscopic features of lichen nitidus include white, well-demarcated circular areas with a brown shadow.⁴ Skin biopsy provides a definitive diagnosis. Lichen nitidus has a distinct histopathologic “ball and claw” appearance of rete ridges clutching a lymphohistiocytic infiltrate.¹

Consider these common conditions in the differential

The differential diagnosis includes lichen spinulosus, papular eczema, lichen planus, keratosis pilaris, and verruca plana (flat warts).

Continue to: Lichen spinulosus

Lichen spinulosus lesions are similar in appearance to lichen nitidus but are grouped in patches on the neck, arms, abdomen, and buttocks.¹ The Koebner phenomenon is not typically present. Lichen spinulosus lesions consist of follicular papules that may exhibit a central keratotic plug.

Papular eczema lesions lack the uniform and discrete appearance observed in lichen nitidus. Pruritus is also more likely to be present in papular eczema.

Lichen planus lesions are typically violaceous, flat, and larger in size than lichen nitidus (measuring 1 mm to 1 cm), and have characteristic Wickham striae. Oral involvement is also more suggestive of lichen planus.

Keratosis pilaris is distinguished by its much more common occurrence and perifollicular erythema.

Verruca plana, in contrast to lichen nitidus, are typically pink, flat-topped lesions. They are also larger in size (2 mm to 5 mm).

Continue to: Topical treatment can help manage the condition

Most patients experience spontaneous resolution of lesions within several years; treatment is primarily for symptomatic or cosmetic purposes. When pruritus is present, topical corticosteroids and oral antihistamines may help (eg, hydrocortisone 2.5% cream and oral hydroxyzine). Topical calcineurin inhibitors, such as pimecrolimus cream, have also been reported as an effective therapy in children with lichen nitidus.¹ In patients with generalized lichen nitidus who have not responded to topical corticosteroids, phototherapy can be used.⁵ There are no randomized controlled trials to assess the effectiveness of different types of treatments.

In this case, the patient was advised to start using an over-the-counter topical steroid, such as 1% hydrocortisone cream, to help control pruritus. He was scheduled for a follow-up appointment in 3 months.

AN 8-YEAR-OLD BOY was evaluated by his family physician for a widespread rash that had first appeared on his arms 4 months earlier. Physical examination revealed 1- to 2-mm hypopigmented, smooth, and dome-shaped papules in clusters and linear arrays on the child’s back, shoulders, and extensor surfaces of both arms (FIGURE). There was no tenderness to palpation of the affected areas, but the patient complained of pruritus. Otherwise, he was in good health.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

This clinical manifestation of multiple, hypopigmented, pinhead-sized papules is most consistent with the diagnosis of lichen nitidus. The linear appearance of the micropapules at sites of trauma or skin pressure (known as the Koebner phenomenon) is a valuable clue in the diagnosis of this skin disorder. In this case, it was most likely the result of the child scratching his skin.

A rare and chronic inflammatory skin condition, lichen nitidus is characterized by numerous small, skin-colored papules that are often arranged in clusters on the upper extremities, the genitalia, and the anterior trunk.¹ The papules are less likely to occur on the face, lower extremities, palms, and soles. Oral mucosal and nail involvement are rare. The condition is usually asymptomatic but can sometimes be associated with pruritus.

Most patients experience spontaneous resolution of lesions within several years; treatment is primarily for symptomatic or cosmetic purposes.

Lichen nitidus occurs more frequently in children or young adults and has a female predominance.¹ It does not exhibit a predilection of any race.² The etiology and pathogenesis of lichen nitidus remain unclear. Genetic factors have been proposed as a potential cause; it has also been reported to be associated with Down syndrome.³

Making the Dx with dermoscopy, skin biopsy

Dermoscopy is a useful technique for diagnosing lichen nitidus. Dermoscopic features of lichen nitidus include white, well-demarcated circular areas with a brown shadow.⁴ Skin biopsy provides a definitive diagnosis. Lichen nitidus has a distinct histopathologic “ball and claw” appearance of rete ridges clutching a lymphohistiocytic infiltrate.¹

Consider these common conditions in the differential

The differential diagnosis includes lichen spinulosus, papular eczema, lichen planus, keratosis pilaris, and verruca plana (flat warts).

Continue to: Lichen spinulosus

Lichen spinulosus lesions are similar in appearance to lichen nitidus but are grouped in patches on the neck, arms, abdomen, and buttocks.¹ The Koebner phenomenon is not typically present. Lichen spinulosus lesions consist of follicular papules that may exhibit a central keratotic plug.

Papular eczema lesions lack the uniform and discrete appearance observed in lichen nitidus. Pruritus is also more likely to be present in papular eczema.

Lichen planus lesions are typically violaceous, flat, and larger in size than lichen nitidus (measuring 1 mm to 1 cm), and have characteristic Wickham striae. Oral involvement is also more suggestive of lichen planus.

Keratosis pilaris is distinguished by its much more common occurrence and perifollicular erythema.

Verruca plana, in contrast to lichen nitidus, are typically pink, flat-topped lesions. They are also larger in size (2 mm to 5 mm).

Continue to: Topical treatment can help manage the condition

Most patients experience spontaneous resolution of lesions within several years; treatment is primarily for symptomatic or cosmetic purposes. When pruritus is present, topical corticosteroids and oral antihistamines may help (eg, hydrocortisone 2.5% cream and oral hydroxyzine). Topical calcineurin inhibitors, such as pimecrolimus cream, have also been reported as an effective therapy in children with lichen nitidus.¹ In patients with generalized lichen nitidus who have not responded to topical corticosteroids, phototherapy can be used.⁵ There are no randomized controlled trials to assess the effectiveness of different types of treatments.

In this case, the patient was advised to start using an over-the-counter topical steroid, such as 1% hydrocortisone cream, to help control pruritus. He was scheduled for a follow-up appointment in 3 months.

AN 8-YEAR-OLD BOY was evaluated by his family physician for a widespread rash that had first appeared on his arms 4 months earlier. Physical examination revealed 1- to 2-mm hypopigmented, smooth, and dome-shaped papules in clusters and linear arrays on the child’s back, shoulders, and extensor surfaces of both arms (FIGURE). There was no tenderness to palpation of the affected areas, but the patient complained of pruritus. Otherwise, he was in good health.

WHAT IS YOUR DIAGNOSIS?
HOW WOULD YOU TREAT THIS PATIENT?

This clinical manifestation of multiple, hypopigmented, pinhead-sized papules is most consistent with the diagnosis of lichen nitidus. The linear appearance of the micropapules at sites of trauma or skin pressure (known as the Koebner phenomenon) is a valuable clue in the diagnosis of this skin disorder. In this case, it was most likely the result of the child scratching his skin.

A rare and chronic inflammatory skin condition, lichen nitidus is characterized by numerous small, skin-colored papules that are often arranged in clusters on the upper extremities, the genitalia, and the anterior trunk.¹ The papules are less likely to occur on the face, lower extremities, palms, and soles. Oral mucosal and nail involvement are rare. The condition is usually asymptomatic but can sometimes be associated with pruritus.

Most patients experience spontaneous resolution of lesions within several years; treatment is primarily for symptomatic or cosmetic purposes.

Lichen nitidus occurs more frequently in children or young adults and has a female predominance.¹ It does not exhibit a predilection of any race.² The etiology and pathogenesis of lichen nitidus remain unclear. Genetic factors have been proposed as a potential cause; it has also been reported to be associated with Down syndrome.³

Making the Dx with dermoscopy, skin biopsy

Dermoscopy is a useful technique for diagnosing lichen nitidus. Dermoscopic features of lichen nitidus include white, well-demarcated circular areas with a brown shadow.⁴ Skin biopsy provides a definitive diagnosis. Lichen nitidus has a distinct histopathologic “ball and claw” appearance of rete ridges clutching a lymphohistiocytic infiltrate.¹

Consider these common conditions in the differential

The differential diagnosis includes lichen spinulosus, papular eczema, lichen planus, keratosis pilaris, and verruca plana (flat warts).

Continue to: Lichen spinulosus

Lichen spinulosus lesions are similar in appearance to lichen nitidus but are grouped in patches on the neck, arms, abdomen, and buttocks.¹ The Koebner phenomenon is not typically present. Lichen spinulosus lesions consist of follicular papules that may exhibit a central keratotic plug.

Papular eczema lesions lack the uniform and discrete appearance observed in lichen nitidus. Pruritus is also more likely to be present in papular eczema.

Lichen planus lesions are typically violaceous, flat, and larger in size than lichen nitidus (measuring 1 mm to 1 cm), and have characteristic Wickham striae. Oral involvement is also more suggestive of lichen planus.

Keratosis pilaris is distinguished by its much more common occurrence and perifollicular erythema.

Verruca plana, in contrast to lichen nitidus, are typically pink, flat-topped lesions. They are also larger in size (2 mm to 5 mm).

Continue to: Topical treatment can help manage the condition

Most patients experience spontaneous resolution of lesions within several years; treatment is primarily for symptomatic or cosmetic purposes. When pruritus is present, topical corticosteroids and oral antihistamines may help (eg, hydrocortisone 2.5% cream and oral hydroxyzine). Topical calcineurin inhibitors, such as pimecrolimus cream, have also been reported as an effective therapy in children with lichen nitidus.¹ In patients with generalized lichen nitidus who have not responded to topical corticosteroids, phototherapy can be used.⁵ There are no randomized controlled trials to assess the effectiveness of different types of treatments.

In this case, the patient was advised to start using an over-the-counter topical steroid, such as 1% hydrocortisone cream, to help control pruritus. He was scheduled for a follow-up appointment in 3 months.

Migraine headaches pose a challenge for many patients and their physicians, so new, effective approaches are always welcome. Sometimes new treatments come as total surprises. For example, who would have guessed that timolol eyedrops could be effective for acute migraine?¹ Granted, the results (discussed in this issue's PURLs) are from a single randomized trial, but they look very promising.

This is not the only new and innovative treatment for migraine. Everyone knows about the heavily marketed calcium gene-related peptide antagonists, which include monoclonal antibodies and the so-called “gepants.” The monoclonal antibodies and atogepant are approved for migraine prevention, and they do a decent job (although at a high price). In randomized trials, these agents reduced migraine days per month by an average of about 1.5 to 2.5 days compared to placebo.^2-5

Who would have guessed that timolol eyedrops could be effective for acute migraine?

Ubrogepant and rimegepant are approved for acute migraine treatment. In clinical trials, about 20% of patients taking ubrogepant or rimegepant were pain free at 2 hours post dose, compared to 12% to 14% taking placebo.^6,7 Unfortunately, that means 80% of patients still have some pain at 2 hours. By comparison, zolmitriptan performs a bit better, with 34% of patients pain free at 2 hours.⁸ However, for those who can’t tolerate zolmitriptan, these newer options provide an alternative.

We also now have nonpharmacologic options. The caloric vestibular stimulation device is essentially a headset with ear probes that change temperature, alternating warm and cold. In a randomized controlled trial, it reduced monthly migraine days by 1.1 compared to placebo, from a baseline of 7.7 to 3.9 days.⁹ It can also be used to treat acute migraine. There is also a vagus nerve–stimulating device that reduced migraine headache severity by 20% on average in 32.2% of patients in 30 minutes. Sham treatment was as effective for 18.5% of patients, giving a number needed to treat of 6 compared to sham.¹⁰

And finally, there are complementary and alternative medicine options. Two recent randomized trials demonstrated that ≥ 2000 IU/d of vitamin D reduced monthly migraine days an average of 2 days, which is comparable to the effectiveness of the calcium gene-related peptide antagonists at a fraction of the cost.^11,12 In another randomized trial, intranasal 1.5% peppermint oil was as effective as topical 4% lidocaine in providing substantial pain relief for acute migraine; about 42% of patients achieved significant relief with either treatment.¹³

While we may not have a perfect treatment for our patients with migraine headache, we certainly have many options to choose from.

Migraine headaches pose a challenge for many patients and their physicians, so new, effective approaches are always welcome. Sometimes new treatments come as total surprises. For example, who would have guessed that timolol eyedrops could be effective for acute migraine?¹ Granted, the results (discussed in this issue's PURLs) are from a single randomized trial, but they look very promising.

This is not the only new and innovative treatment for migraine. Everyone knows about the heavily marketed calcium gene-related peptide antagonists, which include monoclonal antibodies and the so-called “gepants.” The monoclonal antibodies and atogepant are approved for migraine prevention, and they do a decent job (although at a high price). In randomized trials, these agents reduced migraine days per month by an average of about 1.5 to 2.5 days compared to placebo.^2-5

Who would have guessed that timolol eyedrops could be effective for acute migraine?

Ubrogepant and rimegepant are approved for acute migraine treatment. In clinical trials, about 20% of patients taking ubrogepant or rimegepant were pain free at 2 hours post dose, compared to 12% to 14% taking placebo.^6,7 Unfortunately, that means 80% of patients still have some pain at 2 hours. By comparison, zolmitriptan performs a bit better, with 34% of patients pain free at 2 hours.⁸ However, for those who can’t tolerate zolmitriptan, these newer options provide an alternative.

We also now have nonpharmacologic options. The caloric vestibular stimulation device is essentially a headset with ear probes that change temperature, alternating warm and cold. In a randomized controlled trial, it reduced monthly migraine days by 1.1 compared to placebo, from a baseline of 7.7 to 3.9 days.⁹ It can also be used to treat acute migraine. There is also a vagus nerve–stimulating device that reduced migraine headache severity by 20% on average in 32.2% of patients in 30 minutes. Sham treatment was as effective for 18.5% of patients, giving a number needed to treat of 6 compared to sham.¹⁰

And finally, there are complementary and alternative medicine options. Two recent randomized trials demonstrated that ≥ 2000 IU/d of vitamin D reduced monthly migraine days an average of 2 days, which is comparable to the effectiveness of the calcium gene-related peptide antagonists at a fraction of the cost.^11,12 In another randomized trial, intranasal 1.5% peppermint oil was as effective as topical 4% lidocaine in providing substantial pain relief for acute migraine; about 42% of patients achieved significant relief with either treatment.¹³

While we may not have a perfect treatment for our patients with migraine headache, we certainly have many options to choose from.

Migraine headaches pose a challenge for many patients and their physicians, so new, effective approaches are always welcome. Sometimes new treatments come as total surprises. For example, who would have guessed that timolol eyedrops could be effective for acute migraine?¹ Granted, the results (discussed in this issue's PURLs) are from a single randomized trial, but they look very promising.

This is not the only new and innovative treatment for migraine. Everyone knows about the heavily marketed calcium gene-related peptide antagonists, which include monoclonal antibodies and the so-called “gepants.” The monoclonal antibodies and atogepant are approved for migraine prevention, and they do a decent job (although at a high price). In randomized trials, these agents reduced migraine days per month by an average of about 1.5 to 2.5 days compared to placebo.^2-5

Who would have guessed that timolol eyedrops could be effective for acute migraine?

Ubrogepant and rimegepant are approved for acute migraine treatment. In clinical trials, about 20% of patients taking ubrogepant or rimegepant were pain free at 2 hours post dose, compared to 12% to 14% taking placebo.^6,7 Unfortunately, that means 80% of patients still have some pain at 2 hours. By comparison, zolmitriptan performs a bit better, with 34% of patients pain free at 2 hours.⁸ However, for those who can’t tolerate zolmitriptan, these newer options provide an alternative.

We also now have nonpharmacologic options. The caloric vestibular stimulation device is essentially a headset with ear probes that change temperature, alternating warm and cold. In a randomized controlled trial, it reduced monthly migraine days by 1.1 compared to placebo, from a baseline of 7.7 to 3.9 days.⁹ It can also be used to treat acute migraine. There is also a vagus nerve–stimulating device that reduced migraine headache severity by 20% on average in 32.2% of patients in 30 minutes. Sham treatment was as effective for 18.5% of patients, giving a number needed to treat of 6 compared to sham.¹⁰

And finally, there are complementary and alternative medicine options. Two recent randomized trials demonstrated that ≥ 2000 IU/d of vitamin D reduced monthly migraine days an average of 2 days, which is comparable to the effectiveness of the calcium gene-related peptide antagonists at a fraction of the cost.^11,12 In another randomized trial, intranasal 1.5% peppermint oil was as effective as topical 4% lidocaine in providing substantial pain relief for acute migraine; about 42% of patients achieved significant relief with either treatment.¹³

While we may not have a perfect treatment for our patients with migraine headache, we certainly have many options to choose from.

Breast cancer is the most common invasive cancer in women in the United States; it is estimated that there will be 287,850 new cases of breast cancer in the United States during 2022 with 43,250 deaths.¹ Lives are extended and saved every day because of a robust arsenal of treatments and interventions available to those who have been given a diagnosis of breast cancer. And, of course, lives are also extended and saved when we identify women at risk and provide early interventions. But in busy offices where time is short and there are competing demands on our time, proper assessment of a woman’s risk of breast cancer does not always happen. As a result, women with a higher risk of breast cancer may not be getting appropriate management.^2,3

Familiarizing yourself with several risk-assessment tools and knowing when genetic testing is needed can make a big difference. Knowing the timing of mammograms and magnetic resonance imaging (MRI) for women deemed to be at high risk is also key. The following review employs a case-based approach (with an accompanying ALGORITHM) to illustrate how best to identify women who are at heightened risk of breast cancer and maximize their care. We also discuss the chemoprophylaxis regimens that may be used for those at increased risk.

CASE

Rachel P, age 37, presents to establish care. She has an Ashkenazi Jewish background and wonders if she should start doing breast cancer screening before age 40. She has 2 children, ages 4 years and 2 years. Her maternal aunt had unilateral breast cancer at age 54, and her maternal grandmother died of ovarian cancer at age 65.

Risk assessment

The risk assessment process (see ALGORITHM) must start with either the clinician or the patient initiating the discussion about breast cancer risk. The clinician may initiate the discussion with a new patient or at an annual physical examination. The patient may start the discussion because they are experiencing new breast symptoms, have anxiety about developing breast cancer, or have a family member with a new cancer diagnosis.

Risk factors. There are single factors that convey enough risk to automatically designate the patient as high risk (see TABLE 1^4-9). These factors include having a history of chest radiation between the ages of 10 and 30, a history of breast biopsy with either lobular carcinoma in situ (LCIS) or atypical ductal hyperplasia (ADH), past breast and/or ovarian cancer, and either a family or personal history of a high penetrant genetic variant for breast cancer.^4-9

In women with previous chest radiation, breast cancer risk correlates with the total dose of radiation.⁵ For women with a personal history of breast cancer, the younger the age at diagnosis, the higher the risk of contralateral breast cancer.⁵ Precancerous changes such as ADH, LCIS, and ductal carcinoma in situ (DCIS) also confer moderate increases in risk. Women with these diagnoses will commonly have follow-up with specialists.

Risk assessment tools. There are several models available to assess a woman’s breast cancer risk (see TABLE 2^10-12). The Gail model (https://bcrisktool.cancer.gov/) is the oldest, quickest, and most widely known. However, the Gail model only accounts for first-degree relatives diagnosed with breast cancer, may underpredict risk in women with a more extensive family history, and has not been studied in women younger than 35. The International Breast Cancer Intervention Study (IBIS) Risk Evaluation Tool (https://ibis-risk-calculator.magview.com/), commonly referred to as the Tyrer-Cuzick model, incorporates second-degree relatives into the prediction model—although women may not know their full family history. Both the IBIS and the Breast Cancer Surveillance Consortium (BCSC) model (https://tools.bcsc-scc.org/BC5yearRisk/intro.htm) include breast density in the prediction algorithm. The choice of tool depends on clinician comfort and individual patient risk factors. There is no evidence that one model is better than another.^10-12

Continue to: CASE

CASE

Ms. P’s clinician starts with an assessment using the Gail model. However, when the result comes back with average risk, the clinician decides to follow up with the Tyrer-Cuzick model in order to incorporate Ms. P’s multiple ­second-degree relatives with breast and ovarian cancer. (The BCSC model was not used because it only includes first-degree relatives.)

Genetic testing

The National Comprehensive Cancer Network (NCCN) guidelines recommend genetic testing if a woman has a first- or ­second-degree relative with pancreatic cancer, metastatic prostate cancer, male breast cancer, breast cancer at age 45 or younger, 2 or more breast cancers in a single person, 2 or more people on the same side of the family with at least 1 diagnosed at age 50 or younger, or any relative with ovarian cancer (see TABLE 3).⁷ Before ordering genetic testing, it is useful to refer the patient to a genetic counselor for a thorough discussion of options.

Results of genetic testing may include high-risk variants, moderate-risk variants, and variants of unknown significance (VUS), or be negative for any variants. High-risk variants for breast cancer include BRCA1, BRCA2, PALB2, and cancer syndrome variants such as TP53, PTEN, STK11, and CDH1.^5,6,9,13-15 These high-risk variants confer sufficient risk that women with these mutations are automatically categorized in the high-risk group. It is estimated that high-risk variants account for only 25% of the genetic risk for breast cancer.¹⁶

BRCA1/2 and PTEN mutations confer greater than 80% lifetime risk, while other high-risk variants such as TP53, CDH1, and STK11 confer risks between 25% and 40%. These variants are also associated with cancers of other organs, depending on the mutation.¹⁷

Moderate-risk variants—ATM and CHEK2—do not confer sufficient risk to elevate women into the high-risk group. However, they do qualify these intermediate-risk women to participate in a specialized management strategy.^5,9,13,18

VUS are those for which the associated risk is unclear, but more research may be done to categorize the risk.⁹ The clinical management of women with VUS usually entails close monitoring.

In an effort to better characterize breast cancer risk using a combination of pathogenic variants found in broad multi-gene cancer predisposition panels, researchers have developed a method to combine risks in a “polygenic risk score” (PRS) that can be used to counsel women (see “What is a polygenic risk score for breast cancer?” on page 203).^19-21PRS predicts an additional 18% of genetic risk in women of European descent.²¹

Continue to: CASE

CASE

Using the assessment results, the clinician talks to Ms. P about her lifetime risk for breast cancer. The Gail model indicates her lifetime risk is 13.3%, just slightly higher than the average (12.5%), and her 5-year risk is 0.5% (average, 0.4%). The IBIS or Tyrer-­Cuzick model, which takes into account her second-degree relatives with breast and ovarian cancer and her Ashkenazi ethnicity (which confers increased risk due to elevated risk of BRCA mutations), predicts her lifetime risk of breast cancer to be 20.4%. This categorizes Ms. P as high risk.

Enhanced screening recommendations for women at high risk

TABLE 4^8,13,22 summarizes screening recommendations for women deemed to be at high risk for breast cancer. The American Cancer Society (ACS), NCCN, and the American College of Radiology (ACR) recommend that women with at least a 20% lifetime risk have yearly magnetic resonance imaging (MRI) and mammography (staggered so that the patient has 1 test every 6 months) starting 10 years before the age of onset for the youngest affected relative but not before age 30.⁸ For carriers of high-risk (as well as intermediate-risk) genes, NCCN recommends annual MRI screening starting at age 40.¹³BRCA1/2 screening includes annual MRI starting at age 25 and annual mammography every 6 months starting at age 30.²² Clinicians should counsel women with moderate risk factors (elevated breast density; personal history of ADH, LCIS, or DCIS) about the potential risks and benefits of enhanced screening and chemoprophylaxis.

Risk-reduction strategies

Chemoprophylaxis

The US Preventive Services Task Force (USPSTF) recommends that all women at increased risk for breast cancer consider chemoprophylaxis (B recommendation)²³ based on convincing evidence that 5 years of treatment with either a synthetic estrogen reuptake modulator (SERM) or an aromatase inhibitor (AI) decreases the incidence of estrogen receptor positive breast cancers. (See TABLE 5^7,23,24 for absolute risk reduction.) There is no benefit for chemoprophylaxis in women at average risk (D recommendation).²³ It is unclear whether chemoprophylaxis is indicated in women with moderate increased risk (ie, who do not meet the 20% lifetime risk criteria). Chemoprophylaxis may not be effective in women with BRCA1 mutations, as they often develop triple-negative breast cancers.

Accurate risk assessment and shared decision-making enable the clinician and patient to discuss the potential risks and benefits of chemoprophylaxis.^7,24 The USPSTF did not find that any 1 risk prediction tool was better than another to identify women who should be counseled about chemoprophylaxis. Clinicians should counsel all women taking AIs about optimizing bone health with adequate calcium and vitamin D intake and routine bone density tests.

Surgical risk reduction

The NCCN guidelines state that risk-reducing bilateral mastectomy is reserved for individuals with high-risk gene variants and individuals with prior chest radiation between ages 10 and 30.²⁵ NCCN also recommends discussing risk-reducing mastectomy with all women with BRCA mutations.²²

Risk-reducing oophorectomy is the standard of care for women with BRCA mutations to reduce the risk of ovarian cancer.

Bilateral mastectomy is the most effective method to reduce breast cancer risk and should be discussed after age 25 in women with BRCA mutations and at least 8 years after chest radiation is completed.²⁶ There is a reduction in breast cancer incidence of 90%.²⁵ Breast imaging for screening (mammography or MRI) is not indicated after risk-reducing mastectomy. However, clinical breast examinations of the surgical site are important, because there is a small risk of developing breast cancer in that area.²⁶

Risk-reducing oophorectomy is the standard of care for women with BRCA mutations to reduce the risk of ovarian cancer. It can also reduce the risk of breast cancer in women with BRCA mutations.²⁷

Continue to: CASE

CASE

Based on her risk assessment results, family history, and genetic heritage, Ms. P qualifies for referral to a genetic counselor for discussion of BRCA testing. The clinician discusses adding annual MRI to Ms. P’s breast cancer screening regimen, based on ACS, NCCN, and ACR recommendations, due to her 20.4% lifetime risk. Discussion of whether and when to start chemoprophylaxis is typically based on breast cancer risk, projected benefit, and the potential impact of medication adverse effects. A high-risk woman is eligible for 5 years of chemoprophylaxis (tamoxifen if premenopausal) based on her lifetime risk. The clinician discusses timing with Ms. P, and even though she is finished with childbearing, she would like to wait until she is age 45, which is before the age at which her aunt was given a diagnosis of breast cancer.

Conclusion

Primary care clinicians are well positioned to identify women with an elevated risk of breast cancer and refer them for enhanced screening and chemoprophylaxis (see ALGORITHM). Shared decision-making with the inclusion of patient decision aids (https://decisionaid.ohri.ca/AZsearch.php?criteria=breast+cancer) about genetic testing, chemoprophylaxis, and prophylactic mastectomy or oophorectomy may help women at intermediate or high risk of breast cancer feel empowered to make decisions about their breast—and overall—health.

CORRESPONDENCE
Sarina Schrager, MD, MS, Professor, Department of Family Medicine and Community Health, University of Wisconsin, 1100 Delaplaine Court, Madison, WI 53715; [email protected]

Breast cancer is the most common invasive cancer in women in the United States; it is estimated that there will be 287,850 new cases of breast cancer in the United States during 2022 with 43,250 deaths.¹ Lives are extended and saved every day because of a robust arsenal of treatments and interventions available to those who have been given a diagnosis of breast cancer. And, of course, lives are also extended and saved when we identify women at risk and provide early interventions. But in busy offices where time is short and there are competing demands on our time, proper assessment of a woman’s risk of breast cancer does not always happen. As a result, women with a higher risk of breast cancer may not be getting appropriate management.^2,3

Familiarizing yourself with several risk-assessment tools and knowing when genetic testing is needed can make a big difference. Knowing the timing of mammograms and magnetic resonance imaging (MRI) for women deemed to be at high risk is also key. The following review employs a case-based approach (with an accompanying ALGORITHM) to illustrate how best to identify women who are at heightened risk of breast cancer and maximize their care. We also discuss the chemoprophylaxis regimens that may be used for those at increased risk.

CASE

Rachel P, age 37, presents to establish care. She has an Ashkenazi Jewish background and wonders if she should start doing breast cancer screening before age 40. She has 2 children, ages 4 years and 2 years. Her maternal aunt had unilateral breast cancer at age 54, and her maternal grandmother died of ovarian cancer at age 65.

Risk assessment

The risk assessment process (see ALGORITHM) must start with either the clinician or the patient initiating the discussion about breast cancer risk. The clinician may initiate the discussion with a new patient or at an annual physical examination. The patient may start the discussion because they are experiencing new breast symptoms, have anxiety about developing breast cancer, or have a family member with a new cancer diagnosis.

Risk factors. There are single factors that convey enough risk to automatically designate the patient as high risk (see TABLE 1^4-9). These factors include having a history of chest radiation between the ages of 10 and 30, a history of breast biopsy with either lobular carcinoma in situ (LCIS) or atypical ductal hyperplasia (ADH), past breast and/or ovarian cancer, and either a family or personal history of a high penetrant genetic variant for breast cancer.^4-9

In women with previous chest radiation, breast cancer risk correlates with the total dose of radiation.⁵ For women with a personal history of breast cancer, the younger the age at diagnosis, the higher the risk of contralateral breast cancer.⁵ Precancerous changes such as ADH, LCIS, and ductal carcinoma in situ (DCIS) also confer moderate increases in risk. Women with these diagnoses will commonly have follow-up with specialists.

Risk assessment tools. There are several models available to assess a woman’s breast cancer risk (see TABLE 2^10-12). The Gail model (https://bcrisktool.cancer.gov/) is the oldest, quickest, and most widely known. However, the Gail model only accounts for first-degree relatives diagnosed with breast cancer, may underpredict risk in women with a more extensive family history, and has not been studied in women younger than 35. The International Breast Cancer Intervention Study (IBIS) Risk Evaluation Tool (https://ibis-risk-calculator.magview.com/), commonly referred to as the Tyrer-Cuzick model, incorporates second-degree relatives into the prediction model—although women may not know their full family history. Both the IBIS and the Breast Cancer Surveillance Consortium (BCSC) model (https://tools.bcsc-scc.org/BC5yearRisk/intro.htm) include breast density in the prediction algorithm. The choice of tool depends on clinician comfort and individual patient risk factors. There is no evidence that one model is better than another.^10-12

Continue to: CASE

CASE

Ms. P’s clinician starts with an assessment using the Gail model. However, when the result comes back with average risk, the clinician decides to follow up with the Tyrer-Cuzick model in order to incorporate Ms. P’s multiple ­second-degree relatives with breast and ovarian cancer. (The BCSC model was not used because it only includes first-degree relatives.)

Genetic testing

The National Comprehensive Cancer Network (NCCN) guidelines recommend genetic testing if a woman has a first- or ­second-degree relative with pancreatic cancer, metastatic prostate cancer, male breast cancer, breast cancer at age 45 or younger, 2 or more breast cancers in a single person, 2 or more people on the same side of the family with at least 1 diagnosed at age 50 or younger, or any relative with ovarian cancer (see TABLE 3).⁷ Before ordering genetic testing, it is useful to refer the patient to a genetic counselor for a thorough discussion of options.

Results of genetic testing may include high-risk variants, moderate-risk variants, and variants of unknown significance (VUS), or be negative for any variants. High-risk variants for breast cancer include BRCA1, BRCA2, PALB2, and cancer syndrome variants such as TP53, PTEN, STK11, and CDH1.^5,6,9,13-15 These high-risk variants confer sufficient risk that women with these mutations are automatically categorized in the high-risk group. It is estimated that high-risk variants account for only 25% of the genetic risk for breast cancer.¹⁶

BRCA1/2 and PTEN mutations confer greater than 80% lifetime risk, while other high-risk variants such as TP53, CDH1, and STK11 confer risks between 25% and 40%. These variants are also associated with cancers of other organs, depending on the mutation.¹⁷

Moderate-risk variants—ATM and CHEK2—do not confer sufficient risk to elevate women into the high-risk group. However, they do qualify these intermediate-risk women to participate in a specialized management strategy.^5,9,13,18

VUS are those for which the associated risk is unclear, but more research may be done to categorize the risk.⁹ The clinical management of women with VUS usually entails close monitoring.

In an effort to better characterize breast cancer risk using a combination of pathogenic variants found in broad multi-gene cancer predisposition panels, researchers have developed a method to combine risks in a “polygenic risk score” (PRS) that can be used to counsel women (see “What is a polygenic risk score for breast cancer?” on page 203).^19-21PRS predicts an additional 18% of genetic risk in women of European descent.²¹

Continue to: CASE

CASE

Using the assessment results, the clinician talks to Ms. P about her lifetime risk for breast cancer. The Gail model indicates her lifetime risk is 13.3%, just slightly higher than the average (12.5%), and her 5-year risk is 0.5% (average, 0.4%). The IBIS or Tyrer-­Cuzick model, which takes into account her second-degree relatives with breast and ovarian cancer and her Ashkenazi ethnicity (which confers increased risk due to elevated risk of BRCA mutations), predicts her lifetime risk of breast cancer to be 20.4%. This categorizes Ms. P as high risk.

Enhanced screening recommendations for women at high risk

TABLE 4^8,13,22 summarizes screening recommendations for women deemed to be at high risk for breast cancer. The American Cancer Society (ACS), NCCN, and the American College of Radiology (ACR) recommend that women with at least a 20% lifetime risk have yearly magnetic resonance imaging (MRI) and mammography (staggered so that the patient has 1 test every 6 months) starting 10 years before the age of onset for the youngest affected relative but not before age 30.⁸ For carriers of high-risk (as well as intermediate-risk) genes, NCCN recommends annual MRI screening starting at age 40.¹³BRCA1/2 screening includes annual MRI starting at age 25 and annual mammography every 6 months starting at age 30.²² Clinicians should counsel women with moderate risk factors (elevated breast density; personal history of ADH, LCIS, or DCIS) about the potential risks and benefits of enhanced screening and chemoprophylaxis.

Risk-reduction strategies

Chemoprophylaxis

The US Preventive Services Task Force (USPSTF) recommends that all women at increased risk for breast cancer consider chemoprophylaxis (B recommendation)²³ based on convincing evidence that 5 years of treatment with either a synthetic estrogen reuptake modulator (SERM) or an aromatase inhibitor (AI) decreases the incidence of estrogen receptor positive breast cancers. (See TABLE 5^7,23,24 for absolute risk reduction.) There is no benefit for chemoprophylaxis in women at average risk (D recommendation).²³ It is unclear whether chemoprophylaxis is indicated in women with moderate increased risk (ie, who do not meet the 20% lifetime risk criteria). Chemoprophylaxis may not be effective in women with BRCA1 mutations, as they often develop triple-negative breast cancers.

Accurate risk assessment and shared decision-making enable the clinician and patient to discuss the potential risks and benefits of chemoprophylaxis.^7,24 The USPSTF did not find that any 1 risk prediction tool was better than another to identify women who should be counseled about chemoprophylaxis. Clinicians should counsel all women taking AIs about optimizing bone health with adequate calcium and vitamin D intake and routine bone density tests.

Surgical risk reduction

The NCCN guidelines state that risk-reducing bilateral mastectomy is reserved for individuals with high-risk gene variants and individuals with prior chest radiation between ages 10 and 30.²⁵ NCCN also recommends discussing risk-reducing mastectomy with all women with BRCA mutations.²²

Risk-reducing oophorectomy is the standard of care for women with BRCA mutations to reduce the risk of ovarian cancer.

Bilateral mastectomy is the most effective method to reduce breast cancer risk and should be discussed after age 25 in women with BRCA mutations and at least 8 years after chest radiation is completed.²⁶ There is a reduction in breast cancer incidence of 90%.²⁵ Breast imaging for screening (mammography or MRI) is not indicated after risk-reducing mastectomy. However, clinical breast examinations of the surgical site are important, because there is a small risk of developing breast cancer in that area.²⁶

Risk-reducing oophorectomy is the standard of care for women with BRCA mutations to reduce the risk of ovarian cancer. It can also reduce the risk of breast cancer in women with BRCA mutations.²⁷

Continue to: CASE

CASE

Based on her risk assessment results, family history, and genetic heritage, Ms. P qualifies for referral to a genetic counselor for discussion of BRCA testing. The clinician discusses adding annual MRI to Ms. P’s breast cancer screening regimen, based on ACS, NCCN, and ACR recommendations, due to her 20.4% lifetime risk. Discussion of whether and when to start chemoprophylaxis is typically based on breast cancer risk, projected benefit, and the potential impact of medication adverse effects. A high-risk woman is eligible for 5 years of chemoprophylaxis (tamoxifen if premenopausal) based on her lifetime risk. The clinician discusses timing with Ms. P, and even though she is finished with childbearing, she would like to wait until she is age 45, which is before the age at which her aunt was given a diagnosis of breast cancer.

Conclusion

Primary care clinicians are well positioned to identify women with an elevated risk of breast cancer and refer them for enhanced screening and chemoprophylaxis (see ALGORITHM). Shared decision-making with the inclusion of patient decision aids (https://decisionaid.ohri.ca/AZsearch.php?criteria=breast+cancer) about genetic testing, chemoprophylaxis, and prophylactic mastectomy or oophorectomy may help women at intermediate or high risk of breast cancer feel empowered to make decisions about their breast—and overall—health.

CORRESPONDENCE
Sarina Schrager, MD, MS, Professor, Department of Family Medicine and Community Health, University of Wisconsin, 1100 Delaplaine Court, Madison, WI 53715; [email protected]

Breast cancer is the most common invasive cancer in women in the United States; it is estimated that there will be 287,850 new cases of breast cancer in the United States during 2022 with 43,250 deaths.¹ Lives are extended and saved every day because of a robust arsenal of treatments and interventions available to those who have been given a diagnosis of breast cancer. And, of course, lives are also extended and saved when we identify women at risk and provide early interventions. But in busy offices where time is short and there are competing demands on our time, proper assessment of a woman’s risk of breast cancer does not always happen. As a result, women with a higher risk of breast cancer may not be getting appropriate management.^2,3

Familiarizing yourself with several risk-assessment tools and knowing when genetic testing is needed can make a big difference. Knowing the timing of mammograms and magnetic resonance imaging (MRI) for women deemed to be at high risk is also key. The following review employs a case-based approach (with an accompanying ALGORITHM) to illustrate how best to identify women who are at heightened risk of breast cancer and maximize their care. We also discuss the chemoprophylaxis regimens that may be used for those at increased risk.

CASE

Rachel P, age 37, presents to establish care. She has an Ashkenazi Jewish background and wonders if she should start doing breast cancer screening before age 40. She has 2 children, ages 4 years and 2 years. Her maternal aunt had unilateral breast cancer at age 54, and her maternal grandmother died of ovarian cancer at age 65.

Risk assessment

The risk assessment process (see ALGORITHM) must start with either the clinician or the patient initiating the discussion about breast cancer risk. The clinician may initiate the discussion with a new patient or at an annual physical examination. The patient may start the discussion because they are experiencing new breast symptoms, have anxiety about developing breast cancer, or have a family member with a new cancer diagnosis.

Risk factors. There are single factors that convey enough risk to automatically designate the patient as high risk (see TABLE 1^4-9). These factors include having a history of chest radiation between the ages of 10 and 30, a history of breast biopsy with either lobular carcinoma in situ (LCIS) or atypical ductal hyperplasia (ADH), past breast and/or ovarian cancer, and either a family or personal history of a high penetrant genetic variant for breast cancer.^4-9

In women with previous chest radiation, breast cancer risk correlates with the total dose of radiation.⁵ For women with a personal history of breast cancer, the younger the age at diagnosis, the higher the risk of contralateral breast cancer.⁵ Precancerous changes such as ADH, LCIS, and ductal carcinoma in situ (DCIS) also confer moderate increases in risk. Women with these diagnoses will commonly have follow-up with specialists.

Risk assessment tools. There are several models available to assess a woman’s breast cancer risk (see TABLE 2^10-12). The Gail model (https://bcrisktool.cancer.gov/) is the oldest, quickest, and most widely known. However, the Gail model only accounts for first-degree relatives diagnosed with breast cancer, may underpredict risk in women with a more extensive family history, and has not been studied in women younger than 35. The International Breast Cancer Intervention Study (IBIS) Risk Evaluation Tool (https://ibis-risk-calculator.magview.com/), commonly referred to as the Tyrer-Cuzick model, incorporates second-degree relatives into the prediction model—although women may not know their full family history. Both the IBIS and the Breast Cancer Surveillance Consortium (BCSC) model (https://tools.bcsc-scc.org/BC5yearRisk/intro.htm) include breast density in the prediction algorithm. The choice of tool depends on clinician comfort and individual patient risk factors. There is no evidence that one model is better than another.^10-12

Continue to: CASE

CASE

Ms. P’s clinician starts with an assessment using the Gail model. However, when the result comes back with average risk, the clinician decides to follow up with the Tyrer-Cuzick model in order to incorporate Ms. P’s multiple ­second-degree relatives with breast and ovarian cancer. (The BCSC model was not used because it only includes first-degree relatives.)

Genetic testing

The National Comprehensive Cancer Network (NCCN) guidelines recommend genetic testing if a woman has a first- or ­second-degree relative with pancreatic cancer, metastatic prostate cancer, male breast cancer, breast cancer at age 45 or younger, 2 or more breast cancers in a single person, 2 or more people on the same side of the family with at least 1 diagnosed at age 50 or younger, or any relative with ovarian cancer (see TABLE 3).⁷ Before ordering genetic testing, it is useful to refer the patient to a genetic counselor for a thorough discussion of options.

Results of genetic testing may include high-risk variants, moderate-risk variants, and variants of unknown significance (VUS), or be negative for any variants. High-risk variants for breast cancer include BRCA1, BRCA2, PALB2, and cancer syndrome variants such as TP53, PTEN, STK11, and CDH1.^5,6,9,13-15 These high-risk variants confer sufficient risk that women with these mutations are automatically categorized in the high-risk group. It is estimated that high-risk variants account for only 25% of the genetic risk for breast cancer.¹⁶

BRCA1/2 and PTEN mutations confer greater than 80% lifetime risk, while other high-risk variants such as TP53, CDH1, and STK11 confer risks between 25% and 40%. These variants are also associated with cancers of other organs, depending on the mutation.¹⁷

Moderate-risk variants—ATM and CHEK2—do not confer sufficient risk to elevate women into the high-risk group. However, they do qualify these intermediate-risk women to participate in a specialized management strategy.^5,9,13,18

VUS are those for which the associated risk is unclear, but more research may be done to categorize the risk.⁹ The clinical management of women with VUS usually entails close monitoring.

In an effort to better characterize breast cancer risk using a combination of pathogenic variants found in broad multi-gene cancer predisposition panels, researchers have developed a method to combine risks in a “polygenic risk score” (PRS) that can be used to counsel women (see “What is a polygenic risk score for breast cancer?” on page 203).^19-21PRS predicts an additional 18% of genetic risk in women of European descent.²¹

Continue to: CASE

CASE

Using the assessment results, the clinician talks to Ms. P about her lifetime risk for breast cancer. The Gail model indicates her lifetime risk is 13.3%, just slightly higher than the average (12.5%), and her 5-year risk is 0.5% (average, 0.4%). The IBIS or Tyrer-­Cuzick model, which takes into account her second-degree relatives with breast and ovarian cancer and her Ashkenazi ethnicity (which confers increased risk due to elevated risk of BRCA mutations), predicts her lifetime risk of breast cancer to be 20.4%. This categorizes Ms. P as high risk.

Enhanced screening recommendations for women at high risk

TABLE 4^8,13,22 summarizes screening recommendations for women deemed to be at high risk for breast cancer. The American Cancer Society (ACS), NCCN, and the American College of Radiology (ACR) recommend that women with at least a 20% lifetime risk have yearly magnetic resonance imaging (MRI) and mammography (staggered so that the patient has 1 test every 6 months) starting 10 years before the age of onset for the youngest affected relative but not before age 30.⁸ For carriers of high-risk (as well as intermediate-risk) genes, NCCN recommends annual MRI screening starting at age 40.¹³BRCA1/2 screening includes annual MRI starting at age 25 and annual mammography every 6 months starting at age 30.²² Clinicians should counsel women with moderate risk factors (elevated breast density; personal history of ADH, LCIS, or DCIS) about the potential risks and benefits of enhanced screening and chemoprophylaxis.

Risk-reduction strategies

Chemoprophylaxis

The US Preventive Services Task Force (USPSTF) recommends that all women at increased risk for breast cancer consider chemoprophylaxis (B recommendation)²³ based on convincing evidence that 5 years of treatment with either a synthetic estrogen reuptake modulator (SERM) or an aromatase inhibitor (AI) decreases the incidence of estrogen receptor positive breast cancers. (See TABLE 5^7,23,24 for absolute risk reduction.) There is no benefit for chemoprophylaxis in women at average risk (D recommendation).²³ It is unclear whether chemoprophylaxis is indicated in women with moderate increased risk (ie, who do not meet the 20% lifetime risk criteria). Chemoprophylaxis may not be effective in women with BRCA1 mutations, as they often develop triple-negative breast cancers.

Accurate risk assessment and shared decision-making enable the clinician and patient to discuss the potential risks and benefits of chemoprophylaxis.^7,24 The USPSTF did not find that any 1 risk prediction tool was better than another to identify women who should be counseled about chemoprophylaxis. Clinicians should counsel all women taking AIs about optimizing bone health with adequate calcium and vitamin D intake and routine bone density tests.

Surgical risk reduction

The NCCN guidelines state that risk-reducing bilateral mastectomy is reserved for individuals with high-risk gene variants and individuals with prior chest radiation between ages 10 and 30.²⁵ NCCN also recommends discussing risk-reducing mastectomy with all women with BRCA mutations.²²

Risk-reducing oophorectomy is the standard of care for women with BRCA mutations to reduce the risk of ovarian cancer.

Bilateral mastectomy is the most effective method to reduce breast cancer risk and should be discussed after age 25 in women with BRCA mutations and at least 8 years after chest radiation is completed.²⁶ There is a reduction in breast cancer incidence of 90%.²⁵ Breast imaging for screening (mammography or MRI) is not indicated after risk-reducing mastectomy. However, clinical breast examinations of the surgical site are important, because there is a small risk of developing breast cancer in that area.²⁶

Risk-reducing oophorectomy is the standard of care for women with BRCA mutations to reduce the risk of ovarian cancer. It can also reduce the risk of breast cancer in women with BRCA mutations.²⁷

Continue to: CASE

CASE

Based on her risk assessment results, family history, and genetic heritage, Ms. P qualifies for referral to a genetic counselor for discussion of BRCA testing. The clinician discusses adding annual MRI to Ms. P’s breast cancer screening regimen, based on ACS, NCCN, and ACR recommendations, due to her 20.4% lifetime risk. Discussion of whether and when to start chemoprophylaxis is typically based on breast cancer risk, projected benefit, and the potential impact of medication adverse effects. A high-risk woman is eligible for 5 years of chemoprophylaxis (tamoxifen if premenopausal) based on her lifetime risk. The clinician discusses timing with Ms. P, and even though she is finished with childbearing, she would like to wait until she is age 45, which is before the age at which her aunt was given a diagnosis of breast cancer.

Conclusion

Primary care clinicians are well positioned to identify women with an elevated risk of breast cancer and refer them for enhanced screening and chemoprophylaxis (see ALGORITHM). Shared decision-making with the inclusion of patient decision aids (https://decisionaid.ohri.ca/AZsearch.php?criteria=breast+cancer) about genetic testing, chemoprophylaxis, and prophylactic mastectomy or oophorectomy may help women at intermediate or high risk of breast cancer feel empowered to make decisions about their breast—and overall—health.

CORRESPONDENCE
Sarina Schrager, MD, MS, Professor, Department of Family Medicine and Community Health, University of Wisconsin, 1100 Delaplaine Court, Madison, WI 53715; [email protected]

THE CASE

A 78-year-old woman with a past medical history of hypertension, hyperlipidemia, osteoarthritis, and osteopenia was brought to the emergency department (ED) by her daughter. The woman had fallen 2 days earlier and had been experiencing a change in mental status (confusion) for the previous 4 days. Prior to her change in mental status, the patient had been independent in all activities of daily living and instrumental activities of daily living.

Her daughter could not recall any symptoms of illness; new or recently changed medications; complaints of pain, constipation, diarrhea, urinary frequency, or hematuria; or changes in continence prior to the onset of her mother’s confusion.

The patient’s medications included amlodipine, atorvastatin, calcium/vitamin D, and acetaminophen (as needed). In the ED, her vital signs were normal, and her cardiopulmonary and abdominal exams were unremarkable. A limited neurologic exam showed that the patient was oriented only to person and could not answer questions about her symptoms or follow commands. She could move all of her extremities equally and could ambulate; she had no facial asymmetry or slurred speech. Her exam was negative for orthostatic hypotension.

Her complete blood count, comprehensive metabolic panel, and troponin levels were normal. Her electrocardiogram showed normal sinus rhythm with no abnormalities. X-rays of her right hip and elbow were negative for fracture. Computed tomography of her head was negative for acute findings, and a chest x-ray was normal.

Her urinalysis showed many bacteria and large leukocyte esterase, and a urine culture was sent out. She was hemodynamically stable and there were no known urinary symptoms, so no empiric antibiotics were started. She was admitted for further evaluation of her altered mental status (AMS).

On our service, she was given intravenous fluids, and oral intake was encouraged. She had normal levels of B12, folic acid, and thyroid-stimulating hormone. She was negative for HIV and syphilis. Acute coronary syndrome was ruled out with normal electrocardiograms and troponin levels. Her telemetry showed a normal sinus rhythm.

After 2 days, her vital signs and labs remained stable and no other abnormalities were found; however, she had not returned to her baseline mental status. Then the urine culture returned with > 10⁵ CFU/mL of Escherichia coli, prompting a resident to curbside me (AP) and ask: “I shouldn’t treat this patient based on her urine culture—she’s just colonized, right? Or should I treat her because she’s altered?”

Continue to: THE CHALLENGE

Identifying and managing urinary tract infections (UTIs) in older adults often presents a challenge, further complicated if patients have AMS or cognitive impairment and are unable to confirm or deny urinary symptoms.

Consider, for instance, the definition of symptomatic UTI: significant bacteriuria (≥ 10⁵ CFU/mL) and pyuria (> 10 WBC/hpf) with UTI-specific symptoms (fever, acute dysuria, new or worsening urgency or frequency, new urinary incontinence, gross hematuria, and suprapubic or costovertebral angle pain or tenderness).¹ In older adults, these parameters require a more careful look.

For instance, while we use the cutoff of ≥ 10⁵ CFU/mL to define “significant” bacteriuria, the truth is that we don’t know the colony count threshold that can help identify patients who are at risk of serious illness and might benefit from antibiotic treatment.²

After reviewing the culture results, clinicians then face 2 specific challenges: differentiating between acute vs chronic symptoms and related vs unrelated symptoms in the older adult population.

Challenge 1: There is a high prevalence of chronic genitourinary symptoms in older adults that can sometimes make it hard to distinguish between an acute UTI and the acute recognition of a chronic, non-UTI problem.¹

Continue to: Challenge 2

Challenge 2: There is a high prevalence of multimorbidity in older adults. For instance, diuretics for heart failure can cause UTI-specific symptoms such as urinary urgency, frequency, and even incontinence. Cognitive impairment can make it difficult to obtain the key components of the history needed to make a UTI diagnosis.¹

Lastly, there are aspects of normal aging physiology that complicate the detection of infections, such as the fact that older adults may not mount a “true” fever to meet criteria for a symptomatic UTI. Therefore, fever in institutionalized or frail community-dwelling older adults has been redefined as an oral temperature ≥ 100 °F, 2 repeated oral temperatures > 99 °F, or an increase in temperature ≥ 2 °F from baseline.³

So how to proceed with our case patient? The following questions helped guide the approach to her care.

Is this patient asymptomatic?

Yes. The patient presented with nonspecific symptoms (falls and delirium) with bacteriuria suggesting asymptomatic bacteriuria (ASB). These symptoms are referred to as geriatric syndromes that, by definition, are “multifactorial health conditions that occur when the accumulated effects of impairments in multiple systems render an older person vulnerable to situational challenges.”⁴

There are aspects of normal aging physiology that complicate the detection of infections, such as the fact that older adults may not mount a “true” fever to meet criteria for a symptomatic UTI.

As geriatric syndromes, falls and delirium are unlikely to be caused by one process, such as a UTI, but rather from multiple morbid processes. It is also important to note that there is no evidence to support a causal relationship between bacteriuria and delirium or that antibiotic treatment of bacteriuria improves delirium.^2,5

Continue to: So, while we could...

So, while we could have diagnosed a UTI in this older adult with bacteriuria and delirium, it would have been premature closure and an incomplete assessment. We would have risked potentially missing other significant causes of her delirium and unnecessarily exposing the patient to antibiotics.

Are antibiotics generally useful in older adults who you believe to be asymptomatic with a urine culture showing bacteriuria?

No. The goal of antibiotic treatment for a symptomatic UTI is to ameliorate symptoms; therefore, there is no indication for antibiotics in ASB and no evidence of survival benefit.² And, as noted earlier, there is no evidence to support a causal relationship between bacteriuria and delirium or that antibiotic treatment of bacteriuria improves delirium.^2,5

The use of antibiotics in the asymptomatic setting will eradicate any bacteriuria but also increase the risk of reinfection, resistant organisms, antibiotic adverse reactions, and medication interactions.¹

What is the recommendation for management of nonspecific symptoms, such as delirium and falls, in a geriatric patient such as this one with bacteriuria?

The Infectious Diseases Society of America (IDSA)’s 2019 Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria recommends a thorough assessment (for other causes) and careful observation, rather than immediate antimicrobial treatment and cessation of evaluation for other causes.⁵ (IDSA made this recommendation based on low-quality evidence.) The group found a high certainty of harm and low certainty of benefit in treating older adults with antibiotics for ASB.

This recommendation highlights the key geriatric principle of “geriatric syndromes” and the multifactorial nature of findings such as delirium and falls. It encourages clinicians to continue their thorough assessment for other causes in addition to bacteriuria.⁵ Even in the event that antibiotics are immediately initiated, we would recommend avoiding premature closure and continuing to evaluate for other causes.

Continue to: It is reasonable to...

It is reasonable to obtain a dipstick if, after the observation period (1-7 days, with earlier follow-up for frail patients), the patient continues to have the nonspecific symptoms.¹ If the dipstick is negative, there is no need for further evaluation of UTI. If it’s positive, then it’s appropriate to send for urinalysis and urine culture.¹

I emphasized that we were treating bacteriuria with persisting delirium without any other etiology identified.

If the urine culture is negative, continue looking for other etiologies. If it’s positive, but there is resolution of symptoms, there is no need to treat. If it’s positive and symptoms persist, consider antibiotic treatment.¹

CASE RESOLUTION

The team closely monitored the patient and delayed empiric antibiotics while continuing the AMS work-up. After 2 days in the hospital, her delirium persisted, but she had no UTI-specific symptoms and she remained hemodynamically stable.

I (AP) recommended antibiotic treatment guided by the urine culture sensitivity report: initially 1 g of ceftriaxone IV q24h with transition (after symptom improvement and prior to discharge) to oral trimethoprim/sulfamethoxazole 160 mg/800 mg q12h, for a total of 10 days of treatment. I emphasized that we were treating bacteriuria with persisting delirium without any other etiology identified. The patient returned to her baseline mental status after a few days of treatment and was discharged home.

THE TAKEAWAY

Avoid premature closure by stopping at the diagnosis of a “UTI” in an older adult with nonspecific symptoms and bacteriuria to avoid the risk of overlooking other important and potentially life-threatening causes of the patient’s signs and symptoms.

CORRESPONDENCE
L. Amanda Perry, MD, 1919 West Taylor Street, Mail Code 663, Chicago, IL 60612; [email protected]

THE CASE

A 78-year-old woman with a past medical history of hypertension, hyperlipidemia, osteoarthritis, and osteopenia was brought to the emergency department (ED) by her daughter. The woman had fallen 2 days earlier and had been experiencing a change in mental status (confusion) for the previous 4 days. Prior to her change in mental status, the patient had been independent in all activities of daily living and instrumental activities of daily living.

Her daughter could not recall any symptoms of illness; new or recently changed medications; complaints of pain, constipation, diarrhea, urinary frequency, or hematuria; or changes in continence prior to the onset of her mother’s confusion.

The patient’s medications included amlodipine, atorvastatin, calcium/vitamin D, and acetaminophen (as needed). In the ED, her vital signs were normal, and her cardiopulmonary and abdominal exams were unremarkable. A limited neurologic exam showed that the patient was oriented only to person and could not answer questions about her symptoms or follow commands. She could move all of her extremities equally and could ambulate; she had no facial asymmetry or slurred speech. Her exam was negative for orthostatic hypotension.

Her complete blood count, comprehensive metabolic panel, and troponin levels were normal. Her electrocardiogram showed normal sinus rhythm with no abnormalities. X-rays of her right hip and elbow were negative for fracture. Computed tomography of her head was negative for acute findings, and a chest x-ray was normal.

Her urinalysis showed many bacteria and large leukocyte esterase, and a urine culture was sent out. She was hemodynamically stable and there were no known urinary symptoms, so no empiric antibiotics were started. She was admitted for further evaluation of her altered mental status (AMS).

On our service, she was given intravenous fluids, and oral intake was encouraged. She had normal levels of B12, folic acid, and thyroid-stimulating hormone. She was negative for HIV and syphilis. Acute coronary syndrome was ruled out with normal electrocardiograms and troponin levels. Her telemetry showed a normal sinus rhythm.

After 2 days, her vital signs and labs remained stable and no other abnormalities were found; however, she had not returned to her baseline mental status. Then the urine culture returned with > 10⁵ CFU/mL of Escherichia coli, prompting a resident to curbside me (AP) and ask: “I shouldn’t treat this patient based on her urine culture—she’s just colonized, right? Or should I treat her because she’s altered?”

Continue to: THE CHALLENGE

Identifying and managing urinary tract infections (UTIs) in older adults often presents a challenge, further complicated if patients have AMS or cognitive impairment and are unable to confirm or deny urinary symptoms.

Consider, for instance, the definition of symptomatic UTI: significant bacteriuria (≥ 10⁵ CFU/mL) and pyuria (> 10 WBC/hpf) with UTI-specific symptoms (fever, acute dysuria, new or worsening urgency or frequency, new urinary incontinence, gross hematuria, and suprapubic or costovertebral angle pain or tenderness).¹ In older adults, these parameters require a more careful look.

For instance, while we use the cutoff of ≥ 10⁵ CFU/mL to define “significant” bacteriuria, the truth is that we don’t know the colony count threshold that can help identify patients who are at risk of serious illness and might benefit from antibiotic treatment.²

After reviewing the culture results, clinicians then face 2 specific challenges: differentiating between acute vs chronic symptoms and related vs unrelated symptoms in the older adult population.

Challenge 1: There is a high prevalence of chronic genitourinary symptoms in older adults that can sometimes make it hard to distinguish between an acute UTI and the acute recognition of a chronic, non-UTI problem.¹

Continue to: Challenge 2

Challenge 2: There is a high prevalence of multimorbidity in older adults. For instance, diuretics for heart failure can cause UTI-specific symptoms such as urinary urgency, frequency, and even incontinence. Cognitive impairment can make it difficult to obtain the key components of the history needed to make a UTI diagnosis.¹

Lastly, there are aspects of normal aging physiology that complicate the detection of infections, such as the fact that older adults may not mount a “true” fever to meet criteria for a symptomatic UTI. Therefore, fever in institutionalized or frail community-dwelling older adults has been redefined as an oral temperature ≥ 100 °F, 2 repeated oral temperatures > 99 °F, or an increase in temperature ≥ 2 °F from baseline.³

So how to proceed with our case patient? The following questions helped guide the approach to her care.

Is this patient asymptomatic?

Yes. The patient presented with nonspecific symptoms (falls and delirium) with bacteriuria suggesting asymptomatic bacteriuria (ASB). These symptoms are referred to as geriatric syndromes that, by definition, are “multifactorial health conditions that occur when the accumulated effects of impairments in multiple systems render an older person vulnerable to situational challenges.”⁴

There are aspects of normal aging physiology that complicate the detection of infections, such as the fact that older adults may not mount a “true” fever to meet criteria for a symptomatic UTI.

As geriatric syndromes, falls and delirium are unlikely to be caused by one process, such as a UTI, but rather from multiple morbid processes. It is also important to note that there is no evidence to support a causal relationship between bacteriuria and delirium or that antibiotic treatment of bacteriuria improves delirium.^2,5

Continue to: So, while we could...

So, while we could have diagnosed a UTI in this older adult with bacteriuria and delirium, it would have been premature closure and an incomplete assessment. We would have risked potentially missing other significant causes of her delirium and unnecessarily exposing the patient to antibiotics.

Are antibiotics generally useful in older adults who you believe to be asymptomatic with a urine culture showing bacteriuria?

No. The goal of antibiotic treatment for a symptomatic UTI is to ameliorate symptoms; therefore, there is no indication for antibiotics in ASB and no evidence of survival benefit.² And, as noted earlier, there is no evidence to support a causal relationship between bacteriuria and delirium or that antibiotic treatment of bacteriuria improves delirium.^2,5

The use of antibiotics in the asymptomatic setting will eradicate any bacteriuria but also increase the risk of reinfection, resistant organisms, antibiotic adverse reactions, and medication interactions.¹

What is the recommendation for management of nonspecific symptoms, such as delirium and falls, in a geriatric patient such as this one with bacteriuria?

The Infectious Diseases Society of America (IDSA)’s 2019 Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria recommends a thorough assessment (for other causes) and careful observation, rather than immediate antimicrobial treatment and cessation of evaluation for other causes.⁵ (IDSA made this recommendation based on low-quality evidence.) The group found a high certainty of harm and low certainty of benefit in treating older adults with antibiotics for ASB.

This recommendation highlights the key geriatric principle of “geriatric syndromes” and the multifactorial nature of findings such as delirium and falls. It encourages clinicians to continue their thorough assessment for other causes in addition to bacteriuria.⁵ Even in the event that antibiotics are immediately initiated, we would recommend avoiding premature closure and continuing to evaluate for other causes.

Continue to: It is reasonable to...

It is reasonable to obtain a dipstick if, after the observation period (1-7 days, with earlier follow-up for frail patients), the patient continues to have the nonspecific symptoms.¹ If the dipstick is negative, there is no need for further evaluation of UTI. If it’s positive, then it’s appropriate to send for urinalysis and urine culture.¹

I emphasized that we were treating bacteriuria with persisting delirium without any other etiology identified.

If the urine culture is negative, continue looking for other etiologies. If it’s positive, but there is resolution of symptoms, there is no need to treat. If it’s positive and symptoms persist, consider antibiotic treatment.¹

CASE RESOLUTION

The team closely monitored the patient and delayed empiric antibiotics while continuing the AMS work-up. After 2 days in the hospital, her delirium persisted, but she had no UTI-specific symptoms and she remained hemodynamically stable.

I (AP) recommended antibiotic treatment guided by the urine culture sensitivity report: initially 1 g of ceftriaxone IV q24h with transition (after symptom improvement and prior to discharge) to oral trimethoprim/sulfamethoxazole 160 mg/800 mg q12h, for a total of 10 days of treatment. I emphasized that we were treating bacteriuria with persisting delirium without any other etiology identified. The patient returned to her baseline mental status after a few days of treatment and was discharged home.

THE TAKEAWAY

Avoid premature closure by stopping at the diagnosis of a “UTI” in an older adult with nonspecific symptoms and bacteriuria to avoid the risk of overlooking other important and potentially life-threatening causes of the patient’s signs and symptoms.

CORRESPONDENCE
L. Amanda Perry, MD, 1919 West Taylor Street, Mail Code 663, Chicago, IL 60612; [email protected]

THE CASE

A 78-year-old woman with a past medical history of hypertension, hyperlipidemia, osteoarthritis, and osteopenia was brought to the emergency department (ED) by her daughter. The woman had fallen 2 days earlier and had been experiencing a change in mental status (confusion) for the previous 4 days. Prior to her change in mental status, the patient had been independent in all activities of daily living and instrumental activities of daily living.

Her daughter could not recall any symptoms of illness; new or recently changed medications; complaints of pain, constipation, diarrhea, urinary frequency, or hematuria; or changes in continence prior to the onset of her mother’s confusion.

The patient’s medications included amlodipine, atorvastatin, calcium/vitamin D, and acetaminophen (as needed). In the ED, her vital signs were normal, and her cardiopulmonary and abdominal exams were unremarkable. A limited neurologic exam showed that the patient was oriented only to person and could not answer questions about her symptoms or follow commands. She could move all of her extremities equally and could ambulate; she had no facial asymmetry or slurred speech. Her exam was negative for orthostatic hypotension.

Her complete blood count, comprehensive metabolic panel, and troponin levels were normal. Her electrocardiogram showed normal sinus rhythm with no abnormalities. X-rays of her right hip and elbow were negative for fracture. Computed tomography of her head was negative for acute findings, and a chest x-ray was normal.

Her urinalysis showed many bacteria and large leukocyte esterase, and a urine culture was sent out. She was hemodynamically stable and there were no known urinary symptoms, so no empiric antibiotics were started. She was admitted for further evaluation of her altered mental status (AMS).

On our service, she was given intravenous fluids, and oral intake was encouraged. She had normal levels of B12, folic acid, and thyroid-stimulating hormone. She was negative for HIV and syphilis. Acute coronary syndrome was ruled out with normal electrocardiograms and troponin levels. Her telemetry showed a normal sinus rhythm.

After 2 days, her vital signs and labs remained stable and no other abnormalities were found; however, she had not returned to her baseline mental status. Then the urine culture returned with > 10⁵ CFU/mL of Escherichia coli, prompting a resident to curbside me (AP) and ask: “I shouldn’t treat this patient based on her urine culture—she’s just colonized, right? Or should I treat her because she’s altered?”

Continue to: THE CHALLENGE

Identifying and managing urinary tract infections (UTIs) in older adults often presents a challenge, further complicated if patients have AMS or cognitive impairment and are unable to confirm or deny urinary symptoms.

Consider, for instance, the definition of symptomatic UTI: significant bacteriuria (≥ 10⁵ CFU/mL) and pyuria (> 10 WBC/hpf) with UTI-specific symptoms (fever, acute dysuria, new or worsening urgency or frequency, new urinary incontinence, gross hematuria, and suprapubic or costovertebral angle pain or tenderness).¹ In older adults, these parameters require a more careful look.

For instance, while we use the cutoff of ≥ 10⁵ CFU/mL to define “significant” bacteriuria, the truth is that we don’t know the colony count threshold that can help identify patients who are at risk of serious illness and might benefit from antibiotic treatment.²

After reviewing the culture results, clinicians then face 2 specific challenges: differentiating between acute vs chronic symptoms and related vs unrelated symptoms in the older adult population.

Challenge 1: There is a high prevalence of chronic genitourinary symptoms in older adults that can sometimes make it hard to distinguish between an acute UTI and the acute recognition of a chronic, non-UTI problem.¹

Continue to: Challenge 2

Challenge 2: There is a high prevalence of multimorbidity in older adults. For instance, diuretics for heart failure can cause UTI-specific symptoms such as urinary urgency, frequency, and even incontinence. Cognitive impairment can make it difficult to obtain the key components of the history needed to make a UTI diagnosis.¹

Lastly, there are aspects of normal aging physiology that complicate the detection of infections, such as the fact that older adults may not mount a “true” fever to meet criteria for a symptomatic UTI. Therefore, fever in institutionalized or frail community-dwelling older adults has been redefined as an oral temperature ≥ 100 °F, 2 repeated oral temperatures > 99 °F, or an increase in temperature ≥ 2 °F from baseline.³

So how to proceed with our case patient? The following questions helped guide the approach to her care.

Is this patient asymptomatic?

Yes. The patient presented with nonspecific symptoms (falls and delirium) with bacteriuria suggesting asymptomatic bacteriuria (ASB). These symptoms are referred to as geriatric syndromes that, by definition, are “multifactorial health conditions that occur when the accumulated effects of impairments in multiple systems render an older person vulnerable to situational challenges.”⁴

There are aspects of normal aging physiology that complicate the detection of infections, such as the fact that older adults may not mount a “true” fever to meet criteria for a symptomatic UTI.

As geriatric syndromes, falls and delirium are unlikely to be caused by one process, such as a UTI, but rather from multiple morbid processes. It is also important to note that there is no evidence to support a causal relationship between bacteriuria and delirium or that antibiotic treatment of bacteriuria improves delirium.^2,5

Continue to: So, while we could...

So, while we could have diagnosed a UTI in this older adult with bacteriuria and delirium, it would have been premature closure and an incomplete assessment. We would have risked potentially missing other significant causes of her delirium and unnecessarily exposing the patient to antibiotics.

Are antibiotics generally useful in older adults who you believe to be asymptomatic with a urine culture showing bacteriuria?

No. The goal of antibiotic treatment for a symptomatic UTI is to ameliorate symptoms; therefore, there is no indication for antibiotics in ASB and no evidence of survival benefit.² And, as noted earlier, there is no evidence to support a causal relationship between bacteriuria and delirium or that antibiotic treatment of bacteriuria improves delirium.^2,5

The use of antibiotics in the asymptomatic setting will eradicate any bacteriuria but also increase the risk of reinfection, resistant organisms, antibiotic adverse reactions, and medication interactions.¹

What is the recommendation for management of nonspecific symptoms, such as delirium and falls, in a geriatric patient such as this one with bacteriuria?

The Infectious Diseases Society of America (IDSA)’s 2019 Clinical Practice Guideline for the Management of Asymptomatic Bacteriuria recommends a thorough assessment (for other causes) and careful observation, rather than immediate antimicrobial treatment and cessation of evaluation for other causes.⁵ (IDSA made this recommendation based on low-quality evidence.) The group found a high certainty of harm and low certainty of benefit in treating older adults with antibiotics for ASB.

This recommendation highlights the key geriatric principle of “geriatric syndromes” and the multifactorial nature of findings such as delirium and falls. It encourages clinicians to continue their thorough assessment for other causes in addition to bacteriuria.⁵ Even in the event that antibiotics are immediately initiated, we would recommend avoiding premature closure and continuing to evaluate for other causes.

Continue to: It is reasonable to...

It is reasonable to obtain a dipstick if, after the observation period (1-7 days, with earlier follow-up for frail patients), the patient continues to have the nonspecific symptoms.¹ If the dipstick is negative, there is no need for further evaluation of UTI. If it’s positive, then it’s appropriate to send for urinalysis and urine culture.¹

I emphasized that we were treating bacteriuria with persisting delirium without any other etiology identified.

If the urine culture is negative, continue looking for other etiologies. If it’s positive, but there is resolution of symptoms, there is no need to treat. If it’s positive and symptoms persist, consider antibiotic treatment.¹

CASE RESOLUTION

The team closely monitored the patient and delayed empiric antibiotics while continuing the AMS work-up. After 2 days in the hospital, her delirium persisted, but she had no UTI-specific symptoms and she remained hemodynamically stable.

I (AP) recommended antibiotic treatment guided by the urine culture sensitivity report: initially 1 g of ceftriaxone IV q24h with transition (after symptom improvement and prior to discharge) to oral trimethoprim/sulfamethoxazole 160 mg/800 mg q12h, for a total of 10 days of treatment. I emphasized that we were treating bacteriuria with persisting delirium without any other etiology identified. The patient returned to her baseline mental status after a few days of treatment and was discharged home.

THE TAKEAWAY

Avoid premature closure by stopping at the diagnosis of a “UTI” in an older adult with nonspecific symptoms and bacteriuria to avoid the risk of overlooking other important and potentially life-threatening causes of the patient’s signs and symptoms.

CORRESPONDENCE
L. Amanda Perry, MD, 1919 West Taylor Street, Mail Code 663, Chicago, IL 60612; [email protected]

Three conditions seen in primary care—gastroesophageal reflux disease (GERD), Helicobacter pylori (H pylori) infection, and Barrett esophagus (BE)—evolve in a gastric acid environment and are treated in part through gastric acid suppression. While GERD is a risk factor for the development of BE, H pylori is not associated with BE.¹ Patients with H pylori are actually less likely to have GERD symptoms.^2,3 In this article, we describe similarities and differences in patient presentations, diagnostic testing, and management, and review screening recommendations.

Gastroesophageal reflux disease

GERD is a clinical diagnosis based on symptoms of regurgitation and heartburn or the presence of one of its known complications (esophagitis, peptic strictures, or BE).^2,4 Chest pain is also common. Atypical symptoms are dysphagia, bleeding, chronic cough, asthma, chronic laryngitis, hoarseness, wheezing, teeth erosions, belching, and bloating.^2,5-7

The worldwide prevalence of gastroesophageal reflux symptoms in adults is 14.8%.⁸ When using a stringent definition of GERD—weekly symptoms occurring for at least 3 months—prevalence drops to 9.4%.⁹ GERD symptoms vary markedly by geographic location; the highest rates are in Central America (19.6%) and the lowest rates are in Southeast Asia (7.4%).⁸TABLE 1^2,9-11 lists risk factors for GERD.

GERD results from dysfunction of the esophagogastric junction that permits regurgitation of acidic gastric contents into the esophagus. Normally, the lower esophageal sphincter (LES) relaxes temporarily with gastric distention; when this relaxation is frequent and prolonged, it causes GERD.^2,12 Several medications, particularly those with anticholinergic effects (eg, tricyclic antidepressants) can decrease LES tone and contribute to symptoms. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often linked to dyspepsia and gastritis and should be avoided in patients who have symptoms of GERD. Pathologic reflux can also occur in conditions that increase intra-abdominal pressure, such as obesity and pregnancy, and with esophageal dysmotility, hiatal hernia, and delayed gastric emptying.⁵ When gastric contents travel proximally, this contributes to extraesophageal symptoms, such as chronic cough, asthma, laryngitis, dyspepsia, bloating, and belching.^2,4

Treatment

Proton pump inhibitors (PPIs) are the most effective treatment for GERD, but lifestyle modifications are also recommended for all patients.^2,6,13-16 Consider selective elimination of beverages and foods that are commonly associated with heartburn (eg, alcohol, caffeine, chocolate, citrus, and spicy foods) if patients note a correlation to symptoms.^5,6,13 Also, advise weight loss and smoking cessation, as appropriate, and suggest that the patient elevate the head of their bed when sleeping.

All PPIs are equally effective in suppressing acid when given at equivalent doses (TABLE 2¹⁷), so they can be used interchangeably.¹⁷ Treat uncomplicated GERD with a once-daily PPI 30 to 60 minutes prior to a meal for 4 to 8 weeks. If treatment is effective, you’ll want to try to reduce or stop the medication after the 4- to 8-week period. (It’s worth noting that the benefits of treatment for those with extraesophageal GERD are less predictable than for those with heartburn or esophagitis symptoms.⁵)

If GERD symptoms reemerge after the PPI is stopped, the medication can be restarted but should be limited to the least potent effective dose, no matter if it is taken daily or only as needed.^2,6,17 In patients with esophagitis, you may need to continue PPI treatment indefinitely at the lowest possible dose given the increased risk of recurrent esophagitis.^2,13,16

Continue to: Keep in mind...

Keep in mind that the safety of long-term PPI use has not been fully established. While observational studies have shown that long-term PPI use may be associated with adverse events, including kidney damage, Clostridioides difficile infection, osteoporosis, and gastric cancer, subsequent prospective studies have not shown any significant risks with long-term PPI use.^{2,13,14,16,18,19} If a decision is made to discontinue PPIs after long-term use, the patient should be advised that rebound acid hypersecretion may occur, although this possibility can be mitigated by gradually tapering the PPI dose.

Another maintenance therapy option. Histamine-2 receptor antagonists (H2RAs) are a reasonable alternative to PPIs as maintenance therapy, but they are ineffective in healing esophagitis^6,13 and may be best used as adjunctive therapy at bedtime for breakthrough symptoms while a patient is on maintenance PPIs.^6,19 Antacids (eg, calcium carbonate, aluminum hydroxide, or magnesium hydroxide) and alginate may provide some symptomatic relief, as well.

When PPIs don’t work. If initial lifestyle changes and PPI treatment do not provide adequate relief, consider the possibility of nonadherence with medication or lifestyle directives. If nonadherence does not appear to be an issue, twice-daily PPI dosing is also an option. Recognize, though, that PPI treatment failure occurs in as many as 40% of patients and is much more common in those with atypical symptoms.⁶

Consider upper gastrointestinal (GI) endoscopy—and perhaps esophageal manometry or pH testing—if a patient does not respond to empiric treatment with a PPI for 4 to 8 weeks at a standard, once-daily dose.^2,4,13 (Alternative diagnoses may also need to be considered.) Upper endoscopy is also appropriate for patients who have symptoms concerning for malignancy (progressive dysphagia, unintentional weight loss, or bleeding).

Consider endoscopy for patients with GERD symptoms unresponsive to empiric treatment with a proton pump inhibitor.

Esophagitis detected on endoscopy confirms GERD, although it is seen in only 18% to 25% of patients with GERD symptoms.^2,4 (The absence of esophagitis only indicates a lack of mucosal injury and not the absence of GERD.⁴) Acid exposure can cause fibrotic scarring and, in turn, strictures visible on endoscopy.² BE, the precursor to esophageal adenocarcinoma, is also a complication of GERD and is defined by columnar metaplasia replacing the normal squamous cell esophageal epithelium; it is detected on pathology review of biopsies.²

Continue to: GERD confirmed but PPIs aren't working?

GERD confirmed but PPIs aren’t working? Laparoscopic fundoplication is an effective treatment for GERD. However, due to its adverse effects (dysphagia, bloating, flatulence) and risk of treatment failure or breakdown within 5 to 10 years, it should be reserved for those poorly managed with PPIs.^2,13,19

Considerations in pregnancy. GERD is reported by 40% to 85% of pregnant women,^20,21 and its clinical presentation, diagnosis, and treatment are similar to that of nonpregnant adults.²¹ If lifestyle modification is not effective, pharmacologic therapy may be considered. Often, lifestyle modifications and antacids followed by the addition of sucralfate will be used first given the lack of systemic effects. H2RAs can be used next based on long-term historical use and reported safety.²¹ As with nonpregnant patients, PPIs are more effective than other medical therapies. If PPIs are used, dexlansoprazole, lansoprazole, pantoprazole, and rabeprazole are preferred. Omeprazole and esomeprazole are typically avoided due to findings of embryonic and fetal mortality in early animal studies, although subsequent human studies have noted no teratogenicity.^2,20,21

Considerations in children. As with adults, findings in the history and exam are sufficient to diagnose and initiate treatment of GERD in children, provided there are no warning signs (eg, bilious vomiting, GI bleeding, consistent forceful vomiting, fever, lethargy, hepatosplenomegaly, bulging fontanelle, macro- or microcephaly, seizures, abdominal tenderness/distention, or genetic/metabolic syndromes). Lifestyle changes are first-line treatment, followed by medication. Acid suppressants are preferred, with PPIs showing superior efficacy compared with H2RAs.¹⁵ Some PPIs (omeprazole, lansoprazole, and esomeprazole) have US Food and Drug Administration (FDA) approval beginning at age 1 year, while rabeprazole has FDA approval beginning at age 12.²² As in adults, if PPIs are ineffective, consider alternative diagnoses.^15,22

Helicobacter pylori infection

H pylori is a gram-negative spiral-shaped bacterium found in the stomach of humans and other mammals. It survives the acidic environment by metabolizing urea into alkaline ammonia and carbon dioxide. H pylori infection increases the risk of peptic ulcer disease, gastric cancer, iron deficiency anemia, and immune thrombocytopenia. It may be associated with dyspepsia, increased ulcer risk with use of an NSAID, and chronic gastritis.⁹ Infection with H pylori can decrease the risk of GERD.² The bacterial infection causes atrophic gastritis and subsequent hypochlorhydria, which then diminishes the acidity of the reflux contents.¹⁹ There is no link between H pylori infection and BE.¹

TABLE 1^2,9-11 shows those at highest risk of H pylori. The estimated prevalence of infection is 40% to 48%²³ worldwide but lower in North America, at 32% to 42%.²⁴H pylori is often acquired in childhood, and risk of infection is more likely if the parents (particularly mothers) are infected.⁹

Continue to: Whom to test, and how

Test for H pylori in those with active peptic ulcer disease or a history of peptic ulcer disease that was not investigated for H pylori. Also test individuals who have gastric ­mucosa-associated lymphoid tissue lymphoma, have a history of gastric cancer or family history of gastric cancer, are scheduled for endoscopic evaluation for dyspepsia, or are starting chronic NSAID therapy. Patients with typical GERD symptoms do not need to be tested for H pylori.^9,25

Means of testing for H pylori include the urea breath test, stool antigen studies, endoscopically obtained biopsies, or serum antibody tests. Antibody testing is discouraged because it has a lower diagnostic utility and cannot determine if the patient’s infection is current or past. Before undergoing urea breath tests, stool antigen tests, or biopsies for H pylori identification, patients should have abstained from taking the following agents for the time periods indicated: PPIs, 1 to 2 weeks; H2RAs, at least 1 day and preferably 2 weeks; and antibiotics, 4 weeks.⁹

The single greatest predictive factor for H pylori treatment failure is antibiotic resistance, so a detailed antibiotic history is essential.

The urea breath test and endoscopically obtained biopsies have the greatest diagnostic utility and, where available, should be the first-line tests. Stool antigen studies are useful for ruling out H pylori infection (very low negative likelihood ratio), but a positive test result is not as useful for confirming an infection, as false-positives do occur (moderate positive likelihood ratio).^9,26,27 Stool antigen testing is less expensive and, in many cases, more convenient and readily available for patients than urea breath testing and endoscopic biopsies.

Treatment

Offer treatment to all patients who test positive for H pylori. Eradication rates range from 70% to 91% using first-line treatment options.⁹ Treatment regimens consist of acid suppression and 2 to 3 antibiotics in combination (TABLE 3^9,28). The single greatest predictive factor for treatment failure is antibiotic resistance, so a detailed antibiotic history is essential. In particular, ask about macrolide antibiotic usage and penicillin allergies.

People living in areas with population macrolide resistance ≥ 15% should avoid clarithromycin-based regimens unless bacterial sensitivity testing has been done and shows sensitivity to these agents.^9,28,29 For cases that do not resolve with a first-line treatment program, choose an alternative regimen with different antibiotics.^9,29

Continue to: Additionally, adequate...

Additionally, adequate acid suppression is directly related to successful eradication. Thus, the likelihood of treatment success can be improved by using higher doses of PPIs and avoiding ones that are more likely to be metabolized quickly in some patients (lansoprazole, omeprazole). Patient adherence to the treatment regimen is an important determinant of effectiveness.^9,29 Adding vitamin C 400 to 1000 mg/d, vitamin E 100 to 400 mg/d, and probiotics may improve the effectiveness of treatment.^9,30

Duration of treatment is directly related to treatment effectiveness. Whenever possible, opt for 14 days of treatment instead of just 7.⁹

Test of cure. Patients treated for H pylori should be re-tested no sooner than 4 weeks after completion of therapy. Urea breath testing, stool antigen testing, and endoscopic biopsies (if endoscopy is indicated for some other reason) can all be used post treatment for test of cure.⁹

Barrett esophagus

Chronic reflux can lead to BE, in which metaplastic columnar epithelium replaces the normal squamous epithelium lining the distal esophagus. BE is linked to dysplasia and esophageal adenocarcinoma (EAC).¹¹ Endoscopic examination with biopsy is used to diagnosis BE. The global prevalence of histology-confirmed BE in people with GERD symptoms is 7.2%.¹⁰ Similar to GERD and H pylori infections, the prevalence of BE varies significantly with geographic location (14% in North America; 3% in the Middle East).¹⁰ BE is twice as likely to occur in men as in women, and it is rare in children.¹⁰

Whom to screen

The American College of Gastroenterology recommends consideration of screening with upper endoscopy for men with chronic GERD (> 5 years) or frequent GERD symptoms (once weekly or more often), plus 2 or more of the following risk factors: age > 50 years, Caucasian race, central obesity, smoking (current or past), or a family history of BE or EAC (TABLE 1^2,9-11). Screening for BE in women is not routinely recommended but can be considered in individuals with several of the risk factors just described.

Continue to: Not everyone with BE...

Not everyone with BE experiences GERD symptoms; sometimes BE may be diagnosed incidentally on upper endoscopy performed for unrelated symptoms.¹¹ GERD patients who are currently asymptomatic and had a normal prior upper endoscopy do not require surveillance.

Diagnosis and management

BE is diagnosed based on specific endoscopic and histologic findings. The presence of dysplasia (either low grade or high grade) or its absence has important treatment implications. When histology is indefinite for dysplasia, treat reflux and, following acid suppression with PPIs for 3 to 6 months, repeat endoscopy (since reactive changes with reflux may obscure results).¹¹

Not everyone with Barrett esophagus (BE) experiences GERD symptoms; sometimes BE may be diagnosed incidentally on upper endoscopy performed for unrelated symptoms.

Nondysplastic BE has a risk of progressing to cancer in only 0.2% to 0.5% of affected patients per year.¹¹ Guidelines for BE without dysplasia advise repeating surveillance endoscopy every 3 to 5 years after appropriate counseling regarding overall low risk of cancer progression.^11,31 Surveillance endoscopy recommendations exist despite the lack of prospective randomized trials that demonstrate benefit. The rationale for surveillance is that survival in EAC is stage dependent and often EAC metastasizes prior to the development of symptoms from the tumor. Observational cohort studies in BE have demonstrated that surveillance endoscopy programs find EAC at earlier stages with improved survival; however, lead and length time bias may attenuate or eliminate these surveillance benefits.^11,32

Risk for neoplastic progression increases with degree of dysplasia. BE with low-grade dysplasia and high-grade dysplasia have a risk of cancer progression of 0.7% per year and 7% per year, respectively.¹¹

Historically, esophagectomy was the preferred treatment for BE with dysplasia. Now, endoscopic eradication therapies, including radiofrequency ablation and endoscopic mucosal resection for nodular BE, are the usual treatment for either low- or high-grade dysplasia.¹¹

Chemoprophylaxis with PPIs. Most patients with BE have symptoms of GERD or reflux esophagitis, so treatment with a PPI is indicated for symptom control. In patients with BE without GERD, PPI use may still be indicated, although this is controversial. Current guidelines recommend once-daily PPI therapy for BE (twice daily only if needed for symptom control) to reduce reflux-­associated inflammation and recommend against routine prescription of aspirin or NSAIDs for BE.¹¹ In vitro and observational studies support PPI use to prevent progression to EAC^11,33; however, data from randomized controlled trials to support their use are limited.^34,35

CORRESPONDENCE
Megan Everson, MD, Medical College of Wisconsin, 229 South Morrison Street, Appleton WI, 54911; [email protected]

Three conditions seen in primary care—gastroesophageal reflux disease (GERD), Helicobacter pylori (H pylori) infection, and Barrett esophagus (BE)—evolve in a gastric acid environment and are treated in part through gastric acid suppression. While GERD is a risk factor for the development of BE, H pylori is not associated with BE.¹ Patients with H pylori are actually less likely to have GERD symptoms.^2,3 In this article, we describe similarities and differences in patient presentations, diagnostic testing, and management, and review screening recommendations.

Gastroesophageal reflux disease

GERD is a clinical diagnosis based on symptoms of regurgitation and heartburn or the presence of one of its known complications (esophagitis, peptic strictures, or BE).^2,4 Chest pain is also common. Atypical symptoms are dysphagia, bleeding, chronic cough, asthma, chronic laryngitis, hoarseness, wheezing, teeth erosions, belching, and bloating.^2,5-7

The worldwide prevalence of gastroesophageal reflux symptoms in adults is 14.8%.⁸ When using a stringent definition of GERD—weekly symptoms occurring for at least 3 months—prevalence drops to 9.4%.⁹ GERD symptoms vary markedly by geographic location; the highest rates are in Central America (19.6%) and the lowest rates are in Southeast Asia (7.4%).⁸TABLE 1^2,9-11 lists risk factors for GERD.

GERD results from dysfunction of the esophagogastric junction that permits regurgitation of acidic gastric contents into the esophagus. Normally, the lower esophageal sphincter (LES) relaxes temporarily with gastric distention; when this relaxation is frequent and prolonged, it causes GERD.^2,12 Several medications, particularly those with anticholinergic effects (eg, tricyclic antidepressants) can decrease LES tone and contribute to symptoms. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often linked to dyspepsia and gastritis and should be avoided in patients who have symptoms of GERD. Pathologic reflux can also occur in conditions that increase intra-abdominal pressure, such as obesity and pregnancy, and with esophageal dysmotility, hiatal hernia, and delayed gastric emptying.⁵ When gastric contents travel proximally, this contributes to extraesophageal symptoms, such as chronic cough, asthma, laryngitis, dyspepsia, bloating, and belching.^2,4

Treatment

Proton pump inhibitors (PPIs) are the most effective treatment for GERD, but lifestyle modifications are also recommended for all patients.^2,6,13-16 Consider selective elimination of beverages and foods that are commonly associated with heartburn (eg, alcohol, caffeine, chocolate, citrus, and spicy foods) if patients note a correlation to symptoms.^5,6,13 Also, advise weight loss and smoking cessation, as appropriate, and suggest that the patient elevate the head of their bed when sleeping.

All PPIs are equally effective in suppressing acid when given at equivalent doses (TABLE 2¹⁷), so they can be used interchangeably.¹⁷ Treat uncomplicated GERD with a once-daily PPI 30 to 60 minutes prior to a meal for 4 to 8 weeks. If treatment is effective, you’ll want to try to reduce or stop the medication after the 4- to 8-week period. (It’s worth noting that the benefits of treatment for those with extraesophageal GERD are less predictable than for those with heartburn or esophagitis symptoms.⁵)

If GERD symptoms reemerge after the PPI is stopped, the medication can be restarted but should be limited to the least potent effective dose, no matter if it is taken daily or only as needed.^2,6,17 In patients with esophagitis, you may need to continue PPI treatment indefinitely at the lowest possible dose given the increased risk of recurrent esophagitis.^2,13,16

Continue to: Keep in mind...

Keep in mind that the safety of long-term PPI use has not been fully established. While observational studies have shown that long-term PPI use may be associated with adverse events, including kidney damage, Clostridioides difficile infection, osteoporosis, and gastric cancer, subsequent prospective studies have not shown any significant risks with long-term PPI use.^{2,13,14,16,18,19} If a decision is made to discontinue PPIs after long-term use, the patient should be advised that rebound acid hypersecretion may occur, although this possibility can be mitigated by gradually tapering the PPI dose.

Another maintenance therapy option. Histamine-2 receptor antagonists (H2RAs) are a reasonable alternative to PPIs as maintenance therapy, but they are ineffective in healing esophagitis^6,13 and may be best used as adjunctive therapy at bedtime for breakthrough symptoms while a patient is on maintenance PPIs.^6,19 Antacids (eg, calcium carbonate, aluminum hydroxide, or magnesium hydroxide) and alginate may provide some symptomatic relief, as well.

When PPIs don’t work. If initial lifestyle changes and PPI treatment do not provide adequate relief, consider the possibility of nonadherence with medication or lifestyle directives. If nonadherence does not appear to be an issue, twice-daily PPI dosing is also an option. Recognize, though, that PPI treatment failure occurs in as many as 40% of patients and is much more common in those with atypical symptoms.⁶

Consider upper gastrointestinal (GI) endoscopy—and perhaps esophageal manometry or pH testing—if a patient does not respond to empiric treatment with a PPI for 4 to 8 weeks at a standard, once-daily dose.^2,4,13 (Alternative diagnoses may also need to be considered.) Upper endoscopy is also appropriate for patients who have symptoms concerning for malignancy (progressive dysphagia, unintentional weight loss, or bleeding).

Consider endoscopy for patients with GERD symptoms unresponsive to empiric treatment with a proton pump inhibitor.

Esophagitis detected on endoscopy confirms GERD, although it is seen in only 18% to 25% of patients with GERD symptoms.^2,4 (The absence of esophagitis only indicates a lack of mucosal injury and not the absence of GERD.⁴) Acid exposure can cause fibrotic scarring and, in turn, strictures visible on endoscopy.² BE, the precursor to esophageal adenocarcinoma, is also a complication of GERD and is defined by columnar metaplasia replacing the normal squamous cell esophageal epithelium; it is detected on pathology review of biopsies.²

Continue to: GERD confirmed but PPIs aren't working?

GERD confirmed but PPIs aren’t working? Laparoscopic fundoplication is an effective treatment for GERD. However, due to its adverse effects (dysphagia, bloating, flatulence) and risk of treatment failure or breakdown within 5 to 10 years, it should be reserved for those poorly managed with PPIs.^2,13,19

Considerations in pregnancy. GERD is reported by 40% to 85% of pregnant women,^20,21 and its clinical presentation, diagnosis, and treatment are similar to that of nonpregnant adults.²¹ If lifestyle modification is not effective, pharmacologic therapy may be considered. Often, lifestyle modifications and antacids followed by the addition of sucralfate will be used first given the lack of systemic effects. H2RAs can be used next based on long-term historical use and reported safety.²¹ As with nonpregnant patients, PPIs are more effective than other medical therapies. If PPIs are used, dexlansoprazole, lansoprazole, pantoprazole, and rabeprazole are preferred. Omeprazole and esomeprazole are typically avoided due to findings of embryonic and fetal mortality in early animal studies, although subsequent human studies have noted no teratogenicity.^2,20,21

Considerations in children. As with adults, findings in the history and exam are sufficient to diagnose and initiate treatment of GERD in children, provided there are no warning signs (eg, bilious vomiting, GI bleeding, consistent forceful vomiting, fever, lethargy, hepatosplenomegaly, bulging fontanelle, macro- or microcephaly, seizures, abdominal tenderness/distention, or genetic/metabolic syndromes). Lifestyle changes are first-line treatment, followed by medication. Acid suppressants are preferred, with PPIs showing superior efficacy compared with H2RAs.¹⁵ Some PPIs (omeprazole, lansoprazole, and esomeprazole) have US Food and Drug Administration (FDA) approval beginning at age 1 year, while rabeprazole has FDA approval beginning at age 12.²² As in adults, if PPIs are ineffective, consider alternative diagnoses.^15,22

Helicobacter pylori infection

H pylori is a gram-negative spiral-shaped bacterium found in the stomach of humans and other mammals. It survives the acidic environment by metabolizing urea into alkaline ammonia and carbon dioxide. H pylori infection increases the risk of peptic ulcer disease, gastric cancer, iron deficiency anemia, and immune thrombocytopenia. It may be associated with dyspepsia, increased ulcer risk with use of an NSAID, and chronic gastritis.⁹ Infection with H pylori can decrease the risk of GERD.² The bacterial infection causes atrophic gastritis and subsequent hypochlorhydria, which then diminishes the acidity of the reflux contents.¹⁹ There is no link between H pylori infection and BE.¹

TABLE 1^2,9-11 shows those at highest risk of H pylori. The estimated prevalence of infection is 40% to 48%²³ worldwide but lower in North America, at 32% to 42%.²⁴H pylori is often acquired in childhood, and risk of infection is more likely if the parents (particularly mothers) are infected.⁹

Continue to: Whom to test, and how

Test for H pylori in those with active peptic ulcer disease or a history of peptic ulcer disease that was not investigated for H pylori. Also test individuals who have gastric ­mucosa-associated lymphoid tissue lymphoma, have a history of gastric cancer or family history of gastric cancer, are scheduled for endoscopic evaluation for dyspepsia, or are starting chronic NSAID therapy. Patients with typical GERD symptoms do not need to be tested for H pylori.^9,25

Means of testing for H pylori include the urea breath test, stool antigen studies, endoscopically obtained biopsies, or serum antibody tests. Antibody testing is discouraged because it has a lower diagnostic utility and cannot determine if the patient’s infection is current or past. Before undergoing urea breath tests, stool antigen tests, or biopsies for H pylori identification, patients should have abstained from taking the following agents for the time periods indicated: PPIs, 1 to 2 weeks; H2RAs, at least 1 day and preferably 2 weeks; and antibiotics, 4 weeks.⁹

The single greatest predictive factor for H pylori treatment failure is antibiotic resistance, so a detailed antibiotic history is essential.

The urea breath test and endoscopically obtained biopsies have the greatest diagnostic utility and, where available, should be the first-line tests. Stool antigen studies are useful for ruling out H pylori infection (very low negative likelihood ratio), but a positive test result is not as useful for confirming an infection, as false-positives do occur (moderate positive likelihood ratio).^9,26,27 Stool antigen testing is less expensive and, in many cases, more convenient and readily available for patients than urea breath testing and endoscopic biopsies.

Treatment

Offer treatment to all patients who test positive for H pylori. Eradication rates range from 70% to 91% using first-line treatment options.⁹ Treatment regimens consist of acid suppression and 2 to 3 antibiotics in combination (TABLE 3^9,28). The single greatest predictive factor for treatment failure is antibiotic resistance, so a detailed antibiotic history is essential. In particular, ask about macrolide antibiotic usage and penicillin allergies.

People living in areas with population macrolide resistance ≥ 15% should avoid clarithromycin-based regimens unless bacterial sensitivity testing has been done and shows sensitivity to these agents.^9,28,29 For cases that do not resolve with a first-line treatment program, choose an alternative regimen with different antibiotics.^9,29

Continue to: Additionally, adequate...

Additionally, adequate acid suppression is directly related to successful eradication. Thus, the likelihood of treatment success can be improved by using higher doses of PPIs and avoiding ones that are more likely to be metabolized quickly in some patients (lansoprazole, omeprazole). Patient adherence to the treatment regimen is an important determinant of effectiveness.^9,29 Adding vitamin C 400 to 1000 mg/d, vitamin E 100 to 400 mg/d, and probiotics may improve the effectiveness of treatment.^9,30

Duration of treatment is directly related to treatment effectiveness. Whenever possible, opt for 14 days of treatment instead of just 7.⁹

Test of cure. Patients treated for H pylori should be re-tested no sooner than 4 weeks after completion of therapy. Urea breath testing, stool antigen testing, and endoscopic biopsies (if endoscopy is indicated for some other reason) can all be used post treatment for test of cure.⁹

Barrett esophagus

Chronic reflux can lead to BE, in which metaplastic columnar epithelium replaces the normal squamous epithelium lining the distal esophagus. BE is linked to dysplasia and esophageal adenocarcinoma (EAC).¹¹ Endoscopic examination with biopsy is used to diagnosis BE. The global prevalence of histology-confirmed BE in people with GERD symptoms is 7.2%.¹⁰ Similar to GERD and H pylori infections, the prevalence of BE varies significantly with geographic location (14% in North America; 3% in the Middle East).¹⁰ BE is twice as likely to occur in men as in women, and it is rare in children.¹⁰

Whom to screen

The American College of Gastroenterology recommends consideration of screening with upper endoscopy for men with chronic GERD (> 5 years) or frequent GERD symptoms (once weekly or more often), plus 2 or more of the following risk factors: age > 50 years, Caucasian race, central obesity, smoking (current or past), or a family history of BE or EAC (TABLE 1^2,9-11). Screening for BE in women is not routinely recommended but can be considered in individuals with several of the risk factors just described.

Continue to: Not everyone with BE...

Not everyone with BE experiences GERD symptoms; sometimes BE may be diagnosed incidentally on upper endoscopy performed for unrelated symptoms.¹¹ GERD patients who are currently asymptomatic and had a normal prior upper endoscopy do not require surveillance.

Diagnosis and management

BE is diagnosed based on specific endoscopic and histologic findings. The presence of dysplasia (either low grade or high grade) or its absence has important treatment implications. When histology is indefinite for dysplasia, treat reflux and, following acid suppression with PPIs for 3 to 6 months, repeat endoscopy (since reactive changes with reflux may obscure results).¹¹

Not everyone with Barrett esophagus (BE) experiences GERD symptoms; sometimes BE may be diagnosed incidentally on upper endoscopy performed for unrelated symptoms.

Nondysplastic BE has a risk of progressing to cancer in only 0.2% to 0.5% of affected patients per year.¹¹ Guidelines for BE without dysplasia advise repeating surveillance endoscopy every 3 to 5 years after appropriate counseling regarding overall low risk of cancer progression.^11,31 Surveillance endoscopy recommendations exist despite the lack of prospective randomized trials that demonstrate benefit. The rationale for surveillance is that survival in EAC is stage dependent and often EAC metastasizes prior to the development of symptoms from the tumor. Observational cohort studies in BE have demonstrated that surveillance endoscopy programs find EAC at earlier stages with improved survival; however, lead and length time bias may attenuate or eliminate these surveillance benefits.^11,32

Risk for neoplastic progression increases with degree of dysplasia. BE with low-grade dysplasia and high-grade dysplasia have a risk of cancer progression of 0.7% per year and 7% per year, respectively.¹¹

Historically, esophagectomy was the preferred treatment for BE with dysplasia. Now, endoscopic eradication therapies, including radiofrequency ablation and endoscopic mucosal resection for nodular BE, are the usual treatment for either low- or high-grade dysplasia.¹¹

Chemoprophylaxis with PPIs. Most patients with BE have symptoms of GERD or reflux esophagitis, so treatment with a PPI is indicated for symptom control. In patients with BE without GERD, PPI use may still be indicated, although this is controversial. Current guidelines recommend once-daily PPI therapy for BE (twice daily only if needed for symptom control) to reduce reflux-­associated inflammation and recommend against routine prescription of aspirin or NSAIDs for BE.¹¹ In vitro and observational studies support PPI use to prevent progression to EAC^11,33; however, data from randomized controlled trials to support their use are limited.^34,35

CORRESPONDENCE
Megan Everson, MD, Medical College of Wisconsin, 229 South Morrison Street, Appleton WI, 54911; [email protected]

Three conditions seen in primary care—gastroesophageal reflux disease (GERD), Helicobacter pylori (H pylori) infection, and Barrett esophagus (BE)—evolve in a gastric acid environment and are treated in part through gastric acid suppression. While GERD is a risk factor for the development of BE, H pylori is not associated with BE.¹ Patients with H pylori are actually less likely to have GERD symptoms.^2,3 In this article, we describe similarities and differences in patient presentations, diagnostic testing, and management, and review screening recommendations.

Gastroesophageal reflux disease

GERD is a clinical diagnosis based on symptoms of regurgitation and heartburn or the presence of one of its known complications (esophagitis, peptic strictures, or BE).^2,4 Chest pain is also common. Atypical symptoms are dysphagia, bleeding, chronic cough, asthma, chronic laryngitis, hoarseness, wheezing, teeth erosions, belching, and bloating.^2,5-7

The worldwide prevalence of gastroesophageal reflux symptoms in adults is 14.8%.⁸ When using a stringent definition of GERD—weekly symptoms occurring for at least 3 months—prevalence drops to 9.4%.⁹ GERD symptoms vary markedly by geographic location; the highest rates are in Central America (19.6%) and the lowest rates are in Southeast Asia (7.4%).⁸TABLE 1^2,9-11 lists risk factors for GERD.

GERD results from dysfunction of the esophagogastric junction that permits regurgitation of acidic gastric contents into the esophagus. Normally, the lower esophageal sphincter (LES) relaxes temporarily with gastric distention; when this relaxation is frequent and prolonged, it causes GERD.^2,12 Several medications, particularly those with anticholinergic effects (eg, tricyclic antidepressants) can decrease LES tone and contribute to symptoms. Nonsteroidal anti-inflammatory drugs (NSAIDs) are often linked to dyspepsia and gastritis and should be avoided in patients who have symptoms of GERD. Pathologic reflux can also occur in conditions that increase intra-abdominal pressure, such as obesity and pregnancy, and with esophageal dysmotility, hiatal hernia, and delayed gastric emptying.⁵ When gastric contents travel proximally, this contributes to extraesophageal symptoms, such as chronic cough, asthma, laryngitis, dyspepsia, bloating, and belching.^2,4

Treatment

Proton pump inhibitors (PPIs) are the most effective treatment for GERD, but lifestyle modifications are also recommended for all patients.^2,6,13-16 Consider selective elimination of beverages and foods that are commonly associated with heartburn (eg, alcohol, caffeine, chocolate, citrus, and spicy foods) if patients note a correlation to symptoms.^5,6,13 Also, advise weight loss and smoking cessation, as appropriate, and suggest that the patient elevate the head of their bed when sleeping.

All PPIs are equally effective in suppressing acid when given at equivalent doses (TABLE 2¹⁷), so they can be used interchangeably.¹⁷ Treat uncomplicated GERD with a once-daily PPI 30 to 60 minutes prior to a meal for 4 to 8 weeks. If treatment is effective, you’ll want to try to reduce or stop the medication after the 4- to 8-week period. (It’s worth noting that the benefits of treatment for those with extraesophageal GERD are less predictable than for those with heartburn or esophagitis symptoms.⁵)

If GERD symptoms reemerge after the PPI is stopped, the medication can be restarted but should be limited to the least potent effective dose, no matter if it is taken daily or only as needed.^2,6,17 In patients with esophagitis, you may need to continue PPI treatment indefinitely at the lowest possible dose given the increased risk of recurrent esophagitis.^2,13,16

Continue to: Keep in mind...

Keep in mind that the safety of long-term PPI use has not been fully established. While observational studies have shown that long-term PPI use may be associated with adverse events, including kidney damage, Clostridioides difficile infection, osteoporosis, and gastric cancer, subsequent prospective studies have not shown any significant risks with long-term PPI use.^{2,13,14,16,18,19} If a decision is made to discontinue PPIs after long-term use, the patient should be advised that rebound acid hypersecretion may occur, although this possibility can be mitigated by gradually tapering the PPI dose.

Another maintenance therapy option. Histamine-2 receptor antagonists (H2RAs) are a reasonable alternative to PPIs as maintenance therapy, but they are ineffective in healing esophagitis^6,13 and may be best used as adjunctive therapy at bedtime for breakthrough symptoms while a patient is on maintenance PPIs.^6,19 Antacids (eg, calcium carbonate, aluminum hydroxide, or magnesium hydroxide) and alginate may provide some symptomatic relief, as well.

When PPIs don’t work. If initial lifestyle changes and PPI treatment do not provide adequate relief, consider the possibility of nonadherence with medication or lifestyle directives. If nonadherence does not appear to be an issue, twice-daily PPI dosing is also an option. Recognize, though, that PPI treatment failure occurs in as many as 40% of patients and is much more common in those with atypical symptoms.⁶

Consider upper gastrointestinal (GI) endoscopy—and perhaps esophageal manometry or pH testing—if a patient does not respond to empiric treatment with a PPI for 4 to 8 weeks at a standard, once-daily dose.^2,4,13 (Alternative diagnoses may also need to be considered.) Upper endoscopy is also appropriate for patients who have symptoms concerning for malignancy (progressive dysphagia, unintentional weight loss, or bleeding).

Consider endoscopy for patients with GERD symptoms unresponsive to empiric treatment with a proton pump inhibitor.

Esophagitis detected on endoscopy confirms GERD, although it is seen in only 18% to 25% of patients with GERD symptoms.^2,4 (The absence of esophagitis only indicates a lack of mucosal injury and not the absence of GERD.⁴) Acid exposure can cause fibrotic scarring and, in turn, strictures visible on endoscopy.² BE, the precursor to esophageal adenocarcinoma, is also a complication of GERD and is defined by columnar metaplasia replacing the normal squamous cell esophageal epithelium; it is detected on pathology review of biopsies.²

Continue to: GERD confirmed but PPIs aren't working?

GERD confirmed but PPIs aren’t working? Laparoscopic fundoplication is an effective treatment for GERD. However, due to its adverse effects (dysphagia, bloating, flatulence) and risk of treatment failure or breakdown within 5 to 10 years, it should be reserved for those poorly managed with PPIs.^2,13,19

Considerations in pregnancy. GERD is reported by 40% to 85% of pregnant women,^20,21 and its clinical presentation, diagnosis, and treatment are similar to that of nonpregnant adults.²¹ If lifestyle modification is not effective, pharmacologic therapy may be considered. Often, lifestyle modifications and antacids followed by the addition of sucralfate will be used first given the lack of systemic effects. H2RAs can be used next based on long-term historical use and reported safety.²¹ As with nonpregnant patients, PPIs are more effective than other medical therapies. If PPIs are used, dexlansoprazole, lansoprazole, pantoprazole, and rabeprazole are preferred. Omeprazole and esomeprazole are typically avoided due to findings of embryonic and fetal mortality in early animal studies, although subsequent human studies have noted no teratogenicity.^2,20,21

Considerations in children. As with adults, findings in the history and exam are sufficient to diagnose and initiate treatment of GERD in children, provided there are no warning signs (eg, bilious vomiting, GI bleeding, consistent forceful vomiting, fever, lethargy, hepatosplenomegaly, bulging fontanelle, macro- or microcephaly, seizures, abdominal tenderness/distention, or genetic/metabolic syndromes). Lifestyle changes are first-line treatment, followed by medication. Acid suppressants are preferred, with PPIs showing superior efficacy compared with H2RAs.¹⁵ Some PPIs (omeprazole, lansoprazole, and esomeprazole) have US Food and Drug Administration (FDA) approval beginning at age 1 year, while rabeprazole has FDA approval beginning at age 12.²² As in adults, if PPIs are ineffective, consider alternative diagnoses.^15,22

Helicobacter pylori infection

H pylori is a gram-negative spiral-shaped bacterium found in the stomach of humans and other mammals. It survives the acidic environment by metabolizing urea into alkaline ammonia and carbon dioxide. H pylori infection increases the risk of peptic ulcer disease, gastric cancer, iron deficiency anemia, and immune thrombocytopenia. It may be associated with dyspepsia, increased ulcer risk with use of an NSAID, and chronic gastritis.⁹ Infection with H pylori can decrease the risk of GERD.² The bacterial infection causes atrophic gastritis and subsequent hypochlorhydria, which then diminishes the acidity of the reflux contents.¹⁹ There is no link between H pylori infection and BE.¹

TABLE 1^2,9-11 shows those at highest risk of H pylori. The estimated prevalence of infection is 40% to 48%²³ worldwide but lower in North America, at 32% to 42%.²⁴H pylori is often acquired in childhood, and risk of infection is more likely if the parents (particularly mothers) are infected.⁹

Continue to: Whom to test, and how

Test for H pylori in those with active peptic ulcer disease or a history of peptic ulcer disease that was not investigated for H pylori. Also test individuals who have gastric ­mucosa-associated lymphoid tissue lymphoma, have a history of gastric cancer or family history of gastric cancer, are scheduled for endoscopic evaluation for dyspepsia, or are starting chronic NSAID therapy. Patients with typical GERD symptoms do not need to be tested for H pylori.^9,25

Means of testing for H pylori include the urea breath test, stool antigen studies, endoscopically obtained biopsies, or serum antibody tests. Antibody testing is discouraged because it has a lower diagnostic utility and cannot determine if the patient’s infection is current or past. Before undergoing urea breath tests, stool antigen tests, or biopsies for H pylori identification, patients should have abstained from taking the following agents for the time periods indicated: PPIs, 1 to 2 weeks; H2RAs, at least 1 day and preferably 2 weeks; and antibiotics, 4 weeks.⁹

The single greatest predictive factor for H pylori treatment failure is antibiotic resistance, so a detailed antibiotic history is essential.

The urea breath test and endoscopically obtained biopsies have the greatest diagnostic utility and, where available, should be the first-line tests. Stool antigen studies are useful for ruling out H pylori infection (very low negative likelihood ratio), but a positive test result is not as useful for confirming an infection, as false-positives do occur (moderate positive likelihood ratio).^9,26,27 Stool antigen testing is less expensive and, in many cases, more convenient and readily available for patients than urea breath testing and endoscopic biopsies.

Treatment

Offer treatment to all patients who test positive for H pylori. Eradication rates range from 70% to 91% using first-line treatment options.⁹ Treatment regimens consist of acid suppression and 2 to 3 antibiotics in combination (TABLE 3^9,28). The single greatest predictive factor for treatment failure is antibiotic resistance, so a detailed antibiotic history is essential. In particular, ask about macrolide antibiotic usage and penicillin allergies.

People living in areas with population macrolide resistance ≥ 15% should avoid clarithromycin-based regimens unless bacterial sensitivity testing has been done and shows sensitivity to these agents.^9,28,29 For cases that do not resolve with a first-line treatment program, choose an alternative regimen with different antibiotics.^9,29

Continue to: Additionally, adequate...

Additionally, adequate acid suppression is directly related to successful eradication. Thus, the likelihood of treatment success can be improved by using higher doses of PPIs and avoiding ones that are more likely to be metabolized quickly in some patients (lansoprazole, omeprazole). Patient adherence to the treatment regimen is an important determinant of effectiveness.^9,29 Adding vitamin C 400 to 1000 mg/d, vitamin E 100 to 400 mg/d, and probiotics may improve the effectiveness of treatment.^9,30

Duration of treatment is directly related to treatment effectiveness. Whenever possible, opt for 14 days of treatment instead of just 7.⁹

Test of cure. Patients treated for H pylori should be re-tested no sooner than 4 weeks after completion of therapy. Urea breath testing, stool antigen testing, and endoscopic biopsies (if endoscopy is indicated for some other reason) can all be used post treatment for test of cure.⁹

Barrett esophagus

Chronic reflux can lead to BE, in which metaplastic columnar epithelium replaces the normal squamous epithelium lining the distal esophagus. BE is linked to dysplasia and esophageal adenocarcinoma (EAC).¹¹ Endoscopic examination with biopsy is used to diagnosis BE. The global prevalence of histology-confirmed BE in people with GERD symptoms is 7.2%.¹⁰ Similar to GERD and H pylori infections, the prevalence of BE varies significantly with geographic location (14% in North America; 3% in the Middle East).¹⁰ BE is twice as likely to occur in men as in women, and it is rare in children.¹⁰

Whom to screen

The American College of Gastroenterology recommends consideration of screening with upper endoscopy for men with chronic GERD (> 5 years) or frequent GERD symptoms (once weekly or more often), plus 2 or more of the following risk factors: age > 50 years, Caucasian race, central obesity, smoking (current or past), or a family history of BE or EAC (TABLE 1^2,9-11). Screening for BE in women is not routinely recommended but can be considered in individuals with several of the risk factors just described.

Continue to: Not everyone with BE...

Not everyone with BE experiences GERD symptoms; sometimes BE may be diagnosed incidentally on upper endoscopy performed for unrelated symptoms.¹¹ GERD patients who are currently asymptomatic and had a normal prior upper endoscopy do not require surveillance.

Diagnosis and management

BE is diagnosed based on specific endoscopic and histologic findings. The presence of dysplasia (either low grade or high grade) or its absence has important treatment implications. When histology is indefinite for dysplasia, treat reflux and, following acid suppression with PPIs for 3 to 6 months, repeat endoscopy (since reactive changes with reflux may obscure results).¹¹

Not everyone with Barrett esophagus (BE) experiences GERD symptoms; sometimes BE may be diagnosed incidentally on upper endoscopy performed for unrelated symptoms.

Nondysplastic BE has a risk of progressing to cancer in only 0.2% to 0.5% of affected patients per year.¹¹ Guidelines for BE without dysplasia advise repeating surveillance endoscopy every 3 to 5 years after appropriate counseling regarding overall low risk of cancer progression.^11,31 Surveillance endoscopy recommendations exist despite the lack of prospective randomized trials that demonstrate benefit. The rationale for surveillance is that survival in EAC is stage dependent and often EAC metastasizes prior to the development of symptoms from the tumor. Observational cohort studies in BE have demonstrated that surveillance endoscopy programs find EAC at earlier stages with improved survival; however, lead and length time bias may attenuate or eliminate these surveillance benefits.^11,32

Risk for neoplastic progression increases with degree of dysplasia. BE with low-grade dysplasia and high-grade dysplasia have a risk of cancer progression of 0.7% per year and 7% per year, respectively.¹¹

Historically, esophagectomy was the preferred treatment for BE with dysplasia. Now, endoscopic eradication therapies, including radiofrequency ablation and endoscopic mucosal resection for nodular BE, are the usual treatment for either low- or high-grade dysplasia.¹¹

Chemoprophylaxis with PPIs. Most patients with BE have symptoms of GERD or reflux esophagitis, so treatment with a PPI is indicated for symptom control. In patients with BE without GERD, PPI use may still be indicated, although this is controversial. Current guidelines recommend once-daily PPI therapy for BE (twice daily only if needed for symptom control) to reduce reflux-­associated inflammation and recommend against routine prescription of aspirin or NSAIDs for BE.¹¹ In vitro and observational studies support PPI use to prevent progression to EAC^11,33; however, data from randomized controlled trials to support their use are limited.^34,35

CORRESPONDENCE
Megan Everson, MD, Medical College of Wisconsin, 229 South Morrison Street, Appleton WI, 54911; [email protected]