Mark Shen, MD, SFHM, FAAP

Clinical question: What is the association between delayed acyclovir therapy and death in neonates with herpes simplex virus (HSV) infection?

Background: Neonatal HSV infection may result in significant morbidity and mortality if untreated. Because symptoms upon presentation may be nonspecific and testing may take several days, clinicians must often decide whether to initiate empiric therapy with acyclovir. However, this may also have consequences related to increased costs of care and the side effects of acyclovir.

Study design: Multicenter retrospective cohort study.

Setting: Forty-one freestanding tertiary-care children’s hospitals.

Synopsis: The Pediatric Health Information System (PHIS) database was used to identify 1,086 infants <28 days of age with a discharge diagnosis of HSV from 2003 to 2009 who received their first dose of intravenous acyclovir within the first seven days of admission. Delayed acyclovir was defined as administration after hospital Day One. Propensity scores and multivariate logistic regression analysis were used to attempt to account for patient (e.g. severity of illness) and hospital confounders. The mortality rate was 9.5% (95% confidence interval [CI]: 6.3%-13.82%) for delayed therapy compared with 6.6% (95% CI: 5.0%-8.5%) for early therapy.

Limitations of this study include the inability to identify all potential patient-level confounders that might have led clinicians to initiate early acyclovir therapy. Although the authors attempted to account for variables that might have defined sicker patients, such as intubation or vasoactive agent infusion, they could not identify patients with just skin, eye, or mouth disease from this database, nor could they identify specific clinical concerns, such as hypothermia. Thus, while the authors conclude that empiric acyclovir is prudent if HSV testing is performed, more specific clinical indications cannot be gleaned from this review.

Bottom line: Delayed initiation of acyclovir increases mortality in neonatal HSV infection.

Citation: Shah SS, Aronson PL, Mohamad Z, Lorch SA. Delayed acyclovir therapy and death among neonates with herpes simplex virus infection. Pediatrics. 2011;128(6):1153-1160.

Reviewed by Pediatric Editor Mark Shen, MD, SFHM, medical director of hospital medicine at Dell Children's Medical Center, Austin, Texas.

Clinical question: What is the association between delayed acyclovir therapy and death in neonates with herpes simplex virus (HSV) infection?

Background: Neonatal HSV infection may result in significant morbidity and mortality if untreated. Because symptoms upon presentation may be nonspecific and testing may take several days, clinicians must often decide whether to initiate empiric therapy with acyclovir. However, this may also have consequences related to increased costs of care and the side effects of acyclovir.

Study design: Multicenter retrospective cohort study.

Setting: Forty-one freestanding tertiary-care children’s hospitals.

Synopsis: The Pediatric Health Information System (PHIS) database was used to identify 1,086 infants <28 days of age with a discharge diagnosis of HSV from 2003 to 2009 who received their first dose of intravenous acyclovir within the first seven days of admission. Delayed acyclovir was defined as administration after hospital Day One. Propensity scores and multivariate logistic regression analysis were used to attempt to account for patient (e.g. severity of illness) and hospital confounders. The mortality rate was 9.5% (95% confidence interval [CI]: 6.3%-13.82%) for delayed therapy compared with 6.6% (95% CI: 5.0%-8.5%) for early therapy.

Limitations of this study include the inability to identify all potential patient-level confounders that might have led clinicians to initiate early acyclovir therapy. Although the authors attempted to account for variables that might have defined sicker patients, such as intubation or vasoactive agent infusion, they could not identify patients with just skin, eye, or mouth disease from this database, nor could they identify specific clinical concerns, such as hypothermia. Thus, while the authors conclude that empiric acyclovir is prudent if HSV testing is performed, more specific clinical indications cannot be gleaned from this review.

Bottom line: Delayed initiation of acyclovir increases mortality in neonatal HSV infection.

Citation: Shah SS, Aronson PL, Mohamad Z, Lorch SA. Delayed acyclovir therapy and death among neonates with herpes simplex virus infection. Pediatrics. 2011;128(6):1153-1160.

Reviewed by Pediatric Editor Mark Shen, MD, SFHM, medical director of hospital medicine at Dell Children's Medical Center, Austin, Texas.

Clinical question: What is the association between delayed acyclovir therapy and death in neonates with herpes simplex virus (HSV) infection?

Background: Neonatal HSV infection may result in significant morbidity and mortality if untreated. Because symptoms upon presentation may be nonspecific and testing may take several days, clinicians must often decide whether to initiate empiric therapy with acyclovir. However, this may also have consequences related to increased costs of care and the side effects of acyclovir.

Study design: Multicenter retrospective cohort study.

Setting: Forty-one freestanding tertiary-care children’s hospitals.

Synopsis: The Pediatric Health Information System (PHIS) database was used to identify 1,086 infants <28 days of age with a discharge diagnosis of HSV from 2003 to 2009 who received their first dose of intravenous acyclovir within the first seven days of admission. Delayed acyclovir was defined as administration after hospital Day One. Propensity scores and multivariate logistic regression analysis were used to attempt to account for patient (e.g. severity of illness) and hospital confounders. The mortality rate was 9.5% (95% confidence interval [CI]: 6.3%-13.82%) for delayed therapy compared with 6.6% (95% CI: 5.0%-8.5%) for early therapy.

Limitations of this study include the inability to identify all potential patient-level confounders that might have led clinicians to initiate early acyclovir therapy. Although the authors attempted to account for variables that might have defined sicker patients, such as intubation or vasoactive agent infusion, they could not identify patients with just skin, eye, or mouth disease from this database, nor could they identify specific clinical concerns, such as hypothermia. Thus, while the authors conclude that empiric acyclovir is prudent if HSV testing is performed, more specific clinical indications cannot be gleaned from this review.

Bottom line: Delayed initiation of acyclovir increases mortality in neonatal HSV infection.

Citation: Shah SS, Aronson PL, Mohamad Z, Lorch SA. Delayed acyclovir therapy and death among neonates with herpes simplex virus infection. Pediatrics. 2011;128(6):1153-1160.

Reviewed by Pediatric Editor Mark Shen, MD, SFHM, medical director of hospital medicine at Dell Children's Medical Center, Austin, Texas.

Clinical question: What is the association between childhood urinary tract infections (UTIs) and chronic kidney disease (CKD)?

Background: A traditional paradigm in pediatrics is that CKD might be caused by renal scarring as a result of recurrent UTIs, particularly in the presence of vesicoureteral reflux (VUR). Increasingly, this has been called into question as nonintervention for low-grade VUR has not impacted clinical outcomes.

Study design: Retrospective cohort and systematic literature review.

Setting: Tertiary-care hospital in Finland and PubMed database.

Synopsis: A search of the PubMed database for articles published from 1966 to 2009 relating to a potential association between CKD and UTIs yielded 10 studies reporting on 1,576 patients with UTIs and long-term evaluation for CKD. Only three of the 1,576 patients had childhood UTIs without structural kidney abnormalities as a potential cause of the CKD. VUR was not considered a structural abnormality. The authors note that no data on kidney morphology prior to UTI recurrence were available in these cases.

At the same time, the study authors reviewed the records of 366 patients with CKD at a tertiary-care hospital in Finland. They excluded 308 patients with defined noninfectious causes of CKD. Of the 58 remaining patients, three potentially had recurrent UTIs as a contributing cause to eventual CKD. All three patients had structurally abnormal kidneys on first radiologic examination, possibly suggesting pre-existing renal anomalies. The potential association between recurrent childhood UTIs without structural abnormalities and CKD appears to be less than 1%.

Limitations of this study include its retrospective design and incomplete characterization systematic review. Nevertheless, the study appears to support recent work that childhood UTIs without underlying kidney abnormalities are unlikely to result in permanent renal damage.

Bottom line: Childhood UTIs, without structural kidney abnormality, are not a significant cause of chronic kidney disease in adults.

Citation: Salo J, Ilkäheimo R, Tapiainen T, Uhari M. Childhood urinary tract infections as a cause of chronic kidney disease. Pediatrics. 2011;128:840-847.

Reviewed by Pediatric Editor Mark Shen, MD, FHM, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: What is the association between childhood urinary tract infections (UTIs) and chronic kidney disease (CKD)?

Background: A traditional paradigm in pediatrics is that CKD might be caused by renal scarring as a result of recurrent UTIs, particularly in the presence of vesicoureteral reflux (VUR). Increasingly, this has been called into question as nonintervention for low-grade VUR has not impacted clinical outcomes.

Study design: Retrospective cohort and systematic literature review.

Setting: Tertiary-care hospital in Finland and PubMed database.

Synopsis: A search of the PubMed database for articles published from 1966 to 2009 relating to a potential association between CKD and UTIs yielded 10 studies reporting on 1,576 patients with UTIs and long-term evaluation for CKD. Only three of the 1,576 patients had childhood UTIs without structural kidney abnormalities as a potential cause of the CKD. VUR was not considered a structural abnormality. The authors note that no data on kidney morphology prior to UTI recurrence were available in these cases.

At the same time, the study authors reviewed the records of 366 patients with CKD at a tertiary-care hospital in Finland. They excluded 308 patients with defined noninfectious causes of CKD. Of the 58 remaining patients, three potentially had recurrent UTIs as a contributing cause to eventual CKD. All three patients had structurally abnormal kidneys on first radiologic examination, possibly suggesting pre-existing renal anomalies. The potential association between recurrent childhood UTIs without structural abnormalities and CKD appears to be less than 1%.

Limitations of this study include its retrospective design and incomplete characterization systematic review. Nevertheless, the study appears to support recent work that childhood UTIs without underlying kidney abnormalities are unlikely to result in permanent renal damage.

Bottom line: Childhood UTIs, without structural kidney abnormality, are not a significant cause of chronic kidney disease in adults.

Citation: Salo J, Ilkäheimo R, Tapiainen T, Uhari M. Childhood urinary tract infections as a cause of chronic kidney disease. Pediatrics. 2011;128:840-847.

Reviewed by Pediatric Editor Mark Shen, MD, FHM, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

Clinical question: What is the association between childhood urinary tract infections (UTIs) and chronic kidney disease (CKD)?

Background: A traditional paradigm in pediatrics is that CKD might be caused by renal scarring as a result of recurrent UTIs, particularly in the presence of vesicoureteral reflux (VUR). Increasingly, this has been called into question as nonintervention for low-grade VUR has not impacted clinical outcomes.

Study design: Retrospective cohort and systematic literature review.

Setting: Tertiary-care hospital in Finland and PubMed database.

Synopsis: A search of the PubMed database for articles published from 1966 to 2009 relating to a potential association between CKD and UTIs yielded 10 studies reporting on 1,576 patients with UTIs and long-term evaluation for CKD. Only three of the 1,576 patients had childhood UTIs without structural kidney abnormalities as a potential cause of the CKD. VUR was not considered a structural abnormality. The authors note that no data on kidney morphology prior to UTI recurrence were available in these cases.

At the same time, the study authors reviewed the records of 366 patients with CKD at a tertiary-care hospital in Finland. They excluded 308 patients with defined noninfectious causes of CKD. Of the 58 remaining patients, three potentially had recurrent UTIs as a contributing cause to eventual CKD. All three patients had structurally abnormal kidneys on first radiologic examination, possibly suggesting pre-existing renal anomalies. The potential association between recurrent childhood UTIs without structural abnormalities and CKD appears to be less than 1%.

Limitations of this study include its retrospective design and incomplete characterization systematic review. Nevertheless, the study appears to support recent work that childhood UTIs without underlying kidney abnormalities are unlikely to result in permanent renal damage.

Bottom line: Childhood UTIs, without structural kidney abnormality, are not a significant cause of chronic kidney disease in adults.

Citation: Salo J, Ilkäheimo R, Tapiainen T, Uhari M. Childhood urinary tract infections as a cause of chronic kidney disease. Pediatrics. 2011;128:840-847.

Reviewed by Pediatric Editor Mark Shen, MD, FHM, medical director of hospital medicine at Dell Children’s Medical Center, Austin, Texas.

"Palliative care is not about death and dying or just pain management," said Sarah Friebert, MD, at a morning breakout session on Tuesday at HM12. Rather, she said, palliative care is a method of holistic care delivery for individuals with chronic, complex, and/or life-threatening conditions.

"There is a role for [palliative] subspecialty care" beyond just "good care," said Dr. Friebert. It is a model of shared management with other caregivers that is similar to other models of chronic disease. Additionally, palliative care has evolved to embrace an integrated model, such that palliation is longitudinally woven together with care for curing, dying, and bereavement.

Families continue to have many unmet needs, and hospitalists should provide them with clear and honest communication. Involving the palliative care team early on in the course of the illness is important to facilitate effective care.

Takeaways

• Palliative care is not code for "hospice."
• Other care (providers and treatment) does not need to be given up.
• Early integration of the palliative care team is essential.
• Consider using triggers to prompt referral to palliative care.

Dr. Shen is medical director of hospital medicine and assistant professor of pediatrics at UTMB Austin Pediatrics and Dell Children's Medical Center of Central Texas.

"Palliative care is not about death and dying or just pain management," said Sarah Friebert, MD, at a morning breakout session on Tuesday at HM12. Rather, she said, palliative care is a method of holistic care delivery for individuals with chronic, complex, and/or life-threatening conditions.

"There is a role for [palliative] subspecialty care" beyond just "good care," said Dr. Friebert. It is a model of shared management with other caregivers that is similar to other models of chronic disease. Additionally, palliative care has evolved to embrace an integrated model, such that palliation is longitudinally woven together with care for curing, dying, and bereavement.

Families continue to have many unmet needs, and hospitalists should provide them with clear and honest communication. Involving the palliative care team early on in the course of the illness is important to facilitate effective care.

Takeaways

• Palliative care is not code for "hospice."
• Other care (providers and treatment) does not need to be given up.
• Early integration of the palliative care team is essential.
• Consider using triggers to prompt referral to palliative care.

Dr. Shen is medical director of hospital medicine and assistant professor of pediatrics at UTMB Austin Pediatrics and Dell Children's Medical Center of Central Texas.

"Palliative care is not about death and dying or just pain management," said Sarah Friebert, MD, at a morning breakout session on Tuesday at HM12. Rather, she said, palliative care is a method of holistic care delivery for individuals with chronic, complex, and/or life-threatening conditions.

"There is a role for [palliative] subspecialty care" beyond just "good care," said Dr. Friebert. It is a model of shared management with other caregivers that is similar to other models of chronic disease. Additionally, palliative care has evolved to embrace an integrated model, such that palliation is longitudinally woven together with care for curing, dying, and bereavement.

Families continue to have many unmet needs, and hospitalists should provide them with clear and honest communication. Involving the palliative care team early on in the course of the illness is important to facilitate effective care.

Takeaways

• Palliative care is not code for "hospice."
• Other care (providers and treatment) does not need to be given up.
• Early integration of the palliative care team is essential.
• Consider using triggers to prompt referral to palliative care.

Dr. Shen is medical director of hospital medicine and assistant professor of pediatrics at UTMB Austin Pediatrics and Dell Children's Medical Center of Central Texas.

Most would agree that "we are seeing more thrombosis over time" in children over the past decade, and although we don't know why, it is likely due to multifactorial causes, said Leslie Raffini, MD, MSCE, director of the Hemostasis and Thrombosis Center at Children's Hospital of Philadelphia, in a session on Monday at HM12.

Central venous catheters remain a significant risk factor for venous thromboembolism (VTE) and our knowledge of inherited risk factors has expanded in recent years. While it is likely that inherited risk factors increase the risk of thrombosis in children, the question of testing has engendered debate, due in large part to the lack of clear benefit of that information in the majority of situations.

"The decision to test should be made on an individual basis, after counseling," said Dr. Raffini. "Results should be interpreted by an experienced physician with adolescent females most likely to benefit from the testing. There are no recommendations for what to do with pediatric patients" despite the fact that this is an important cause of morbidity in high-risk patients.

Dr. Raffini describes efforts at Children's Hospital of Philadelphia that led to a VTE prophylaxis guideline. Successful implementation of the guideline required significant multidisciplinary collaboration, and an analysis of outcomes is underway.

Takeaways

• The decision to test for inherited risk factors should be individualized.
• Adolescent females are most likely to benefit from testing for inherited risk factors.
• Implementation of guidelines requires intentional multidisciplinary collaboration.

Most would agree that "we are seeing more thrombosis over time" in children over the past decade, and although we don't know why, it is likely due to multifactorial causes, said Leslie Raffini, MD, MSCE, director of the Hemostasis and Thrombosis Center at Children's Hospital of Philadelphia, in a session on Monday at HM12.

Central venous catheters remain a significant risk factor for venous thromboembolism (VTE) and our knowledge of inherited risk factors has expanded in recent years. While it is likely that inherited risk factors increase the risk of thrombosis in children, the question of testing has engendered debate, due in large part to the lack of clear benefit of that information in the majority of situations.

"The decision to test should be made on an individual basis, after counseling," said Dr. Raffini. "Results should be interpreted by an experienced physician with adolescent females most likely to benefit from the testing. There are no recommendations for what to do with pediatric patients" despite the fact that this is an important cause of morbidity in high-risk patients.

Dr. Raffini describes efforts at Children's Hospital of Philadelphia that led to a VTE prophylaxis guideline. Successful implementation of the guideline required significant multidisciplinary collaboration, and an analysis of outcomes is underway.

Takeaways

• The decision to test for inherited risk factors should be individualized.
• Adolescent females are most likely to benefit from testing for inherited risk factors.
• Implementation of guidelines requires intentional multidisciplinary collaboration.

Most would agree that "we are seeing more thrombosis over time" in children over the past decade, and although we don't know why, it is likely due to multifactorial causes, said Leslie Raffini, MD, MSCE, director of the Hemostasis and Thrombosis Center at Children's Hospital of Philadelphia, in a session on Monday at HM12.

Central venous catheters remain a significant risk factor for venous thromboembolism (VTE) and our knowledge of inherited risk factors has expanded in recent years. While it is likely that inherited risk factors increase the risk of thrombosis in children, the question of testing has engendered debate, due in large part to the lack of clear benefit of that information in the majority of situations.

"The decision to test should be made on an individual basis, after counseling," said Dr. Raffini. "Results should be interpreted by an experienced physician with adolescent females most likely to benefit from the testing. There are no recommendations for what to do with pediatric patients" despite the fact that this is an important cause of morbidity in high-risk patients.

Dr. Raffini describes efforts at Children's Hospital of Philadelphia that led to a VTE prophylaxis guideline. Successful implementation of the guideline required significant multidisciplinary collaboration, and an analysis of outcomes is underway.

Takeaways

• The decision to test for inherited risk factors should be individualized.
• Adolescent females are most likely to benefit from testing for inherited risk factors.
• Implementation of guidelines requires intentional multidisciplinary collaboration.

"Hopefully there will be a test available to physicians for diagnosing KD in the next 5 years," said Adriana Tremoulet, MD, MAS, who is the Associate Director of the Kawasaki Disease Research Center at Rady Children's Hospital/UC San Diego. Research into biomarkers looks promising and there is even some work underway to develop an app to help with the diagnostic algorithm for atypical cases, shared Dr. Tremoulet.

While many of the ways in which we make the diagnosis of KD have remained the same over the years, with little insight into the etiology, beware of clusters of certain presentations, to include shock, or "Kawashocki" Disease.

Treatment with IVIG remains first-line therapy, but there is a need to do more research into effective treatment for high risk populations—IVIG-resistant children. "The future of this disease is how we will treat all children," Dr. Tremoulet said as she described the research design challenges for children that have already failed therapy. Controlled trials are underway to evaluate new treatments in this population.

Exciting collaborations with climate scientists have produced potential leads into associations with tropospheric wind patterns. "We cannot do this work alone," and physicians on the West Coast are urged to participate in an ongoing collaborative related to this research.

Key Takeaways:

• For unclear reasons, presentations of KD continue to cluster; climate may play a role;
• Use IVIG for children that present with "Kawashocki" Disease;
• Research may soon provide us with diagnostic biomarkers as well as treatments for high-risk children; and
• Contact Olivia Fabri, Research Coordinator, to receive more information related to the West Coast KD Epidemiology Consortium (WIND study).

"Hopefully there will be a test available to physicians for diagnosing KD in the next 5 years," said Adriana Tremoulet, MD, MAS, who is the Associate Director of the Kawasaki Disease Research Center at Rady Children's Hospital/UC San Diego. Research into biomarkers looks promising and there is even some work underway to develop an app to help with the diagnostic algorithm for atypical cases, shared Dr. Tremoulet.

While many of the ways in which we make the diagnosis of KD have remained the same over the years, with little insight into the etiology, beware of clusters of certain presentations, to include shock, or "Kawashocki" Disease.

Treatment with IVIG remains first-line therapy, but there is a need to do more research into effective treatment for high risk populations—IVIG-resistant children. "The future of this disease is how we will treat all children," Dr. Tremoulet said as she described the research design challenges for children that have already failed therapy. Controlled trials are underway to evaluate new treatments in this population.

Exciting collaborations with climate scientists have produced potential leads into associations with tropospheric wind patterns. "We cannot do this work alone," and physicians on the West Coast are urged to participate in an ongoing collaborative related to this research.

Key Takeaways:

• For unclear reasons, presentations of KD continue to cluster; climate may play a role;
• Use IVIG for children that present with "Kawashocki" Disease;
• Research may soon provide us with diagnostic biomarkers as well as treatments for high-risk children; and
• Contact Olivia Fabri, Research Coordinator, to receive more information related to the West Coast KD Epidemiology Consortium (WIND study).

"Hopefully there will be a test available to physicians for diagnosing KD in the next 5 years," said Adriana Tremoulet, MD, MAS, who is the Associate Director of the Kawasaki Disease Research Center at Rady Children's Hospital/UC San Diego. Research into biomarkers looks promising and there is even some work underway to develop an app to help with the diagnostic algorithm for atypical cases, shared Dr. Tremoulet.

While many of the ways in which we make the diagnosis of KD have remained the same over the years, with little insight into the etiology, beware of clusters of certain presentations, to include shock, or "Kawashocki" Disease.

Treatment with IVIG remains first-line therapy, but there is a need to do more research into effective treatment for high risk populations—IVIG-resistant children. "The future of this disease is how we will treat all children," Dr. Tremoulet said as she described the research design challenges for children that have already failed therapy. Controlled trials are underway to evaluate new treatments in this population.

Exciting collaborations with climate scientists have produced potential leads into associations with tropospheric wind patterns. "We cannot do this work alone," and physicians on the West Coast are urged to participate in an ongoing collaborative related to this research.

Key Takeaways:

• For unclear reasons, presentations of KD continue to cluster; climate may play a role;
• Use IVIG for children that present with "Kawashocki" Disease;
• Research may soon provide us with diagnostic biomarkers as well as treatments for high-risk children; and
• Contact Olivia Fabri, Research Coordinator, to receive more information related to the West Coast KD Epidemiology Consortium (WIND study).