Pediatrics

CHICAGO – Adolescents with obesity show brain changes consistent with degradation of circuitry controlling appetite, reward, and decision making, according to a Brazilian study that used MRI to detect these changes.

Kari Oakes

Brain changes were significantly correlated with increased levels of insulin, leptin, and other appetite- and diet-related hormones and neurohormones, as well as with inflammatory markers.

In an interview at the annual meeting of the Radiological Society of North America, Pamela Bertolazzi, a PhD student at the University of São Paulo, explained that childhood obesity in Brazil is estimated to have climbed by up to 40% in recent years, with almost one-third of Brazilian children and adolescents experiencing obesity. Epidemiologists estimate that there’s the potential for 2.6 million premature deaths from this level of overweight and obesity, she said. Brazil has over 211 million residents.

Previous studies have established diffusion tensor imaging as an MRI technique to assess white-matter integrity and architecture. Fractional anisotropy (FA) is a measure of brain tract integrity, and decreased FA can indicate demyelination or axonal degeneration.

Ms. Bertolazzi and colleagues compared 60 healthy weight adolescents with 57 adolescents with obesity to see how cerebral connectivity differed, and further correlated MRI findings with a serum assay of 57 analytes including inflammatory markers, neuropeptides, and hormones.

Adolescents aged 12-16 years were included if they met World Health Organization criteria for obesity or for healthy weight. The z score for the participants with obesity was 2.74, and 0.25 for the healthy-weight participants (P less than .001). Individuals who were underweight or overweight (but not obese) were excluded. Those with known significant psychiatric diagnoses or prior traumatic brain injury or neurosurgery also were excluded.

The mean age of participants was 14 years, and 29 of the 57 (51%) participants with obesity were female, as were 33 of 60 (55%) healthy weight participants. There was no significant difference in socioeconomic status between the two groups.

When participants’ brain MRI results were reviewed, Ms. Bertolazzi and associates saw several regions that had decreased FA only in the adolescents with obesity. In general terms, these brain areas are known to be concerned with appetite and reward.

Decreased FA – indicating demyelination or axonal degeneration – was seen particularly on the left-hand side of the corpus callosum, “the largest association pathway in the human brain,” said Ms. Bertolazzi. Looking at the interaction between decreased FA in this area and levels of various analytes, leptin, insulin, C-peptide, and total glucagonlike peptide–1 levels all were negatively associated with FA levels. A ratio of leptin to the anti-inflammatory cytokine interleukin-10 also had a negative correlation with FA levels. All of these associations were statistically significant.

Decreased FA also was seen in the orbitofrontal gyrus, an area of the prefrontal cortex that links decision making with emotions and reward. Here, significant negative associations were seen with C-peptide, amylin, and the ratios of several other inflammatory markers to IL-10.

moodboard/thinkstockphotos.com

“Obesity was associated with a reduction of cerebral integrity in obese adolescents,” said Ms. Bertolazzi. The clinical significance of these findings is not yet known. However, she said that the disruption in regulation of reward and appetite circuitry her study found may set up adolescents with excess body mass for a maladaptive positive feedback loop: elevated insulin, leptin, and inflammatory cytokine levels may be contributing to disrupted appetite, which in turn contributes to ongoing increases in body mass index.

She and her colleagues are planning to enroll adolescents with obesity and their families in nutritional education and exercise programs, hoping to interrupt the cycle. They plan to obtain a baseline serum assay and MRI scan with diffusion tensor imaging and FA, and to repeat the studies about 3 months into an intensive intervention, to test the hypothesis that increased exercise and improved diet will result in reversal of the brain changes they found in this exploratory study. In particular, said Ms. Bertolazzi, they hope that encouraging physical activity will boost levels of HDL cholesterol, which may have a neuroprotective effect.

Ms. Bertolazzi reported no outside sources of funding and no conflicts of interest.

[email protected]

CHICAGO – Adolescents with obesity show brain changes consistent with degradation of circuitry controlling appetite, reward, and decision making, according to a Brazilian study that used MRI to detect these changes.

Kari Oakes

Brain changes were significantly correlated with increased levels of insulin, leptin, and other appetite- and diet-related hormones and neurohormones, as well as with inflammatory markers.

In an interview at the annual meeting of the Radiological Society of North America, Pamela Bertolazzi, a PhD student at the University of São Paulo, explained that childhood obesity in Brazil is estimated to have climbed by up to 40% in recent years, with almost one-third of Brazilian children and adolescents experiencing obesity. Epidemiologists estimate that there’s the potential for 2.6 million premature deaths from this level of overweight and obesity, she said. Brazil has over 211 million residents.

Previous studies have established diffusion tensor imaging as an MRI technique to assess white-matter integrity and architecture. Fractional anisotropy (FA) is a measure of brain tract integrity, and decreased FA can indicate demyelination or axonal degeneration.

Ms. Bertolazzi and colleagues compared 60 healthy weight adolescents with 57 adolescents with obesity to see how cerebral connectivity differed, and further correlated MRI findings with a serum assay of 57 analytes including inflammatory markers, neuropeptides, and hormones.

Adolescents aged 12-16 years were included if they met World Health Organization criteria for obesity or for healthy weight. The z score for the participants with obesity was 2.74, and 0.25 for the healthy-weight participants (P less than .001). Individuals who were underweight or overweight (but not obese) were excluded. Those with known significant psychiatric diagnoses or prior traumatic brain injury or neurosurgery also were excluded.

The mean age of participants was 14 years, and 29 of the 57 (51%) participants with obesity were female, as were 33 of 60 (55%) healthy weight participants. There was no significant difference in socioeconomic status between the two groups.

When participants’ brain MRI results were reviewed, Ms. Bertolazzi and associates saw several regions that had decreased FA only in the adolescents with obesity. In general terms, these brain areas are known to be concerned with appetite and reward.

Decreased FA – indicating demyelination or axonal degeneration – was seen particularly on the left-hand side of the corpus callosum, “the largest association pathway in the human brain,” said Ms. Bertolazzi. Looking at the interaction between decreased FA in this area and levels of various analytes, leptin, insulin, C-peptide, and total glucagonlike peptide–1 levels all were negatively associated with FA levels. A ratio of leptin to the anti-inflammatory cytokine interleukin-10 also had a negative correlation with FA levels. All of these associations were statistically significant.

Decreased FA also was seen in the orbitofrontal gyrus, an area of the prefrontal cortex that links decision making with emotions and reward. Here, significant negative associations were seen with C-peptide, amylin, and the ratios of several other inflammatory markers to IL-10.

moodboard/thinkstockphotos.com

“Obesity was associated with a reduction of cerebral integrity in obese adolescents,” said Ms. Bertolazzi. The clinical significance of these findings is not yet known. However, she said that the disruption in regulation of reward and appetite circuitry her study found may set up adolescents with excess body mass for a maladaptive positive feedback loop: elevated insulin, leptin, and inflammatory cytokine levels may be contributing to disrupted appetite, which in turn contributes to ongoing increases in body mass index.

She and her colleagues are planning to enroll adolescents with obesity and their families in nutritional education and exercise programs, hoping to interrupt the cycle. They plan to obtain a baseline serum assay and MRI scan with diffusion tensor imaging and FA, and to repeat the studies about 3 months into an intensive intervention, to test the hypothesis that increased exercise and improved diet will result in reversal of the brain changes they found in this exploratory study. In particular, said Ms. Bertolazzi, they hope that encouraging physical activity will boost levels of HDL cholesterol, which may have a neuroprotective effect.

Ms. Bertolazzi reported no outside sources of funding and no conflicts of interest.

[email protected]

CHICAGO – Adolescents with obesity show brain changes consistent with degradation of circuitry controlling appetite, reward, and decision making, according to a Brazilian study that used MRI to detect these changes.

Kari Oakes

Brain changes were significantly correlated with increased levels of insulin, leptin, and other appetite- and diet-related hormones and neurohormones, as well as with inflammatory markers.

In an interview at the annual meeting of the Radiological Society of North America, Pamela Bertolazzi, a PhD student at the University of São Paulo, explained that childhood obesity in Brazil is estimated to have climbed by up to 40% in recent years, with almost one-third of Brazilian children and adolescents experiencing obesity. Epidemiologists estimate that there’s the potential for 2.6 million premature deaths from this level of overweight and obesity, she said. Brazil has over 211 million residents.

Previous studies have established diffusion tensor imaging as an MRI technique to assess white-matter integrity and architecture. Fractional anisotropy (FA) is a measure of brain tract integrity, and decreased FA can indicate demyelination or axonal degeneration.

Ms. Bertolazzi and colleagues compared 60 healthy weight adolescents with 57 adolescents with obesity to see how cerebral connectivity differed, and further correlated MRI findings with a serum assay of 57 analytes including inflammatory markers, neuropeptides, and hormones.

Adolescents aged 12-16 years were included if they met World Health Organization criteria for obesity or for healthy weight. The z score for the participants with obesity was 2.74, and 0.25 for the healthy-weight participants (P less than .001). Individuals who were underweight or overweight (but not obese) were excluded. Those with known significant psychiatric diagnoses or prior traumatic brain injury or neurosurgery also were excluded.

The mean age of participants was 14 years, and 29 of the 57 (51%) participants with obesity were female, as were 33 of 60 (55%) healthy weight participants. There was no significant difference in socioeconomic status between the two groups.

When participants’ brain MRI results were reviewed, Ms. Bertolazzi and associates saw several regions that had decreased FA only in the adolescents with obesity. In general terms, these brain areas are known to be concerned with appetite and reward.

Decreased FA – indicating demyelination or axonal degeneration – was seen particularly on the left-hand side of the corpus callosum, “the largest association pathway in the human brain,” said Ms. Bertolazzi. Looking at the interaction between decreased FA in this area and levels of various analytes, leptin, insulin, C-peptide, and total glucagonlike peptide–1 levels all were negatively associated with FA levels. A ratio of leptin to the anti-inflammatory cytokine interleukin-10 also had a negative correlation with FA levels. All of these associations were statistically significant.

Decreased FA also was seen in the orbitofrontal gyrus, an area of the prefrontal cortex that links decision making with emotions and reward. Here, significant negative associations were seen with C-peptide, amylin, and the ratios of several other inflammatory markers to IL-10.

moodboard/thinkstockphotos.com

“Obesity was associated with a reduction of cerebral integrity in obese adolescents,” said Ms. Bertolazzi. The clinical significance of these findings is not yet known. However, she said that the disruption in regulation of reward and appetite circuitry her study found may set up adolescents with excess body mass for a maladaptive positive feedback loop: elevated insulin, leptin, and inflammatory cytokine levels may be contributing to disrupted appetite, which in turn contributes to ongoing increases in body mass index.

She and her colleagues are planning to enroll adolescents with obesity and their families in nutritional education and exercise programs, hoping to interrupt the cycle. They plan to obtain a baseline serum assay and MRI scan with diffusion tensor imaging and FA, and to repeat the studies about 3 months into an intensive intervention, to test the hypothesis that increased exercise and improved diet will result in reversal of the brain changes they found in this exploratory study. In particular, said Ms. Bertolazzi, they hope that encouraging physical activity will boost levels of HDL cholesterol, which may have a neuroprotective effect.

Ms. Bertolazzi reported no outside sources of funding and no conflicts of interest.

[email protected]

The Food and Drug Administration has expanded the indication for Toujeo (insulin glargine 300 units/mL injection; Sanofi) to include children as young as 6 years of age with type 1 diabetes.

The FDA first approved Toujeo in 2015 for adults with type 1 and type 2 diabetes, designed as a more potent follow-up to Sanofi’s top-selling insulin glargine (Lantus).

Last month, Sanofi reported positive results from the phase 3 EDITION JUNIOR trial of Toujeo in children and adolescents with type 1 diabetes. These were presented at the International Society for Pediatric and Adolescent Diabetes 45th Annual Conference in Boston.

In the trial, 463 children and adolescents (aged 6-17 years) treated for type 1 diabetes for at least 1 year and with A1c between 7.5% and 11.0% at screening were randomized to Toujeo or insulin glargine 100 units/mL (Gla-100); participants continued to take their existing mealtime insulin.

The primary endpoint was noninferior reduction in A_1c after 26 weeks.

The study met its primary endpoint, confirming a noninferior reduction in A_1c with Toujeo versus Gla-100 after 26 weeks (mean reduction, 0.4% vs. 0.4%; difference, 0.004%; 95% confidence interval, –0.17 to 0.18; upper bound was below the prespecified noninferiority margin of 0.3%).

Over 26 weeks, a comparable number of patients in each group experienced one or more hypoglycemic events documented at anytime over 24 hours. Numerically fewer patients taking Toujeo experienced severe hypoglycemia or experienced one or more episodes of hyperglycemia with ketosis compared with those taking Gla-100.

No unexpected safety concerns were reported based on the established profiles of both products, the company said.

In October 2019, the European Medicines Agency Committee for Medicinal Products for Human Use recommended approval of Toujeo for children age 6 years and older with diabetes.

For more diabetes and endocrinology news, follow us on Twitter and Facebook.
 

This story first appeared on Medscape.com.

The Food and Drug Administration has expanded the indication for Toujeo (insulin glargine 300 units/mL injection; Sanofi) to include children as young as 6 years of age with type 1 diabetes.

The FDA first approved Toujeo in 2015 for adults with type 1 and type 2 diabetes, designed as a more potent follow-up to Sanofi’s top-selling insulin glargine (Lantus).

Last month, Sanofi reported positive results from the phase 3 EDITION JUNIOR trial of Toujeo in children and adolescents with type 1 diabetes. These were presented at the International Society for Pediatric and Adolescent Diabetes 45th Annual Conference in Boston.

In the trial, 463 children and adolescents (aged 6-17 years) treated for type 1 diabetes for at least 1 year and with A1c between 7.5% and 11.0% at screening were randomized to Toujeo or insulin glargine 100 units/mL (Gla-100); participants continued to take their existing mealtime insulin.

The primary endpoint was noninferior reduction in A_1c after 26 weeks.

The study met its primary endpoint, confirming a noninferior reduction in A_1c with Toujeo versus Gla-100 after 26 weeks (mean reduction, 0.4% vs. 0.4%; difference, 0.004%; 95% confidence interval, –0.17 to 0.18; upper bound was below the prespecified noninferiority margin of 0.3%).

Over 26 weeks, a comparable number of patients in each group experienced one or more hypoglycemic events documented at anytime over 24 hours. Numerically fewer patients taking Toujeo experienced severe hypoglycemia or experienced one or more episodes of hyperglycemia with ketosis compared with those taking Gla-100.

No unexpected safety concerns were reported based on the established profiles of both products, the company said.

In October 2019, the European Medicines Agency Committee for Medicinal Products for Human Use recommended approval of Toujeo for children age 6 years and older with diabetes.

For more diabetes and endocrinology news, follow us on Twitter and Facebook.
 

This story first appeared on Medscape.com.

The Food and Drug Administration has expanded the indication for Toujeo (insulin glargine 300 units/mL injection; Sanofi) to include children as young as 6 years of age with type 1 diabetes.

The FDA first approved Toujeo in 2015 for adults with type 1 and type 2 diabetes, designed as a more potent follow-up to Sanofi’s top-selling insulin glargine (Lantus).

Last month, Sanofi reported positive results from the phase 3 EDITION JUNIOR trial of Toujeo in children and adolescents with type 1 diabetes. These were presented at the International Society for Pediatric and Adolescent Diabetes 45th Annual Conference in Boston.

In the trial, 463 children and adolescents (aged 6-17 years) treated for type 1 diabetes for at least 1 year and with A1c between 7.5% and 11.0% at screening were randomized to Toujeo or insulin glargine 100 units/mL (Gla-100); participants continued to take their existing mealtime insulin.

The primary endpoint was noninferior reduction in A_1c after 26 weeks.

The study met its primary endpoint, confirming a noninferior reduction in A_1c with Toujeo versus Gla-100 after 26 weeks (mean reduction, 0.4% vs. 0.4%; difference, 0.004%; 95% confidence interval, –0.17 to 0.18; upper bound was below the prespecified noninferiority margin of 0.3%).

Over 26 weeks, a comparable number of patients in each group experienced one or more hypoglycemic events documented at anytime over 24 hours. Numerically fewer patients taking Toujeo experienced severe hypoglycemia or experienced one or more episodes of hyperglycemia with ketosis compared with those taking Gla-100.

No unexpected safety concerns were reported based on the established profiles of both products, the company said.

In October 2019, the European Medicines Agency Committee for Medicinal Products for Human Use recommended approval of Toujeo for children age 6 years and older with diabetes.

For more diabetes and endocrinology news, follow us on Twitter and Facebook.
 

This story first appeared on Medscape.com.

From the University of Miami, Department of Pediatrics and Department of Medicine, Miami, FL.

Abstract

• Objective: Pediatric fungemia is associated with a low risk of fungal endocarditis and renal infections. The majority of current guidelines do not recommend routine abdominal imaging/echocardiograms in the evaluation of fungemia, but such imaging has been routinely ordered for patients on the pediatric gastroenterology service at our institution. Our goals were to assess the financial impact of this deviation from current clinical guidelines and redefine the standard work to reduce overutilization of abdominal ultrasounds and echocardiograms. Specifically, our goal was to reduce imaging by 50% by 18 months.
• Methods: Root cause analysis showed a lack of familiarity with current evidence. Using this data, countermeasures were implemented, including practitioner education of guidelines and creation of a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Balancing measures were missed episodes of fungal endocarditis and renal infection.
• Results: During the period January 1, 2016 to November 19, 2017, 18 of 21 episodes of fungemia in our pediatric institution occurred in patients admitted to the pediatric gastroenterology service. Abdominal imaging and echocardiograms were done 100% of the time, with no positive findings and an estimated cost of approximately $58,000. Post-intervention from November 20, 2017 to April 3, 2019, 7 of 13 episodes of fungemia occurred on this service. Frequency of abdominal imaging and echocardiograms decreased to 43% and 57%, respectively. No episodes of fungal endocarditis or renal infection were identified.
• Conclusion: Overutilization of abdominal imaging and echocardiograms in pediatric fungemia evaluation can be safely decreased.

Keywords: guidelines; cost; candidemia; endocarditis.

Practitioners may remain under the impression that routine abdominal ultrasounds (US) and echocardiograms (echo) are indicated in fungemia to evaluate for fungal endocarditis and renal infection, although these conditions are rare and limited to a subset of the population.^1-10 Risk factors include prematurity, immunosuppression, prior bacterial endocarditis, abnormal cardiac valves, and previous urogenital surgeries.¹¹

The 2016 Infectious Diseases Society of America (IDSA) guidelines do not recommend routine US or echo but rather provide scenarios in which Candida endocarditis should be suspected, and these include: persistently positive blood cultures, persistent fevers despite appropriate therapy, and clinical signs that may suggest endocarditis, such as a new heart murmur, heart failure, or embolic phenomena.¹¹ IDSA recommends abdominal imaging in neonates with persistently positive blood cultures to evaluate the urogenital system, in addition to the liver and spleen. They also recommend abdominal imaging in symptomatic ascending Candida pyelonephritis beyond the neonatal period and in chronic disseminated candidiasis; the latter is uncommon and seen almost exclusively in patients recovering from neutropenia with a hematologic malignancy.¹¹

We also reviewed guidelines on fungemia originating outside the United States. The 2010 Canadian clinical guidelines on invasive candidiasis do not explicitly recommend routine imaging, but rather state that various imaging studies, including US and echo among others, may be helpful.¹² The German Speaking Mycological Society and the Paul-Ehrlich-Society for Chemotherapy published a joint recommendation against routine US and echo in uncomplicated candidemia in 2011.¹³

The European Society for Clinical Microbiology and Infectious Diseases is the only society that recommends routine echo. Their 2012 guidelines on candidiasis recommend transesophageal echo in adults¹⁴ and echocardiography in children,¹⁵ as well as abdominal imaging in the diagnosis of chronic disseminated candidiasis in adults with hematological malignancies/hematopoietic stem cell transplantation.¹⁶

The 2013 Brazilian guidelines explicitly recommend against routine abdominal imaging and echo because of the low frequency of visceral lesions in adults with candidemia and recommend reserving imaging for those with persistently positive blood cultures or with clinical signs/symptoms suggestive of endocarditis/abdominal infection or clinical deterioration.¹⁷ The 2014 Japanese guidelines recommend ruling out chronic disseminated candidiasis in these patients with symptoms during the neutrophil recovery phase, but do not mention routinely imaging other patients. They do not address the role of echocardiography.¹⁸

Although physicians in the United Sates typically follow IDSA guidelines, abdominal US and echo were ordered routinely for patients with fungemia on the pediatric gastroenterology service at our institution, leading to higher medical costs and waste of medical resources. Our goals were to assess the current standard work for fungemia evaluation on this service, assess the impact of its deviation from current clinical guidelines, and redefine the standard work by (1) presenting current evidence to practitioners taking care of patients on this service, (2) providing a clinical pathway that allowed for variations where appropriate, and (3) providing a plan for pediatric fungemia management. Our SMART (Specific, Measurable, Attainable, Relevant and Timely) goal was to reduce overutilization of abdominal US and echo in pediatric patients with fungemia on the pediatric gastroenterology service by 50%.

Methods

Study, Setting, and Participants

We executed this quality improvement project at a quaternary care pediatric hospital affiliated with a school of medicine. The project scope consisted of inpatient pediatric patients with fungemia on the pediatric gastroenterology service admitted to the wards or pediatric critical care unit at this institution, along with the practitioners caring for these patients. The project was part of an institutional quality improvement initiative program. The quality improvement team included quality improvement experts from the departments of medicine and pediatrics, a pediatric resident and student, and physicians from the divisions of pediatric infectious disease, pediatric critical care, and pediatric gastroenterology. This study qualified for Institutional Review Board (IRB) exemption based on the University’s IRB stipulations.

Current Condition

Root cause analysis was performed by creating a process map of the current standard work and a fishbone diagram (Figure 1). We incorporated feedback from voice of the customer in the root cause analysis. In this analysis, the voice of the customer came from the bedside floor nurses, ultrasound clerk and sonographer, echo technician, cardiology fellow, and microbiology medical technician. We got their feedback on our process map, its accuracy and ways to expand, their thoughts on the problem and why we have this problem, and any solutions they could offer to help improve the problem. Some of the key points obtained were: echos were not routinely done on the floors and were not considered urgent as they often did not change management; the sonographer and those from the cardiology department felt imaging was often overutilized because of misconceptions and lack of available hospital guidelines. Suggested solutions included provider education with reference to Duke’s criteria and establishing a clinical pathway approved by all concerned departments.

Prior to education, we surveyed current practices of practitioners on teams caring for these patients, which included physicians of all levels (attendings, fellows, residents) as well as nurse practitioners and medical students from the department of pediatrics and divisions of pediatric gastroenterology, pediatric infectious disease, and pediatric critical care medicine.

Practitioner Education. In October 2017 practitioners were given a 20-minute presentation on the latest international guidelines on fungemia. Fifty-nine practitioners completed pre- and post-test surveys. Eight respondents were excluded due to incomplete surveys. We compared self-reported frequencies of ordering abdominal imaging and echo before the presentation with intention to order post education. Intention to change clinical practice after the presentation was also surveyed.

Clinical Pathway. Education alone may not result in sustainability, and thus we provided a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Inter-department buy-in was also necessary for success. It was important to get the input from the various teams (infectious disease, cardiology, gastroenterology, and critical care), which was done by incorporating members from those divisions in the project or getting their feedback through voice of the customer analysis.

We redefined standard work based on current evidence and created a clinical pathway during March 2018 that included variations when appropriate (Figure 2). We presented the clinical pathway to practitioners and distributed it via email. We also made it available to pediatric residents and fellows on their mobile institutional work resource application.

Electronic Order Set. We created an electronic order set for pediatric fungemia management and made it available in the electronic health record May 2018.

Measurement

Cases of fungemia were identified through the electronic health record pre-intervention (January 1, 2016 through November 19, 2017) and post-intervention (November 20, 2019 through April 3, 2019). An episode of fungemia was defined as an encounter with 1 or more positive blood culture(s) for Candida species or Cryptococcus species. We manually identified patients belonging to the pediatric gastroenterology service and reviewed these charts to determine the presenting complaint, organism isolated, transplant status, central lines status, risk factors, if abdominal imaging or echocardiography were done for the episode of fungemia, and their corresponding results. We calculated overall and per patient medical charges by using the average charges at our institution of US and echocardiography with a cardiology consult. These average charges were provided by patient financial services and the pediatric cardiology department, respectively. To address non-technical expenditures, we calculated the average time taken for transport to and from radiology and the echo suite for each identified patient. We identified missed fungal endocarditis and fungal balls as balancing measures.

Survey

Among the 51 practitioners surveyed, 36% were performing routine echo and 22% self-reported performing routine abdominal imaging. After education, no respondents planned to routinely do echo or abdominal imaging. All but 1 respondent planned to change their practice for evaluation of fungemia patients based on the presentation (eFigure 1).

Baseline Data

Over the 23-month period from January 1, 2016 to November 19, 2017, there were 21 episodes of fungemia, 18 of which occurred in patients on the pediatric gastroenterology service (2 of the 18 were transplant recipients). For the 18 episodes on this service, abdominal imaging and echo were done 100% of the time, with 0 positive findings (eFigure 2).

Of those 18 episodes, the average age was 4.6 years, with two-thirds of the population being male. There were 3 patients with multiple episodes that accounted for 8 of the episodes (3, 3, and 2 episodes each). Fever was the most common presenting complaint. The most common organism was Candida parapsilosis (6 of the 18 episodes). All episodes but one involved a central line, and all central lines were removed when present except for one case. Of the risk factors, 3 episodes occurred in neutropenic patients, and for 1 episode the patient had a questionable history of fungal endocarditis (and was on fungal prophylaxis). There were no patients with recent cardiac/urogenital surgery or prior fungal balls. No episodes had clinical symptoms suggestive of fungal endocarditis or fungal balls.

Post-Intervention Data

Over the subsequent 17-month period (November 11, 2017 to April 3, 2019), there were 13 episodes of candidemia. There were no episodes of Cryptococcus fungemia. Seven episodes occurred in patients on the pediatric gastroenterology service (2 of the 7 occurred in transplant recipients). Abdominal imaging was done in 3 of these episodes (43%), and in 2 of these 3 episodes, imaging was done at an outside institution prior to arrival, with no positive results (eFigure 2).

Echocardiography was done 57% of the time (n = 4), with echo being done at an outside institution prior to arrival half of the time (n = 2), with no endocarditis identified. The cases of abdominal imaging and echo done at outside institutions prior to arrival were not impacted by the countermeasures. Excluding those 2 patients who had both abdominal imaging and echocardiography done prior to arrival, the overall rate of imaging (both abdominal imaging and echo) done after countermeasures were instituted was 30% (Figure 3).

Of those 7 episodes, the average age was 6.8 years (57% female). There were no patients with multiple episodes. The most common presenting complaint was fever. The most common organism was Candida albicans (3 of the 7 episodes). All episodes involved a central line, which was removed in all cases except for one. Of the risk factors, 2 episodes were in neutropenic patients, and 1 episode had a history of bacterial endocarditis (not related to fungemia). No episodes occurred in patients with prior fungal renal infection, urogenital malformations, or recent cardiac/urogenital surgery. No episodes had clinical symptoms suggestive of fungal endocarditis or renal infection. No episodes of fungal endocarditis or renal infection were identified.

On average, a patient at our institution undergoing abdominal US and echo with a cardiology consult results in medical waste of approximately $3200 per patient. This cost does not take into account other miscellaneous charges possibly incurred, such as the radiologist interpreting the findings and transportation. Baseline data calculations show that patients waste on average 55 minutes in physical transport, and this does not take into account wait times.

Discussion

Candidemia contributes to 10% of central-line associated blood stream infections (CLABSI).¹⁹ Increased usage of indwelling central catheters for administration of parenteral nutrition will inevitably result in practitioners encountering cases of candidemia when caring for this population. As seen from our results, the majority of episodes of candidemia at our institution occurred on the pediatric gastroenterology service, and thus redefining standard work on this service will be impactful.

Candida parapsilosis and Candida albicans were the most common causative agents before and after intervention, respectively, but overall the most common organism was Candida albicans, which is in keeping with that of CLABSI in the literature.¹⁹ Growth of Candida parapsilosis has been particularly linked to CLABSI.¹⁹ The third most common organism in our study was Candida glabrata, which is the second most common cause of candidemia in CLABSI.¹⁹

The cases of positive abdominal imaging in fungemia in the literature are limited to the neonatal population^1-4 and chronic disseminated candidiasis in patients with hematologic malignancies/neutropenia/immunosuppression.^5,6 In fungal endocarditis, the reported cases were generally in neonates,^1,3,7 critically ill patients,⁸ patients with hematologic malignancies/neutropenia/immunosuppression,^6,9 or those with a cardiac history.^9,10 This population differs from the patient population on the pediatric gastroenterology service. Patients on this service may not need US or echo. Performing abdominal US and echo in fungemia patients in whom such imaging is not indicated may result in medical waste of approximately $3200 per patient. There is also a waste of medical resources and time.

We found almost all practitioners are willing to change clinical practice once provided with current guidelines. Face-to-face oral presentations allowed for questions and interaction, making this form of information dissemination better than e-mails or handouts.

Though the numbers were small over the short study period, we were able to decrease overutilization of abdominal imaging and echo after implementing countermeasures. Frequency decreased from 100% to 43% and 57% for abdominal imaging and echo, respectively. Imaging that was done after the countermeasures were implemented was mainly attributed to imaging patients underwent prior to presenting to our institution. This reinforces the need for education at other institutions as well. Of the balancing measures assessed, there were no missed cases of fungal balls or fungal endocarditis. Additionally, of the total 34 episodes of fungemia assessed (21 before and 13 after), even among those with risk factors, there were no cases of fungal endocarditis or renal infection.

The findings from this quality improvement project underscore current recommendations that, despite common misconceptions, routine abdominal US and echo are not indicated in all cases of fungemia. Case-by-case assessment based on the clinical scenario remains key to management of fungemia to avoid unnecessary medical interventions.

Corresponding author: Donna Cheung, MBBS, 200 Hawkins Drive, BT 1120-G, Iowa City, IA 52242; [email protected].

Financial support: None.

From the University of Miami, Department of Pediatrics and Department of Medicine, Miami, FL.

Abstract

• Objective: Pediatric fungemia is associated with a low risk of fungal endocarditis and renal infections. The majority of current guidelines do not recommend routine abdominal imaging/echocardiograms in the evaluation of fungemia, but such imaging has been routinely ordered for patients on the pediatric gastroenterology service at our institution. Our goals were to assess the financial impact of this deviation from current clinical guidelines and redefine the standard work to reduce overutilization of abdominal ultrasounds and echocardiograms. Specifically, our goal was to reduce imaging by 50% by 18 months.
• Methods: Root cause analysis showed a lack of familiarity with current evidence. Using this data, countermeasures were implemented, including practitioner education of guidelines and creation of a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Balancing measures were missed episodes of fungal endocarditis and renal infection.
• Results: During the period January 1, 2016 to November 19, 2017, 18 of 21 episodes of fungemia in our pediatric institution occurred in patients admitted to the pediatric gastroenterology service. Abdominal imaging and echocardiograms were done 100% of the time, with no positive findings and an estimated cost of approximately $58,000. Post-intervention from November 20, 2017 to April 3, 2019, 7 of 13 episodes of fungemia occurred on this service. Frequency of abdominal imaging and echocardiograms decreased to 43% and 57%, respectively. No episodes of fungal endocarditis or renal infection were identified.
• Conclusion: Overutilization of abdominal imaging and echocardiograms in pediatric fungemia evaluation can be safely decreased.

Keywords: guidelines; cost; candidemia; endocarditis.

Practitioners may remain under the impression that routine abdominal ultrasounds (US) and echocardiograms (echo) are indicated in fungemia to evaluate for fungal endocarditis and renal infection, although these conditions are rare and limited to a subset of the population.^1-10 Risk factors include prematurity, immunosuppression, prior bacterial endocarditis, abnormal cardiac valves, and previous urogenital surgeries.¹¹

The 2016 Infectious Diseases Society of America (IDSA) guidelines do not recommend routine US or echo but rather provide scenarios in which Candida endocarditis should be suspected, and these include: persistently positive blood cultures, persistent fevers despite appropriate therapy, and clinical signs that may suggest endocarditis, such as a new heart murmur, heart failure, or embolic phenomena.¹¹ IDSA recommends abdominal imaging in neonates with persistently positive blood cultures to evaluate the urogenital system, in addition to the liver and spleen. They also recommend abdominal imaging in symptomatic ascending Candida pyelonephritis beyond the neonatal period and in chronic disseminated candidiasis; the latter is uncommon and seen almost exclusively in patients recovering from neutropenia with a hematologic malignancy.¹¹

We also reviewed guidelines on fungemia originating outside the United States. The 2010 Canadian clinical guidelines on invasive candidiasis do not explicitly recommend routine imaging, but rather state that various imaging studies, including US and echo among others, may be helpful.¹² The German Speaking Mycological Society and the Paul-Ehrlich-Society for Chemotherapy published a joint recommendation against routine US and echo in uncomplicated candidemia in 2011.¹³

The European Society for Clinical Microbiology and Infectious Diseases is the only society that recommends routine echo. Their 2012 guidelines on candidiasis recommend transesophageal echo in adults¹⁴ and echocardiography in children,¹⁵ as well as abdominal imaging in the diagnosis of chronic disseminated candidiasis in adults with hematological malignancies/hematopoietic stem cell transplantation.¹⁶

The 2013 Brazilian guidelines explicitly recommend against routine abdominal imaging and echo because of the low frequency of visceral lesions in adults with candidemia and recommend reserving imaging for those with persistently positive blood cultures or with clinical signs/symptoms suggestive of endocarditis/abdominal infection or clinical deterioration.¹⁷ The 2014 Japanese guidelines recommend ruling out chronic disseminated candidiasis in these patients with symptoms during the neutrophil recovery phase, but do not mention routinely imaging other patients. They do not address the role of echocardiography.¹⁸

Although physicians in the United Sates typically follow IDSA guidelines, abdominal US and echo were ordered routinely for patients with fungemia on the pediatric gastroenterology service at our institution, leading to higher medical costs and waste of medical resources. Our goals were to assess the current standard work for fungemia evaluation on this service, assess the impact of its deviation from current clinical guidelines, and redefine the standard work by (1) presenting current evidence to practitioners taking care of patients on this service, (2) providing a clinical pathway that allowed for variations where appropriate, and (3) providing a plan for pediatric fungemia management. Our SMART (Specific, Measurable, Attainable, Relevant and Timely) goal was to reduce overutilization of abdominal US and echo in pediatric patients with fungemia on the pediatric gastroenterology service by 50%.

Methods

Study, Setting, and Participants

We executed this quality improvement project at a quaternary care pediatric hospital affiliated with a school of medicine. The project scope consisted of inpatient pediatric patients with fungemia on the pediatric gastroenterology service admitted to the wards or pediatric critical care unit at this institution, along with the practitioners caring for these patients. The project was part of an institutional quality improvement initiative program. The quality improvement team included quality improvement experts from the departments of medicine and pediatrics, a pediatric resident and student, and physicians from the divisions of pediatric infectious disease, pediatric critical care, and pediatric gastroenterology. This study qualified for Institutional Review Board (IRB) exemption based on the University’s IRB stipulations.

Current Condition

Root cause analysis was performed by creating a process map of the current standard work and a fishbone diagram (Figure 1). We incorporated feedback from voice of the customer in the root cause analysis. In this analysis, the voice of the customer came from the bedside floor nurses, ultrasound clerk and sonographer, echo technician, cardiology fellow, and microbiology medical technician. We got their feedback on our process map, its accuracy and ways to expand, their thoughts on the problem and why we have this problem, and any solutions they could offer to help improve the problem. Some of the key points obtained were: echos were not routinely done on the floors and were not considered urgent as they often did not change management; the sonographer and those from the cardiology department felt imaging was often overutilized because of misconceptions and lack of available hospital guidelines. Suggested solutions included provider education with reference to Duke’s criteria and establishing a clinical pathway approved by all concerned departments.

Prior to education, we surveyed current practices of practitioners on teams caring for these patients, which included physicians of all levels (attendings, fellows, residents) as well as nurse practitioners and medical students from the department of pediatrics and divisions of pediatric gastroenterology, pediatric infectious disease, and pediatric critical care medicine.

Practitioner Education. In October 2017 practitioners were given a 20-minute presentation on the latest international guidelines on fungemia. Fifty-nine practitioners completed pre- and post-test surveys. Eight respondents were excluded due to incomplete surveys. We compared self-reported frequencies of ordering abdominal imaging and echo before the presentation with intention to order post education. Intention to change clinical practice after the presentation was also surveyed.

Clinical Pathway. Education alone may not result in sustainability, and thus we provided a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Inter-department buy-in was also necessary for success. It was important to get the input from the various teams (infectious disease, cardiology, gastroenterology, and critical care), which was done by incorporating members from those divisions in the project or getting their feedback through voice of the customer analysis.

We redefined standard work based on current evidence and created a clinical pathway during March 2018 that included variations when appropriate (Figure 2). We presented the clinical pathway to practitioners and distributed it via email. We also made it available to pediatric residents and fellows on their mobile institutional work resource application.

Electronic Order Set. We created an electronic order set for pediatric fungemia management and made it available in the electronic health record May 2018.

Measurement

Cases of fungemia were identified through the electronic health record pre-intervention (January 1, 2016 through November 19, 2017) and post-intervention (November 20, 2019 through April 3, 2019). An episode of fungemia was defined as an encounter with 1 or more positive blood culture(s) for Candida species or Cryptococcus species. We manually identified patients belonging to the pediatric gastroenterology service and reviewed these charts to determine the presenting complaint, organism isolated, transplant status, central lines status, risk factors, if abdominal imaging or echocardiography were done for the episode of fungemia, and their corresponding results. We calculated overall and per patient medical charges by using the average charges at our institution of US and echocardiography with a cardiology consult. These average charges were provided by patient financial services and the pediatric cardiology department, respectively. To address non-technical expenditures, we calculated the average time taken for transport to and from radiology and the echo suite for each identified patient. We identified missed fungal endocarditis and fungal balls as balancing measures.

Survey

Among the 51 practitioners surveyed, 36% were performing routine echo and 22% self-reported performing routine abdominal imaging. After education, no respondents planned to routinely do echo or abdominal imaging. All but 1 respondent planned to change their practice for evaluation of fungemia patients based on the presentation (eFigure 1).

Baseline Data

Over the 23-month period from January 1, 2016 to November 19, 2017, there were 21 episodes of fungemia, 18 of which occurred in patients on the pediatric gastroenterology service (2 of the 18 were transplant recipients). For the 18 episodes on this service, abdominal imaging and echo were done 100% of the time, with 0 positive findings (eFigure 2).

Of those 18 episodes, the average age was 4.6 years, with two-thirds of the population being male. There were 3 patients with multiple episodes that accounted for 8 of the episodes (3, 3, and 2 episodes each). Fever was the most common presenting complaint. The most common organism was Candida parapsilosis (6 of the 18 episodes). All episodes but one involved a central line, and all central lines were removed when present except for one case. Of the risk factors, 3 episodes occurred in neutropenic patients, and for 1 episode the patient had a questionable history of fungal endocarditis (and was on fungal prophylaxis). There were no patients with recent cardiac/urogenital surgery or prior fungal balls. No episodes had clinical symptoms suggestive of fungal endocarditis or fungal balls.

Post-Intervention Data

Over the subsequent 17-month period (November 11, 2017 to April 3, 2019), there were 13 episodes of candidemia. There were no episodes of Cryptococcus fungemia. Seven episodes occurred in patients on the pediatric gastroenterology service (2 of the 7 occurred in transplant recipients). Abdominal imaging was done in 3 of these episodes (43%), and in 2 of these 3 episodes, imaging was done at an outside institution prior to arrival, with no positive results (eFigure 2).

Echocardiography was done 57% of the time (n = 4), with echo being done at an outside institution prior to arrival half of the time (n = 2), with no endocarditis identified. The cases of abdominal imaging and echo done at outside institutions prior to arrival were not impacted by the countermeasures. Excluding those 2 patients who had both abdominal imaging and echocardiography done prior to arrival, the overall rate of imaging (both abdominal imaging and echo) done after countermeasures were instituted was 30% (Figure 3).

Of those 7 episodes, the average age was 6.8 years (57% female). There were no patients with multiple episodes. The most common presenting complaint was fever. The most common organism was Candida albicans (3 of the 7 episodes). All episodes involved a central line, which was removed in all cases except for one. Of the risk factors, 2 episodes were in neutropenic patients, and 1 episode had a history of bacterial endocarditis (not related to fungemia). No episodes occurred in patients with prior fungal renal infection, urogenital malformations, or recent cardiac/urogenital surgery. No episodes had clinical symptoms suggestive of fungal endocarditis or renal infection. No episodes of fungal endocarditis or renal infection were identified.

On average, a patient at our institution undergoing abdominal US and echo with a cardiology consult results in medical waste of approximately $3200 per patient. This cost does not take into account other miscellaneous charges possibly incurred, such as the radiologist interpreting the findings and transportation. Baseline data calculations show that patients waste on average 55 minutes in physical transport, and this does not take into account wait times.

Discussion

Candidemia contributes to 10% of central-line associated blood stream infections (CLABSI).¹⁹ Increased usage of indwelling central catheters for administration of parenteral nutrition will inevitably result in practitioners encountering cases of candidemia when caring for this population. As seen from our results, the majority of episodes of candidemia at our institution occurred on the pediatric gastroenterology service, and thus redefining standard work on this service will be impactful.

Candida parapsilosis and Candida albicans were the most common causative agents before and after intervention, respectively, but overall the most common organism was Candida albicans, which is in keeping with that of CLABSI in the literature.¹⁹ Growth of Candida parapsilosis has been particularly linked to CLABSI.¹⁹ The third most common organism in our study was Candida glabrata, which is the second most common cause of candidemia in CLABSI.¹⁹

The cases of positive abdominal imaging in fungemia in the literature are limited to the neonatal population^1-4 and chronic disseminated candidiasis in patients with hematologic malignancies/neutropenia/immunosuppression.^5,6 In fungal endocarditis, the reported cases were generally in neonates,^1,3,7 critically ill patients,⁸ patients with hematologic malignancies/neutropenia/immunosuppression,^6,9 or those with a cardiac history.^9,10 This population differs from the patient population on the pediatric gastroenterology service. Patients on this service may not need US or echo. Performing abdominal US and echo in fungemia patients in whom such imaging is not indicated may result in medical waste of approximately $3200 per patient. There is also a waste of medical resources and time.

We found almost all practitioners are willing to change clinical practice once provided with current guidelines. Face-to-face oral presentations allowed for questions and interaction, making this form of information dissemination better than e-mails or handouts.

Though the numbers were small over the short study period, we were able to decrease overutilization of abdominal imaging and echo after implementing countermeasures. Frequency decreased from 100% to 43% and 57% for abdominal imaging and echo, respectively. Imaging that was done after the countermeasures were implemented was mainly attributed to imaging patients underwent prior to presenting to our institution. This reinforces the need for education at other institutions as well. Of the balancing measures assessed, there were no missed cases of fungal balls or fungal endocarditis. Additionally, of the total 34 episodes of fungemia assessed (21 before and 13 after), even among those with risk factors, there were no cases of fungal endocarditis or renal infection.

The findings from this quality improvement project underscore current recommendations that, despite common misconceptions, routine abdominal US and echo are not indicated in all cases of fungemia. Case-by-case assessment based on the clinical scenario remains key to management of fungemia to avoid unnecessary medical interventions.

Corresponding author: Donna Cheung, MBBS, 200 Hawkins Drive, BT 1120-G, Iowa City, IA 52242; [email protected].

Financial support: None.

From the University of Miami, Department of Pediatrics and Department of Medicine, Miami, FL.

Abstract

• Objective: Pediatric fungemia is associated with a low risk of fungal endocarditis and renal infections. The majority of current guidelines do not recommend routine abdominal imaging/echocardiograms in the evaluation of fungemia, but such imaging has been routinely ordered for patients on the pediatric gastroenterology service at our institution. Our goals were to assess the financial impact of this deviation from current clinical guidelines and redefine the standard work to reduce overutilization of abdominal ultrasounds and echocardiograms. Specifically, our goal was to reduce imaging by 50% by 18 months.
• Methods: Root cause analysis showed a lack of familiarity with current evidence. Using this data, countermeasures were implemented, including practitioner education of guidelines and creation of a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Balancing measures were missed episodes of fungal endocarditis and renal infection.
• Results: During the period January 1, 2016 to November 19, 2017, 18 of 21 episodes of fungemia in our pediatric institution occurred in patients admitted to the pediatric gastroenterology service. Abdominal imaging and echocardiograms were done 100% of the time, with no positive findings and an estimated cost of approximately $58,000. Post-intervention from November 20, 2017 to April 3, 2019, 7 of 13 episodes of fungemia occurred on this service. Frequency of abdominal imaging and echocardiograms decreased to 43% and 57%, respectively. No episodes of fungal endocarditis or renal infection were identified.
• Conclusion: Overutilization of abdominal imaging and echocardiograms in pediatric fungemia evaluation can be safely decreased.

Keywords: guidelines; cost; candidemia; endocarditis.

Practitioners may remain under the impression that routine abdominal ultrasounds (US) and echocardiograms (echo) are indicated in fungemia to evaluate for fungal endocarditis and renal infection, although these conditions are rare and limited to a subset of the population.^1-10 Risk factors include prematurity, immunosuppression, prior bacterial endocarditis, abnormal cardiac valves, and previous urogenital surgeries.¹¹

The 2016 Infectious Diseases Society of America (IDSA) guidelines do not recommend routine US or echo but rather provide scenarios in which Candida endocarditis should be suspected, and these include: persistently positive blood cultures, persistent fevers despite appropriate therapy, and clinical signs that may suggest endocarditis, such as a new heart murmur, heart failure, or embolic phenomena.¹¹ IDSA recommends abdominal imaging in neonates with persistently positive blood cultures to evaluate the urogenital system, in addition to the liver and spleen. They also recommend abdominal imaging in symptomatic ascending Candida pyelonephritis beyond the neonatal period and in chronic disseminated candidiasis; the latter is uncommon and seen almost exclusively in patients recovering from neutropenia with a hematologic malignancy.¹¹

We also reviewed guidelines on fungemia originating outside the United States. The 2010 Canadian clinical guidelines on invasive candidiasis do not explicitly recommend routine imaging, but rather state that various imaging studies, including US and echo among others, may be helpful.¹² The German Speaking Mycological Society and the Paul-Ehrlich-Society for Chemotherapy published a joint recommendation against routine US and echo in uncomplicated candidemia in 2011.¹³

The European Society for Clinical Microbiology and Infectious Diseases is the only society that recommends routine echo. Their 2012 guidelines on candidiasis recommend transesophageal echo in adults¹⁴ and echocardiography in children,¹⁵ as well as abdominal imaging in the diagnosis of chronic disseminated candidiasis in adults with hematological malignancies/hematopoietic stem cell transplantation.¹⁶

The 2013 Brazilian guidelines explicitly recommend against routine abdominal imaging and echo because of the low frequency of visceral lesions in adults with candidemia and recommend reserving imaging for those with persistently positive blood cultures or with clinical signs/symptoms suggestive of endocarditis/abdominal infection or clinical deterioration.¹⁷ The 2014 Japanese guidelines recommend ruling out chronic disseminated candidiasis in these patients with symptoms during the neutrophil recovery phase, but do not mention routinely imaging other patients. They do not address the role of echocardiography.¹⁸

Although physicians in the United Sates typically follow IDSA guidelines, abdominal US and echo were ordered routinely for patients with fungemia on the pediatric gastroenterology service at our institution, leading to higher medical costs and waste of medical resources. Our goals were to assess the current standard work for fungemia evaluation on this service, assess the impact of its deviation from current clinical guidelines, and redefine the standard work by (1) presenting current evidence to practitioners taking care of patients on this service, (2) providing a clinical pathway that allowed for variations where appropriate, and (3) providing a plan for pediatric fungemia management. Our SMART (Specific, Measurable, Attainable, Relevant and Timely) goal was to reduce overutilization of abdominal US and echo in pediatric patients with fungemia on the pediatric gastroenterology service by 50%.

Methods

Study, Setting, and Participants

We executed this quality improvement project at a quaternary care pediatric hospital affiliated with a school of medicine. The project scope consisted of inpatient pediatric patients with fungemia on the pediatric gastroenterology service admitted to the wards or pediatric critical care unit at this institution, along with the practitioners caring for these patients. The project was part of an institutional quality improvement initiative program. The quality improvement team included quality improvement experts from the departments of medicine and pediatrics, a pediatric resident and student, and physicians from the divisions of pediatric infectious disease, pediatric critical care, and pediatric gastroenterology. This study qualified for Institutional Review Board (IRB) exemption based on the University’s IRB stipulations.

Current Condition

Root cause analysis was performed by creating a process map of the current standard work and a fishbone diagram (Figure 1). We incorporated feedback from voice of the customer in the root cause analysis. In this analysis, the voice of the customer came from the bedside floor nurses, ultrasound clerk and sonographer, echo technician, cardiology fellow, and microbiology medical technician. We got their feedback on our process map, its accuracy and ways to expand, their thoughts on the problem and why we have this problem, and any solutions they could offer to help improve the problem. Some of the key points obtained were: echos were not routinely done on the floors and were not considered urgent as they often did not change management; the sonographer and those from the cardiology department felt imaging was often overutilized because of misconceptions and lack of available hospital guidelines. Suggested solutions included provider education with reference to Duke’s criteria and establishing a clinical pathway approved by all concerned departments.

Prior to education, we surveyed current practices of practitioners on teams caring for these patients, which included physicians of all levels (attendings, fellows, residents) as well as nurse practitioners and medical students from the department of pediatrics and divisions of pediatric gastroenterology, pediatric infectious disease, and pediatric critical care medicine.

Practitioner Education. In October 2017 practitioners were given a 20-minute presentation on the latest international guidelines on fungemia. Fifty-nine practitioners completed pre- and post-test surveys. Eight respondents were excluded due to incomplete surveys. We compared self-reported frequencies of ordering abdominal imaging and echo before the presentation with intention to order post education. Intention to change clinical practice after the presentation was also surveyed.

Clinical Pathway. Education alone may not result in sustainability, and thus we provided a readily accessible clinical pathway and an electronic order set for pediatric fungemia management. Inter-department buy-in was also necessary for success. It was important to get the input from the various teams (infectious disease, cardiology, gastroenterology, and critical care), which was done by incorporating members from those divisions in the project or getting their feedback through voice of the customer analysis.

We redefined standard work based on current evidence and created a clinical pathway during March 2018 that included variations when appropriate (Figure 2). We presented the clinical pathway to practitioners and distributed it via email. We also made it available to pediatric residents and fellows on their mobile institutional work resource application.

Electronic Order Set. We created an electronic order set for pediatric fungemia management and made it available in the electronic health record May 2018.

Measurement

Cases of fungemia were identified through the electronic health record pre-intervention (January 1, 2016 through November 19, 2017) and post-intervention (November 20, 2019 through April 3, 2019). An episode of fungemia was defined as an encounter with 1 or more positive blood culture(s) for Candida species or Cryptococcus species. We manually identified patients belonging to the pediatric gastroenterology service and reviewed these charts to determine the presenting complaint, organism isolated, transplant status, central lines status, risk factors, if abdominal imaging or echocardiography were done for the episode of fungemia, and their corresponding results. We calculated overall and per patient medical charges by using the average charges at our institution of US and echocardiography with a cardiology consult. These average charges were provided by patient financial services and the pediatric cardiology department, respectively. To address non-technical expenditures, we calculated the average time taken for transport to and from radiology and the echo suite for each identified patient. We identified missed fungal endocarditis and fungal balls as balancing measures.

Survey

Among the 51 practitioners surveyed, 36% were performing routine echo and 22% self-reported performing routine abdominal imaging. After education, no respondents planned to routinely do echo or abdominal imaging. All but 1 respondent planned to change their practice for evaluation of fungemia patients based on the presentation (eFigure 1).

Baseline Data

Over the 23-month period from January 1, 2016 to November 19, 2017, there were 21 episodes of fungemia, 18 of which occurred in patients on the pediatric gastroenterology service (2 of the 18 were transplant recipients). For the 18 episodes on this service, abdominal imaging and echo were done 100% of the time, with 0 positive findings (eFigure 2).

Of those 18 episodes, the average age was 4.6 years, with two-thirds of the population being male. There were 3 patients with multiple episodes that accounted for 8 of the episodes (3, 3, and 2 episodes each). Fever was the most common presenting complaint. The most common organism was Candida parapsilosis (6 of the 18 episodes). All episodes but one involved a central line, and all central lines were removed when present except for one case. Of the risk factors, 3 episodes occurred in neutropenic patients, and for 1 episode the patient had a questionable history of fungal endocarditis (and was on fungal prophylaxis). There were no patients with recent cardiac/urogenital surgery or prior fungal balls. No episodes had clinical symptoms suggestive of fungal endocarditis or fungal balls.

Post-Intervention Data

Over the subsequent 17-month period (November 11, 2017 to April 3, 2019), there were 13 episodes of candidemia. There were no episodes of Cryptococcus fungemia. Seven episodes occurred in patients on the pediatric gastroenterology service (2 of the 7 occurred in transplant recipients). Abdominal imaging was done in 3 of these episodes (43%), and in 2 of these 3 episodes, imaging was done at an outside institution prior to arrival, with no positive results (eFigure 2).

Echocardiography was done 57% of the time (n = 4), with echo being done at an outside institution prior to arrival half of the time (n = 2), with no endocarditis identified. The cases of abdominal imaging and echo done at outside institutions prior to arrival were not impacted by the countermeasures. Excluding those 2 patients who had both abdominal imaging and echocardiography done prior to arrival, the overall rate of imaging (both abdominal imaging and echo) done after countermeasures were instituted was 30% (Figure 3).

Of those 7 episodes, the average age was 6.8 years (57% female). There were no patients with multiple episodes. The most common presenting complaint was fever. The most common organism was Candida albicans (3 of the 7 episodes). All episodes involved a central line, which was removed in all cases except for one. Of the risk factors, 2 episodes were in neutropenic patients, and 1 episode had a history of bacterial endocarditis (not related to fungemia). No episodes occurred in patients with prior fungal renal infection, urogenital malformations, or recent cardiac/urogenital surgery. No episodes had clinical symptoms suggestive of fungal endocarditis or renal infection. No episodes of fungal endocarditis or renal infection were identified.

On average, a patient at our institution undergoing abdominal US and echo with a cardiology consult results in medical waste of approximately $3200 per patient. This cost does not take into account other miscellaneous charges possibly incurred, such as the radiologist interpreting the findings and transportation. Baseline data calculations show that patients waste on average 55 minutes in physical transport, and this does not take into account wait times.

Discussion

Candidemia contributes to 10% of central-line associated blood stream infections (CLABSI).¹⁹ Increased usage of indwelling central catheters for administration of parenteral nutrition will inevitably result in practitioners encountering cases of candidemia when caring for this population. As seen from our results, the majority of episodes of candidemia at our institution occurred on the pediatric gastroenterology service, and thus redefining standard work on this service will be impactful.

Candida parapsilosis and Candida albicans were the most common causative agents before and after intervention, respectively, but overall the most common organism was Candida albicans, which is in keeping with that of CLABSI in the literature.¹⁹ Growth of Candida parapsilosis has been particularly linked to CLABSI.¹⁹ The third most common organism in our study was Candida glabrata, which is the second most common cause of candidemia in CLABSI.¹⁹

The cases of positive abdominal imaging in fungemia in the literature are limited to the neonatal population^1-4 and chronic disseminated candidiasis in patients with hematologic malignancies/neutropenia/immunosuppression.^5,6 In fungal endocarditis, the reported cases were generally in neonates,^1,3,7 critically ill patients,⁸ patients with hematologic malignancies/neutropenia/immunosuppression,^6,9 or those with a cardiac history.^9,10 This population differs from the patient population on the pediatric gastroenterology service. Patients on this service may not need US or echo. Performing abdominal US and echo in fungemia patients in whom such imaging is not indicated may result in medical waste of approximately $3200 per patient. There is also a waste of medical resources and time.

We found almost all practitioners are willing to change clinical practice once provided with current guidelines. Face-to-face oral presentations allowed for questions and interaction, making this form of information dissemination better than e-mails or handouts.

Though the numbers were small over the short study period, we were able to decrease overutilization of abdominal imaging and echo after implementing countermeasures. Frequency decreased from 100% to 43% and 57% for abdominal imaging and echo, respectively. Imaging that was done after the countermeasures were implemented was mainly attributed to imaging patients underwent prior to presenting to our institution. This reinforces the need for education at other institutions as well. Of the balancing measures assessed, there were no missed cases of fungal balls or fungal endocarditis. Additionally, of the total 34 episodes of fungemia assessed (21 before and 13 after), even among those with risk factors, there were no cases of fungal endocarditis or renal infection.

The findings from this quality improvement project underscore current recommendations that, despite common misconceptions, routine abdominal US and echo are not indicated in all cases of fungemia. Case-by-case assessment based on the clinical scenario remains key to management of fungemia to avoid unnecessary medical interventions.

Corresponding author: Donna Cheung, MBBS, 200 Hawkins Drive, BT 1120-G, Iowa City, IA 52242; [email protected].

Financial support: None.

CHARLOTTE, N.C. – Most children who undergo hemispherectomy for severe, intractable epilepsy report headaches after the procedure, according to a study presented at the annual meeting of the Child Neurology Society. Patients with headache before hemispherectomy may be at risk of increased headache frequency after the procedure. The most common type of headache reported is nonmigrainous headache.

“We recommend that hemispherectomy patients be evaluated and followed closely postoperatively and questioned regarding the presence of headache,” said William Bingaman, MD, vice-chair of the neurological institute and head of the section of epilepsy surgery at the Cleveland Clinic, and colleagues. “Patients should be assessed and treated quickly to decrease prolonged pain and suffering and increase function.”

The two main types of hemispherectomy are anatomical and functional. Anatomical hemispherectomy entails the removal of a large amount of brain mass. Functional hemispherectomy entails the removal of a smaller amount of brain mass, as well as the disconnection of the brain’s hemispheres. Most patients are seizure free or have reduced seizure frequency after hemispherectomy. Other common postoperative outcomes include changes in behavior, cognition, motor function, and speech. Many studies have explored these outcomes, but few have examined the frequency of postoperative headache in children who undergo hemispherectomy.

Dr. Bingaman and colleagues retrospectively reviewed the charts of 74 children who underwent hemispherectomy at the Cleveland Clinic during the previous 5 years. They excluded 14 patients who were too young to respond for the analysis. The investigators sent the remaining 60 patients an informative letter and followed up with a 10-minute phone questionnaire about patients’ postoperative headache symptoms.

Twenty-two (36.7%) eligible patients completed the questionnaire. Thirty-eight patients could not be reached or declined to participate. Half of the 22 respondents were male. Participants’ median age at surgery was 6.5 years. The most common types of hemispherectomy were left functional (50%) and right functional (31.8%).

Nine (39.1%) of the 22 respondents had headache before surgery, and seven (31.8%) reported a family history of headache. In all, 19 (86.4%) patients had headache after surgery, and 10 (45.5%) had headaches that began after the surgery. Of the nine patients with preoperative headache, six (66.6%) had an increase in headache frequency after surgery, two (22.2%) reported no change, and one (11.1%) had decreased headache frequency. The most common type of headache reported was tension-type headache, and migraine was the second most common.

“The cause of any posthemispherectomy headache has thus far only been attributed to hydrocephalus,” wrote Dr. Bingaman and colleagues. “The tendency of headache to worsen following stresses such as illness, stroke, trauma, etc. has been studied extensively. The pathophysiology of posthemispherectomy headache can be investigated further by classifying hemispherectomy as a type of trauma or injury, which would explain the development of postoperative headache. Previous studies on posttraumatic headache have ascribed these headaches to neuroinflammation following the injury. Additionally, posthemispherectomy headache could also be due to the buildup of debris and fluid following the operation. Future hemispherectomy patients should be treated prophylactically for headache.”

The authors did not report funding for their study or declare any disclosures.

[email protected]

SOURCE: Pandit I et al. CNS 2019. Abstract 99.

CHARLOTTE, N.C. – Most children who undergo hemispherectomy for severe, intractable epilepsy report headaches after the procedure, according to a study presented at the annual meeting of the Child Neurology Society. Patients with headache before hemispherectomy may be at risk of increased headache frequency after the procedure. The most common type of headache reported is nonmigrainous headache.

“We recommend that hemispherectomy patients be evaluated and followed closely postoperatively and questioned regarding the presence of headache,” said William Bingaman, MD, vice-chair of the neurological institute and head of the section of epilepsy surgery at the Cleveland Clinic, and colleagues. “Patients should be assessed and treated quickly to decrease prolonged pain and suffering and increase function.”

The two main types of hemispherectomy are anatomical and functional. Anatomical hemispherectomy entails the removal of a large amount of brain mass. Functional hemispherectomy entails the removal of a smaller amount of brain mass, as well as the disconnection of the brain’s hemispheres. Most patients are seizure free or have reduced seizure frequency after hemispherectomy. Other common postoperative outcomes include changes in behavior, cognition, motor function, and speech. Many studies have explored these outcomes, but few have examined the frequency of postoperative headache in children who undergo hemispherectomy.

Dr. Bingaman and colleagues retrospectively reviewed the charts of 74 children who underwent hemispherectomy at the Cleveland Clinic during the previous 5 years. They excluded 14 patients who were too young to respond for the analysis. The investigators sent the remaining 60 patients an informative letter and followed up with a 10-minute phone questionnaire about patients’ postoperative headache symptoms.

Twenty-two (36.7%) eligible patients completed the questionnaire. Thirty-eight patients could not be reached or declined to participate. Half of the 22 respondents were male. Participants’ median age at surgery was 6.5 years. The most common types of hemispherectomy were left functional (50%) and right functional (31.8%).

Nine (39.1%) of the 22 respondents had headache before surgery, and seven (31.8%) reported a family history of headache. In all, 19 (86.4%) patients had headache after surgery, and 10 (45.5%) had headaches that began after the surgery. Of the nine patients with preoperative headache, six (66.6%) had an increase in headache frequency after surgery, two (22.2%) reported no change, and one (11.1%) had decreased headache frequency. The most common type of headache reported was tension-type headache, and migraine was the second most common.

“The cause of any posthemispherectomy headache has thus far only been attributed to hydrocephalus,” wrote Dr. Bingaman and colleagues. “The tendency of headache to worsen following stresses such as illness, stroke, trauma, etc. has been studied extensively. The pathophysiology of posthemispherectomy headache can be investigated further by classifying hemispherectomy as a type of trauma or injury, which would explain the development of postoperative headache. Previous studies on posttraumatic headache have ascribed these headaches to neuroinflammation following the injury. Additionally, posthemispherectomy headache could also be due to the buildup of debris and fluid following the operation. Future hemispherectomy patients should be treated prophylactically for headache.”

The authors did not report funding for their study or declare any disclosures.

[email protected]

SOURCE: Pandit I et al. CNS 2019. Abstract 99.

CHARLOTTE, N.C. – Most children who undergo hemispherectomy for severe, intractable epilepsy report headaches after the procedure, according to a study presented at the annual meeting of the Child Neurology Society. Patients with headache before hemispherectomy may be at risk of increased headache frequency after the procedure. The most common type of headache reported is nonmigrainous headache.

“We recommend that hemispherectomy patients be evaluated and followed closely postoperatively and questioned regarding the presence of headache,” said William Bingaman, MD, vice-chair of the neurological institute and head of the section of epilepsy surgery at the Cleveland Clinic, and colleagues. “Patients should be assessed and treated quickly to decrease prolonged pain and suffering and increase function.”

The two main types of hemispherectomy are anatomical and functional. Anatomical hemispherectomy entails the removal of a large amount of brain mass. Functional hemispherectomy entails the removal of a smaller amount of brain mass, as well as the disconnection of the brain’s hemispheres. Most patients are seizure free or have reduced seizure frequency after hemispherectomy. Other common postoperative outcomes include changes in behavior, cognition, motor function, and speech. Many studies have explored these outcomes, but few have examined the frequency of postoperative headache in children who undergo hemispherectomy.

Dr. Bingaman and colleagues retrospectively reviewed the charts of 74 children who underwent hemispherectomy at the Cleveland Clinic during the previous 5 years. They excluded 14 patients who were too young to respond for the analysis. The investigators sent the remaining 60 patients an informative letter and followed up with a 10-minute phone questionnaire about patients’ postoperative headache symptoms.

Twenty-two (36.7%) eligible patients completed the questionnaire. Thirty-eight patients could not be reached or declined to participate. Half of the 22 respondents were male. Participants’ median age at surgery was 6.5 years. The most common types of hemispherectomy were left functional (50%) and right functional (31.8%).

Nine (39.1%) of the 22 respondents had headache before surgery, and seven (31.8%) reported a family history of headache. In all, 19 (86.4%) patients had headache after surgery, and 10 (45.5%) had headaches that began after the surgery. Of the nine patients with preoperative headache, six (66.6%) had an increase in headache frequency after surgery, two (22.2%) reported no change, and one (11.1%) had decreased headache frequency. The most common type of headache reported was tension-type headache, and migraine was the second most common.

“The cause of any posthemispherectomy headache has thus far only been attributed to hydrocephalus,” wrote Dr. Bingaman and colleagues. “The tendency of headache to worsen following stresses such as illness, stroke, trauma, etc. has been studied extensively. The pathophysiology of posthemispherectomy headache can be investigated further by classifying hemispherectomy as a type of trauma or injury, which would explain the development of postoperative headache. Previous studies on posttraumatic headache have ascribed these headaches to neuroinflammation following the injury. Additionally, posthemispherectomy headache could also be due to the buildup of debris and fluid following the operation. Future hemispherectomy patients should be treated prophylactically for headache.”

The authors did not report funding for their study or declare any disclosures.

[email protected]

SOURCE: Pandit I et al. CNS 2019. Abstract 99.

CHICAGO – Pediatric thyroid nodule cytopathology classified according to the Bethesda system and tracked over a 16-year period at a single center showed a higher rate of malignancy than that reported in adults.

Especially for nodules that fall into indeterminate categories, “the rate of malignancy in thyroid nodules is higher [in pediatric patients] than that reported in adults,” said Wen Jiang, MD, of the University of California San Diego and Rady Children’s Hospital, also in San Diego.

Current pediatric guidelines recommend that thyroid fine-needle aspiration (FNA) be performed only under ultrasound guidance, noted Dr. Jiang, a pediatric otolaryngologist, at the annual meeting of the American Thyroid Association. In addition, the Bethesda thyroid cytopathology system should be used to report FNA cytology results, and when cytopathology of FNA for a thyroid nodule is indeterminate, thyroid lobectomy is preferred over repeat FNA for most children with thyroid nodules.

To assess how well pediatric patients fared using the Bethesda system for thyroid cytopathology, Dr. Jiang and colleagues performed a retrospective review of children with thyroid nodules who received FNA at Rady Children’s Hospital during 2002-2018. The investigators used the Bethesda system to classify FNA results.

In addition to collecting the initial cytologic findings and demographic data, Dr. Jiang and colleagues also tracked repeat cytology and histopathology, as well as any radiographic and clinical follow-up data that were available.

A total of 203 cytologic samples were available from 171 patients. In all, 50 patients (29.2%) had malignancy. The mean age was about 15 years (range, 6-18 years), and the ratio of 140 female to 31 male participants was 4.5:1.

All but 21 of the samples were performed under ultrasound guidance. The nondiagnostic rate for ultrasound-guided samples was 11.5%, and for those obtained without use of ultrasound – which occurred in older cases – the nondiagnostic rate was 38.5%. “Ultrasound guidance improves the diagnostic rate,” said Dr. Jiang, adding that incorporation of on-site adequacy testing also “significantly decreased the nondiagnostic rate over the study period.”

The Bethesda system has the following six diagnostic categories, with each accompanied by follow-up recommendations in the adult population.

• Category I is nondiagnostic, and a repeat ultrasound-guided FNA is recommended for adults in this category.
• Category II is benign. Patients with these nodules should receive clinical follow-up and repeat ultrasound examination.
• Category III nodules may show atypia of undetermined significance or be judged a follicular lesion of undetermined significance. Here, adult management options include repeat FNA, molecular testing, or thyroid lobectomy.
• Category IV nodules may be assessed as follicular neoplasm or as suspicious for follicular neoplasm. Molecular testing or lobectomy are the adult management options.
• Category V describes nodules suspicious for malignancy. Either lobectomy or total thyroidectomy are options for adult management.
• Category VI is reserved for clearly malignant nodules. Again, lobectomy or total thyroidectomy are the adult management options.

In terms of the real-world outcomes in this cohort of pediatric patients with nodules, 14.8% of the 29 nodules with Bethesda category I – nondiagnostic – status were later found to be malignant, a higher rate than the 5%-10% expected in adults. Of 106 Bethesda category II – benign – nodules, 4% were malignant. In adults, 0%-3% of category II nodules turn out to be malignant.

Cytopathology from FNA of 22 nodules fell into the Bethesda category III, and 25% were malignant, which was within the expected range of 10%-30% for adults. “Bethesda class II accurately identified benign nodules with low risk of subsequent malignancy,” said Dr. Jiang.

Fourteen nodules were Bethesda category IV, and of those, 42.9% were malignant, again slightly higher than the 25%-40% expected in adults.

Just six nodules had FNA results falling into Bethesda category V, of which 83.3% were malignant, a higher rate than the 50%-75% expected for adult category V cytopathology results. All category V nodules were papillary thyroid carcinoma.

All 26 Bethesda category VI nodules were malignant; in adult category VI nodules, 97%-99% are expected to be malignant. All but four of the cases were found to be papillary thyroid carcinoma.

Dr. Jiang explained that at Rady Children’s Hospital, all FNA cytology slides received a second-opinion assessment by pathologists at the University of California San Diego. Of all the samples assessed in the study, there was disagreement about one slide, with a difference of one Bethesda category. “Malignant class cytology is quite reliable,” she said, adding the caveat that “second-opinion confirmation adds additional confidence to the cytologic diagnosis.”

She emphasized again that the initiation of on-site testing for sample adequacy significantly decreased the nondiagnostic rate seen over the course of the study.

Dr. Jiang reported no relevant conflicts of interest and no outside sources of funding.

[email protected]

SOURCE: Jiang W et al. ATA 2019, Oral Abstract 34.

CHICAGO – Pediatric thyroid nodule cytopathology classified according to the Bethesda system and tracked over a 16-year period at a single center showed a higher rate of malignancy than that reported in adults.

Especially for nodules that fall into indeterminate categories, “the rate of malignancy in thyroid nodules is higher [in pediatric patients] than that reported in adults,” said Wen Jiang, MD, of the University of California San Diego and Rady Children’s Hospital, also in San Diego.

Current pediatric guidelines recommend that thyroid fine-needle aspiration (FNA) be performed only under ultrasound guidance, noted Dr. Jiang, a pediatric otolaryngologist, at the annual meeting of the American Thyroid Association. In addition, the Bethesda thyroid cytopathology system should be used to report FNA cytology results, and when cytopathology of FNA for a thyroid nodule is indeterminate, thyroid lobectomy is preferred over repeat FNA for most children with thyroid nodules.

To assess how well pediatric patients fared using the Bethesda system for thyroid cytopathology, Dr. Jiang and colleagues performed a retrospective review of children with thyroid nodules who received FNA at Rady Children’s Hospital during 2002-2018. The investigators used the Bethesda system to classify FNA results.

In addition to collecting the initial cytologic findings and demographic data, Dr. Jiang and colleagues also tracked repeat cytology and histopathology, as well as any radiographic and clinical follow-up data that were available.

A total of 203 cytologic samples were available from 171 patients. In all, 50 patients (29.2%) had malignancy. The mean age was about 15 years (range, 6-18 years), and the ratio of 140 female to 31 male participants was 4.5:1.

All but 21 of the samples were performed under ultrasound guidance. The nondiagnostic rate for ultrasound-guided samples was 11.5%, and for those obtained without use of ultrasound – which occurred in older cases – the nondiagnostic rate was 38.5%. “Ultrasound guidance improves the diagnostic rate,” said Dr. Jiang, adding that incorporation of on-site adequacy testing also “significantly decreased the nondiagnostic rate over the study period.”

The Bethesda system has the following six diagnostic categories, with each accompanied by follow-up recommendations in the adult population.

• Category I is nondiagnostic, and a repeat ultrasound-guided FNA is recommended for adults in this category.
• Category II is benign. Patients with these nodules should receive clinical follow-up and repeat ultrasound examination.
• Category III nodules may show atypia of undetermined significance or be judged a follicular lesion of undetermined significance. Here, adult management options include repeat FNA, molecular testing, or thyroid lobectomy.
• Category IV nodules may be assessed as follicular neoplasm or as suspicious for follicular neoplasm. Molecular testing or lobectomy are the adult management options.
• Category V describes nodules suspicious for malignancy. Either lobectomy or total thyroidectomy are options for adult management.
• Category VI is reserved for clearly malignant nodules. Again, lobectomy or total thyroidectomy are the adult management options.

In terms of the real-world outcomes in this cohort of pediatric patients with nodules, 14.8% of the 29 nodules with Bethesda category I – nondiagnostic – status were later found to be malignant, a higher rate than the 5%-10% expected in adults. Of 106 Bethesda category II – benign – nodules, 4% were malignant. In adults, 0%-3% of category II nodules turn out to be malignant.

Cytopathology from FNA of 22 nodules fell into the Bethesda category III, and 25% were malignant, which was within the expected range of 10%-30% for adults. “Bethesda class II accurately identified benign nodules with low risk of subsequent malignancy,” said Dr. Jiang.

Fourteen nodules were Bethesda category IV, and of those, 42.9% were malignant, again slightly higher than the 25%-40% expected in adults.

Just six nodules had FNA results falling into Bethesda category V, of which 83.3% were malignant, a higher rate than the 50%-75% expected for adult category V cytopathology results. All category V nodules were papillary thyroid carcinoma.

All 26 Bethesda category VI nodules were malignant; in adult category VI nodules, 97%-99% are expected to be malignant. All but four of the cases were found to be papillary thyroid carcinoma.

Dr. Jiang explained that at Rady Children’s Hospital, all FNA cytology slides received a second-opinion assessment by pathologists at the University of California San Diego. Of all the samples assessed in the study, there was disagreement about one slide, with a difference of one Bethesda category. “Malignant class cytology is quite reliable,” she said, adding the caveat that “second-opinion confirmation adds additional confidence to the cytologic diagnosis.”

She emphasized again that the initiation of on-site testing for sample adequacy significantly decreased the nondiagnostic rate seen over the course of the study.

Dr. Jiang reported no relevant conflicts of interest and no outside sources of funding.

[email protected]

SOURCE: Jiang W et al. ATA 2019, Oral Abstract 34.

CHICAGO – Pediatric thyroid nodule cytopathology classified according to the Bethesda system and tracked over a 16-year period at a single center showed a higher rate of malignancy than that reported in adults.

Especially for nodules that fall into indeterminate categories, “the rate of malignancy in thyroid nodules is higher [in pediatric patients] than that reported in adults,” said Wen Jiang, MD, of the University of California San Diego and Rady Children’s Hospital, also in San Diego.

Current pediatric guidelines recommend that thyroid fine-needle aspiration (FNA) be performed only under ultrasound guidance, noted Dr. Jiang, a pediatric otolaryngologist, at the annual meeting of the American Thyroid Association. In addition, the Bethesda thyroid cytopathology system should be used to report FNA cytology results, and when cytopathology of FNA for a thyroid nodule is indeterminate, thyroid lobectomy is preferred over repeat FNA for most children with thyroid nodules.

To assess how well pediatric patients fared using the Bethesda system for thyroid cytopathology, Dr. Jiang and colleagues performed a retrospective review of children with thyroid nodules who received FNA at Rady Children’s Hospital during 2002-2018. The investigators used the Bethesda system to classify FNA results.

In addition to collecting the initial cytologic findings and demographic data, Dr. Jiang and colleagues also tracked repeat cytology and histopathology, as well as any radiographic and clinical follow-up data that were available.

A total of 203 cytologic samples were available from 171 patients. In all, 50 patients (29.2%) had malignancy. The mean age was about 15 years (range, 6-18 years), and the ratio of 140 female to 31 male participants was 4.5:1.

All but 21 of the samples were performed under ultrasound guidance. The nondiagnostic rate for ultrasound-guided samples was 11.5%, and for those obtained without use of ultrasound – which occurred in older cases – the nondiagnostic rate was 38.5%. “Ultrasound guidance improves the diagnostic rate,” said Dr. Jiang, adding that incorporation of on-site adequacy testing also “significantly decreased the nondiagnostic rate over the study period.”

The Bethesda system has the following six diagnostic categories, with each accompanied by follow-up recommendations in the adult population.

• Category I is nondiagnostic, and a repeat ultrasound-guided FNA is recommended for adults in this category.
• Category II is benign. Patients with these nodules should receive clinical follow-up and repeat ultrasound examination.
• Category III nodules may show atypia of undetermined significance or be judged a follicular lesion of undetermined significance. Here, adult management options include repeat FNA, molecular testing, or thyroid lobectomy.
• Category IV nodules may be assessed as follicular neoplasm or as suspicious for follicular neoplasm. Molecular testing or lobectomy are the adult management options.
• Category V describes nodules suspicious for malignancy. Either lobectomy or total thyroidectomy are options for adult management.
• Category VI is reserved for clearly malignant nodules. Again, lobectomy or total thyroidectomy are the adult management options.

In terms of the real-world outcomes in this cohort of pediatric patients with nodules, 14.8% of the 29 nodules with Bethesda category I – nondiagnostic – status were later found to be malignant, a higher rate than the 5%-10% expected in adults. Of 106 Bethesda category II – benign – nodules, 4% were malignant. In adults, 0%-3% of category II nodules turn out to be malignant.

Cytopathology from FNA of 22 nodules fell into the Bethesda category III, and 25% were malignant, which was within the expected range of 10%-30% for adults. “Bethesda class II accurately identified benign nodules with low risk of subsequent malignancy,” said Dr. Jiang.

Fourteen nodules were Bethesda category IV, and of those, 42.9% were malignant, again slightly higher than the 25%-40% expected in adults.

Just six nodules had FNA results falling into Bethesda category V, of which 83.3% were malignant, a higher rate than the 50%-75% expected for adult category V cytopathology results. All category V nodules were papillary thyroid carcinoma.

All 26 Bethesda category VI nodules were malignant; in adult category VI nodules, 97%-99% are expected to be malignant. All but four of the cases were found to be papillary thyroid carcinoma.

Dr. Jiang explained that at Rady Children’s Hospital, all FNA cytology slides received a second-opinion assessment by pathologists at the University of California San Diego. Of all the samples assessed in the study, there was disagreement about one slide, with a difference of one Bethesda category. “Malignant class cytology is quite reliable,” she said, adding the caveat that “second-opinion confirmation adds additional confidence to the cytologic diagnosis.”

She emphasized again that the initiation of on-site testing for sample adequacy significantly decreased the nondiagnostic rate seen over the course of the study.

Dr. Jiang reported no relevant conflicts of interest and no outside sources of funding.

[email protected]

SOURCE: Jiang W et al. ATA 2019, Oral Abstract 34.

After only 8 weeks, the 2019-2020 influenza season already has made itself noteworthy.

For the week ending Nov. 23, there were five states, along with Puerto Rico, at the highest level of the Centers for Disease Control and Prevention’s 1-10 scale of flu activity. That’s more than any year since 2012, including the pandemic season of 2017-2018, according to CDC data, and may suggest either an early peak or the beginning of a particularly bad winter.

“Nationally, ILI [influenza-like illness] activity has been at or above baseline for 3 weeks; however, the amount of influenza activity across the country varies with the south and parts of the west seeing elevated activity while other parts of the country are still seeing low activity,” the CDC’s influenza division said in its weekly FluView report.

The five highest-activity states – Alabama, Georgia, Louisiana, Mississippi, and Texas – are all at level 10, and they join two others – South Carolina and Tennessee, which are at level 8 – in the “high” range from 8-10 on the ILI activity scale; Puerto Rico also is at level 10. ILI is defined as “fever (temperature of 100° F [37.8° C] or greater) and a cough and/or a sore throat without a known cause other than influenza,” the CDC said.

The activity scale is based on the percentage of outpatient visits for ILI in each state, which is reported to the CDC’s Outpatient Influenza-like Illness Surveillance Network (ILINet) each week. The national rate for the week ending Nov. 23 was 2.9%, which is above the new-for-this-season baseline rate of 2.4%. For the three previous flu seasons, the national baseline was 2.2%, having been raised from its previous level of 2.1% in 2015-2016, CDC data show.

The peak month of flu activity occurs most often in February – 15 times from 1982-1983 to 2017-2018 – but there were seven peaks in December and six each in January and March over that time period, along with one peak each in October and November, the CDC said. The October peak occurred during the H1N1 pandemic year of 2009, when the national outpatient ILI rate climbed to just over 7.7%.
 

[email protected]

After only 8 weeks, the 2019-2020 influenza season already has made itself noteworthy.

For the week ending Nov. 23, there were five states, along with Puerto Rico, at the highest level of the Centers for Disease Control and Prevention’s 1-10 scale of flu activity. That’s more than any year since 2012, including the pandemic season of 2017-2018, according to CDC data, and may suggest either an early peak or the beginning of a particularly bad winter.

“Nationally, ILI [influenza-like illness] activity has been at or above baseline for 3 weeks; however, the amount of influenza activity across the country varies with the south and parts of the west seeing elevated activity while other parts of the country are still seeing low activity,” the CDC’s influenza division said in its weekly FluView report.

The five highest-activity states – Alabama, Georgia, Louisiana, Mississippi, and Texas – are all at level 10, and they join two others – South Carolina and Tennessee, which are at level 8 – in the “high” range from 8-10 on the ILI activity scale; Puerto Rico also is at level 10. ILI is defined as “fever (temperature of 100° F [37.8° C] or greater) and a cough and/or a sore throat without a known cause other than influenza,” the CDC said.

The activity scale is based on the percentage of outpatient visits for ILI in each state, which is reported to the CDC’s Outpatient Influenza-like Illness Surveillance Network (ILINet) each week. The national rate for the week ending Nov. 23 was 2.9%, which is above the new-for-this-season baseline rate of 2.4%. For the three previous flu seasons, the national baseline was 2.2%, having been raised from its previous level of 2.1% in 2015-2016, CDC data show.

The peak month of flu activity occurs most often in February – 15 times from 1982-1983 to 2017-2018 – but there were seven peaks in December and six each in January and March over that time period, along with one peak each in October and November, the CDC said. The October peak occurred during the H1N1 pandemic year of 2009, when the national outpatient ILI rate climbed to just over 7.7%.
 

[email protected]

After only 8 weeks, the 2019-2020 influenza season already has made itself noteworthy.

For the week ending Nov. 23, there were five states, along with Puerto Rico, at the highest level of the Centers for Disease Control and Prevention’s 1-10 scale of flu activity. That’s more than any year since 2012, including the pandemic season of 2017-2018, according to CDC data, and may suggest either an early peak or the beginning of a particularly bad winter.

“Nationally, ILI [influenza-like illness] activity has been at or above baseline for 3 weeks; however, the amount of influenza activity across the country varies with the south and parts of the west seeing elevated activity while other parts of the country are still seeing low activity,” the CDC’s influenza division said in its weekly FluView report.

The five highest-activity states – Alabama, Georgia, Louisiana, Mississippi, and Texas – are all at level 10, and they join two others – South Carolina and Tennessee, which are at level 8 – in the “high” range from 8-10 on the ILI activity scale; Puerto Rico also is at level 10. ILI is defined as “fever (temperature of 100° F [37.8° C] or greater) and a cough and/or a sore throat without a known cause other than influenza,” the CDC said.

The activity scale is based on the percentage of outpatient visits for ILI in each state, which is reported to the CDC’s Outpatient Influenza-like Illness Surveillance Network (ILINet) each week. The national rate for the week ending Nov. 23 was 2.9%, which is above the new-for-this-season baseline rate of 2.4%. For the three previous flu seasons, the national baseline was 2.2%, having been raised from its previous level of 2.1% in 2015-2016, CDC data show.

The peak month of flu activity occurs most often in February – 15 times from 1982-1983 to 2017-2018 – but there were seven peaks in December and six each in January and March over that time period, along with one peak each in October and November, the CDC said. The October peak occurred during the H1N1 pandemic year of 2009, when the national outpatient ILI rate climbed to just over 7.7%.
 

[email protected]

Nearly one in five adolescents and one in four young adults in the United States have prediabetes, with a higher prevalence among males, a study has found.

copyright Martynasfoto/Thinkstock

Linda J. Andes, PhD, from the Centers for Disease Control and Prevention and coauthors reported in JAMA Pediatrics their analysis of data from 2,606 adolescent (12-18 years) and 3,180 young adult (19-34 years) participants in the 2005-2016 National Health and Nutrition Examination Surveys.

This found that the percentage with prediabetes – defined as either impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or increased hemoglobin A_1c (HbA_1c) level – was 18% among adolescents and 24% among young adults.

The most common condition was IFG, which was seen in 11% of adolescents and 16% of young adults. The rate of IGT was 4% in adolescents and 6% of young adults, while elevated HbA_1c levels were seen in 5% of adolescents and 8% of young adults.

This information is important because “In adults, these three phenotypes increase the risk of developing type 2 diabetes as well as cardiovascular diseases,” Dr. Andes and coauthors wrote. “In 2011-2012, the overall prevalence of prediabetes among U.S. adults, defined as the presence of any of the three glucose metabolism dysregulation phenotypes, was 38% and it increased to about 50% in persons 65 years and older.”

Dr. Andes and associates noted that isolated IFG was the most common glucose dysregulation seen in both adolescents and young adults. “While individuals with IFG are at increased risk for type 2 diabetes, few primary prevention trials have included individuals selected for the presence of IFG and none have been conducted in adolescents with IFG or IGT to our knowledge.”

The study saw some key gender differences in prevalence. For example, the prevalence of IFG was significantly lower in adolescent girls than in boys (7% vs. 15%; P less than .001), and in young women, compared with young men (10% vs. 22%; P less than .001).

“These findings are consistent with those of other studies in adults; however, the underlying mechanisms for explaining this discrepancy are still unclear,” Dr. Andes and coauthors wrote.

Ethnicity also appeared to influence risk, with the prevalence of IFG significantly lower in non-Hispanic black adolescents, compared with Hispanic adolescents. However, increased HbA_1c levels were significantly more prevalent in non-Hispanic black adolescents, compared with Hispanic or non-Hispanic white adolescents.

“These findings highlight the need for additional studies on the long-term consequences and preventive strategies of abnormal glucose metabolism as measured by HbA_1c levels in adolescents and young adults, especially of minority racial/ethnic groups,” the authors wrote.

Adolescents with prediabetes had significantly higher systolic blood pressure, non-HDL cholesterol, waist-to-height ratio, higher body mass index, and lower insulin sensitivity, compared with those with normal glucose tolerance. Among young adults with prediabetes, there was significantly higher systolic blood pressure and non-HDL cholesterol, compared with individuals with normal glucose tolerance.

No funding or conflicts of interest were declared.

SOURCE: Andes LJ et al. JAMA Pediatr. 2019 Dec 2. doi: 10.1001/jamapediatrics.2019.4498.

Nearly one in five adolescents and one in four young adults in the United States have prediabetes, with a higher prevalence among males, a study has found.

copyright Martynasfoto/Thinkstock

Linda J. Andes, PhD, from the Centers for Disease Control and Prevention and coauthors reported in JAMA Pediatrics their analysis of data from 2,606 adolescent (12-18 years) and 3,180 young adult (19-34 years) participants in the 2005-2016 National Health and Nutrition Examination Surveys.

This found that the percentage with prediabetes – defined as either impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or increased hemoglobin A_1c (HbA_1c) level – was 18% among adolescents and 24% among young adults.

The most common condition was IFG, which was seen in 11% of adolescents and 16% of young adults. The rate of IGT was 4% in adolescents and 6% of young adults, while elevated HbA_1c levels were seen in 5% of adolescents and 8% of young adults.

This information is important because “In adults, these three phenotypes increase the risk of developing type 2 diabetes as well as cardiovascular diseases,” Dr. Andes and coauthors wrote. “In 2011-2012, the overall prevalence of prediabetes among U.S. adults, defined as the presence of any of the three glucose metabolism dysregulation phenotypes, was 38% and it increased to about 50% in persons 65 years and older.”

Dr. Andes and associates noted that isolated IFG was the most common glucose dysregulation seen in both adolescents and young adults. “While individuals with IFG are at increased risk for type 2 diabetes, few primary prevention trials have included individuals selected for the presence of IFG and none have been conducted in adolescents with IFG or IGT to our knowledge.”

The study saw some key gender differences in prevalence. For example, the prevalence of IFG was significantly lower in adolescent girls than in boys (7% vs. 15%; P less than .001), and in young women, compared with young men (10% vs. 22%; P less than .001).

“These findings are consistent with those of other studies in adults; however, the underlying mechanisms for explaining this discrepancy are still unclear,” Dr. Andes and coauthors wrote.

Ethnicity also appeared to influence risk, with the prevalence of IFG significantly lower in non-Hispanic black adolescents, compared with Hispanic adolescents. However, increased HbA_1c levels were significantly more prevalent in non-Hispanic black adolescents, compared with Hispanic or non-Hispanic white adolescents.

“These findings highlight the need for additional studies on the long-term consequences and preventive strategies of abnormal glucose metabolism as measured by HbA_1c levels in adolescents and young adults, especially of minority racial/ethnic groups,” the authors wrote.

Adolescents with prediabetes had significantly higher systolic blood pressure, non-HDL cholesterol, waist-to-height ratio, higher body mass index, and lower insulin sensitivity, compared with those with normal glucose tolerance. Among young adults with prediabetes, there was significantly higher systolic blood pressure and non-HDL cholesterol, compared with individuals with normal glucose tolerance.

No funding or conflicts of interest were declared.

SOURCE: Andes LJ et al. JAMA Pediatr. 2019 Dec 2. doi: 10.1001/jamapediatrics.2019.4498.

Nearly one in five adolescents and one in four young adults in the United States have prediabetes, with a higher prevalence among males, a study has found.

copyright Martynasfoto/Thinkstock

Linda J. Andes, PhD, from the Centers for Disease Control and Prevention and coauthors reported in JAMA Pediatrics their analysis of data from 2,606 adolescent (12-18 years) and 3,180 young adult (19-34 years) participants in the 2005-2016 National Health and Nutrition Examination Surveys.

This found that the percentage with prediabetes – defined as either impaired fasting glucose (IFG), impaired glucose tolerance (IGT) or increased hemoglobin A_1c (HbA_1c) level – was 18% among adolescents and 24% among young adults.

The most common condition was IFG, which was seen in 11% of adolescents and 16% of young adults. The rate of IGT was 4% in adolescents and 6% of young adults, while elevated HbA_1c levels were seen in 5% of adolescents and 8% of young adults.

This information is important because “In adults, these three phenotypes increase the risk of developing type 2 diabetes as well as cardiovascular diseases,” Dr. Andes and coauthors wrote. “In 2011-2012, the overall prevalence of prediabetes among U.S. adults, defined as the presence of any of the three glucose metabolism dysregulation phenotypes, was 38% and it increased to about 50% in persons 65 years and older.”

Dr. Andes and associates noted that isolated IFG was the most common glucose dysregulation seen in both adolescents and young adults. “While individuals with IFG are at increased risk for type 2 diabetes, few primary prevention trials have included individuals selected for the presence of IFG and none have been conducted in adolescents with IFG or IGT to our knowledge.”

The study saw some key gender differences in prevalence. For example, the prevalence of IFG was significantly lower in adolescent girls than in boys (7% vs. 15%; P less than .001), and in young women, compared with young men (10% vs. 22%; P less than .001).

“These findings are consistent with those of other studies in adults; however, the underlying mechanisms for explaining this discrepancy are still unclear,” Dr. Andes and coauthors wrote.

Ethnicity also appeared to influence risk, with the prevalence of IFG significantly lower in non-Hispanic black adolescents, compared with Hispanic adolescents. However, increased HbA_1c levels were significantly more prevalent in non-Hispanic black adolescents, compared with Hispanic or non-Hispanic white adolescents.

“These findings highlight the need for additional studies on the long-term consequences and preventive strategies of abnormal glucose metabolism as measured by HbA_1c levels in adolescents and young adults, especially of minority racial/ethnic groups,” the authors wrote.

Adolescents with prediabetes had significantly higher systolic blood pressure, non-HDL cholesterol, waist-to-height ratio, higher body mass index, and lower insulin sensitivity, compared with those with normal glucose tolerance. Among young adults with prediabetes, there was significantly higher systolic blood pressure and non-HDL cholesterol, compared with individuals with normal glucose tolerance.

No funding or conflicts of interest were declared.

SOURCE: Andes LJ et al. JAMA Pediatr. 2019 Dec 2. doi: 10.1001/jamapediatrics.2019.4498.

Initiating antiretroviral therapy within an hour after birth, rather than waiting a few weeks, lowers the reservoir of HIV virus and improves immune response, early results from an ongoing study in Botswana, Africa, showed.

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Despite advances in treatment programs during pregnancy that prevent mother to child HIV transmission, 300-500 pediatric HIV infections occur each day in sub-Saharan Africa, Roger Shapiro, MD, MPH, said during a media teleconference organized by the American Association for the Advancement of Science. “Most pediatric HIV diagnosis programs currently test children at 4-6 weeks of age to identify infections that occur either in pregnancy or during delivery,” said Dr. Shapiro, associate professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, Boston. “However, these programs miss the opportunity to begin immediate antiretroviral treatment for children who can be identified earlier. There are benefits to starting treatment and arresting HIV replication in the first week of life. These include limiting the viral reservoir or the population of infected cells, limiting potentially harmful immune responses to the virus, and preventing the rapid decline in health that can occur in the early weeks of HIV infection in infants. Without treatment, 50% of HIV-infected children regress to death by 2 years. Starting treatment in the first weeks or months of life has been shown to improve survival.”

With these benefits in mind, he and his associates initiated the Early Infant Treatment (EIT) study in 2015 to diagnose and treat HIV infected infants in Botswana in the first week of life or as early as possible after infection. They screened more than 10,000 children and identified 40 that were HIV infected. “This low transmission rate is a testament to the fact that most HIV-positive women in Botswana receive three-drug treatment in pregnancy, which is highly successful in blocking transmission,” Dr. Shapiro said. “When we identified an HIV-infected infant, we consented mothers to allow us to start treatment right away. We used a series of regimens because there are limited options. The available options include older drugs, some of which are no longer used for adults but which were the only options for children.”

The researchers initiated three initial drugs approved for newborns: nevirapine, zidovudine, and lamivudine, and then changed the regimen slightly after a few weeks, when they used ritonavir-boosted lopinavir, plus the lamivudine and zidovudine. “We followed the children weekly at first, then at monthly refill visits, and kept close track of how they were taking the medicines and the level of virus in each child’s blood,” Dr. Shapiro said.

In a manuscript published online in Science Translational Medicine on Nov. 27, 2019, he and his associates reported results of the first 10 children enrolled in the EIT study who reached about 96 weeks on treatment. For comparison, they also enrolled a group of children as controls, who started treatment later in the first year of life, after being identified at a more standard time of 4-6 weeks. Tests performed included droplet digital polymerase chain reaction, HIV near-full-genome sequencing, whole-genome amplification, and flow cytometry.

“What we wanted to focus on are the HIV reservoir cells that are persisting in the setting of antiretroviral treatment,” study coauthor Mathias Lichterfeld, MD, PhD, explained during the teleconference. “Those are the cells that would cause viral rebound if treatment were to be interrupted. We used complex technology to look at these cells, using next-generation sequencing, which allows us to identify those cells that harbor HIV that has the ability to initiate new viral replication.”

He and his colleagues observed that the number of reservoir cells was significantly smaller than in adults who were on ART for a median of 16 years. It also was smaller than in infected infants who started ART treatment weeks after birth.

In addition, immune activation was reduced in the cohort of infants who were treated immediately after birth.

“We are seeing a distinct advantage of early treatment initiation,” said Dr. Lichterfeld of the infectious disease division at Brigham and Women’s Hospital, Boston. “By doing these assays we see both virological benefits in terms of a very-low reservoir size, and we see immune system characteristics that are also associated with better abilities for antimicrobial immune defense and a lower level of immune activation.”

Another study coauthor, Daniel R. Kuritzkes, MD, chief of the infectious disease division at Brigham and Women’s Hospital, said the findings show “how critically important” it is to extend studies of HIV cure or long-term remission to infants and children. “Very-early intervention in neonates limits the size of the reservoir and offers us the best opportunity for future interventions aimed at cure and long-term drug-free remission of HIV infection,” he said. “We don’t think the current intervention is itself curative, but it sets the stage for the capacity to offer additional innovative interventions in the future. Beyond the importance of this work for cure research per se, this very early intervention in neonates also has the potential of conferring important clinical benefits to the children who participated in this study. Finally, our study demonstrates the feasibility and importance of doing this type of research in neonates in resource-limited settings, given the appropriate infrastructure.”

EIT is supported by the National Institutes of Health. Dr. Lichterfeld disclosed having received speaking and consulting honoraria from Merck and Gilead. Dr. Kuritzkes disclosed having received consulting honoraria and/or research support from Gilead, Merck, and ViiV.

[email protected]

SOURCE: Garcia-Broncano P et al. Sci Transl Med. 2019 Nov 27. eaax7350.

Initiating antiretroviral therapy within an hour after birth, rather than waiting a few weeks, lowers the reservoir of HIV virus and improves immune response, early results from an ongoing study in Botswana, Africa, showed.

Comstock/Thinkstock

Despite advances in treatment programs during pregnancy that prevent mother to child HIV transmission, 300-500 pediatric HIV infections occur each day in sub-Saharan Africa, Roger Shapiro, MD, MPH, said during a media teleconference organized by the American Association for the Advancement of Science. “Most pediatric HIV diagnosis programs currently test children at 4-6 weeks of age to identify infections that occur either in pregnancy or during delivery,” said Dr. Shapiro, associate professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, Boston. “However, these programs miss the opportunity to begin immediate antiretroviral treatment for children who can be identified earlier. There are benefits to starting treatment and arresting HIV replication in the first week of life. These include limiting the viral reservoir or the population of infected cells, limiting potentially harmful immune responses to the virus, and preventing the rapid decline in health that can occur in the early weeks of HIV infection in infants. Without treatment, 50% of HIV-infected children regress to death by 2 years. Starting treatment in the first weeks or months of life has been shown to improve survival.”

With these benefits in mind, he and his associates initiated the Early Infant Treatment (EIT) study in 2015 to diagnose and treat HIV infected infants in Botswana in the first week of life or as early as possible after infection. They screened more than 10,000 children and identified 40 that were HIV infected. “This low transmission rate is a testament to the fact that most HIV-positive women in Botswana receive three-drug treatment in pregnancy, which is highly successful in blocking transmission,” Dr. Shapiro said. “When we identified an HIV-infected infant, we consented mothers to allow us to start treatment right away. We used a series of regimens because there are limited options. The available options include older drugs, some of which are no longer used for adults but which were the only options for children.”

The researchers initiated three initial drugs approved for newborns: nevirapine, zidovudine, and lamivudine, and then changed the regimen slightly after a few weeks, when they used ritonavir-boosted lopinavir, plus the lamivudine and zidovudine. “We followed the children weekly at first, then at monthly refill visits, and kept close track of how they were taking the medicines and the level of virus in each child’s blood,” Dr. Shapiro said.

In a manuscript published online in Science Translational Medicine on Nov. 27, 2019, he and his associates reported results of the first 10 children enrolled in the EIT study who reached about 96 weeks on treatment. For comparison, they also enrolled a group of children as controls, who started treatment later in the first year of life, after being identified at a more standard time of 4-6 weeks. Tests performed included droplet digital polymerase chain reaction, HIV near-full-genome sequencing, whole-genome amplification, and flow cytometry.

“What we wanted to focus on are the HIV reservoir cells that are persisting in the setting of antiretroviral treatment,” study coauthor Mathias Lichterfeld, MD, PhD, explained during the teleconference. “Those are the cells that would cause viral rebound if treatment were to be interrupted. We used complex technology to look at these cells, using next-generation sequencing, which allows us to identify those cells that harbor HIV that has the ability to initiate new viral replication.”

He and his colleagues observed that the number of reservoir cells was significantly smaller than in adults who were on ART for a median of 16 years. It also was smaller than in infected infants who started ART treatment weeks after birth.

In addition, immune activation was reduced in the cohort of infants who were treated immediately after birth.

“We are seeing a distinct advantage of early treatment initiation,” said Dr. Lichterfeld of the infectious disease division at Brigham and Women’s Hospital, Boston. “By doing these assays we see both virological benefits in terms of a very-low reservoir size, and we see immune system characteristics that are also associated with better abilities for antimicrobial immune defense and a lower level of immune activation.”

Another study coauthor, Daniel R. Kuritzkes, MD, chief of the infectious disease division at Brigham and Women’s Hospital, said the findings show “how critically important” it is to extend studies of HIV cure or long-term remission to infants and children. “Very-early intervention in neonates limits the size of the reservoir and offers us the best opportunity for future interventions aimed at cure and long-term drug-free remission of HIV infection,” he said. “We don’t think the current intervention is itself curative, but it sets the stage for the capacity to offer additional innovative interventions in the future. Beyond the importance of this work for cure research per se, this very early intervention in neonates also has the potential of conferring important clinical benefits to the children who participated in this study. Finally, our study demonstrates the feasibility and importance of doing this type of research in neonates in resource-limited settings, given the appropriate infrastructure.”

EIT is supported by the National Institutes of Health. Dr. Lichterfeld disclosed having received speaking and consulting honoraria from Merck and Gilead. Dr. Kuritzkes disclosed having received consulting honoraria and/or research support from Gilead, Merck, and ViiV.

[email protected]

SOURCE: Garcia-Broncano P et al. Sci Transl Med. 2019 Nov 27. eaax7350.

Initiating antiretroviral therapy within an hour after birth, rather than waiting a few weeks, lowers the reservoir of HIV virus and improves immune response, early results from an ongoing study in Botswana, Africa, showed.

Comstock/Thinkstock

Despite advances in treatment programs during pregnancy that prevent mother to child HIV transmission, 300-500 pediatric HIV infections occur each day in sub-Saharan Africa, Roger Shapiro, MD, MPH, said during a media teleconference organized by the American Association for the Advancement of Science. “Most pediatric HIV diagnosis programs currently test children at 4-6 weeks of age to identify infections that occur either in pregnancy or during delivery,” said Dr. Shapiro, associate professor of immunology and infectious diseases at the Harvard T.H. Chan School of Public Health, Boston. “However, these programs miss the opportunity to begin immediate antiretroviral treatment for children who can be identified earlier. There are benefits to starting treatment and arresting HIV replication in the first week of life. These include limiting the viral reservoir or the population of infected cells, limiting potentially harmful immune responses to the virus, and preventing the rapid decline in health that can occur in the early weeks of HIV infection in infants. Without treatment, 50% of HIV-infected children regress to death by 2 years. Starting treatment in the first weeks or months of life has been shown to improve survival.”

With these benefits in mind, he and his associates initiated the Early Infant Treatment (EIT) study in 2015 to diagnose and treat HIV infected infants in Botswana in the first week of life or as early as possible after infection. They screened more than 10,000 children and identified 40 that were HIV infected. “This low transmission rate is a testament to the fact that most HIV-positive women in Botswana receive three-drug treatment in pregnancy, which is highly successful in blocking transmission,” Dr. Shapiro said. “When we identified an HIV-infected infant, we consented mothers to allow us to start treatment right away. We used a series of regimens because there are limited options. The available options include older drugs, some of which are no longer used for adults but which were the only options for children.”

The researchers initiated three initial drugs approved for newborns: nevirapine, zidovudine, and lamivudine, and then changed the regimen slightly after a few weeks, when they used ritonavir-boosted lopinavir, plus the lamivudine and zidovudine. “We followed the children weekly at first, then at monthly refill visits, and kept close track of how they were taking the medicines and the level of virus in each child’s blood,” Dr. Shapiro said.

In a manuscript published online in Science Translational Medicine on Nov. 27, 2019, he and his associates reported results of the first 10 children enrolled in the EIT study who reached about 96 weeks on treatment. For comparison, they also enrolled a group of children as controls, who started treatment later in the first year of life, after being identified at a more standard time of 4-6 weeks. Tests performed included droplet digital polymerase chain reaction, HIV near-full-genome sequencing, whole-genome amplification, and flow cytometry.

“What we wanted to focus on are the HIV reservoir cells that are persisting in the setting of antiretroviral treatment,” study coauthor Mathias Lichterfeld, MD, PhD, explained during the teleconference. “Those are the cells that would cause viral rebound if treatment were to be interrupted. We used complex technology to look at these cells, using next-generation sequencing, which allows us to identify those cells that harbor HIV that has the ability to initiate new viral replication.”

He and his colleagues observed that the number of reservoir cells was significantly smaller than in adults who were on ART for a median of 16 years. It also was smaller than in infected infants who started ART treatment weeks after birth.

In addition, immune activation was reduced in the cohort of infants who were treated immediately after birth.

“We are seeing a distinct advantage of early treatment initiation,” said Dr. Lichterfeld of the infectious disease division at Brigham and Women’s Hospital, Boston. “By doing these assays we see both virological benefits in terms of a very-low reservoir size, and we see immune system characteristics that are also associated with better abilities for antimicrobial immune defense and a lower level of immune activation.”

Another study coauthor, Daniel R. Kuritzkes, MD, chief of the infectious disease division at Brigham and Women’s Hospital, said the findings show “how critically important” it is to extend studies of HIV cure or long-term remission to infants and children. “Very-early intervention in neonates limits the size of the reservoir and offers us the best opportunity for future interventions aimed at cure and long-term drug-free remission of HIV infection,” he said. “We don’t think the current intervention is itself curative, but it sets the stage for the capacity to offer additional innovative interventions in the future. Beyond the importance of this work for cure research per se, this very early intervention in neonates also has the potential of conferring important clinical benefits to the children who participated in this study. Finally, our study demonstrates the feasibility and importance of doing this type of research in neonates in resource-limited settings, given the appropriate infrastructure.”

EIT is supported by the National Institutes of Health. Dr. Lichterfeld disclosed having received speaking and consulting honoraria from Merck and Gilead. Dr. Kuritzkes disclosed having received consulting honoraria and/or research support from Gilead, Merck, and ViiV.

[email protected]

SOURCE: Garcia-Broncano P et al. Sci Transl Med. 2019 Nov 27. eaax7350.

The Food and Drug Administration has approved the Tubes Under Local Anesthesia (Tula) System for treatment of recurrent ear infections (otitis media) via tympanostomy in young children, according to a release from the agency.

Olivier Le Moal/Getty Images

Consisting of Tymbion anesthetic, tympanostomy tubes developed by Tusker Medical, and several devices that deliver them into the ear drum, the system can be used in an office setting under local anesthesia rather than in hospital settings with general anesthesia.

“This approval has the potential to expand patient access to a treatment that can be administered in a physician’s office with local anesthesia and minimal discomfort,” said Jeff Shuren, MD, director of the FDA’s Center for Devices and Radiological Health.

The approval was based on data from 222 children treated with the device, with a procedural success rate of 86% in children under 5 years and 89% in children aged 5-12 years. The most common adverse event was insufficient anesthetic.

The system should not be used in children with allergies to some local anesthetics or those younger than 6 months. It also is not intended for patients with preexisting issues with their eardrums, such as perforated ear drums, according to the press release.

The Tula system was granted a Breakthrough Device designation, which means the FDA provided intensive engagement and guidance during its development. The full release can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved the Tubes Under Local Anesthesia (Tula) System for treatment of recurrent ear infections (otitis media) via tympanostomy in young children, according to a release from the agency.

Olivier Le Moal/Getty Images

Consisting of Tymbion anesthetic, tympanostomy tubes developed by Tusker Medical, and several devices that deliver them into the ear drum, the system can be used in an office setting under local anesthesia rather than in hospital settings with general anesthesia.

“This approval has the potential to expand patient access to a treatment that can be administered in a physician’s office with local anesthesia and minimal discomfort,” said Jeff Shuren, MD, director of the FDA’s Center for Devices and Radiological Health.

The approval was based on data from 222 children treated with the device, with a procedural success rate of 86% in children under 5 years and 89% in children aged 5-12 years. The most common adverse event was insufficient anesthetic.

The system should not be used in children with allergies to some local anesthetics or those younger than 6 months. It also is not intended for patients with preexisting issues with their eardrums, such as perforated ear drums, according to the press release.

The Tula system was granted a Breakthrough Device designation, which means the FDA provided intensive engagement and guidance during its development. The full release can be found on the FDA website.

[email protected]

The Food and Drug Administration has approved the Tubes Under Local Anesthesia (Tula) System for treatment of recurrent ear infections (otitis media) via tympanostomy in young children, according to a release from the agency.

Olivier Le Moal/Getty Images

Consisting of Tymbion anesthetic, tympanostomy tubes developed by Tusker Medical, and several devices that deliver them into the ear drum, the system can be used in an office setting under local anesthesia rather than in hospital settings with general anesthesia.

“This approval has the potential to expand patient access to a treatment that can be administered in a physician’s office with local anesthesia and minimal discomfort,” said Jeff Shuren, MD, director of the FDA’s Center for Devices and Radiological Health.

The approval was based on data from 222 children treated with the device, with a procedural success rate of 86% in children under 5 years and 89% in children aged 5-12 years. The most common adverse event was insufficient anesthetic.

The system should not be used in children with allergies to some local anesthetics or those younger than 6 months. It also is not intended for patients with preexisting issues with their eardrums, such as perforated ear drums, according to the press release.

The Tula system was granted a Breakthrough Device designation, which means the FDA provided intensive engagement and guidance during its development. The full release can be found on the FDA website.

[email protected]

PHM19 session

MOC Part 4 projects for community pediatric hospitalists

Presenters

Jack M. Percelay, MD, MPH, FAAP, MHM

Nancy Chen, MD, FAAP

Elizabeth Dobler, MD, FAAP

Lindsay Fox, MD

Beth C. Natt, MD, MPH, SFHM

Clota Snow, MD, FAAP

Session summary

Dr. Jack Percelay, of Sutter Health in San Francisco, started this session at Pediatric Hospital Medicine 2019 by outlining the process of submitting a small group (n = 1-10) project for Maintenance of Certification (MOC) Part 4 credit including the basics of what is needed for the application:

• Aim statement.
• Metrics used.
• Data required (3 data points: pre, post, and sustain).

He also shared the requirement of “meaningful participation” for participants to be eligible for MOC Part 4 credit.
 

Examples of successful projects were shared by members of the presenting group:

• Dr. Natt: Improving the timing of the birth dose of the hepatitis B vaccination.
• Dr. Dobler: Improving the hepatitis B vaccination rate within 24 hours of birth.
• Dr. Snow: Supplementing vitamin D in the newborn nursery.
• Dr. Fox: Improving newborn discharge efficiency, improving screening for smoking exposure, and offering smoking cessation.
• Dr. Percelay: Improving hospitalist billing and coding using time as a factor.
• Dr. Chen: Improving patient satisfaction through improvement of family-centered rounds.

The workshop audience divided into groups to brainstorm/troubleshoot projects and to elicit general advice regarding the process. Sample submissions were provided.
 

Key takeaways

• Even small projects (i.e. single metric) can be submitted/accepted with pre- and postintervention data.
• Be creative! Think about changes you are making at your institution and gather the data to support the intervention.
• Always double-dip on QI projects to gain valuable MOC Part 4 credit!

Dr. Fox is site director, Pediatric Hospital Medicine Division at MetroWest Medical Center, Framingham, Mass.

PHM19 session

MOC Part 4 projects for community pediatric hospitalists

Presenters

Jack M. Percelay, MD, MPH, FAAP, MHM

Nancy Chen, MD, FAAP

Elizabeth Dobler, MD, FAAP

Lindsay Fox, MD

Beth C. Natt, MD, MPH, SFHM

Clota Snow, MD, FAAP

Session summary

Dr. Jack Percelay, of Sutter Health in San Francisco, started this session at Pediatric Hospital Medicine 2019 by outlining the process of submitting a small group (n = 1-10) project for Maintenance of Certification (MOC) Part 4 credit including the basics of what is needed for the application:

• Aim statement.
• Metrics used.
• Data required (3 data points: pre, post, and sustain).

He also shared the requirement of “meaningful participation” for participants to be eligible for MOC Part 4 credit.
 

Examples of successful projects were shared by members of the presenting group:

• Dr. Natt: Improving the timing of the birth dose of the hepatitis B vaccination.
• Dr. Dobler: Improving the hepatitis B vaccination rate within 24 hours of birth.
• Dr. Snow: Supplementing vitamin D in the newborn nursery.
• Dr. Fox: Improving newborn discharge efficiency, improving screening for smoking exposure, and offering smoking cessation.
• Dr. Percelay: Improving hospitalist billing and coding using time as a factor.
• Dr. Chen: Improving patient satisfaction through improvement of family-centered rounds.

The workshop audience divided into groups to brainstorm/troubleshoot projects and to elicit general advice regarding the process. Sample submissions were provided.
 

Key takeaways

• Even small projects (i.e. single metric) can be submitted/accepted with pre- and postintervention data.
• Be creative! Think about changes you are making at your institution and gather the data to support the intervention.
• Always double-dip on QI projects to gain valuable MOC Part 4 credit!

Dr. Fox is site director, Pediatric Hospital Medicine Division at MetroWest Medical Center, Framingham, Mass.

PHM19 session

MOC Part 4 projects for community pediatric hospitalists

Presenters

Jack M. Percelay, MD, MPH, FAAP, MHM

Nancy Chen, MD, FAAP

Elizabeth Dobler, MD, FAAP

Lindsay Fox, MD

Beth C. Natt, MD, MPH, SFHM

Clota Snow, MD, FAAP

Session summary

Dr. Jack Percelay, of Sutter Health in San Francisco, started this session at Pediatric Hospital Medicine 2019 by outlining the process of submitting a small group (n = 1-10) project for Maintenance of Certification (MOC) Part 4 credit including the basics of what is needed for the application:

• Aim statement.
• Metrics used.
• Data required (3 data points: pre, post, and sustain).

He also shared the requirement of “meaningful participation” for participants to be eligible for MOC Part 4 credit.
 

Examples of successful projects were shared by members of the presenting group:

• Dr. Natt: Improving the timing of the birth dose of the hepatitis B vaccination.
• Dr. Dobler: Improving the hepatitis B vaccination rate within 24 hours of birth.
• Dr. Snow: Supplementing vitamin D in the newborn nursery.
• Dr. Fox: Improving newborn discharge efficiency, improving screening for smoking exposure, and offering smoking cessation.
• Dr. Percelay: Improving hospitalist billing and coding using time as a factor.
• Dr. Chen: Improving patient satisfaction through improvement of family-centered rounds.

The workshop audience divided into groups to brainstorm/troubleshoot projects and to elicit general advice regarding the process. Sample submissions were provided.
 

Key takeaways

• Even small projects (i.e. single metric) can be submitted/accepted with pre- and postintervention data.
• Be creative! Think about changes you are making at your institution and gather the data to support the intervention.
• Always double-dip on QI projects to gain valuable MOC Part 4 credit!

Dr. Fox is site director, Pediatric Hospital Medicine Division at MetroWest Medical Center, Framingham, Mass.