Acute kidney injury (AKI) occurs in 5%-30% of noncritically ill hospitalized children.¹ Initially thought to be simply a symptom of more severe pathologies, it is now recognized that AKI independently increases mortality and is associated with the development of chronic kidney disease (CKD), even in children.² The wide acceptance of the Kidney Disease Improving Global Outcome (KDIGO) diagnostic criteria has enabled a more uniform definition of AKI from both clinical and research perspectives.² A better understanding of the pathophysiology and risk factors for AKI has led to new methods for early detection and prevention efforts. While serum creatinine (SCr) was historically one of the sole markers of AKI, novel biomarkers can facilitate earlier diagnosis of AKI, identify subclinical AKI, and guide clinical management. This clinical practice update addresses the latest clinical advances in risk assessment, diagnosis, and prevention of pediatric AKI, with a focus on AKI biomarkers.

Several sets of criteria have been used to diagnose AKI. The KDIGO classification, based on a systematic review of the literature and developed through expert consensus, is the current recommended definition.³ Increasing AKI stage, as defined by the KDIGO classification, is associated with increased mortality, the need for renal replacement therapy, length of stay, and CKD, thus underscoring the importance of accurate classification.³ Stage 1 AKI is defined by a rise in SCr of ≥0.3 mg/dL,1.5-1.9 times the baseline SCr, or urine output <0.5 ml/kg/h for six to 12 hours; stage 2 by a rise of ≥2.0-2.9 times the baseline SCr or urine output <0.5 ml/kg/h for >12 hours; and stage 3 by a rise of ≥4.0 mg/dL, ≥three times the baseline SCr, initiation of renal replacement therapy, urine output <0.3 ml/kg/h for ≥24 hours, or anuria ≥12 hours. However, these criteria rely on SCr, which is a suboptimal marker of renal dysfunction, as it rises only once the glomerular filtration rate (GFR) has already decreased, in some cases by as much as 50%. Additionally, interpretation of SCr in the diagnosis of AKI requires a prior Scr measurement to determine the magnitude of change from the baseline value, which is often lacking in children. To mitigate this limitation, different formulas exist to estimate a baseline SCr value based on height or age, an approach that assumes patients have preexisting normal renal function.

The limitations of SCr have led to interest in identifying more accurate biomarkers of AKI. Although many candidates have been identified, we will limit our discussion to those currently available for clinical use: serum cystatin C, urine neutrophil gelatinase-associated lipocalin (NGAL), urine TIMP-2, and urine IGFBP7 (Table).^4-8 While urine NGAL and cystatin C are measured individually, TIMP-2 and IGFBP7 are measured on the same panel and the product of their multiplied values is used for clinical guidance. While each of these biomarkers have good predictive accuracy for AKI when used independently, their combined use increases the accuracy of AKI diagnosis. These biomarkers can be divided into broad categories based on their utility as either functional markers or markers of injury.⁶ Serum cystatin C is a functional marker and as such can be used to estimate GFR more accurately than SCr.⁹ Comparatively, urine NGAL is a marker of renal injury, while TIMP2 and IGFBP7 are markers of renal stress. These markers are not useful in estimating GFR, but rather aid in the prediction and diagnosis of AKI (Figure). Despite the limitations of SCr, these biomarkers have yet to be incorporated into the diagnostic criteria. They have, however, helped to refine our understanding of the pathophysiology of AKI.

The renal angina index (RAI) identifies critically ill children at high risk for AKI. The RAI combines traditional markers of AKI, such as a change in estimated creatinine clearance and fluid overload, with patient factors, including need for ventilation, inotropic support, and history of transplantation (solid organ or bone marrow) to identify those patients who are at high risk for severe AKI. Patients identified as high risk by the patient factors component of the RAI have a much lower threshold for both a decrease in creatinine clearance and fluid overload to be considered at risk for severe AKI, as these early signs are more likely to reflect an early impending severe AKI in this high-risk group. Conversely, patients that do not meet these patient factors are more likely to simply have a transient or functional AKI, and therefore have a higher threshold for both a change in creatinine clearance and fluid overload in order to be considered at high risk for severe AKI.

The RAI has been validated in the critical care setting as a method to predict severe AKI at day three of admission to the pediatric intensive care unit, with a negative predictive value of 92%-99% when the score is negative in the first 12 hours.¹⁰ In selected high-risk patients (RAI ≥ 8), biomarkers become even more reliable for AKI prediction (eg, injury markers have an excellent area under the receiver operating characteristic curve (AUC) of 0.97 for severe AKI prediction in this high-risk group).¹¹ While only validated for critically ill patients, the concept of renal angina is still applicable in the complex populations managed by hospitalists who practice outside of the intensive care unit setting. Early signs of renal dysfunction (eg, rising SCr, fluid overload ≥5%) in patients with risk factors (see below) should prompt a thorough evaluation, including urinalysis, daily SCr, nephrotoxin avoidance, and tissue injury biomarkers, if available.

The risk factors for AKI are numerous and tend to potentiate one another. The most frequent predisposing comorbidities include CKD, heart failure or congenital heart diseases, transplantation (bone marrow or solid organs), and diabetes. Disease-related factors include sepsis, cardiac surgery, cardio-pulmonary bypass, mechanical ventilation, and vasopressor use. Potentially modifiable factors include hypovolemia and multiple nephrotoxic exposures. ^2,3

Nephrotoxic medications are now among the most common causes of AKI in hospitalized children.¹² Approximately 80% of children are exposed to at least one nephrotoxin during an inpatient admission.¹² Exposure to a single nephrotoxic medication is sufficient to place a child at risk of AKI, and each additional nephrotoxin further increases the risk.¹² While some drugs are routinely recognized to be nephrotoxic (eg, ibuprofen), others are commonly overlooked, notably certain antibiotics (eg, cefotaxime, ceftazidime, cefuroxime, nafcillin, and piperacillin) and anticonvulsants (eg, zonisamide).¹² Furthermore, the combination of multiple nephrotoxins can potentiate the risk of AKI. For example, the combination of vancomycin and piperacillin/tazobactam increases the risk of AKI by 3.4 times compared with the combination of vancomycin with another antipseudomonal beta-lactam antibiotic.¹³

Adequate monitoring, including daily SCr measurements and risk awareness, are critical as nephrotoxin-associated AKI can be easily missed in the absence of routine SCr monitoring, especially since these children are typically nonoliguric¹². Quality improvement efforts focused on obtaining daily SCr in patients exposed to either three or more nephrotoxins or three days of either aminoglycoside or vancomycin, even without concomitant exposure to other nephrotoxins, have shown success in decreasing both the number of nephrotoxins and the rate of nephrotoxin-associated AKI.¹²

While a significant injury cannot always be avoided, a mindful clinical approach and management can help to prevent some complications of AKI. An awareness of fluid status is critical, as fluid overload greater than 10% of the patient’s weight independently increases the risk of mortality in both adults and children.¹⁴ To assess the risk of AKI progression and potential failure of conservative management with diuretics, a furosemide stress test (FST) is an easy, safe, and accessible functional assessment of tubular reserve in a patient without intravascular depletion.¹⁵ A growing body of literature in adults shows that FST-responders are less likely to progress to stage 3 AKI or need renal replacement therapy than nonresponders.¹⁵ The FST is currently being investigated and standardized in children.

Research in AKI has made significant strides over the last few years. Nevertheless, many areas of research remain to be explored (eg, the impact of IV fluid type in the pediatric population, AKD characterization and impact on CKD development). AKI is common, associated with significant morbidity and mortality and, in some instances, preventable. While no targeted therapeutic options are currently under investigation, recent advances allow for better identification of high-risk patients and offer opportunities for impactful preventive approaches. Thoughtful use of nephrotoxic medications, early identification of patients at high risk for AKI, and accurate diagnosis and appropriate management of AKI are the recommended best practice.

Disclosures

The authors have nothing to disclose.

Acute kidney injury (AKI) occurs in 5%-30% of noncritically ill hospitalized children.¹ Initially thought to be simply a symptom of more severe pathologies, it is now recognized that AKI independently increases mortality and is associated with the development of chronic kidney disease (CKD), even in children.² The wide acceptance of the Kidney Disease Improving Global Outcome (KDIGO) diagnostic criteria has enabled a more uniform definition of AKI from both clinical and research perspectives.² A better understanding of the pathophysiology and risk factors for AKI has led to new methods for early detection and prevention efforts. While serum creatinine (SCr) was historically one of the sole markers of AKI, novel biomarkers can facilitate earlier diagnosis of AKI, identify subclinical AKI, and guide clinical management. This clinical practice update addresses the latest clinical advances in risk assessment, diagnosis, and prevention of pediatric AKI, with a focus on AKI biomarkers.

Several sets of criteria have been used to diagnose AKI. The KDIGO classification, based on a systematic review of the literature and developed through expert consensus, is the current recommended definition.³ Increasing AKI stage, as defined by the KDIGO classification, is associated with increased mortality, the need for renal replacement therapy, length of stay, and CKD, thus underscoring the importance of accurate classification.³ Stage 1 AKI is defined by a rise in SCr of ≥0.3 mg/dL,1.5-1.9 times the baseline SCr, or urine output <0.5 ml/kg/h for six to 12 hours; stage 2 by a rise of ≥2.0-2.9 times the baseline SCr or urine output <0.5 ml/kg/h for >12 hours; and stage 3 by a rise of ≥4.0 mg/dL, ≥three times the baseline SCr, initiation of renal replacement therapy, urine output <0.3 ml/kg/h for ≥24 hours, or anuria ≥12 hours. However, these criteria rely on SCr, which is a suboptimal marker of renal dysfunction, as it rises only once the glomerular filtration rate (GFR) has already decreased, in some cases by as much as 50%. Additionally, interpretation of SCr in the diagnosis of AKI requires a prior Scr measurement to determine the magnitude of change from the baseline value, which is often lacking in children. To mitigate this limitation, different formulas exist to estimate a baseline SCr value based on height or age, an approach that assumes patients have preexisting normal renal function.

The limitations of SCr have led to interest in identifying more accurate biomarkers of AKI. Although many candidates have been identified, we will limit our discussion to those currently available for clinical use: serum cystatin C, urine neutrophil gelatinase-associated lipocalin (NGAL), urine TIMP-2, and urine IGFBP7 (Table).^4-8 While urine NGAL and cystatin C are measured individually, TIMP-2 and IGFBP7 are measured on the same panel and the product of their multiplied values is used for clinical guidance. While each of these biomarkers have good predictive accuracy for AKI when used independently, their combined use increases the accuracy of AKI diagnosis. These biomarkers can be divided into broad categories based on their utility as either functional markers or markers of injury.⁶ Serum cystatin C is a functional marker and as such can be used to estimate GFR more accurately than SCr.⁹ Comparatively, urine NGAL is a marker of renal injury, while TIMP2 and IGFBP7 are markers of renal stress. These markers are not useful in estimating GFR, but rather aid in the prediction and diagnosis of AKI (Figure). Despite the limitations of SCr, these biomarkers have yet to be incorporated into the diagnostic criteria. They have, however, helped to refine our understanding of the pathophysiology of AKI.

The renal angina index (RAI) identifies critically ill children at high risk for AKI. The RAI combines traditional markers of AKI, such as a change in estimated creatinine clearance and fluid overload, with patient factors, including need for ventilation, inotropic support, and history of transplantation (solid organ or bone marrow) to identify those patients who are at high risk for severe AKI. Patients identified as high risk by the patient factors component of the RAI have a much lower threshold for both a decrease in creatinine clearance and fluid overload to be considered at risk for severe AKI, as these early signs are more likely to reflect an early impending severe AKI in this high-risk group. Conversely, patients that do not meet these patient factors are more likely to simply have a transient or functional AKI, and therefore have a higher threshold for both a change in creatinine clearance and fluid overload in order to be considered at high risk for severe AKI.

The RAI has been validated in the critical care setting as a method to predict severe AKI at day three of admission to the pediatric intensive care unit, with a negative predictive value of 92%-99% when the score is negative in the first 12 hours.¹⁰ In selected high-risk patients (RAI ≥ 8), biomarkers become even more reliable for AKI prediction (eg, injury markers have an excellent area under the receiver operating characteristic curve (AUC) of 0.97 for severe AKI prediction in this high-risk group).¹¹ While only validated for critically ill patients, the concept of renal angina is still applicable in the complex populations managed by hospitalists who practice outside of the intensive care unit setting. Early signs of renal dysfunction (eg, rising SCr, fluid overload ≥5%) in patients with risk factors (see below) should prompt a thorough evaluation, including urinalysis, daily SCr, nephrotoxin avoidance, and tissue injury biomarkers, if available.

The risk factors for AKI are numerous and tend to potentiate one another. The most frequent predisposing comorbidities include CKD, heart failure or congenital heart diseases, transplantation (bone marrow or solid organs), and diabetes. Disease-related factors include sepsis, cardiac surgery, cardio-pulmonary bypass, mechanical ventilation, and vasopressor use. Potentially modifiable factors include hypovolemia and multiple nephrotoxic exposures. ^2,3

Nephrotoxic medications are now among the most common causes of AKI in hospitalized children.¹² Approximately 80% of children are exposed to at least one nephrotoxin during an inpatient admission.¹² Exposure to a single nephrotoxic medication is sufficient to place a child at risk of AKI, and each additional nephrotoxin further increases the risk.¹² While some drugs are routinely recognized to be nephrotoxic (eg, ibuprofen), others are commonly overlooked, notably certain antibiotics (eg, cefotaxime, ceftazidime, cefuroxime, nafcillin, and piperacillin) and anticonvulsants (eg, zonisamide).¹² Furthermore, the combination of multiple nephrotoxins can potentiate the risk of AKI. For example, the combination of vancomycin and piperacillin/tazobactam increases the risk of AKI by 3.4 times compared with the combination of vancomycin with another antipseudomonal beta-lactam antibiotic.¹³

Adequate monitoring, including daily SCr measurements and risk awareness, are critical as nephrotoxin-associated AKI can be easily missed in the absence of routine SCr monitoring, especially since these children are typically nonoliguric¹². Quality improvement efforts focused on obtaining daily SCr in patients exposed to either three or more nephrotoxins or three days of either aminoglycoside or vancomycin, even without concomitant exposure to other nephrotoxins, have shown success in decreasing both the number of nephrotoxins and the rate of nephrotoxin-associated AKI.¹²

While a significant injury cannot always be avoided, a mindful clinical approach and management can help to prevent some complications of AKI. An awareness of fluid status is critical, as fluid overload greater than 10% of the patient’s weight independently increases the risk of mortality in both adults and children.¹⁴ To assess the risk of AKI progression and potential failure of conservative management with diuretics, a furosemide stress test (FST) is an easy, safe, and accessible functional assessment of tubular reserve in a patient without intravascular depletion.¹⁵ A growing body of literature in adults shows that FST-responders are less likely to progress to stage 3 AKI or need renal replacement therapy than nonresponders.¹⁵ The FST is currently being investigated and standardized in children.

Research in AKI has made significant strides over the last few years. Nevertheless, many areas of research remain to be explored (eg, the impact of IV fluid type in the pediatric population, AKD characterization and impact on CKD development). AKI is common, associated with significant morbidity and mortality and, in some instances, preventable. While no targeted therapeutic options are currently under investigation, recent advances allow for better identification of high-risk patients and offer opportunities for impactful preventive approaches. Thoughtful use of nephrotoxic medications, early identification of patients at high risk for AKI, and accurate diagnosis and appropriate management of AKI are the recommended best practice.

Disclosures

The authors have nothing to disclose.

Acute kidney injury (AKI) occurs in 5%-30% of noncritically ill hospitalized children.¹ Initially thought to be simply a symptom of more severe pathologies, it is now recognized that AKI independently increases mortality and is associated with the development of chronic kidney disease (CKD), even in children.² The wide acceptance of the Kidney Disease Improving Global Outcome (KDIGO) diagnostic criteria has enabled a more uniform definition of AKI from both clinical and research perspectives.² A better understanding of the pathophysiology and risk factors for AKI has led to new methods for early detection and prevention efforts. While serum creatinine (SCr) was historically one of the sole markers of AKI, novel biomarkers can facilitate earlier diagnosis of AKI, identify subclinical AKI, and guide clinical management. This clinical practice update addresses the latest clinical advances in risk assessment, diagnosis, and prevention of pediatric AKI, with a focus on AKI biomarkers.

Several sets of criteria have been used to diagnose AKI. The KDIGO classification, based on a systematic review of the literature and developed through expert consensus, is the current recommended definition.³ Increasing AKI stage, as defined by the KDIGO classification, is associated with increased mortality, the need for renal replacement therapy, length of stay, and CKD, thus underscoring the importance of accurate classification.³ Stage 1 AKI is defined by a rise in SCr of ≥0.3 mg/dL,1.5-1.9 times the baseline SCr, or urine output <0.5 ml/kg/h for six to 12 hours; stage 2 by a rise of ≥2.0-2.9 times the baseline SCr or urine output <0.5 ml/kg/h for >12 hours; and stage 3 by a rise of ≥4.0 mg/dL, ≥three times the baseline SCr, initiation of renal replacement therapy, urine output <0.3 ml/kg/h for ≥24 hours, or anuria ≥12 hours. However, these criteria rely on SCr, which is a suboptimal marker of renal dysfunction, as it rises only once the glomerular filtration rate (GFR) has already decreased, in some cases by as much as 50%. Additionally, interpretation of SCr in the diagnosis of AKI requires a prior Scr measurement to determine the magnitude of change from the baseline value, which is often lacking in children. To mitigate this limitation, different formulas exist to estimate a baseline SCr value based on height or age, an approach that assumes patients have preexisting normal renal function.

The limitations of SCr have led to interest in identifying more accurate biomarkers of AKI. Although many candidates have been identified, we will limit our discussion to those currently available for clinical use: serum cystatin C, urine neutrophil gelatinase-associated lipocalin (NGAL), urine TIMP-2, and urine IGFBP7 (Table).^4-8 While urine NGAL and cystatin C are measured individually, TIMP-2 and IGFBP7 are measured on the same panel and the product of their multiplied values is used for clinical guidance. While each of these biomarkers have good predictive accuracy for AKI when used independently, their combined use increases the accuracy of AKI diagnosis. These biomarkers can be divided into broad categories based on their utility as either functional markers or markers of injury.⁶ Serum cystatin C is a functional marker and as such can be used to estimate GFR more accurately than SCr.⁹ Comparatively, urine NGAL is a marker of renal injury, while TIMP2 and IGFBP7 are markers of renal stress. These markers are not useful in estimating GFR, but rather aid in the prediction and diagnosis of AKI (Figure). Despite the limitations of SCr, these biomarkers have yet to be incorporated into the diagnostic criteria. They have, however, helped to refine our understanding of the pathophysiology of AKI.

The renal angina index (RAI) identifies critically ill children at high risk for AKI. The RAI combines traditional markers of AKI, such as a change in estimated creatinine clearance and fluid overload, with patient factors, including need for ventilation, inotropic support, and history of transplantation (solid organ or bone marrow) to identify those patients who are at high risk for severe AKI. Patients identified as high risk by the patient factors component of the RAI have a much lower threshold for both a decrease in creatinine clearance and fluid overload to be considered at risk for severe AKI, as these early signs are more likely to reflect an early impending severe AKI in this high-risk group. Conversely, patients that do not meet these patient factors are more likely to simply have a transient or functional AKI, and therefore have a higher threshold for both a change in creatinine clearance and fluid overload in order to be considered at high risk for severe AKI.

The RAI has been validated in the critical care setting as a method to predict severe AKI at day three of admission to the pediatric intensive care unit, with a negative predictive value of 92%-99% when the score is negative in the first 12 hours.¹⁰ In selected high-risk patients (RAI ≥ 8), biomarkers become even more reliable for AKI prediction (eg, injury markers have an excellent area under the receiver operating characteristic curve (AUC) of 0.97 for severe AKI prediction in this high-risk group).¹¹ While only validated for critically ill patients, the concept of renal angina is still applicable in the complex populations managed by hospitalists who practice outside of the intensive care unit setting. Early signs of renal dysfunction (eg, rising SCr, fluid overload ≥5%) in patients with risk factors (see below) should prompt a thorough evaluation, including urinalysis, daily SCr, nephrotoxin avoidance, and tissue injury biomarkers, if available.

The risk factors for AKI are numerous and tend to potentiate one another. The most frequent predisposing comorbidities include CKD, heart failure or congenital heart diseases, transplantation (bone marrow or solid organs), and diabetes. Disease-related factors include sepsis, cardiac surgery, cardio-pulmonary bypass, mechanical ventilation, and vasopressor use. Potentially modifiable factors include hypovolemia and multiple nephrotoxic exposures. ^2,3

Nephrotoxic medications are now among the most common causes of AKI in hospitalized children.¹² Approximately 80% of children are exposed to at least one nephrotoxin during an inpatient admission.¹² Exposure to a single nephrotoxic medication is sufficient to place a child at risk of AKI, and each additional nephrotoxin further increases the risk.¹² While some drugs are routinely recognized to be nephrotoxic (eg, ibuprofen), others are commonly overlooked, notably certain antibiotics (eg, cefotaxime, ceftazidime, cefuroxime, nafcillin, and piperacillin) and anticonvulsants (eg, zonisamide).¹² Furthermore, the combination of multiple nephrotoxins can potentiate the risk of AKI. For example, the combination of vancomycin and piperacillin/tazobactam increases the risk of AKI by 3.4 times compared with the combination of vancomycin with another antipseudomonal beta-lactam antibiotic.¹³

Adequate monitoring, including daily SCr measurements and risk awareness, are critical as nephrotoxin-associated AKI can be easily missed in the absence of routine SCr monitoring, especially since these children are typically nonoliguric¹². Quality improvement efforts focused on obtaining daily SCr in patients exposed to either three or more nephrotoxins or three days of either aminoglycoside or vancomycin, even without concomitant exposure to other nephrotoxins, have shown success in decreasing both the number of nephrotoxins and the rate of nephrotoxin-associated AKI.¹²

While a significant injury cannot always be avoided, a mindful clinical approach and management can help to prevent some complications of AKI. An awareness of fluid status is critical, as fluid overload greater than 10% of the patient’s weight independently increases the risk of mortality in both adults and children.¹⁴ To assess the risk of AKI progression and potential failure of conservative management with diuretics, a furosemide stress test (FST) is an easy, safe, and accessible functional assessment of tubular reserve in a patient without intravascular depletion.¹⁵ A growing body of literature in adults shows that FST-responders are less likely to progress to stage 3 AKI or need renal replacement therapy than nonresponders.¹⁵ The FST is currently being investigated and standardized in children.

Research in AKI has made significant strides over the last few years. Nevertheless, many areas of research remain to be explored (eg, the impact of IV fluid type in the pediatric population, AKD characterization and impact on CKD development). AKI is common, associated with significant morbidity and mortality and, in some instances, preventable. While no targeted therapeutic options are currently under investigation, recent advances allow for better identification of high-risk patients and offer opportunities for impactful preventive approaches. Thoughtful use of nephrotoxic medications, early identification of patients at high risk for AKI, and accurate diagnosis and appropriate management of AKI are the recommended best practice.

Disclosures

The authors have nothing to disclose.

Systematic efforts to measure and compare work hours emerged in the 19^th century as laborers shifted from artisanal shops to factories, sparking debate over the appropriate length and intensity of work.¹ Two centuries of unionization and regulation defined work hours for many United States employees, including graduate medical trainees, but left attending physicians largely untouched. Instead, the medical workforce has long relied on survey data to shape jobs that balance professional norms with local market demands. Leaders in young, dynamic specialties, such as pediatric hospital medicine (PHM), particularly require such data to recruit and retain talent.

PHM progressed swiftly from acknowledgment as a “distinct area of practice” in 1999 to a subspecialty recognition.² Currently, at least 3,000 pediatric hospitalists³ practice in more than 800 US sites (Snow C, Personal communication regarding community PHM workforce survey). Approximately half of them work at community hospitals, where PHM groups often comprise fewer than five full-time equivalents (FTEs) and face unique challenges. Community PHM practices may assume broader responsibilities than university/children’s hospital colleagues, including advocacy for the needs of children in predominantly adult-oriented hospitals.⁴ Although data regarding academic PHM work demands are available,⁵ there is little information pertaining to community hospitalists regarding typical workloads or other characteristics of thriving practices.

In this issue of the Journal of Hospital Medicine, Alvarez et al. present the findings of structured interviews with 70 community PHM group leaders.⁶ Each participant answered 12 questions about their group, addressing the definition of a full-time workload and hours, the design of backup systems, and the respondent’s perception of the program’s sustainability. The sample is robust, with the caveats that it disproportionately represents the Midwest and West (34.3% each) and more than half of the groups were employed by an academic institution. The authors found a median work expectation per FTE of 1,882 hours/year and 21 weekends per year, although they noted significant variability in employers’ demands and services provided. The majority of hospitalist groups lacked census caps, formal backup systems, or processes to expand coverage during busy seasons. Among the site leaders, 63% perceived their program as sustainable, but no program design or employer characteristic was clearly associated with this perception.

The importance of this study derives from aggregating data about the largest cross section of community PHM groups yet reported. For many PHM group leaders, this will offer a new point of reference for key practice characteristics. Furthermore, the authors should be commended for attempting to distinguish how program sustainability manifests in community PHM, where hospitalists shoulder longer patient care hours and many of them sustain academic endeavors. It is concerning that more than a third of leaders do not perceive their program as sustainable, but the implications for the field are unclear. Perhaps part of this uncertainty arises from the terminology, as sustainability lacks a technical or a consensus definition and the authors purposefully did not define the term for the respondents. While many respondents probably worried about physician burnout, others might have channeled fears about group finances or competition with adult service lines for beds. In addition, leaders’ fears about sustainability may not exactly represent the concerns of front-line employees.

Sustainable work environments are complex constructs with several inputs. For example, supportive leaders, efficient delivery systems, optimized EHRs, competitive pay, and confidence about service line stability might all mitigate higher workloads. Ultimately, this complexity underscores an important caution about all workplace surveys in medicine; ie, average values can inform practice design, but hospitalists and administrators should always consider the local context. Blindly applying medians as benchmarks and ignoring the myriad other contributors to sustainable practice risk disrupting successful PHM programs. In other words, surveys describe how the world is, not how it should be. The spectrum of academic work and norms permeating community PHM groups instead call for a nuanced approach.

How does the field build upon this useful paper? First, the Society of Hospital Medicine (SHM) should engage PHM leaders to increase participation in regular remeasurement, a critical endeavor for this dynamic field. SHM’s State of Hospital Medicine Report queries about a wider variety of practice characteristics, but it has a smaller sample size that must grow to fill this void.⁷ As the work of repeated surveys transitions from academic inquiry to professional society service, SHM’s Practice Analysis Committee can meet the needs of PHM through relevant questions and efforts to foster adequate participation. Second, all practice leaders should follow the ballooning bodies of literature about burnout and healthcare value. Just as labor leaders had discovered in the industrial revolution, sustainable careers require not only measuring work hours but also advocating for safe, meaningful, and engaging work conditions. By continuously creating value for patients, families, and hospitals, we can strengthen our claim to the resources needed to optimize the work environment.

Disclosure

Andrew White is Chair of the Society of Hospital Medicine’s Practice Analysis Committee, an unpaid position. Dr. Marek serves on the American Academy of Pediatrics Section on Hospital Medicine Executive Committee which is a voluntary, unpaid, elected position.

Systematic efforts to measure and compare work hours emerged in the 19^th century as laborers shifted from artisanal shops to factories, sparking debate over the appropriate length and intensity of work.¹ Two centuries of unionization and regulation defined work hours for many United States employees, including graduate medical trainees, but left attending physicians largely untouched. Instead, the medical workforce has long relied on survey data to shape jobs that balance professional norms with local market demands. Leaders in young, dynamic specialties, such as pediatric hospital medicine (PHM), particularly require such data to recruit and retain talent.

PHM progressed swiftly from acknowledgment as a “distinct area of practice” in 1999 to a subspecialty recognition.² Currently, at least 3,000 pediatric hospitalists³ practice in more than 800 US sites (Snow C, Personal communication regarding community PHM workforce survey). Approximately half of them work at community hospitals, where PHM groups often comprise fewer than five full-time equivalents (FTEs) and face unique challenges. Community PHM practices may assume broader responsibilities than university/children’s hospital colleagues, including advocacy for the needs of children in predominantly adult-oriented hospitals.⁴ Although data regarding academic PHM work demands are available,⁵ there is little information pertaining to community hospitalists regarding typical workloads or other characteristics of thriving practices.

In this issue of the Journal of Hospital Medicine, Alvarez et al. present the findings of structured interviews with 70 community PHM group leaders.⁶ Each participant answered 12 questions about their group, addressing the definition of a full-time workload and hours, the design of backup systems, and the respondent’s perception of the program’s sustainability. The sample is robust, with the caveats that it disproportionately represents the Midwest and West (34.3% each) and more than half of the groups were employed by an academic institution. The authors found a median work expectation per FTE of 1,882 hours/year and 21 weekends per year, although they noted significant variability in employers’ demands and services provided. The majority of hospitalist groups lacked census caps, formal backup systems, or processes to expand coverage during busy seasons. Among the site leaders, 63% perceived their program as sustainable, but no program design or employer characteristic was clearly associated with this perception.

The importance of this study derives from aggregating data about the largest cross section of community PHM groups yet reported. For many PHM group leaders, this will offer a new point of reference for key practice characteristics. Furthermore, the authors should be commended for attempting to distinguish how program sustainability manifests in community PHM, where hospitalists shoulder longer patient care hours and many of them sustain academic endeavors. It is concerning that more than a third of leaders do not perceive their program as sustainable, but the implications for the field are unclear. Perhaps part of this uncertainty arises from the terminology, as sustainability lacks a technical or a consensus definition and the authors purposefully did not define the term for the respondents. While many respondents probably worried about physician burnout, others might have channeled fears about group finances or competition with adult service lines for beds. In addition, leaders’ fears about sustainability may not exactly represent the concerns of front-line employees.

Sustainable work environments are complex constructs with several inputs. For example, supportive leaders, efficient delivery systems, optimized EHRs, competitive pay, and confidence about service line stability might all mitigate higher workloads. Ultimately, this complexity underscores an important caution about all workplace surveys in medicine; ie, average values can inform practice design, but hospitalists and administrators should always consider the local context. Blindly applying medians as benchmarks and ignoring the myriad other contributors to sustainable practice risk disrupting successful PHM programs. In other words, surveys describe how the world is, not how it should be. The spectrum of academic work and norms permeating community PHM groups instead call for a nuanced approach.

How does the field build upon this useful paper? First, the Society of Hospital Medicine (SHM) should engage PHM leaders to increase participation in regular remeasurement, a critical endeavor for this dynamic field. SHM’s State of Hospital Medicine Report queries about a wider variety of practice characteristics, but it has a smaller sample size that must grow to fill this void.⁷ As the work of repeated surveys transitions from academic inquiry to professional society service, SHM’s Practice Analysis Committee can meet the needs of PHM through relevant questions and efforts to foster adequate participation. Second, all practice leaders should follow the ballooning bodies of literature about burnout and healthcare value. Just as labor leaders had discovered in the industrial revolution, sustainable careers require not only measuring work hours but also advocating for safe, meaningful, and engaging work conditions. By continuously creating value for patients, families, and hospitals, we can strengthen our claim to the resources needed to optimize the work environment.

Disclosure

Andrew White is Chair of the Society of Hospital Medicine’s Practice Analysis Committee, an unpaid position. Dr. Marek serves on the American Academy of Pediatrics Section on Hospital Medicine Executive Committee which is a voluntary, unpaid, elected position.

Systematic efforts to measure and compare work hours emerged in the 19^th century as laborers shifted from artisanal shops to factories, sparking debate over the appropriate length and intensity of work.¹ Two centuries of unionization and regulation defined work hours for many United States employees, including graduate medical trainees, but left attending physicians largely untouched. Instead, the medical workforce has long relied on survey data to shape jobs that balance professional norms with local market demands. Leaders in young, dynamic specialties, such as pediatric hospital medicine (PHM), particularly require such data to recruit and retain talent.

PHM progressed swiftly from acknowledgment as a “distinct area of practice” in 1999 to a subspecialty recognition.² Currently, at least 3,000 pediatric hospitalists³ practice in more than 800 US sites (Snow C, Personal communication regarding community PHM workforce survey). Approximately half of them work at community hospitals, where PHM groups often comprise fewer than five full-time equivalents (FTEs) and face unique challenges. Community PHM practices may assume broader responsibilities than university/children’s hospital colleagues, including advocacy for the needs of children in predominantly adult-oriented hospitals.⁴ Although data regarding academic PHM work demands are available,⁵ there is little information pertaining to community hospitalists regarding typical workloads or other characteristics of thriving practices.

In this issue of the Journal of Hospital Medicine, Alvarez et al. present the findings of structured interviews with 70 community PHM group leaders.⁶ Each participant answered 12 questions about their group, addressing the definition of a full-time workload and hours, the design of backup systems, and the respondent’s perception of the program’s sustainability. The sample is robust, with the caveats that it disproportionately represents the Midwest and West (34.3% each) and more than half of the groups were employed by an academic institution. The authors found a median work expectation per FTE of 1,882 hours/year and 21 weekends per year, although they noted significant variability in employers’ demands and services provided. The majority of hospitalist groups lacked census caps, formal backup systems, or processes to expand coverage during busy seasons. Among the site leaders, 63% perceived their program as sustainable, but no program design or employer characteristic was clearly associated with this perception.

The importance of this study derives from aggregating data about the largest cross section of community PHM groups yet reported. For many PHM group leaders, this will offer a new point of reference for key practice characteristics. Furthermore, the authors should be commended for attempting to distinguish how program sustainability manifests in community PHM, where hospitalists shoulder longer patient care hours and many of them sustain academic endeavors. It is concerning that more than a third of leaders do not perceive their program as sustainable, but the implications for the field are unclear. Perhaps part of this uncertainty arises from the terminology, as sustainability lacks a technical or a consensus definition and the authors purposefully did not define the term for the respondents. While many respondents probably worried about physician burnout, others might have channeled fears about group finances or competition with adult service lines for beds. In addition, leaders’ fears about sustainability may not exactly represent the concerns of front-line employees.

Sustainable work environments are complex constructs with several inputs. For example, supportive leaders, efficient delivery systems, optimized EHRs, competitive pay, and confidence about service line stability might all mitigate higher workloads. Ultimately, this complexity underscores an important caution about all workplace surveys in medicine; ie, average values can inform practice design, but hospitalists and administrators should always consider the local context. Blindly applying medians as benchmarks and ignoring the myriad other contributors to sustainable practice risk disrupting successful PHM programs. In other words, surveys describe how the world is, not how it should be. The spectrum of academic work and norms permeating community PHM groups instead call for a nuanced approach.

How does the field build upon this useful paper? First, the Society of Hospital Medicine (SHM) should engage PHM leaders to increase participation in regular remeasurement, a critical endeavor for this dynamic field. SHM’s State of Hospital Medicine Report queries about a wider variety of practice characteristics, but it has a smaller sample size that must grow to fill this void.⁷ As the work of repeated surveys transitions from academic inquiry to professional society service, SHM’s Practice Analysis Committee can meet the needs of PHM through relevant questions and efforts to foster adequate participation. Second, all practice leaders should follow the ballooning bodies of literature about burnout and healthcare value. Just as labor leaders had discovered in the industrial revolution, sustainable careers require not only measuring work hours but also advocating for safe, meaningful, and engaging work conditions. By continuously creating value for patients, families, and hospitals, we can strengthen our claim to the resources needed to optimize the work environment.

Disclosure

Andrew White is Chair of the Society of Hospital Medicine’s Practice Analysis Committee, an unpaid position. Dr. Marek serves on the American Academy of Pediatrics Section on Hospital Medicine Executive Committee which is a voluntary, unpaid, elected position.

Combination brentuximab vedotin and nivolumab showed manageable safety and high activity in patients with relapsed/refractory primary mediastinal B-cell lymphoma (PMBL), according to results from a phase 2 trial.

“We evaluated whether the combination of nivolumab and [brentuximab vedotin] was safe and synergistically effective in patients with [relapsed/refractory] PMBL,” Pier Luigi Zinzani, MD, PhD, of the University of Bologna (Italy), and colleagues wrote in the Journal of Clinical Oncology.

The CheckMate 436 study is a multicenter, open-label, phase 1-2 study that included patients with relapsed/refractory disease who had previously received autologous stem cell transplantation (ASCT) or had two or more previous chemotherapy regimens for those ineligible for ASCT.

The phase 2 component evaluated the safety and efficacy of the two-drug combo in an expansion cohort of 30 patients. Study participants received intravenous brentuximab vedotin at 1.8 mg/kg and nivolumab at 240 mg every 3 weeks until cancer progression or intolerable adverse effects.

The primary outcomes were the investigator-evaluated objective response rate and safety. Secondary outcomes included progression-free survival, complete remission rate, overall duration of response, among other measures.

After analysis, the researchers reported that 53% of patients had grade 3 or 4 treatment-related toxicities following a median of five treatment cycles. The most common treatment-related toxicities were neutropenia (30%) and peripheral neuropathy (27%).

Five patients died during the study follow-up, four because of disease progression and one as a result of sepsis that was not considered related to treatment.

At a median follow-up of 11.1 months, the objective response rate was 73% in study participants, including 11 patients (37%) who achieved a complete response and 11 patients (37%) who had a partial response. An additional three patients had stable disease.

The median progression-free survival, duration of response, and overall survival were not reached in this study.

“The combination of nivolumab and [brentuximab vedotin] may be synergistic and is highly active in patients with [relapsed/refractory] PMBL, serving as a potential bridge to other consolidative therapies of curative intent,” the researchers wrote.

The study was funded by Bristol-Myers Squibb and Seattle Genetics. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Zinzani PL et al. J Clin Oncol. 2019 Aug 9. doi: 10.1200/JCO.19.01492.

Combination brentuximab vedotin and nivolumab showed manageable safety and high activity in patients with relapsed/refractory primary mediastinal B-cell lymphoma (PMBL), according to results from a phase 2 trial.

“We evaluated whether the combination of nivolumab and [brentuximab vedotin] was safe and synergistically effective in patients with [relapsed/refractory] PMBL,” Pier Luigi Zinzani, MD, PhD, of the University of Bologna (Italy), and colleagues wrote in the Journal of Clinical Oncology.

The CheckMate 436 study is a multicenter, open-label, phase 1-2 study that included patients with relapsed/refractory disease who had previously received autologous stem cell transplantation (ASCT) or had two or more previous chemotherapy regimens for those ineligible for ASCT.

The phase 2 component evaluated the safety and efficacy of the two-drug combo in an expansion cohort of 30 patients. Study participants received intravenous brentuximab vedotin at 1.8 mg/kg and nivolumab at 240 mg every 3 weeks until cancer progression or intolerable adverse effects.

The primary outcomes were the investigator-evaluated objective response rate and safety. Secondary outcomes included progression-free survival, complete remission rate, overall duration of response, among other measures.

After analysis, the researchers reported that 53% of patients had grade 3 or 4 treatment-related toxicities following a median of five treatment cycles. The most common treatment-related toxicities were neutropenia (30%) and peripheral neuropathy (27%).

Five patients died during the study follow-up, four because of disease progression and one as a result of sepsis that was not considered related to treatment.

At a median follow-up of 11.1 months, the objective response rate was 73% in study participants, including 11 patients (37%) who achieved a complete response and 11 patients (37%) who had a partial response. An additional three patients had stable disease.

The median progression-free survival, duration of response, and overall survival were not reached in this study.

“The combination of nivolumab and [brentuximab vedotin] may be synergistic and is highly active in patients with [relapsed/refractory] PMBL, serving as a potential bridge to other consolidative therapies of curative intent,” the researchers wrote.

The study was funded by Bristol-Myers Squibb and Seattle Genetics. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Zinzani PL et al. J Clin Oncol. 2019 Aug 9. doi: 10.1200/JCO.19.01492.

Combination brentuximab vedotin and nivolumab showed manageable safety and high activity in patients with relapsed/refractory primary mediastinal B-cell lymphoma (PMBL), according to results from a phase 2 trial.

“We evaluated whether the combination of nivolumab and [brentuximab vedotin] was safe and synergistically effective in patients with [relapsed/refractory] PMBL,” Pier Luigi Zinzani, MD, PhD, of the University of Bologna (Italy), and colleagues wrote in the Journal of Clinical Oncology.

The CheckMate 436 study is a multicenter, open-label, phase 1-2 study that included patients with relapsed/refractory disease who had previously received autologous stem cell transplantation (ASCT) or had two or more previous chemotherapy regimens for those ineligible for ASCT.

The phase 2 component evaluated the safety and efficacy of the two-drug combo in an expansion cohort of 30 patients. Study participants received intravenous brentuximab vedotin at 1.8 mg/kg and nivolumab at 240 mg every 3 weeks until cancer progression or intolerable adverse effects.

The primary outcomes were the investigator-evaluated objective response rate and safety. Secondary outcomes included progression-free survival, complete remission rate, overall duration of response, among other measures.

After analysis, the researchers reported that 53% of patients had grade 3 or 4 treatment-related toxicities following a median of five treatment cycles. The most common treatment-related toxicities were neutropenia (30%) and peripheral neuropathy (27%).

Five patients died during the study follow-up, four because of disease progression and one as a result of sepsis that was not considered related to treatment.

At a median follow-up of 11.1 months, the objective response rate was 73% in study participants, including 11 patients (37%) who achieved a complete response and 11 patients (37%) who had a partial response. An additional three patients had stable disease.

The median progression-free survival, duration of response, and overall survival were not reached in this study.

“The combination of nivolumab and [brentuximab vedotin] may be synergistic and is highly active in patients with [relapsed/refractory] PMBL, serving as a potential bridge to other consolidative therapies of curative intent,” the researchers wrote.

The study was funded by Bristol-Myers Squibb and Seattle Genetics. The authors reported financial affiliations with the study sponsors and several other companies.

SOURCE: Zinzani PL et al. J Clin Oncol. 2019 Aug 9. doi: 10.1200/JCO.19.01492.

Both overall and unsubsidized enrollment in the various state and federal health insurance exchanges dropped in 2018, but new data on payments for those policies show that more people paid their premiums in 2019, according to the Centers for Medicare & Medicaid Services.

The number of policies selected with the individual insurance exchanges in late 2018 for which premiums were paid in February 2019 (termed the effectuated enrollment) was almost 10.6 million, or more than 92% of the 11.4 million plans selected during open enrollment, CMS reported. For February 2018, effectuated enrollment was just over 10.5 million, which represented 89.5% of the nearly 11.8 million policies selected during the previous open enrollment.

Over the longer term, the trend has been a rise and a fall as average monthly effectuated enrollment peaked in 2016 and dropped 16.5% by 2018, CMS data show.

A look at the advance premium tax credit (APTC) provides some insight into that decline. The population subsidized by the APTC has been fairly stable since 2016 – effectuated enrollment rose by just over 1% – but the number of unsubsidized enrollees has dropped 40% as 2.5 million people who did not qualify for the APTC left the market, the CMS said.

From 2017 to 2018, there were 47 states with declines in unsubsidized enrollment, with 9 states losing more than 40% of such enrollees. The largest drop in the unsubsidized population (85%) came in Iowa, while Alaska’s 7% gain was the largest increase, the CMS reported.

“As President Trump predicted, people are fleeing the individual market. Obamacare is failing the American people, and the ongoing exodus of the unsubsidized population from the market proves that Obamacare’s sky-high premiums are unaffordable,” CMS Administrator Seema Verma said in a written statement.

[email protected]

Both overall and unsubsidized enrollment in the various state and federal health insurance exchanges dropped in 2018, but new data on payments for those policies show that more people paid their premiums in 2019, according to the Centers for Medicare & Medicaid Services.

The number of policies selected with the individual insurance exchanges in late 2018 for which premiums were paid in February 2019 (termed the effectuated enrollment) was almost 10.6 million, or more than 92% of the 11.4 million plans selected during open enrollment, CMS reported. For February 2018, effectuated enrollment was just over 10.5 million, which represented 89.5% of the nearly 11.8 million policies selected during the previous open enrollment.

Over the longer term, the trend has been a rise and a fall as average monthly effectuated enrollment peaked in 2016 and dropped 16.5% by 2018, CMS data show.

A look at the advance premium tax credit (APTC) provides some insight into that decline. The population subsidized by the APTC has been fairly stable since 2016 – effectuated enrollment rose by just over 1% – but the number of unsubsidized enrollees has dropped 40% as 2.5 million people who did not qualify for the APTC left the market, the CMS said.

From 2017 to 2018, there were 47 states with declines in unsubsidized enrollment, with 9 states losing more than 40% of such enrollees. The largest drop in the unsubsidized population (85%) came in Iowa, while Alaska’s 7% gain was the largest increase, the CMS reported.

“As President Trump predicted, people are fleeing the individual market. Obamacare is failing the American people, and the ongoing exodus of the unsubsidized population from the market proves that Obamacare’s sky-high premiums are unaffordable,” CMS Administrator Seema Verma said in a written statement.

[email protected]

Both overall and unsubsidized enrollment in the various state and federal health insurance exchanges dropped in 2018, but new data on payments for those policies show that more people paid their premiums in 2019, according to the Centers for Medicare & Medicaid Services.

The number of policies selected with the individual insurance exchanges in late 2018 for which premiums were paid in February 2019 (termed the effectuated enrollment) was almost 10.6 million, or more than 92% of the 11.4 million plans selected during open enrollment, CMS reported. For February 2018, effectuated enrollment was just over 10.5 million, which represented 89.5% of the nearly 11.8 million policies selected during the previous open enrollment.

Over the longer term, the trend has been a rise and a fall as average monthly effectuated enrollment peaked in 2016 and dropped 16.5% by 2018, CMS data show.

A look at the advance premium tax credit (APTC) provides some insight into that decline. The population subsidized by the APTC has been fairly stable since 2016 – effectuated enrollment rose by just over 1% – but the number of unsubsidized enrollees has dropped 40% as 2.5 million people who did not qualify for the APTC left the market, the CMS said.

From 2017 to 2018, there were 47 states with declines in unsubsidized enrollment, with 9 states losing more than 40% of such enrollees. The largest drop in the unsubsidized population (85%) came in Iowa, while Alaska’s 7% gain was the largest increase, the CMS reported.

“As President Trump predicted, people are fleeing the individual market. Obamacare is failing the American people, and the ongoing exodus of the unsubsidized population from the market proves that Obamacare’s sky-high premiums are unaffordable,” CMS Administrator Seema Verma said in a written statement.

[email protected]

To the Editor:

Long, dark, and thick eyelashes have been a focal point of society’s perception of beauty for thousands of years,¹ and the use of makeup products such as mascaras, eyeliners, and eye shadows has further increased the perception of attractiveness of the eyes.² Many eyelash enhancement methods have been developed or in some instances have been serendipitously discovered. Bimatoprost ophthalmic solution 0.03% originally was developed as an eye drop that was approved by the US Food and Drug Association (FDA) in 2001 for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. An unexpected side effect of this product was eyelash hypertrichosis.^3,4 As a result, the FDA approved bimatoprost ophthalmic solution 0.03% as an eyelash solution with an eyelid applicator for treatment of eyelash hypotrichosis in 2008.⁵

Because all follicular development occurs during embryogenesis, the number of eyelash follicles does not increase over time.⁶ Bitmatoprost eyelash solution works by prolonging the anagen (growth) phase of the eyelashes and stimulating the transition from the telogen (dormant) phase to the anagen phase. It also has been shown to increase the hair bulb diameter of follicles undergoing the anagen phase, resulting in thicker eyelashes.⁷ Although many patients have enjoyed this unexpected indication, prostaglandin (PG) analogues such as bimatoprost and latanoprost have a well-documented history of ocular side effects when applied directly to the eye. The most common adverse reactions include eye pruritus, conjunctival hyperemia, and eyelid pigmentation.³ The product safety information indicates that eyelid pigmentation typically is reversible.^3,5 Iris pigmentation is perhaps the least desirable side effect of PG analogues and was first noted in latanoprost studies on primates.⁸ The underlying mechanism appears to be due to an increase in melanogenesis that results in an increase in melanin granules without concomitant proliferation of melanocytes, cellular atypia, or evidence of inflammatory reaction. Unfortunately, this pigmentation typically is permanent.^3,5,9

Studies have shown that iris hyperpigmentation can occur when bimatoprost eye drops are applied to the eyes for the treatment of glaucoma and ocular hypertension, but reports associated with bimatoprost eyelash solution are rare.^3,4,10 We report a case of iris hyperpigmentation following cosmetic use of bimatoprost eyelash solution.

An otherwise healthy 63-year-old woman presented to our clinic for an annual skin examination. She noted that she had worsening dark pigmentation of the bilateral irises. The patient did not have any personal or family history of melanoma or ocular nevi, and there were no associated symptoms of eye tearing, pruritus, burning, or discharge. No prior surgical procedures had been performed on or around the eyes, and the patient never used contact lenses. She had been intermittently using bimatoprost eyelash solution prescribed by an outside physician for approximately 3 years to enhance her eyelashes. Although she never applied the product directly into her eyes, she noted that she often was unmethodical in application of the product and that runoff from the product may have occasionally leaked into the eyes. Physical examination revealed bilateral blue irises with ink spot–like, grayish black patches encircling the bilateral pupils (Figure).

There have been several studies of iris hyperpigmentation with use of PG analogues in the treatment of glaucoma. In a phase 3 clinical trial of the safety and efficacy of latanoprost for treatment of ocular hypertension, it was noted that 24 (12%) of 198 patients experienced iris hyperpigmentation and that patients with heterogeneous pigmentation (ie, hazel irises and mixed coloring) were at an increased risk.¹¹ Other studies also have shown an increased risk of iris hyperpigmentation due to heterogeneous phenotype¹² as well as older age.¹³

Reports of bimatoprost eye drops used for treatment of glaucoma have shown a high incidence of iris hyperpigmentation with long-term use. A prospective study conducted in 2012 investigated the adverse events of bimatoprost eye drops in 52 Japanese patients with glaucoma or ocular hypertension. Clinical photographs of the irises, eyelids, and eyelashes were taken at baseline and after 6 months of treatment. It was noted that 50% (26/52) of participants experienced iris hyperpigmentation upon completion of treatment.¹⁰

In our patient, bimatoprost eyelash solution was applied to the top eyelid margins using an applicator; our patient did not use the eye drop formulation, which is directed for use in ocular hypertension or glaucoma. A PubMed search of articles indexed for MEDLINE using the terms bimatoprost and iris hyperpigmentation yielded no published peer-reviewed studies or case reports of iris hyperpigmentation caused by bimatoprost eyelash solution for treatment of eyelid hypotrichosis, which makes this case report novel. With that said, the package insert states iris hyperpigmentation as a side effect in the prescribing information for both a bimatoprost eye drop formulation used to treat ocular hypertension³ as well as a formulation for topical application on the eyelids/eyelashes.⁵ A 2014 retrospective review of long-term safety with bimatoprost eyelash solution for eyelash hypotrichosis reported 4 instances (0.7%) of documented adverse events after 12 months of use in 585 patients, including dry eye, eyelid erythema, ocular pruritus, and low ocular pressure. Iris hyperpigmentation was not reported.¹⁴

The method of bimatoprost application likely is a determining factor in the number of reported adverse events. Studies with similar treatment periods have demonstrated more adverse events associated with bimatoprost eye drops vs eyelash solution.^15,16 When bimatoprost is used in the eye drop formulation for treatment of glaucoma, iris hyperpigmentation has been estimated to occur in 1.5%⁴ to 50%⁹ of cases. To our knowledge, there are no documented cases when bimatoprost eyelash solution is applied with a dermal applicator for treatment of eyelash hypotrichosis.^15,17 These results may be explained using an ocular splash test. In one study using lissamine green dye, decreased delivery of bimatoprost eyelash solution with the dermal applicator was noted vs eye drop application. Additionally, it has been demonstrated that approximately 5% (based on weight) of a one-drop dose of bimatoprost eyelash solution applied to the dermal applicator is actually delivered to the patient.¹⁸ The rest of the solution remains on the applicator.

It is important that patients use bimatoprost eyelash solution as instructed in the prescribing information (eg, clean the face, remove makeup and contact lenses prior to applying the product). The eyelid should not be rinsed after application, which limits the possibility of the bimatoprost solution from contacting or pooling in the eye. One drop of bimatoprost eyelash solution should be applied to the applicator supplied by the manufacturer and distributed evenly along the skin of the upper eyelid margin at the base of the eyelashes. It is important to blot any excess solution runoff outside the upper eyelid margin.⁵ Of note, our patient admitted to not always doing this step, which may have contributed to her susceptibility to this rare side effect.

Prostaglandin analogues have been observed to cause iris hyperpigmentation when applied directly to the eye for use in the treatment of glaucoma.¹⁹ Theoretically, the same side-effect profile should apply in their use as a dermal application on the eyelids. For this reason, one manufacturer includes iris hyperpigmentation as an adverse side effect in the prescribing information.⁵ It is important for physicians who prescribe bimatoprost eyelash solution to inform patients of this rare yet possible side effect and to instruct patients on proper application to minimize hyperpigmentation.

Our literature review did not demonstrate previous cases of iris hyperpigmentation associated with bimatoprost eyelash solution. One study suggested that 2 patients experienced hypopigmentation; however, this was not clinically significant and was not consistent with the proposed iris pigmentation thought to be caused by bimatoprost eyelash solution.²⁰

Potential future applications and off-label uses of bimatoprost include treatment of eyelash hypotrichosis on the lower eyelid margin and eyebrow hypertrichosis, as well as androgenic alopecia, alopecia areata, chemotherapy-induced alopecia, vitiligo, and hypopigmented scarring.²¹ Currently, investigational studies are looking at bimatoprost ophthalmic solution 0.03% for chemotherapy-induced eyelash hypotrichosis with positive results.²² In the future, bimatoprost may be used for other off-label and possibly FDA-approved uses.

To the Editor:

Long, dark, and thick eyelashes have been a focal point of society’s perception of beauty for thousands of years,¹ and the use of makeup products such as mascaras, eyeliners, and eye shadows has further increased the perception of attractiveness of the eyes.² Many eyelash enhancement methods have been developed or in some instances have been serendipitously discovered. Bimatoprost ophthalmic solution 0.03% originally was developed as an eye drop that was approved by the US Food and Drug Association (FDA) in 2001 for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. An unexpected side effect of this product was eyelash hypertrichosis.^3,4 As a result, the FDA approved bimatoprost ophthalmic solution 0.03% as an eyelash solution with an eyelid applicator for treatment of eyelash hypotrichosis in 2008.⁵

Because all follicular development occurs during embryogenesis, the number of eyelash follicles does not increase over time.⁶ Bitmatoprost eyelash solution works by prolonging the anagen (growth) phase of the eyelashes and stimulating the transition from the telogen (dormant) phase to the anagen phase. It also has been shown to increase the hair bulb diameter of follicles undergoing the anagen phase, resulting in thicker eyelashes.⁷ Although many patients have enjoyed this unexpected indication, prostaglandin (PG) analogues such as bimatoprost and latanoprost have a well-documented history of ocular side effects when applied directly to the eye. The most common adverse reactions include eye pruritus, conjunctival hyperemia, and eyelid pigmentation.³ The product safety information indicates that eyelid pigmentation typically is reversible.^3,5 Iris pigmentation is perhaps the least desirable side effect of PG analogues and was first noted in latanoprost studies on primates.⁸ The underlying mechanism appears to be due to an increase in melanogenesis that results in an increase in melanin granules without concomitant proliferation of melanocytes, cellular atypia, or evidence of inflammatory reaction. Unfortunately, this pigmentation typically is permanent.^3,5,9

Studies have shown that iris hyperpigmentation can occur when bimatoprost eye drops are applied to the eyes for the treatment of glaucoma and ocular hypertension, but reports associated with bimatoprost eyelash solution are rare.^3,4,10 We report a case of iris hyperpigmentation following cosmetic use of bimatoprost eyelash solution.

An otherwise healthy 63-year-old woman presented to our clinic for an annual skin examination. She noted that she had worsening dark pigmentation of the bilateral irises. The patient did not have any personal or family history of melanoma or ocular nevi, and there were no associated symptoms of eye tearing, pruritus, burning, or discharge. No prior surgical procedures had been performed on or around the eyes, and the patient never used contact lenses. She had been intermittently using bimatoprost eyelash solution prescribed by an outside physician for approximately 3 years to enhance her eyelashes. Although she never applied the product directly into her eyes, she noted that she often was unmethodical in application of the product and that runoff from the product may have occasionally leaked into the eyes. Physical examination revealed bilateral blue irises with ink spot–like, grayish black patches encircling the bilateral pupils (Figure).

There have been several studies of iris hyperpigmentation with use of PG analogues in the treatment of glaucoma. In a phase 3 clinical trial of the safety and efficacy of latanoprost for treatment of ocular hypertension, it was noted that 24 (12%) of 198 patients experienced iris hyperpigmentation and that patients with heterogeneous pigmentation (ie, hazel irises and mixed coloring) were at an increased risk.¹¹ Other studies also have shown an increased risk of iris hyperpigmentation due to heterogeneous phenotype¹² as well as older age.¹³

Reports of bimatoprost eye drops used for treatment of glaucoma have shown a high incidence of iris hyperpigmentation with long-term use. A prospective study conducted in 2012 investigated the adverse events of bimatoprost eye drops in 52 Japanese patients with glaucoma or ocular hypertension. Clinical photographs of the irises, eyelids, and eyelashes were taken at baseline and after 6 months of treatment. It was noted that 50% (26/52) of participants experienced iris hyperpigmentation upon completion of treatment.¹⁰

In our patient, bimatoprost eyelash solution was applied to the top eyelid margins using an applicator; our patient did not use the eye drop formulation, which is directed for use in ocular hypertension or glaucoma. A PubMed search of articles indexed for MEDLINE using the terms bimatoprost and iris hyperpigmentation yielded no published peer-reviewed studies or case reports of iris hyperpigmentation caused by bimatoprost eyelash solution for treatment of eyelid hypotrichosis, which makes this case report novel. With that said, the package insert states iris hyperpigmentation as a side effect in the prescribing information for both a bimatoprost eye drop formulation used to treat ocular hypertension³ as well as a formulation for topical application on the eyelids/eyelashes.⁵ A 2014 retrospective review of long-term safety with bimatoprost eyelash solution for eyelash hypotrichosis reported 4 instances (0.7%) of documented adverse events after 12 months of use in 585 patients, including dry eye, eyelid erythema, ocular pruritus, and low ocular pressure. Iris hyperpigmentation was not reported.¹⁴

The method of bimatoprost application likely is a determining factor in the number of reported adverse events. Studies with similar treatment periods have demonstrated more adverse events associated with bimatoprost eye drops vs eyelash solution.^15,16 When bimatoprost is used in the eye drop formulation for treatment of glaucoma, iris hyperpigmentation has been estimated to occur in 1.5%⁴ to 50%⁹ of cases. To our knowledge, there are no documented cases when bimatoprost eyelash solution is applied with a dermal applicator for treatment of eyelash hypotrichosis.^15,17 These results may be explained using an ocular splash test. In one study using lissamine green dye, decreased delivery of bimatoprost eyelash solution with the dermal applicator was noted vs eye drop application. Additionally, it has been demonstrated that approximately 5% (based on weight) of a one-drop dose of bimatoprost eyelash solution applied to the dermal applicator is actually delivered to the patient.¹⁸ The rest of the solution remains on the applicator.

It is important that patients use bimatoprost eyelash solution as instructed in the prescribing information (eg, clean the face, remove makeup and contact lenses prior to applying the product). The eyelid should not be rinsed after application, which limits the possibility of the bimatoprost solution from contacting or pooling in the eye. One drop of bimatoprost eyelash solution should be applied to the applicator supplied by the manufacturer and distributed evenly along the skin of the upper eyelid margin at the base of the eyelashes. It is important to blot any excess solution runoff outside the upper eyelid margin.⁵ Of note, our patient admitted to not always doing this step, which may have contributed to her susceptibility to this rare side effect.

Prostaglandin analogues have been observed to cause iris hyperpigmentation when applied directly to the eye for use in the treatment of glaucoma.¹⁹ Theoretically, the same side-effect profile should apply in their use as a dermal application on the eyelids. For this reason, one manufacturer includes iris hyperpigmentation as an adverse side effect in the prescribing information.⁵ It is important for physicians who prescribe bimatoprost eyelash solution to inform patients of this rare yet possible side effect and to instruct patients on proper application to minimize hyperpigmentation.

Our literature review did not demonstrate previous cases of iris hyperpigmentation associated with bimatoprost eyelash solution. One study suggested that 2 patients experienced hypopigmentation; however, this was not clinically significant and was not consistent with the proposed iris pigmentation thought to be caused by bimatoprost eyelash solution.²⁰

Potential future applications and off-label uses of bimatoprost include treatment of eyelash hypotrichosis on the lower eyelid margin and eyebrow hypertrichosis, as well as androgenic alopecia, alopecia areata, chemotherapy-induced alopecia, vitiligo, and hypopigmented scarring.²¹ Currently, investigational studies are looking at bimatoprost ophthalmic solution 0.03% for chemotherapy-induced eyelash hypotrichosis with positive results.²² In the future, bimatoprost may be used for other off-label and possibly FDA-approved uses.

To the Editor:

Long, dark, and thick eyelashes have been a focal point of society’s perception of beauty for thousands of years,¹ and the use of makeup products such as mascaras, eyeliners, and eye shadows has further increased the perception of attractiveness of the eyes.² Many eyelash enhancement methods have been developed or in some instances have been serendipitously discovered. Bimatoprost ophthalmic solution 0.03% originally was developed as an eye drop that was approved by the US Food and Drug Association (FDA) in 2001 for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension. An unexpected side effect of this product was eyelash hypertrichosis.^3,4 As a result, the FDA approved bimatoprost ophthalmic solution 0.03% as an eyelash solution with an eyelid applicator for treatment of eyelash hypotrichosis in 2008.⁵

Because all follicular development occurs during embryogenesis, the number of eyelash follicles does not increase over time.⁶ Bitmatoprost eyelash solution works by prolonging the anagen (growth) phase of the eyelashes and stimulating the transition from the telogen (dormant) phase to the anagen phase. It also has been shown to increase the hair bulb diameter of follicles undergoing the anagen phase, resulting in thicker eyelashes.⁷ Although many patients have enjoyed this unexpected indication, prostaglandin (PG) analogues such as bimatoprost and latanoprost have a well-documented history of ocular side effects when applied directly to the eye. The most common adverse reactions include eye pruritus, conjunctival hyperemia, and eyelid pigmentation.³ The product safety information indicates that eyelid pigmentation typically is reversible.^3,5 Iris pigmentation is perhaps the least desirable side effect of PG analogues and was first noted in latanoprost studies on primates.⁸ The underlying mechanism appears to be due to an increase in melanogenesis that results in an increase in melanin granules without concomitant proliferation of melanocytes, cellular atypia, or evidence of inflammatory reaction. Unfortunately, this pigmentation typically is permanent.^3,5,9

Studies have shown that iris hyperpigmentation can occur when bimatoprost eye drops are applied to the eyes for the treatment of glaucoma and ocular hypertension, but reports associated with bimatoprost eyelash solution are rare.^3,4,10 We report a case of iris hyperpigmentation following cosmetic use of bimatoprost eyelash solution.

An otherwise healthy 63-year-old woman presented to our clinic for an annual skin examination. She noted that she had worsening dark pigmentation of the bilateral irises. The patient did not have any personal or family history of melanoma or ocular nevi, and there were no associated symptoms of eye tearing, pruritus, burning, or discharge. No prior surgical procedures had been performed on or around the eyes, and the patient never used contact lenses. She had been intermittently using bimatoprost eyelash solution prescribed by an outside physician for approximately 3 years to enhance her eyelashes. Although she never applied the product directly into her eyes, she noted that she often was unmethodical in application of the product and that runoff from the product may have occasionally leaked into the eyes. Physical examination revealed bilateral blue irises with ink spot–like, grayish black patches encircling the bilateral pupils (Figure).

There have been several studies of iris hyperpigmentation with use of PG analogues in the treatment of glaucoma. In a phase 3 clinical trial of the safety and efficacy of latanoprost for treatment of ocular hypertension, it was noted that 24 (12%) of 198 patients experienced iris hyperpigmentation and that patients with heterogeneous pigmentation (ie, hazel irises and mixed coloring) were at an increased risk.¹¹ Other studies also have shown an increased risk of iris hyperpigmentation due to heterogeneous phenotype¹² as well as older age.¹³

Reports of bimatoprost eye drops used for treatment of glaucoma have shown a high incidence of iris hyperpigmentation with long-term use. A prospective study conducted in 2012 investigated the adverse events of bimatoprost eye drops in 52 Japanese patients with glaucoma or ocular hypertension. Clinical photographs of the irises, eyelids, and eyelashes were taken at baseline and after 6 months of treatment. It was noted that 50% (26/52) of participants experienced iris hyperpigmentation upon completion of treatment.¹⁰

In our patient, bimatoprost eyelash solution was applied to the top eyelid margins using an applicator; our patient did not use the eye drop formulation, which is directed for use in ocular hypertension or glaucoma. A PubMed search of articles indexed for MEDLINE using the terms bimatoprost and iris hyperpigmentation yielded no published peer-reviewed studies or case reports of iris hyperpigmentation caused by bimatoprost eyelash solution for treatment of eyelid hypotrichosis, which makes this case report novel. With that said, the package insert states iris hyperpigmentation as a side effect in the prescribing information for both a bimatoprost eye drop formulation used to treat ocular hypertension³ as well as a formulation for topical application on the eyelids/eyelashes.⁵ A 2014 retrospective review of long-term safety with bimatoprost eyelash solution for eyelash hypotrichosis reported 4 instances (0.7%) of documented adverse events after 12 months of use in 585 patients, including dry eye, eyelid erythema, ocular pruritus, and low ocular pressure. Iris hyperpigmentation was not reported.¹⁴

The method of bimatoprost application likely is a determining factor in the number of reported adverse events. Studies with similar treatment periods have demonstrated more adverse events associated with bimatoprost eye drops vs eyelash solution.^15,16 When bimatoprost is used in the eye drop formulation for treatment of glaucoma, iris hyperpigmentation has been estimated to occur in 1.5%⁴ to 50%⁹ of cases. To our knowledge, there are no documented cases when bimatoprost eyelash solution is applied with a dermal applicator for treatment of eyelash hypotrichosis.^15,17 These results may be explained using an ocular splash test. In one study using lissamine green dye, decreased delivery of bimatoprost eyelash solution with the dermal applicator was noted vs eye drop application. Additionally, it has been demonstrated that approximately 5% (based on weight) of a one-drop dose of bimatoprost eyelash solution applied to the dermal applicator is actually delivered to the patient.¹⁸ The rest of the solution remains on the applicator.

It is important that patients use bimatoprost eyelash solution as instructed in the prescribing information (eg, clean the face, remove makeup and contact lenses prior to applying the product). The eyelid should not be rinsed after application, which limits the possibility of the bimatoprost solution from contacting or pooling in the eye. One drop of bimatoprost eyelash solution should be applied to the applicator supplied by the manufacturer and distributed evenly along the skin of the upper eyelid margin at the base of the eyelashes. It is important to blot any excess solution runoff outside the upper eyelid margin.⁵ Of note, our patient admitted to not always doing this step, which may have contributed to her susceptibility to this rare side effect.

Prostaglandin analogues have been observed to cause iris hyperpigmentation when applied directly to the eye for use in the treatment of glaucoma.¹⁹ Theoretically, the same side-effect profile should apply in their use as a dermal application on the eyelids. For this reason, one manufacturer includes iris hyperpigmentation as an adverse side effect in the prescribing information.⁵ It is important for physicians who prescribe bimatoprost eyelash solution to inform patients of this rare yet possible side effect and to instruct patients on proper application to minimize hyperpigmentation.

Our literature review did not demonstrate previous cases of iris hyperpigmentation associated with bimatoprost eyelash solution. One study suggested that 2 patients experienced hypopigmentation; however, this was not clinically significant and was not consistent with the proposed iris pigmentation thought to be caused by bimatoprost eyelash solution.²⁰

Potential future applications and off-label uses of bimatoprost include treatment of eyelash hypotrichosis on the lower eyelid margin and eyebrow hypertrichosis, as well as androgenic alopecia, alopecia areata, chemotherapy-induced alopecia, vitiligo, and hypopigmented scarring.²¹ Currently, investigational studies are looking at bimatoprost ophthalmic solution 0.03% for chemotherapy-induced eyelash hypotrichosis with positive results.²² In the future, bimatoprost may be used for other off-label and possibly FDA-approved uses.

I wear a suit every day to work. I count the time between shifts in months, not days. Rather than looking for subtle diagnostic clues hidden in clinical information, I find myself up to my elbows in performance and financial data. Instead of meetings complicated by challenging family dynamics, I spend my time calming the waters between clinical departments that each feel slighted.

And yet, when people ask me what I do, I do not say I am a health system CEO. Rather, I am a hospitalist. I say it, not out of habit, but with pride and clear intention. Almost 20 years ago, I had to explain to my parents what a hospitalist was as I made the transition from primary care doctor to hospitalist. I told them that hospitalists take care of sick people who are in the hospital, but also are charged with making the hospital a better place to take care of people. I hope that in some small way, in every role I have had over the past 20 years as a hospitalist, I have been able to do that.

While the small changes we can all make every day are important, massive changes to health care, hospitals, and providers are coming. The forces driving these changes are manifold, complex, and powerful. Individual hospitalists, hospital groups, and hospitals will be challenged to keep up with responding to these changes. I hope, though, that our field, hospital medicine, will not be sitting there, waiting for the changes to come, but will instead be one of the forces for change.

I also believe that hospital medicine and health care delivery systems should drive the change in a coordinated and collaborative partnership. A partnership not built on self-advocacy but one in which we remember why we exist – to take care of people. A force for change that preserves the essential, evolves what needs improvement, and revolutionizes the archaic.

Partnerships between hospitalist groups and health care administration will always face the day-to-day challenges of balancing the need for resources with the ability to provide them, agreeing on how to measure and assess quality, and aligning rewards with priorities. However, by working together in venues that allow us to think beyond the day-to-day issues, we in hospital medicine will be leaders in the change that is coming. I believe that today, the Society of Hospital Medicine must be one of those venues. Through its committees, meetings, advocacy, publications, and most importantly, members, SHM will continue to shape the future of care delivery in this country and beyond.

SHM has been my professional home for almost 20 years, helping me think about how to make the hospital a better place to take care of people. Recent examples of SHM and its members partnering in this area include advocacy work to improve alternative payment models, such as Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), as well as educational efforts for its members on how to navigate the current rules around MACRA.

For many years, SHM has been the leader in professional organizations for leading the way on quality improvement. Through the Center for Quality Improvement, SHM not only offers robust educational tools to better enable members to lead efforts at their home institutions but also has led multi-institutional efforts to reduce harm that have been recognized nationally for their impact.

As we move further down the path from volume to value toward population health, the SHM Board will be sure that the society continues to be a leader for both its members and the health system at large as we face these changes. We have the opportunity in front of us to collectively embrace and create the changes coming toward us with that shared purpose of making wherever it is that we care for people better places to provide that care. How could one not be proud to say, with intent, “I am a hospitalist,” regardless of what it is that brings each of us to SHM.
 

Dr. Whelan is CEO of Banner–University Medical Center Tucson (Ariz.) and a member of the SHM Board of Directors.

I wear a suit every day to work. I count the time between shifts in months, not days. Rather than looking for subtle diagnostic clues hidden in clinical information, I find myself up to my elbows in performance and financial data. Instead of meetings complicated by challenging family dynamics, I spend my time calming the waters between clinical departments that each feel slighted.

And yet, when people ask me what I do, I do not say I am a health system CEO. Rather, I am a hospitalist. I say it, not out of habit, but with pride and clear intention. Almost 20 years ago, I had to explain to my parents what a hospitalist was as I made the transition from primary care doctor to hospitalist. I told them that hospitalists take care of sick people who are in the hospital, but also are charged with making the hospital a better place to take care of people. I hope that in some small way, in every role I have had over the past 20 years as a hospitalist, I have been able to do that.

While the small changes we can all make every day are important, massive changes to health care, hospitals, and providers are coming. The forces driving these changes are manifold, complex, and powerful. Individual hospitalists, hospital groups, and hospitals will be challenged to keep up with responding to these changes. I hope, though, that our field, hospital medicine, will not be sitting there, waiting for the changes to come, but will instead be one of the forces for change.

I also believe that hospital medicine and health care delivery systems should drive the change in a coordinated and collaborative partnership. A partnership not built on self-advocacy but one in which we remember why we exist – to take care of people. A force for change that preserves the essential, evolves what needs improvement, and revolutionizes the archaic.

Partnerships between hospitalist groups and health care administration will always face the day-to-day challenges of balancing the need for resources with the ability to provide them, agreeing on how to measure and assess quality, and aligning rewards with priorities. However, by working together in venues that allow us to think beyond the day-to-day issues, we in hospital medicine will be leaders in the change that is coming. I believe that today, the Society of Hospital Medicine must be one of those venues. Through its committees, meetings, advocacy, publications, and most importantly, members, SHM will continue to shape the future of care delivery in this country and beyond.

SHM has been my professional home for almost 20 years, helping me think about how to make the hospital a better place to take care of people. Recent examples of SHM and its members partnering in this area include advocacy work to improve alternative payment models, such as Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), as well as educational efforts for its members on how to navigate the current rules around MACRA.

For many years, SHM has been the leader in professional organizations for leading the way on quality improvement. Through the Center for Quality Improvement, SHM not only offers robust educational tools to better enable members to lead efforts at their home institutions but also has led multi-institutional efforts to reduce harm that have been recognized nationally for their impact.

As we move further down the path from volume to value toward population health, the SHM Board will be sure that the society continues to be a leader for both its members and the health system at large as we face these changes. We have the opportunity in front of us to collectively embrace and create the changes coming toward us with that shared purpose of making wherever it is that we care for people better places to provide that care. How could one not be proud to say, with intent, “I am a hospitalist,” regardless of what it is that brings each of us to SHM.
 

Dr. Whelan is CEO of Banner–University Medical Center Tucson (Ariz.) and a member of the SHM Board of Directors.

I wear a suit every day to work. I count the time between shifts in months, not days. Rather than looking for subtle diagnostic clues hidden in clinical information, I find myself up to my elbows in performance and financial data. Instead of meetings complicated by challenging family dynamics, I spend my time calming the waters between clinical departments that each feel slighted.

And yet, when people ask me what I do, I do not say I am a health system CEO. Rather, I am a hospitalist. I say it, not out of habit, but with pride and clear intention. Almost 20 years ago, I had to explain to my parents what a hospitalist was as I made the transition from primary care doctor to hospitalist. I told them that hospitalists take care of sick people who are in the hospital, but also are charged with making the hospital a better place to take care of people. I hope that in some small way, in every role I have had over the past 20 years as a hospitalist, I have been able to do that.

While the small changes we can all make every day are important, massive changes to health care, hospitals, and providers are coming. The forces driving these changes are manifold, complex, and powerful. Individual hospitalists, hospital groups, and hospitals will be challenged to keep up with responding to these changes. I hope, though, that our field, hospital medicine, will not be sitting there, waiting for the changes to come, but will instead be one of the forces for change.

I also believe that hospital medicine and health care delivery systems should drive the change in a coordinated and collaborative partnership. A partnership not built on self-advocacy but one in which we remember why we exist – to take care of people. A force for change that preserves the essential, evolves what needs improvement, and revolutionizes the archaic.

Partnerships between hospitalist groups and health care administration will always face the day-to-day challenges of balancing the need for resources with the ability to provide them, agreeing on how to measure and assess quality, and aligning rewards with priorities. However, by working together in venues that allow us to think beyond the day-to-day issues, we in hospital medicine will be leaders in the change that is coming. I believe that today, the Society of Hospital Medicine must be one of those venues. Through its committees, meetings, advocacy, publications, and most importantly, members, SHM will continue to shape the future of care delivery in this country and beyond.

SHM has been my professional home for almost 20 years, helping me think about how to make the hospital a better place to take care of people. Recent examples of SHM and its members partnering in this area include advocacy work to improve alternative payment models, such as Medicare Access and CHIP Reauthorization Act of 2015 (MACRA), as well as educational efforts for its members on how to navigate the current rules around MACRA.

For many years, SHM has been the leader in professional organizations for leading the way on quality improvement. Through the Center for Quality Improvement, SHM not only offers robust educational tools to better enable members to lead efforts at their home institutions but also has led multi-institutional efforts to reduce harm that have been recognized nationally for their impact.

As we move further down the path from volume to value toward population health, the SHM Board will be sure that the society continues to be a leader for both its members and the health system at large as we face these changes. We have the opportunity in front of us to collectively embrace and create the changes coming toward us with that shared purpose of making wherever it is that we care for people better places to provide that care. How could one not be proud to say, with intent, “I am a hospitalist,” regardless of what it is that brings each of us to SHM.
 

Dr. Whelan is CEO of Banner–University Medical Center Tucson (Ariz.) and a member of the SHM Board of Directors.

The Diagnosis: Granulosis Rubra Nasi 

A history of prominent nasal sweating was later elicited and the patient was subsequently diagnosed with granulosis rubra nasi. She was instructed to continue daily use of topical pimecrolimus with the addition of topical atropine, resulting in complete resolution of the eruption at 6-week follow-up (Figure, A). She was then maintained on topical atropine monotherapy, only noting recurrence with cessation of the atropine (Figure, B).  

Other successful treatment regimens of granulosis rubra nasi include injection of botulinum toxin into the nose,¹ monotherapy with topical tacrolimus,² topical indomethacin, steroids, and cryotherapy, among other modalities.¹ Topical atropine and pimecrolimus were selected as first-line agents for treating our pediatric patient due to tolerability and their anti-inflammatory and anticholinergic properties.  

Granulosis rubra nasi is a form of focal hyperhidrosis that presents as erythematous papules, pustules, and vesicles of the midface, especially the nose.3 It is a fairly rare condition that can mimic many other common clinical entities, including comedonal acne, nevus comedonicus, periorificial dermatitis, and tinea faciei, but is resistant to treatments aimed at these disorders. It was first described as a "peculiar disease of the skin of the nose in children" in a case report by Jadassohn⁴ in 1901. It is most common in children aged 7 to 12 years and typically resolves at puberty; adults rarely are affected. Although the etiology has not yet been elucidated, autosomal-dominant transmission has been described, and the cutaneous changes are hypothesized to be secondary to hyperhidrosis.⁵ This postulation is further corroborated by a case report of a pheochromocytoma-associated granulosis rubra nasi that resolved with surgical excision of the pheochromocytoma.⁶ It is not uncommon for patients to have concomitant palmoplantar hyperhidrosis and acrocyanosis.⁵ Histopathologic examination is not necessary for diagnosis, but when performed, it discloses a mononuclear cellular infiltrate surrounding eccrine sweat ducts, blood vessels, and lymphatics without other abnormalities of the epidermis or pilosebaceous unit.^1-3,7 
 

The Diagnosis: Granulosis Rubra Nasi 

A history of prominent nasal sweating was later elicited and the patient was subsequently diagnosed with granulosis rubra nasi. She was instructed to continue daily use of topical pimecrolimus with the addition of topical atropine, resulting in complete resolution of the eruption at 6-week follow-up (Figure, A). She was then maintained on topical atropine monotherapy, only noting recurrence with cessation of the atropine (Figure, B).  

Other successful treatment regimens of granulosis rubra nasi include injection of botulinum toxin into the nose,¹ monotherapy with topical tacrolimus,² topical indomethacin, steroids, and cryotherapy, among other modalities.¹ Topical atropine and pimecrolimus were selected as first-line agents for treating our pediatric patient due to tolerability and their anti-inflammatory and anticholinergic properties.  

Granulosis rubra nasi is a form of focal hyperhidrosis that presents as erythematous papules, pustules, and vesicles of the midface, especially the nose.3 It is a fairly rare condition that can mimic many other common clinical entities, including comedonal acne, nevus comedonicus, periorificial dermatitis, and tinea faciei, but is resistant to treatments aimed at these disorders. It was first described as a "peculiar disease of the skin of the nose in children" in a case report by Jadassohn⁴ in 1901. It is most common in children aged 7 to 12 years and typically resolves at puberty; adults rarely are affected. Although the etiology has not yet been elucidated, autosomal-dominant transmission has been described, and the cutaneous changes are hypothesized to be secondary to hyperhidrosis.⁵ This postulation is further corroborated by a case report of a pheochromocytoma-associated granulosis rubra nasi that resolved with surgical excision of the pheochromocytoma.⁶ It is not uncommon for patients to have concomitant palmoplantar hyperhidrosis and acrocyanosis.⁵ Histopathologic examination is not necessary for diagnosis, but when performed, it discloses a mononuclear cellular infiltrate surrounding eccrine sweat ducts, blood vessels, and lymphatics without other abnormalities of the epidermis or pilosebaceous unit.^1-3,7 
 

The Diagnosis: Granulosis Rubra Nasi 

A history of prominent nasal sweating was later elicited and the patient was subsequently diagnosed with granulosis rubra nasi. She was instructed to continue daily use of topical pimecrolimus with the addition of topical atropine, resulting in complete resolution of the eruption at 6-week follow-up (Figure, A). She was then maintained on topical atropine monotherapy, only noting recurrence with cessation of the atropine (Figure, B).  

Other successful treatment regimens of granulosis rubra nasi include injection of botulinum toxin into the nose,¹ monotherapy with topical tacrolimus,² topical indomethacin, steroids, and cryotherapy, among other modalities.¹ Topical atropine and pimecrolimus were selected as first-line agents for treating our pediatric patient due to tolerability and their anti-inflammatory and anticholinergic properties.  

Granulosis rubra nasi is a form of focal hyperhidrosis that presents as erythematous papules, pustules, and vesicles of the midface, especially the nose.3 It is a fairly rare condition that can mimic many other common clinical entities, including comedonal acne, nevus comedonicus, periorificial dermatitis, and tinea faciei, but is resistant to treatments aimed at these disorders. It was first described as a "peculiar disease of the skin of the nose in children" in a case report by Jadassohn⁴ in 1901. It is most common in children aged 7 to 12 years and typically resolves at puberty; adults rarely are affected. Although the etiology has not yet been elucidated, autosomal-dominant transmission has been described, and the cutaneous changes are hypothesized to be secondary to hyperhidrosis.⁵ This postulation is further corroborated by a case report of a pheochromocytoma-associated granulosis rubra nasi that resolved with surgical excision of the pheochromocytoma.⁶ It is not uncommon for patients to have concomitant palmoplantar hyperhidrosis and acrocyanosis.⁵ Histopathologic examination is not necessary for diagnosis, but when performed, it discloses a mononuclear cellular infiltrate surrounding eccrine sweat ducts, blood vessels, and lymphatics without other abnormalities of the epidermis or pilosebaceous unit.^1-3,7 
 

Peripheral nervous system disease, predominantly neuropathies, constitutes a substantial proportion of the manifestations of neuropsychiatric systemic lupus erythematosus (SLE) and has a lasting negative impact on health-related quality of life, John G. Hanly, MD, of Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, N.S., and associates reported in Arthritis & Rheumatology.

According to the study of 1,827 SLE patients who had been recently diagnosed and enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) network at sites in Europe, Asia, and North America during 1999-2011, 161 peripheral nervous system (PNS) events occurred in 139 of the patients (8%) over a mean 7.6 years of follow-up.

Using the seven American College of Rheumatology case definitions for PNS disease in neuropsychiatric SLE, most of the events were peripheral neuropathy (41%), mononeuropathy (27%), and cranial neuropathy (24%). For 110 with peripheral neuropathy or mononeuropathy who underwent electrophysiologic testing, axonal damage was often present (42%), followed by demyelination (22%).

The PNS events were attributed to SLE in about 58%-75% of the patients. Based on these data the investigators estimated that after 10 years the cumulative incidence of any PNS event regardless of its attribution was about 9%, and it was nearly 7% for events attributed to SLE.

The probability that the neuropathies would not resolve over time was estimated at about 43% for peripheral neuropathy, 29% for mononeuropathy, and 30% for cranial neuropathy. Resolution of neuropathy was most rapid for cranial neuropathy, followed by mononeuropathy and peripheral neuropathy.

Patients with PNS events had significantly lower physical and mental health component scores on the 36-item Short Form Health Survey than did patients without a neuropsychiatric event up to the study assessment, and these differences persisted for 10 years of follow-up.

These “findings provide a benchmark for the assessment of future treatment modalities,” the investigators concluded.

[email protected]

SOURCE: Hanly JG et al. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41070.

Peripheral nervous system disease, predominantly neuropathies, constitutes a substantial proportion of the manifestations of neuropsychiatric systemic lupus erythematosus (SLE) and has a lasting negative impact on health-related quality of life, John G. Hanly, MD, of Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, N.S., and associates reported in Arthritis & Rheumatology.

According to the study of 1,827 SLE patients who had been recently diagnosed and enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) network at sites in Europe, Asia, and North America during 1999-2011, 161 peripheral nervous system (PNS) events occurred in 139 of the patients (8%) over a mean 7.6 years of follow-up.

Using the seven American College of Rheumatology case definitions for PNS disease in neuropsychiatric SLE, most of the events were peripheral neuropathy (41%), mononeuropathy (27%), and cranial neuropathy (24%). For 110 with peripheral neuropathy or mononeuropathy who underwent electrophysiologic testing, axonal damage was often present (42%), followed by demyelination (22%).

The PNS events were attributed to SLE in about 58%-75% of the patients. Based on these data the investigators estimated that after 10 years the cumulative incidence of any PNS event regardless of its attribution was about 9%, and it was nearly 7% for events attributed to SLE.

The probability that the neuropathies would not resolve over time was estimated at about 43% for peripheral neuropathy, 29% for mononeuropathy, and 30% for cranial neuropathy. Resolution of neuropathy was most rapid for cranial neuropathy, followed by mononeuropathy and peripheral neuropathy.

Patients with PNS events had significantly lower physical and mental health component scores on the 36-item Short Form Health Survey than did patients without a neuropsychiatric event up to the study assessment, and these differences persisted for 10 years of follow-up.

These “findings provide a benchmark for the assessment of future treatment modalities,” the investigators concluded.

[email protected]

SOURCE: Hanly JG et al. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41070.

Peripheral nervous system disease, predominantly neuropathies, constitutes a substantial proportion of the manifestations of neuropsychiatric systemic lupus erythematosus (SLE) and has a lasting negative impact on health-related quality of life, John G. Hanly, MD, of Queen Elizabeth II Health Sciences Center and Dalhousie University, Halifax, N.S., and associates reported in Arthritis & Rheumatology.

According to the study of 1,827 SLE patients who had been recently diagnosed and enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) network at sites in Europe, Asia, and North America during 1999-2011, 161 peripheral nervous system (PNS) events occurred in 139 of the patients (8%) over a mean 7.6 years of follow-up.

Using the seven American College of Rheumatology case definitions for PNS disease in neuropsychiatric SLE, most of the events were peripheral neuropathy (41%), mononeuropathy (27%), and cranial neuropathy (24%). For 110 with peripheral neuropathy or mononeuropathy who underwent electrophysiologic testing, axonal damage was often present (42%), followed by demyelination (22%).

The PNS events were attributed to SLE in about 58%-75% of the patients. Based on these data the investigators estimated that after 10 years the cumulative incidence of any PNS event regardless of its attribution was about 9%, and it was nearly 7% for events attributed to SLE.

The probability that the neuropathies would not resolve over time was estimated at about 43% for peripheral neuropathy, 29% for mononeuropathy, and 30% for cranial neuropathy. Resolution of neuropathy was most rapid for cranial neuropathy, followed by mononeuropathy and peripheral neuropathy.

Patients with PNS events had significantly lower physical and mental health component scores on the 36-item Short Form Health Survey than did patients without a neuropsychiatric event up to the study assessment, and these differences persisted for 10 years of follow-up.

These “findings provide a benchmark for the assessment of future treatment modalities,” the investigators concluded.

[email protected]

SOURCE: Hanly JG et al. Arthritis Rheumatol. 2019 Aug 7. doi: 10.1002/art.41070.

The Food and Drug Administration has approved pitolisant (Wakix) for excessive daytime sleepiness among patients with narcolepsy, according to a release from the drug’s developer.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval of this once-daily, selective histamine 3–receptor antagonist/inverse agonist was based on a pair of multicenter, randomized, double-blind, placebo-controlled studies that included a total of 261 patients. Patients in both studies experienced statistically significant improvements in excessive daytime sleepiness according to Epworth Sleepiness Scale scores.

Rates of adverse advents at or greater than 5% and more than double that of placebo included insomnia (6%), nausea (6%), and anxiety (5%). Patients with severe liver disease should not use pitolisant. Pitolisant has not been evaluated in patients under 18 years of age, and patients who are pregnant or planning to become pregnant are encouraged to enroll in a pregnancy exposure registry.

Full prescribing information, including contraindications and warnings, can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved pitolisant (Wakix) for excessive daytime sleepiness among patients with narcolepsy, according to a release from the drug’s developer.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval of this once-daily, selective histamine 3–receptor antagonist/inverse agonist was based on a pair of multicenter, randomized, double-blind, placebo-controlled studies that included a total of 261 patients. Patients in both studies experienced statistically significant improvements in excessive daytime sleepiness according to Epworth Sleepiness Scale scores.

Rates of adverse advents at or greater than 5% and more than double that of placebo included insomnia (6%), nausea (6%), and anxiety (5%). Patients with severe liver disease should not use pitolisant. Pitolisant has not been evaluated in patients under 18 years of age, and patients who are pregnant or planning to become pregnant are encouraged to enroll in a pregnancy exposure registry.

Full prescribing information, including contraindications and warnings, can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved pitolisant (Wakix) for excessive daytime sleepiness among patients with narcolepsy, according to a release from the drug’s developer.

Wikimedia Commons/FitzColinGerald/Creative Commons License

Approval of this once-daily, selective histamine 3–receptor antagonist/inverse agonist was based on a pair of multicenter, randomized, double-blind, placebo-controlled studies that included a total of 261 patients. Patients in both studies experienced statistically significant improvements in excessive daytime sleepiness according to Epworth Sleepiness Scale scores.

Rates of adverse advents at or greater than 5% and more than double that of placebo included insomnia (6%), nausea (6%), and anxiety (5%). Patients with severe liver disease should not use pitolisant. Pitolisant has not been evaluated in patients under 18 years of age, and patients who are pregnant or planning to become pregnant are encouraged to enroll in a pregnancy exposure registry.

Full prescribing information, including contraindications and warnings, can be found on the FDA website.

[email protected]

Use of nonselective beta-blockers to reduce portal pressure in cirrhosis improved outcomes in adults with or without ascites, based on data from a meta-analysis of more than 1,000 patients.

Wikimedia Commons/Cancer Research UK

Previous research has suggested that nonselective beta-blockers (NSBBs) might have a negative effect on patients with refractory ascites, but the effect on patients with and without ascites has not been assessed, wrote Laura Turco, MD, of the University of Modena and Reggio Emilia, Emilia-Romagna, Italy, and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers analyzed 1,113 cirrhosis patients including 452 with ascites. Overall, 968 patients had received treatment with NSBBs. Response to pressure reduction was defined as a decrease of more than 20% from baseline or a decrease to less than 12 mm Hg.

A total of 329 of the 661 patients without ascites (50%) met the definition as responders. These responders had significantly lower odds than did nonresponders of a combination of clinical events including ascites, variceal hemorrhage, or encephalopathy (odds ratio, 0.35) and also had significantly lower odds than nonresponders of liver transplantation or death (OR, 0.50).

A total of 188 of the 452 patients with ascites were responders (42%). These responders had significantly lower odds than those of nonresponders (OR, 0.27) of variceal hemorrhage, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome. The responders also had significantly lower odds of liver transplantation or death (OR, 0.47).

The results are important in light of concerns about the impact of NSBBs on renal function and mortality in cirrhosis patients with ascites, the researchers said.

The study findings were limited by several factors, including the use of retrospective data from prospective studies, and the incomplete collection of data on the variables of comorbidities, hepatocellular carcinoma, and other predictive scores; alcohol use or abstinence was a potential confounder as well, the researchers noted.

However, “By showing that reductions in portal pressure induced by NSBB-based pharmacologic therapy improve outcomes and decrease mortality, our study supports the use of NSBB in all clinical settings (primary or secondary prophylaxis) and in both patients with or without ascites,” they concluded. They found no heterogeneity among the studies included in the analysis.

The study was supported by multiple sources including the University of Modena and Reggio Emilia, Yale Liver Center, National Institutes of Health, and Instituto de Salud Carlos III, and was cofunded by the European Union. The researchers had no financial conflicts to disclose.

SOURCE: Turco L et al. Clin Gastroenterol Hepatol. 2019 June 5. doi: 10.1016/j.cgh.2019.05.050.

Use of nonselective beta-blockers to reduce portal pressure in cirrhosis improved outcomes in adults with or without ascites, based on data from a meta-analysis of more than 1,000 patients.

Wikimedia Commons/Cancer Research UK

Previous research has suggested that nonselective beta-blockers (NSBBs) might have a negative effect on patients with refractory ascites, but the effect on patients with and without ascites has not been assessed, wrote Laura Turco, MD, of the University of Modena and Reggio Emilia, Emilia-Romagna, Italy, and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers analyzed 1,113 cirrhosis patients including 452 with ascites. Overall, 968 patients had received treatment with NSBBs. Response to pressure reduction was defined as a decrease of more than 20% from baseline or a decrease to less than 12 mm Hg.

A total of 329 of the 661 patients without ascites (50%) met the definition as responders. These responders had significantly lower odds than did nonresponders of a combination of clinical events including ascites, variceal hemorrhage, or encephalopathy (odds ratio, 0.35) and also had significantly lower odds than nonresponders of liver transplantation or death (OR, 0.50).

A total of 188 of the 452 patients with ascites were responders (42%). These responders had significantly lower odds than those of nonresponders (OR, 0.27) of variceal hemorrhage, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome. The responders also had significantly lower odds of liver transplantation or death (OR, 0.47).

The results are important in light of concerns about the impact of NSBBs on renal function and mortality in cirrhosis patients with ascites, the researchers said.

The study findings were limited by several factors, including the use of retrospective data from prospective studies, and the incomplete collection of data on the variables of comorbidities, hepatocellular carcinoma, and other predictive scores; alcohol use or abstinence was a potential confounder as well, the researchers noted.

However, “By showing that reductions in portal pressure induced by NSBB-based pharmacologic therapy improve outcomes and decrease mortality, our study supports the use of NSBB in all clinical settings (primary or secondary prophylaxis) and in both patients with or without ascites,” they concluded. They found no heterogeneity among the studies included in the analysis.

The study was supported by multiple sources including the University of Modena and Reggio Emilia, Yale Liver Center, National Institutes of Health, and Instituto de Salud Carlos III, and was cofunded by the European Union. The researchers had no financial conflicts to disclose.

SOURCE: Turco L et al. Clin Gastroenterol Hepatol. 2019 June 5. doi: 10.1016/j.cgh.2019.05.050.

Use of nonselective beta-blockers to reduce portal pressure in cirrhosis improved outcomes in adults with or without ascites, based on data from a meta-analysis of more than 1,000 patients.

Wikimedia Commons/Cancer Research UK

Previous research has suggested that nonselective beta-blockers (NSBBs) might have a negative effect on patients with refractory ascites, but the effect on patients with and without ascites has not been assessed, wrote Laura Turco, MD, of the University of Modena and Reggio Emilia, Emilia-Romagna, Italy, and colleagues.

In a study published in Clinical Gastroenterology and Hepatology, the researchers analyzed 1,113 cirrhosis patients including 452 with ascites. Overall, 968 patients had received treatment with NSBBs. Response to pressure reduction was defined as a decrease of more than 20% from baseline or a decrease to less than 12 mm Hg.

A total of 329 of the 661 patients without ascites (50%) met the definition as responders. These responders had significantly lower odds than did nonresponders of a combination of clinical events including ascites, variceal hemorrhage, or encephalopathy (odds ratio, 0.35) and also had significantly lower odds than nonresponders of liver transplantation or death (OR, 0.50).

A total of 188 of the 452 patients with ascites were responders (42%). These responders had significantly lower odds than those of nonresponders (OR, 0.27) of variceal hemorrhage, refractory ascites, spontaneous bacterial peritonitis, or hepatorenal syndrome. The responders also had significantly lower odds of liver transplantation or death (OR, 0.47).

The results are important in light of concerns about the impact of NSBBs on renal function and mortality in cirrhosis patients with ascites, the researchers said.

The study findings were limited by several factors, including the use of retrospective data from prospective studies, and the incomplete collection of data on the variables of comorbidities, hepatocellular carcinoma, and other predictive scores; alcohol use or abstinence was a potential confounder as well, the researchers noted.

However, “By showing that reductions in portal pressure induced by NSBB-based pharmacologic therapy improve outcomes and decrease mortality, our study supports the use of NSBB in all clinical settings (primary or secondary prophylaxis) and in both patients with or without ascites,” they concluded. They found no heterogeneity among the studies included in the analysis.

The study was supported by multiple sources including the University of Modena and Reggio Emilia, Yale Liver Center, National Institutes of Health, and Instituto de Salud Carlos III, and was cofunded by the European Union. The researchers had no financial conflicts to disclose.

SOURCE: Turco L et al. Clin Gastroenterol Hepatol. 2019 June 5. doi: 10.1016/j.cgh.2019.05.050.