The “Things We Do for No Reason” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/

An 8-year-old previously healthy girl presented to the emergency department (ED) with 2 days of warmth, swelling, and pain over her right upper thigh. Three days prior before presentation, a “pimple” appeared on her leg and drained a small amount of pus. Over the next 24 hours, the lesion became swollen, red, and painful. Her pediatrician prescribed trimethoprim-sulfamethoxazole. The patient took 3 doses of this medication but still experienced worsening pain and swelling.

In the ED, she had normal vital signs for her age except for temperature of 100.8 °F. A 2 cm × 3 cm area of fluctuance, erythema, and warmth was noted, and bedside ultrasound demonstrated a simple fluid collection. Incision and drainage was performed with expression of several milliliters of pus. The patient was referred for admission due to worsening symptoms despite outpatient antibiotic therapy. The ED providers ordered a blood culture at the time of admission.

Skin and soft tissue infections (SSTIs) are common pediatric diagnoses, which account for an estimated 390,000 ED visits annually¹ and represent the 7^th most common reason for pediatric hospital admission in the United States.² The rates of SSTIs have increased over the past several decades partly due to the rise of methicillin-resistant Staphylococcus aureus (MRSA).³

Why You Might Think Blood Cultures are Helpful In Children with SSTIs?

Prior to the introduction of the Haemophilus influenzae vaccine, the rates of SSTI-associated bacteremia ranged from 8% to 20%.^4,5 Although the rate of bacteremia has declined significantly, blood cultures are still commonly performed as part of the evaluation of uncomplicated SSTIs in children; studies have shown that blood culture rates are 46% in the combined outpatient/inpatient setting,⁶ 34% in the ED setting,⁷ and 47%-94% in the inpatient setting.^7-11 Clinicians still feel that bacteremia detection is important to guide the selection of antibiotics and treatment duration. Providers may also underestimate the risk of obtaining a contaminant result and associated charges. Lastly, clinicians may perform blood cultures due to cultural norms at their institution.

Why Blood Cultures are Unnecessary in Children with Uncomplicated SSTIs

Several decades into the post vaccine era, the current guidelines from the Infectious Diseases Society of America (IDSA) do not recommend blood cultures as part of the routine evaluation of uncomplicated SSTIs.¹² Multiple single-center studies have failed to demonstrate the benefits of obtaining blood cultures in pediatric patients with uncomplicated SSTIs in the post-H. influenzae vaccine era.^6–11

Sadow et al¹¹ performed a retrospective case series of 381 children hospitalized with cellulitis to determine the rate and yield of blood cultures. Of the 266 (70%) patients who had a blood culture performed, 5 (1.9%) were true positives and 13 (5.4%) were contaminants. Notably, the true positive results included 3 children with active varicella infection and 2 children with septic joints; the latter would qualify as a complicated SSTI or as a separate infectious process altogether. No significant change in management resulted the positive blood cultures.

Harms Associated With Unnecessary Blood Cultures in SSTIs

Blood cultures necessitate venipunctures, which are painful for children and families. The inevitable false-positive contaminants also lead to repeat venipunctures and, potentially, unnecessary antibiotic exposure. From a high-value care perspective, Parikh et al reported hospital charges of $300 per blood culture and $250 for identification and sensitivity of positives.⁶ Assuming that these single-center charges are representative of national charges and using 0.5% true positivity and 1.5% false positivity rates, subjecting all children with uncomplicated SSTIs to blood culture would result in $60,250 charges to find one true positive blood culture, with no resultant changes in management. Additionally, among the 200 children cultured to find one true positive, there would be 3 false positives, necessitating another $1650 in charges for identification, sensitivity analysis, and repeat culture. These amounts do not factor in the significant expenditures associated with increased LOS. The potential savings associated with forgoing blood cultures in children with SSTIs should be an incentive for institutional change.

When Blood Cultures May Be Reasonable

The current IDSA guidelines recommend blood cultures for SSTIs in patients with immunodeficiency, animal bites, and immersion injuries (soft tissue injuries occurring in fresh or saltwater).¹² Previous studies also delineated criteria for “complicated” SSTIs, typically defined as surgical or traumatic wounds, infections requiring surgical intervention (not including simple incision and drainage), or infected ulcers or burns.^8,9 In the study of Malone et al, 10 (12.5%) positives were found among 80 patients with complicated SSTIs who had blood cultures performed.⁸ Although this work had a single-center study design with a relatively small sample size, no unusual organisms were found; the grown cultures included MRSA, MSSA, and S. pneumoniae. In addition to patients with complicated SSTIs, immunocompromised children, such as those receiving chemotherapy or other immunosuppressive agents, were excluded from the studies of blood culture yield in SSTIs and may warrant blood cultures given the risk of overwhelming infection and susceptibility to rare or invasive organisms.¹² In a study of 57 pediatric patients with leukemia and no central catheters who experienced skin or soft tissue complications, Demircioglu et al¹³ reported 6 positive blood cultures, including Klebsiella oxytoca, Pseudomonas aeruginosa, and Escherichia coli. These organisms would not be covered by typical SSTI antibiotic regimens, illustrating the value of blood cultures in this selected group of patients. Lastly, although the above studies included some infants, the data on utility of blood cultures in neonates are limited. Blood cultures may be reasonable in this group given the relative immunocompromised state of neonates compared with older children. Additionally, any infants aged

What You Should Do Instead Of Blood Cultures for Uncomplicated SSTIs

Gram stain and wound culture of any purulent material may assist with choice of empiric antibiotic therapy and appropriate narrowing of regimen for antibiotic stewardship. Wound cultures of purulent material can identify the causative organism in 58%-66% of the cases.^9,14 The rate of wound culture varies widely from 29% to 81% in studies across different healthcare systems.^9,10,15 The use of visually appealing posters advising clinicians to “culture pus, not blood” has been shown to significantly decreased the number of blood cultures performed at a single pediatric hospital.¹⁰

• Do not obtain blood cultures in pediatric patients with uncomplicated SSTIs.
• If purulent material is available spontaneously or after incision and drainage, then send it for Gram stain and bacterial culture.
• Blood cultures are reasonable in patients with complicated SSTIs and in immunocompromised patients with SSTIs.
• Despite limited data, blood cultures may be reasonable in neonates with SSTIs. Febrile infants with SSTIs aged less than 90 days should be managed under existing febrile infant guidelines.

Blood cultures in pediatric patients with uncomplicated SSTIs have no proven benefit and are associated with increased LOS, non-negligible false-positive rate, and associated increase in financial charges to the patient and healthcare system. The patient described in the clinical scenario would have an extremely low likelihood of having any meaningful clinical information provided by blood culture as part of her evaluation.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason?” Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason” topics by emailing [email protected].

DISCLOSURES

The authors have no conflicts of interest relevant to this article to disclose.

The “Things We Do for No Reason” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/

An 8-year-old previously healthy girl presented to the emergency department (ED) with 2 days of warmth, swelling, and pain over her right upper thigh. Three days prior before presentation, a “pimple” appeared on her leg and drained a small amount of pus. Over the next 24 hours, the lesion became swollen, red, and painful. Her pediatrician prescribed trimethoprim-sulfamethoxazole. The patient took 3 doses of this medication but still experienced worsening pain and swelling.

In the ED, she had normal vital signs for her age except for temperature of 100.8 °F. A 2 cm × 3 cm area of fluctuance, erythema, and warmth was noted, and bedside ultrasound demonstrated a simple fluid collection. Incision and drainage was performed with expression of several milliliters of pus. The patient was referred for admission due to worsening symptoms despite outpatient antibiotic therapy. The ED providers ordered a blood culture at the time of admission.

Skin and soft tissue infections (SSTIs) are common pediatric diagnoses, which account for an estimated 390,000 ED visits annually¹ and represent the 7^th most common reason for pediatric hospital admission in the United States.² The rates of SSTIs have increased over the past several decades partly due to the rise of methicillin-resistant Staphylococcus aureus (MRSA).³

Why You Might Think Blood Cultures are Helpful In Children with SSTIs?

Prior to the introduction of the Haemophilus influenzae vaccine, the rates of SSTI-associated bacteremia ranged from 8% to 20%.^4,5 Although the rate of bacteremia has declined significantly, blood cultures are still commonly performed as part of the evaluation of uncomplicated SSTIs in children; studies have shown that blood culture rates are 46% in the combined outpatient/inpatient setting,⁶ 34% in the ED setting,⁷ and 47%-94% in the inpatient setting.^7-11 Clinicians still feel that bacteremia detection is important to guide the selection of antibiotics and treatment duration. Providers may also underestimate the risk of obtaining a contaminant result and associated charges. Lastly, clinicians may perform blood cultures due to cultural norms at their institution.

Why Blood Cultures are Unnecessary in Children with Uncomplicated SSTIs

Several decades into the post vaccine era, the current guidelines from the Infectious Diseases Society of America (IDSA) do not recommend blood cultures as part of the routine evaluation of uncomplicated SSTIs.¹² Multiple single-center studies have failed to demonstrate the benefits of obtaining blood cultures in pediatric patients with uncomplicated SSTIs in the post-H. influenzae vaccine era.^6–11

Sadow et al¹¹ performed a retrospective case series of 381 children hospitalized with cellulitis to determine the rate and yield of blood cultures. Of the 266 (70%) patients who had a blood culture performed, 5 (1.9%) were true positives and 13 (5.4%) were contaminants. Notably, the true positive results included 3 children with active varicella infection and 2 children with septic joints; the latter would qualify as a complicated SSTI or as a separate infectious process altogether. No significant change in management resulted the positive blood cultures.

Harms Associated With Unnecessary Blood Cultures in SSTIs

Blood cultures necessitate venipunctures, which are painful for children and families. The inevitable false-positive contaminants also lead to repeat venipunctures and, potentially, unnecessary antibiotic exposure. From a high-value care perspective, Parikh et al reported hospital charges of $300 per blood culture and $250 for identification and sensitivity of positives.⁶ Assuming that these single-center charges are representative of national charges and using 0.5% true positivity and 1.5% false positivity rates, subjecting all children with uncomplicated SSTIs to blood culture would result in $60,250 charges to find one true positive blood culture, with no resultant changes in management. Additionally, among the 200 children cultured to find one true positive, there would be 3 false positives, necessitating another $1650 in charges for identification, sensitivity analysis, and repeat culture. These amounts do not factor in the significant expenditures associated with increased LOS. The potential savings associated with forgoing blood cultures in children with SSTIs should be an incentive for institutional change.

When Blood Cultures May Be Reasonable

The current IDSA guidelines recommend blood cultures for SSTIs in patients with immunodeficiency, animal bites, and immersion injuries (soft tissue injuries occurring in fresh or saltwater).¹² Previous studies also delineated criteria for “complicated” SSTIs, typically defined as surgical or traumatic wounds, infections requiring surgical intervention (not including simple incision and drainage), or infected ulcers or burns.^8,9 In the study of Malone et al, 10 (12.5%) positives were found among 80 patients with complicated SSTIs who had blood cultures performed.⁸ Although this work had a single-center study design with a relatively small sample size, no unusual organisms were found; the grown cultures included MRSA, MSSA, and S. pneumoniae. In addition to patients with complicated SSTIs, immunocompromised children, such as those receiving chemotherapy or other immunosuppressive agents, were excluded from the studies of blood culture yield in SSTIs and may warrant blood cultures given the risk of overwhelming infection and susceptibility to rare or invasive organisms.¹² In a study of 57 pediatric patients with leukemia and no central catheters who experienced skin or soft tissue complications, Demircioglu et al¹³ reported 6 positive blood cultures, including Klebsiella oxytoca, Pseudomonas aeruginosa, and Escherichia coli. These organisms would not be covered by typical SSTI antibiotic regimens, illustrating the value of blood cultures in this selected group of patients. Lastly, although the above studies included some infants, the data on utility of blood cultures in neonates are limited. Blood cultures may be reasonable in this group given the relative immunocompromised state of neonates compared with older children. Additionally, any infants aged

What You Should Do Instead Of Blood Cultures for Uncomplicated SSTIs

Gram stain and wound culture of any purulent material may assist with choice of empiric antibiotic therapy and appropriate narrowing of regimen for antibiotic stewardship. Wound cultures of purulent material can identify the causative organism in 58%-66% of the cases.^9,14 The rate of wound culture varies widely from 29% to 81% in studies across different healthcare systems.^9,10,15 The use of visually appealing posters advising clinicians to “culture pus, not blood” has been shown to significantly decreased the number of blood cultures performed at a single pediatric hospital.¹⁰

• Do not obtain blood cultures in pediatric patients with uncomplicated SSTIs.
• If purulent material is available spontaneously or after incision and drainage, then send it for Gram stain and bacterial culture.
• Blood cultures are reasonable in patients with complicated SSTIs and in immunocompromised patients with SSTIs.
• Despite limited data, blood cultures may be reasonable in neonates with SSTIs. Febrile infants with SSTIs aged less than 90 days should be managed under existing febrile infant guidelines.

Blood cultures in pediatric patients with uncomplicated SSTIs have no proven benefit and are associated with increased LOS, non-negligible false-positive rate, and associated increase in financial charges to the patient and healthcare system. The patient described in the clinical scenario would have an extremely low likelihood of having any meaningful clinical information provided by blood culture as part of her evaluation.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason?” Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason” topics by emailing [email protected].

DISCLOSURES

The authors have no conflicts of interest relevant to this article to disclose.

The “Things We Do for No Reason” (TWDFNR) series reviews practices that have become common parts of hospital care but may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent “black and white” conclusions or clinical practice standards but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/

An 8-year-old previously healthy girl presented to the emergency department (ED) with 2 days of warmth, swelling, and pain over her right upper thigh. Three days prior before presentation, a “pimple” appeared on her leg and drained a small amount of pus. Over the next 24 hours, the lesion became swollen, red, and painful. Her pediatrician prescribed trimethoprim-sulfamethoxazole. The patient took 3 doses of this medication but still experienced worsening pain and swelling.

In the ED, she had normal vital signs for her age except for temperature of 100.8 °F. A 2 cm × 3 cm area of fluctuance, erythema, and warmth was noted, and bedside ultrasound demonstrated a simple fluid collection. Incision and drainage was performed with expression of several milliliters of pus. The patient was referred for admission due to worsening symptoms despite outpatient antibiotic therapy. The ED providers ordered a blood culture at the time of admission.

Skin and soft tissue infections (SSTIs) are common pediatric diagnoses, which account for an estimated 390,000 ED visits annually¹ and represent the 7^th most common reason for pediatric hospital admission in the United States.² The rates of SSTIs have increased over the past several decades partly due to the rise of methicillin-resistant Staphylococcus aureus (MRSA).³

Why You Might Think Blood Cultures are Helpful In Children with SSTIs?

Prior to the introduction of the Haemophilus influenzae vaccine, the rates of SSTI-associated bacteremia ranged from 8% to 20%.^4,5 Although the rate of bacteremia has declined significantly, blood cultures are still commonly performed as part of the evaluation of uncomplicated SSTIs in children; studies have shown that blood culture rates are 46% in the combined outpatient/inpatient setting,⁶ 34% in the ED setting,⁷ and 47%-94% in the inpatient setting.^7-11 Clinicians still feel that bacteremia detection is important to guide the selection of antibiotics and treatment duration. Providers may also underestimate the risk of obtaining a contaminant result and associated charges. Lastly, clinicians may perform blood cultures due to cultural norms at their institution.

Why Blood Cultures are Unnecessary in Children with Uncomplicated SSTIs

Several decades into the post vaccine era, the current guidelines from the Infectious Diseases Society of America (IDSA) do not recommend blood cultures as part of the routine evaluation of uncomplicated SSTIs.¹² Multiple single-center studies have failed to demonstrate the benefits of obtaining blood cultures in pediatric patients with uncomplicated SSTIs in the post-H. influenzae vaccine era.^6–11

Sadow et al¹¹ performed a retrospective case series of 381 children hospitalized with cellulitis to determine the rate and yield of blood cultures. Of the 266 (70%) patients who had a blood culture performed, 5 (1.9%) were true positives and 13 (5.4%) were contaminants. Notably, the true positive results included 3 children with active varicella infection and 2 children with septic joints; the latter would qualify as a complicated SSTI or as a separate infectious process altogether. No significant change in management resulted the positive blood cultures.

Harms Associated With Unnecessary Blood Cultures in SSTIs

Blood cultures necessitate venipunctures, which are painful for children and families. The inevitable false-positive contaminants also lead to repeat venipunctures and, potentially, unnecessary antibiotic exposure. From a high-value care perspective, Parikh et al reported hospital charges of $300 per blood culture and $250 for identification and sensitivity of positives.⁶ Assuming that these single-center charges are representative of national charges and using 0.5% true positivity and 1.5% false positivity rates, subjecting all children with uncomplicated SSTIs to blood culture would result in $60,250 charges to find one true positive blood culture, with no resultant changes in management. Additionally, among the 200 children cultured to find one true positive, there would be 3 false positives, necessitating another $1650 in charges for identification, sensitivity analysis, and repeat culture. These amounts do not factor in the significant expenditures associated with increased LOS. The potential savings associated with forgoing blood cultures in children with SSTIs should be an incentive for institutional change.

When Blood Cultures May Be Reasonable

The current IDSA guidelines recommend blood cultures for SSTIs in patients with immunodeficiency, animal bites, and immersion injuries (soft tissue injuries occurring in fresh or saltwater).¹² Previous studies also delineated criteria for “complicated” SSTIs, typically defined as surgical or traumatic wounds, infections requiring surgical intervention (not including simple incision and drainage), or infected ulcers or burns.^8,9 In the study of Malone et al, 10 (12.5%) positives were found among 80 patients with complicated SSTIs who had blood cultures performed.⁸ Although this work had a single-center study design with a relatively small sample size, no unusual organisms were found; the grown cultures included MRSA, MSSA, and S. pneumoniae. In addition to patients with complicated SSTIs, immunocompromised children, such as those receiving chemotherapy or other immunosuppressive agents, were excluded from the studies of blood culture yield in SSTIs and may warrant blood cultures given the risk of overwhelming infection and susceptibility to rare or invasive organisms.¹² In a study of 57 pediatric patients with leukemia and no central catheters who experienced skin or soft tissue complications, Demircioglu et al¹³ reported 6 positive blood cultures, including Klebsiella oxytoca, Pseudomonas aeruginosa, and Escherichia coli. These organisms would not be covered by typical SSTI antibiotic regimens, illustrating the value of blood cultures in this selected group of patients. Lastly, although the above studies included some infants, the data on utility of blood cultures in neonates are limited. Blood cultures may be reasonable in this group given the relative immunocompromised state of neonates compared with older children. Additionally, any infants aged

What You Should Do Instead Of Blood Cultures for Uncomplicated SSTIs

Gram stain and wound culture of any purulent material may assist with choice of empiric antibiotic therapy and appropriate narrowing of regimen for antibiotic stewardship. Wound cultures of purulent material can identify the causative organism in 58%-66% of the cases.^9,14 The rate of wound culture varies widely from 29% to 81% in studies across different healthcare systems.^9,10,15 The use of visually appealing posters advising clinicians to “culture pus, not blood” has been shown to significantly decreased the number of blood cultures performed at a single pediatric hospital.¹⁰

• Do not obtain blood cultures in pediatric patients with uncomplicated SSTIs.
• If purulent material is available spontaneously or after incision and drainage, then send it for Gram stain and bacterial culture.
• Blood cultures are reasonable in patients with complicated SSTIs and in immunocompromised patients with SSTIs.
• Despite limited data, blood cultures may be reasonable in neonates with SSTIs. Febrile infants with SSTIs aged less than 90 days should be managed under existing febrile infant guidelines.

Blood cultures in pediatric patients with uncomplicated SSTIs have no proven benefit and are associated with increased LOS, non-negligible false-positive rate, and associated increase in financial charges to the patient and healthcare system. The patient described in the clinical scenario would have an extremely low likelihood of having any meaningful clinical information provided by blood culture as part of her evaluation.

Do you think this is a low-value practice? Is this truly a “Thing We Do for No Reason?” Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other “Things We Do for No Reason” topics by emailing [email protected].

DISCLOSURES

The authors have no conflicts of interest relevant to this article to disclose.

Readmission prevention is a focus of national efforts to improve the quality of hospital care for children.^1-5 Several factors contribute to the risk of readmission for hospitalized children, including age, race or ethnicity, payer, and the type and number of comorbid health conditions.^6-9 Mental health conditions (MHCs) are a prevalent comorbidity in children hospitalized for physical health reasons that could influence their postdischarge health and safety.

MHCs are increasingly common in children hospitalized for physical health indications; a comorbid MHC is currently present in 10% to 25% of hospitalized children ages 3 years and older.^10,11 Hospital length of stay (LOS) and cost are higher in children with an MHC.^12,13 Increased resource use may occur because MHCs can impede hospital treatment effectiveness and the child’s recovery from physical illness. MHCs are associated with a lower adherence with medications^14-16 and a lower ability to cope with health events and problems.^17-19 In adults, MHCs are a well-established risk factor for hospital readmission for a variety of physical health conditions.^20-24 Although the influence of MHCs on readmissions in children has not been extensively investigated, higher readmission rates have been reported in adolescents hospitalized for diabetes with an MHC compared with those with no MHC.^25,26

To our knowledge, no large studies have examined the relationship between the presence of a comorbid MHC and hospital readmissions in children or adolescents hospitalized for a broad array of medical or procedure conditions. Therefore, we conducted this study to (1) assess the likelihood of 30-day hospital readmission in children with versus without MHC who were hospitalized for one of 10 medical or 10 procedure conditions, and (2) to assess which MHCs are associated with the highest likelihood of hospital readmission.

Study Design and Setting

We conducted a national, retrospective cohort study of index hospitalizations for children ages 3 to 21 years who were discharged from January 1, 2013, to November 30, 2013, in the Agency for Healthcare Research and Quality’s (AHRQ) Nationwide Readmissions Database (NRD). Admissions occurring in December 2013 were excluded because they did not have a 30-day timeframe available for readmission measurement. The 2013 NRD includes administrative data for a nationally representative sample of 14 million hospitalizations in 21 states, accounting for 49% of all US hospitalizations and weighted to represent 35.6 million hospitalizations. The database includes deidentified, verified patient linkage numbers so that patients can be tracked across multiple hospitalizations at the same institution or different institutions within a state. The NRD includes hospital information, patient demographic information, and the International Classification of Diseases, 9th Revision-Clinical Modification (ICD-9-CM) discharge diagnoses and procedures, with 1 primary diagnosis and up to 24 additional fields for comorbid diagnoses. This study was approved for exemption by the Children’s Hospital of Philadelphia Institutional Review Board.

Index Admissions

We used the methods described below to create a study cohort of the 10 medical and 10 procedure index admissions associated with the highest volume (ie, the greatest absolute number) of 30-day hospital readmissions. Conditions with a high volume of readmissions were chosen in an effort to identify conditions in which readmission-prevention interventions had the greatest potential to reduce the absolute number of readmissions. We first categorized index hospitalizations for medical and procedure conditions by using the All Patient Refined Diagnosis Related Groups (APR-DRGs; 3M Health Information Systems, Wallingford, CT).²⁷ APR-DRGs use all diagnosis and/or procedure ICD-9-CM codes registered for a hospital discharge to assign 1 reason that best explains the need for hospitalization. We then excluded obstetric hospitalizations, psychiatric hospitalizations, and hospitalizations resulting in death or transfer from being considered as index admissions. Afterwards, we ranked each APR-DRG index hospitalization by the total number of 30-day hospital readmissions that occurred afterward and selected the 10 medical and 10 procedure index admissions with the highest number of readmissions. The APR-DRG index admissions are listed in Figures 1 and 2. For the APR-DRG “digestive system diagnoses,” the most common diagnosis was constipation, and we refer to that category as “constipation.” The most common diagnosis for the APR-DRG called “other operating room procedure for neoplasm” was tumor biopsy, and we refer to that category as “tumor biopsy.”

Main Outcome Measure

The primary study outcome was unplanned, all-cause readmission to any hospital within 30 days of index hospitalization. All-cause readmissions include any hospitalization for the same or different condition as the index admission, including conditions not eligible to be considered as index admissions (obstetric, psychiatric, and hospitalizations resulting in death or transfer). Planned readmissions, identified by using pediatric-specific measure specifications endorsed by AHRQ and the National Quality Forum,²⁸ were excluded from measurement. For index admissions with multiple 30-day readmissions, only the first readmission was counted. Each readmission was treated as an index admission.

Main Independent Variable

The main independent variable was the presence of an MHC documented during the index hospitalization. MHCs were identified and classified into diagnosis categories derived from the AHRQ Chronic Condition Indicator system by using ICD-9-CM codes.²⁹ MHC categories included anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), autism, depression, and substance abuse. Less common MHCs included bipolar disorder, schizophrenia, disruptive behavior disorders, somatoform disorders, and eating disorders. These conditions are included in the group with any MHC, but we did not calculate the adjusted odds ratios (AORs) of readmission for these conditions. Children were identified as having multiple MHCs if they had more than 1 MHC.

Other Characteristics of Index Hospitalizations

A priori, we selected for analysis the known demographic, clinical, and hospital factors associated with the risk of readmission.^20-24 The demographic characteristics included patient age, gender, payer category, urban or rural residence, and the median income quartile for a patient’s ZIP code. The hospital characteristics included location, ownership, and teaching hospital designation. The clinical characteristics included the number of chronic conditions³⁰ and indicators for the presence of a complex chronic condition in each of 12 organ systems.³¹

Statistical Analysis

We calculated descriptive summary statistics for the characteristics of index hospitalizations. We compared characteristics in index admissions of children with versus without MHC by using Wilcoxon Rank-Sum tests for continuous variables and Wald χ² tests for categorical variables. In the multivariable analysis, we derived logistic regression models to assess the relationship of 30-day hospital readmission with each type of MHC, adjusting for index admission demographic, hospital, and clinical characteristics. MHCs were modeled as binary indicator variables with the presence of any MHC, more than 1 MHC, or each of 5 MHC categories (anxiety disorders, ADHD, autism, depression, substance abuse) compared with no MHC. Four types of logistic regression models were derived (1) for the combined sample of all 10 index medical admissions with each MHC category versus no MHC as a primary predictor, (2) for each medical index admission with any MHC versus no MHC as the primary predictor, (3) for the combined sample of all 10 index procedure admissions with each MHC category versus no MHC as a primary predictor, and (4) for each procedure index admission with any MHC versus no MHC as the primary predictor. All analyses were weighted to achieve national estimates and clustered by hospital by using AHRQ-recommended survey procedures. SAS version 9.4 (SAS Institute, Cary, NC) was used for all analyses. All tests were two-sided, and a P < .05 was
considered statistically significant.

Study Population

Across all index admissions, 16.3% were for children with an MHC. Overall, children with MHCs were older and more likely to have a chronic³⁰ or complex chronic³¹ physical health condition than children with no MHCs (Table).

Index Medical Admissions, Mental Health Conditions, and Hospital Readmission

The 10 index medical hospitalizations with the most readmissions for children ages 3 to 20 years were asthma, chemotherapy, constipation, diabetes, gastroenteritis, inflammatory bowel disease, neutropenia, pneumonia, seizure, and sickle cell crisis. Across all index medical hospitalizations, 17.5% were for patients with an MHC (Figure 1). Of index medical admissions with any MHC, 26.3% had ADHD, 22.9% had an anxiety disorder, 14.9% had autism, 18.3% had depression, and 30.9% had substance abuse. Among all admissions with MHCs, 28.9% had 2 or more MHCs.

Index Medical Admissions Combined

For all index medical hospitalizations combined, 17.0% (n = 59,138) had an unplanned, 30-day hospital readmission. The rate of 30-day hospital readmissions was higher with versus without an MHC (17.5 vs 16.8%; P < .001). In a multivariable analysis, presence of an MHC was associated with a higher likelihood of hospital readmission following an index medical admission (AOR, 1.23; 95% confidence interval [CI], 1.19-1.26); Figure 1). All MHCs except autism and ADHD had a higher likelihood of readmission (Figure 3). 

Specific Index Medical Admissions

Index Procedure Admissions, Mental Health Conditions, and Hospital Readmission

Index Procedure Admissions Combined

Specific Index Procedure Admissions

For specific index procedure admissions, the rate of 30-day hospital readmission ranged from 2.2% for knee procedures to 33.6% for tumor biopsy. For 3 (ie, urinary tract, ventricular shunt, and bowel procedures) of the 10 specific index procedure hospitalizations, having an MHC was associated with higher adjusted odds of 30-day readmission (AOR range, 1.38-2.27; Figure 2).

In total, adjusting for sociodemographic, clinical, and hospital characteristics, MHCs were associated with an additional 2501 medical readmissions and 217 procedure readmissions beyond what would have been expected if MHCs were not associated with readmissions.

MHCs are common among pediatric hospitalizations with the highest volume of readmissions; MHCs were present in approximately 1 in 5 medical and 1 in 7 procedure index hospitalizations. Across medical and procedure admissions, the adjusted likelihood of unplanned, all-cause 30-day readmission was 25% higher for children with versus without an MHC. The readmission likelihood varied by the type of medical or procedure admission and by the type of MHC. MHCs had the strongest associations with readmissions following hospitalization for diabetes and urinary tract procedures. The MHC categories associated with the highest readmission likelihood were depression, substance abuse, and multiple MHCs.

The current study complements existing literature by helping establish MHCs as a prevalent and important risk factor for hospital readmission in children. Estimates of the prevalence of MHCs in hospitalized children are between 10% and 25%,^10,11,32 and prevalence has increased by as much as 160% over the last 10 years.²⁹ Prior investigations have found that children with an MHC tend to stay longer in the hospital compared with children with no MHC.³² Results from the present study suggest that children with MHCs also experience more inpatient days because of rehospitalizations. Subsequent investigations should strive to understand the mechanisms in the hospital, community, and family environment that are responsible for the increased inpatient utilization in children with MHCs. Understanding how the receipt of mental health services before, during, and after hospitalization influences readmissions could help identify opportunities for practice improvement. Families report the need for better coordination of their child’s medical and mental health care,³³ and opportunities exist to improve attendance at mental health visits after acute care encounters.³⁴ Among adults, interventions that address posthospital access to mental healthcare have prevented readmissions.³⁵

Depression was associated with an increased risk of readmission in medical and procedure hospitalizations. As a well-known risk factor for readmission in adult patients,²¹ depression can adversely affect and exacerbate the physical health recovery of patients experiencing acute and chronic illnesses.^14,36,37 Depression is considered a modifiable contributor that, when controlled, may help lower readmission risk. Optimal adherence with behavior and medication treatment for depression is associated with a lower risk of unplanned 30-day readmissions.^14-16,19 Emerging evidence demonstrates how multifaceted, psychosocial approaches can improve patients’ adherence with depression treatment plans.³⁸ Increased attention to depression in hospitalized children may uncover new ways to manage symptoms as children transition from hospital to home.

Other MHCs were associated with a different risk of readmission among medical and procedure hospitalizations. For example, ADHD or autism documented during index hospitalization was associated with an increased risk of readmission following procedure hospitalizations and a decreased risk following medical hospitalizations. Perhaps children with ADHD or autism who exhibit hyperactive, impulsive, or repetitive behaviors^39,40 are at risk for disrupting their postprocedure wound healing, nutrition recovery, or pain tolerance, which might contribute to increased readmission risk.

MHCs were associated with different readmission risks across specific types of medical or procedure hospitalizations. For example, among medical conditions, the association of readmissions with MHCs was highest for diabetes, which is consistent with prior research.²⁶ Factors that might mediate this relationship include changes in diet and appetite, difficulty with diabetes care plan adherence, and intentional nonadherence as a form of self-harm. Similarly, a higher risk of readmission in chronic medical conditions like asthma, constipation, and sickle cell disease might be mediated by difficulty adhering to medical plans or managing exacerbations at home. In contrast, MHCs had no association with readmission following chemotherapy. In our clinical experience, readmissions following chemotherapy are driven by physiologic problems, such as thrombocytopenia, fever, and/or neutropenia. MHCs might have limited influence over those health issues. For procedure hospitalizations, MHCs had 1 of the strongest associations with ventricular shunt procedures. We hypothesize that MHCs might lead some children to experience general health symptoms that might be associated with shunt malfunction (eg, fatigue, headache, behavior change), which could lead to an increased risk of readmission to evaluate for shunt malfunction. Conversely, we found no relationship between MHCs and readmissions following appendectomy. For appendectomy, MHCs might have limited influence over the development of postsurgical complications (eg, wound infection or ileus). Future research to better elucidate mediators of increased risk of readmission associated with MHCs in certain medical and procedure conditions could help explain these relationships and identify possible future intervention targets to prevent readmissions.

This study has several limitations. The administrative data are not positioned to discover the mechanisms by which MHCs are associated with a higher likelihood of readmission. We used hospital ICD-9-CM codes to identify patients with MHCs. Other methods using more clinically rich data (eg, chart review, prescription medications, etc.) may be preferable to identify patients with MHCs. Although the use of ICD-9-CM codes may have sufficient specificity, some hospitalized children may have an MHC that is not coded. Patients identified by using diagnosis codes could represent patients with a higher severity of illness, patients using medications, or patients whose outpatient records are accessible to make the hospital team aware of the MHC. If documentation of MHCs during hospitalization represents a higher severity of illness, findings may not extrapolate to lower-severity MHCs. As hospitals transition from ICD-9 -CM to ICD-10 coding, and health systems develop more integrated inpatient and outpatient EHRs, diagnostic specificity may improve. We could not analyze the relationships with several potential confounders and explanatory variables that may be related both to the likelihood of having an MHC and the risk of readmission, including medication administration, psychiatric consultation, and parent mental health. Postdischarge health services, including access to a medical home or a usual source of mental healthcare and measures of medication adherence, were not available in the NRD.

Despite these limitations, the current study underscores the importance of MHCs in hospitalized children upon discharge. As subsequent investigations uncover the key drivers explaining the influence of MHCs on hospital readmission risk, hospitals and their local outpatient and community practices may find it useful to consider MHCs when (1) developing contingency plans and establishing follow-up care at discharge,⁴¹ (2) exploring opportunities of care integration between mental and physical health care professionals, and (3) devising strategies to reduce hospital readmissions among populations of children.

MHCs are prevalent in hospitalized children and are associated with an increased risk of 30-day, unplanned hospital readmission. Future readmission prevention efforts may uncover new ways to improve children’s transitions from hospital to home by investigating strategies to address their MHCs.

Acknowledgments

The authors thank Donjo Lau and Troy Richardson for their assistance with the analysis.

Disclosures

Dr. Doupnik was supported by a Ruth L. Kirschstein National Research Service Award institutional training grant (T32-HP010026), funded by the National Institutes of Health. Dr. Zima was supported by the Behavioral Health Centers of Excellence for California (SB852). Dr. Bardach was supported by the National Institute of Child Health and Human Development (K23-HD065836). Dr. Berry was supported by the Agency for Healthcare Research and Quality (R21 HS023092-01). The authors have no financial relationships relevant to this article to disclose. The authors have no potential conflicts of interest to disclose. Dr. Doupnik led the study design and analysis and drafted the initial manuscript. Mr. Lawlor performed the data analysis. Dr. Hall provided statistical consultation. All authors participated in the design of the study, interpretation of the data, revised the manuscript for key intellectual content, and all authors read and approved the final manuscript.

Readmission prevention is a focus of national efforts to improve the quality of hospital care for children.^1-5 Several factors contribute to the risk of readmission for hospitalized children, including age, race or ethnicity, payer, and the type and number of comorbid health conditions.^6-9 Mental health conditions (MHCs) are a prevalent comorbidity in children hospitalized for physical health reasons that could influence their postdischarge health and safety.

MHCs are increasingly common in children hospitalized for physical health indications; a comorbid MHC is currently present in 10% to 25% of hospitalized children ages 3 years and older.^10,11 Hospital length of stay (LOS) and cost are higher in children with an MHC.^12,13 Increased resource use may occur because MHCs can impede hospital treatment effectiveness and the child’s recovery from physical illness. MHCs are associated with a lower adherence with medications^14-16 and a lower ability to cope with health events and problems.^17-19 In adults, MHCs are a well-established risk factor for hospital readmission for a variety of physical health conditions.^20-24 Although the influence of MHCs on readmissions in children has not been extensively investigated, higher readmission rates have been reported in adolescents hospitalized for diabetes with an MHC compared with those with no MHC.^25,26

To our knowledge, no large studies have examined the relationship between the presence of a comorbid MHC and hospital readmissions in children or adolescents hospitalized for a broad array of medical or procedure conditions. Therefore, we conducted this study to (1) assess the likelihood of 30-day hospital readmission in children with versus without MHC who were hospitalized for one of 10 medical or 10 procedure conditions, and (2) to assess which MHCs are associated with the highest likelihood of hospital readmission.

Study Design and Setting

We conducted a national, retrospective cohort study of index hospitalizations for children ages 3 to 21 years who were discharged from January 1, 2013, to November 30, 2013, in the Agency for Healthcare Research and Quality’s (AHRQ) Nationwide Readmissions Database (NRD). Admissions occurring in December 2013 were excluded because they did not have a 30-day timeframe available for readmission measurement. The 2013 NRD includes administrative data for a nationally representative sample of 14 million hospitalizations in 21 states, accounting for 49% of all US hospitalizations and weighted to represent 35.6 million hospitalizations. The database includes deidentified, verified patient linkage numbers so that patients can be tracked across multiple hospitalizations at the same institution or different institutions within a state. The NRD includes hospital information, patient demographic information, and the International Classification of Diseases, 9th Revision-Clinical Modification (ICD-9-CM) discharge diagnoses and procedures, with 1 primary diagnosis and up to 24 additional fields for comorbid diagnoses. This study was approved for exemption by the Children’s Hospital of Philadelphia Institutional Review Board.

Index Admissions

We used the methods described below to create a study cohort of the 10 medical and 10 procedure index admissions associated with the highest volume (ie, the greatest absolute number) of 30-day hospital readmissions. Conditions with a high volume of readmissions were chosen in an effort to identify conditions in which readmission-prevention interventions had the greatest potential to reduce the absolute number of readmissions. We first categorized index hospitalizations for medical and procedure conditions by using the All Patient Refined Diagnosis Related Groups (APR-DRGs; 3M Health Information Systems, Wallingford, CT).²⁷ APR-DRGs use all diagnosis and/or procedure ICD-9-CM codes registered for a hospital discharge to assign 1 reason that best explains the need for hospitalization. We then excluded obstetric hospitalizations, psychiatric hospitalizations, and hospitalizations resulting in death or transfer from being considered as index admissions. Afterwards, we ranked each APR-DRG index hospitalization by the total number of 30-day hospital readmissions that occurred afterward and selected the 10 medical and 10 procedure index admissions with the highest number of readmissions. The APR-DRG index admissions are listed in Figures 1 and 2. For the APR-DRG “digestive system diagnoses,” the most common diagnosis was constipation, and we refer to that category as “constipation.” The most common diagnosis for the APR-DRG called “other operating room procedure for neoplasm” was tumor biopsy, and we refer to that category as “tumor biopsy.”

Main Outcome Measure

The primary study outcome was unplanned, all-cause readmission to any hospital within 30 days of index hospitalization. All-cause readmissions include any hospitalization for the same or different condition as the index admission, including conditions not eligible to be considered as index admissions (obstetric, psychiatric, and hospitalizations resulting in death or transfer). Planned readmissions, identified by using pediatric-specific measure specifications endorsed by AHRQ and the National Quality Forum,²⁸ were excluded from measurement. For index admissions with multiple 30-day readmissions, only the first readmission was counted. Each readmission was treated as an index admission.

Main Independent Variable

The main independent variable was the presence of an MHC documented during the index hospitalization. MHCs were identified and classified into diagnosis categories derived from the AHRQ Chronic Condition Indicator system by using ICD-9-CM codes.²⁹ MHC categories included anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), autism, depression, and substance abuse. Less common MHCs included bipolar disorder, schizophrenia, disruptive behavior disorders, somatoform disorders, and eating disorders. These conditions are included in the group with any MHC, but we did not calculate the adjusted odds ratios (AORs) of readmission for these conditions. Children were identified as having multiple MHCs if they had more than 1 MHC.

Other Characteristics of Index Hospitalizations

A priori, we selected for analysis the known demographic, clinical, and hospital factors associated with the risk of readmission.^20-24 The demographic characteristics included patient age, gender, payer category, urban or rural residence, and the median income quartile for a patient’s ZIP code. The hospital characteristics included location, ownership, and teaching hospital designation. The clinical characteristics included the number of chronic conditions³⁰ and indicators for the presence of a complex chronic condition in each of 12 organ systems.³¹

Statistical Analysis

We calculated descriptive summary statistics for the characteristics of index hospitalizations. We compared characteristics in index admissions of children with versus without MHC by using Wilcoxon Rank-Sum tests for continuous variables and Wald χ² tests for categorical variables. In the multivariable analysis, we derived logistic regression models to assess the relationship of 30-day hospital readmission with each type of MHC, adjusting for index admission demographic, hospital, and clinical characteristics. MHCs were modeled as binary indicator variables with the presence of any MHC, more than 1 MHC, or each of 5 MHC categories (anxiety disorders, ADHD, autism, depression, substance abuse) compared with no MHC. Four types of logistic regression models were derived (1) for the combined sample of all 10 index medical admissions with each MHC category versus no MHC as a primary predictor, (2) for each medical index admission with any MHC versus no MHC as the primary predictor, (3) for the combined sample of all 10 index procedure admissions with each MHC category versus no MHC as a primary predictor, and (4) for each procedure index admission with any MHC versus no MHC as the primary predictor. All analyses were weighted to achieve national estimates and clustered by hospital by using AHRQ-recommended survey procedures. SAS version 9.4 (SAS Institute, Cary, NC) was used for all analyses. All tests were two-sided, and a P < .05 was
considered statistically significant.

Study Population

Across all index admissions, 16.3% were for children with an MHC. Overall, children with MHCs were older and more likely to have a chronic³⁰ or complex chronic³¹ physical health condition than children with no MHCs (Table).

Index Medical Admissions, Mental Health Conditions, and Hospital Readmission

The 10 index medical hospitalizations with the most readmissions for children ages 3 to 20 years were asthma, chemotherapy, constipation, diabetes, gastroenteritis, inflammatory bowel disease, neutropenia, pneumonia, seizure, and sickle cell crisis. Across all index medical hospitalizations, 17.5% were for patients with an MHC (Figure 1). Of index medical admissions with any MHC, 26.3% had ADHD, 22.9% had an anxiety disorder, 14.9% had autism, 18.3% had depression, and 30.9% had substance abuse. Among all admissions with MHCs, 28.9% had 2 or more MHCs.

Index Medical Admissions Combined

For all index medical hospitalizations combined, 17.0% (n = 59,138) had an unplanned, 30-day hospital readmission. The rate of 30-day hospital readmissions was higher with versus without an MHC (17.5 vs 16.8%; P < .001). In a multivariable analysis, presence of an MHC was associated with a higher likelihood of hospital readmission following an index medical admission (AOR, 1.23; 95% confidence interval [CI], 1.19-1.26); Figure 1). All MHCs except autism and ADHD had a higher likelihood of readmission (Figure 3). 

Specific Index Medical Admissions

Index Procedure Admissions, Mental Health Conditions, and Hospital Readmission

Index Procedure Admissions Combined

Specific Index Procedure Admissions

For specific index procedure admissions, the rate of 30-day hospital readmission ranged from 2.2% for knee procedures to 33.6% for tumor biopsy. For 3 (ie, urinary tract, ventricular shunt, and bowel procedures) of the 10 specific index procedure hospitalizations, having an MHC was associated with higher adjusted odds of 30-day readmission (AOR range, 1.38-2.27; Figure 2).

In total, adjusting for sociodemographic, clinical, and hospital characteristics, MHCs were associated with an additional 2501 medical readmissions and 217 procedure readmissions beyond what would have been expected if MHCs were not associated with readmissions.

MHCs are common among pediatric hospitalizations with the highest volume of readmissions; MHCs were present in approximately 1 in 5 medical and 1 in 7 procedure index hospitalizations. Across medical and procedure admissions, the adjusted likelihood of unplanned, all-cause 30-day readmission was 25% higher for children with versus without an MHC. The readmission likelihood varied by the type of medical or procedure admission and by the type of MHC. MHCs had the strongest associations with readmissions following hospitalization for diabetes and urinary tract procedures. The MHC categories associated with the highest readmission likelihood were depression, substance abuse, and multiple MHCs.

The current study complements existing literature by helping establish MHCs as a prevalent and important risk factor for hospital readmission in children. Estimates of the prevalence of MHCs in hospitalized children are between 10% and 25%,^10,11,32 and prevalence has increased by as much as 160% over the last 10 years.²⁹ Prior investigations have found that children with an MHC tend to stay longer in the hospital compared with children with no MHC.³² Results from the present study suggest that children with MHCs also experience more inpatient days because of rehospitalizations. Subsequent investigations should strive to understand the mechanisms in the hospital, community, and family environment that are responsible for the increased inpatient utilization in children with MHCs. Understanding how the receipt of mental health services before, during, and after hospitalization influences readmissions could help identify opportunities for practice improvement. Families report the need for better coordination of their child’s medical and mental health care,³³ and opportunities exist to improve attendance at mental health visits after acute care encounters.³⁴ Among adults, interventions that address posthospital access to mental healthcare have prevented readmissions.³⁵

Depression was associated with an increased risk of readmission in medical and procedure hospitalizations. As a well-known risk factor for readmission in adult patients,²¹ depression can adversely affect and exacerbate the physical health recovery of patients experiencing acute and chronic illnesses.^14,36,37 Depression is considered a modifiable contributor that, when controlled, may help lower readmission risk. Optimal adherence with behavior and medication treatment for depression is associated with a lower risk of unplanned 30-day readmissions.^14-16,19 Emerging evidence demonstrates how multifaceted, psychosocial approaches can improve patients’ adherence with depression treatment plans.³⁸ Increased attention to depression in hospitalized children may uncover new ways to manage symptoms as children transition from hospital to home.

Other MHCs were associated with a different risk of readmission among medical and procedure hospitalizations. For example, ADHD or autism documented during index hospitalization was associated with an increased risk of readmission following procedure hospitalizations and a decreased risk following medical hospitalizations. Perhaps children with ADHD or autism who exhibit hyperactive, impulsive, or repetitive behaviors^39,40 are at risk for disrupting their postprocedure wound healing, nutrition recovery, or pain tolerance, which might contribute to increased readmission risk.

MHCs were associated with different readmission risks across specific types of medical or procedure hospitalizations. For example, among medical conditions, the association of readmissions with MHCs was highest for diabetes, which is consistent with prior research.²⁶ Factors that might mediate this relationship include changes in diet and appetite, difficulty with diabetes care plan adherence, and intentional nonadherence as a form of self-harm. Similarly, a higher risk of readmission in chronic medical conditions like asthma, constipation, and sickle cell disease might be mediated by difficulty adhering to medical plans or managing exacerbations at home. In contrast, MHCs had no association with readmission following chemotherapy. In our clinical experience, readmissions following chemotherapy are driven by physiologic problems, such as thrombocytopenia, fever, and/or neutropenia. MHCs might have limited influence over those health issues. For procedure hospitalizations, MHCs had 1 of the strongest associations with ventricular shunt procedures. We hypothesize that MHCs might lead some children to experience general health symptoms that might be associated with shunt malfunction (eg, fatigue, headache, behavior change), which could lead to an increased risk of readmission to evaluate for shunt malfunction. Conversely, we found no relationship between MHCs and readmissions following appendectomy. For appendectomy, MHCs might have limited influence over the development of postsurgical complications (eg, wound infection or ileus). Future research to better elucidate mediators of increased risk of readmission associated with MHCs in certain medical and procedure conditions could help explain these relationships and identify possible future intervention targets to prevent readmissions.

This study has several limitations. The administrative data are not positioned to discover the mechanisms by which MHCs are associated with a higher likelihood of readmission. We used hospital ICD-9-CM codes to identify patients with MHCs. Other methods using more clinically rich data (eg, chart review, prescription medications, etc.) may be preferable to identify patients with MHCs. Although the use of ICD-9-CM codes may have sufficient specificity, some hospitalized children may have an MHC that is not coded. Patients identified by using diagnosis codes could represent patients with a higher severity of illness, patients using medications, or patients whose outpatient records are accessible to make the hospital team aware of the MHC. If documentation of MHCs during hospitalization represents a higher severity of illness, findings may not extrapolate to lower-severity MHCs. As hospitals transition from ICD-9 -CM to ICD-10 coding, and health systems develop more integrated inpatient and outpatient EHRs, diagnostic specificity may improve. We could not analyze the relationships with several potential confounders and explanatory variables that may be related both to the likelihood of having an MHC and the risk of readmission, including medication administration, psychiatric consultation, and parent mental health. Postdischarge health services, including access to a medical home or a usual source of mental healthcare and measures of medication adherence, were not available in the NRD.

Despite these limitations, the current study underscores the importance of MHCs in hospitalized children upon discharge. As subsequent investigations uncover the key drivers explaining the influence of MHCs on hospital readmission risk, hospitals and their local outpatient and community practices may find it useful to consider MHCs when (1) developing contingency plans and establishing follow-up care at discharge,⁴¹ (2) exploring opportunities of care integration between mental and physical health care professionals, and (3) devising strategies to reduce hospital readmissions among populations of children.

MHCs are prevalent in hospitalized children and are associated with an increased risk of 30-day, unplanned hospital readmission. Future readmission prevention efforts may uncover new ways to improve children’s transitions from hospital to home by investigating strategies to address their MHCs.

Acknowledgments

The authors thank Donjo Lau and Troy Richardson for their assistance with the analysis.

Disclosures

Dr. Doupnik was supported by a Ruth L. Kirschstein National Research Service Award institutional training grant (T32-HP010026), funded by the National Institutes of Health. Dr. Zima was supported by the Behavioral Health Centers of Excellence for California (SB852). Dr. Bardach was supported by the National Institute of Child Health and Human Development (K23-HD065836). Dr. Berry was supported by the Agency for Healthcare Research and Quality (R21 HS023092-01). The authors have no financial relationships relevant to this article to disclose. The authors have no potential conflicts of interest to disclose. Dr. Doupnik led the study design and analysis and drafted the initial manuscript. Mr. Lawlor performed the data analysis. Dr. Hall provided statistical consultation. All authors participated in the design of the study, interpretation of the data, revised the manuscript for key intellectual content, and all authors read and approved the final manuscript.

Readmission prevention is a focus of national efforts to improve the quality of hospital care for children.^1-5 Several factors contribute to the risk of readmission for hospitalized children, including age, race or ethnicity, payer, and the type and number of comorbid health conditions.^6-9 Mental health conditions (MHCs) are a prevalent comorbidity in children hospitalized for physical health reasons that could influence their postdischarge health and safety.

MHCs are increasingly common in children hospitalized for physical health indications; a comorbid MHC is currently present in 10% to 25% of hospitalized children ages 3 years and older.^10,11 Hospital length of stay (LOS) and cost are higher in children with an MHC.^12,13 Increased resource use may occur because MHCs can impede hospital treatment effectiveness and the child’s recovery from physical illness. MHCs are associated with a lower adherence with medications^14-16 and a lower ability to cope with health events and problems.^17-19 In adults, MHCs are a well-established risk factor for hospital readmission for a variety of physical health conditions.^20-24 Although the influence of MHCs on readmissions in children has not been extensively investigated, higher readmission rates have been reported in adolescents hospitalized for diabetes with an MHC compared with those with no MHC.^25,26

To our knowledge, no large studies have examined the relationship between the presence of a comorbid MHC and hospital readmissions in children or adolescents hospitalized for a broad array of medical or procedure conditions. Therefore, we conducted this study to (1) assess the likelihood of 30-day hospital readmission in children with versus without MHC who were hospitalized for one of 10 medical or 10 procedure conditions, and (2) to assess which MHCs are associated with the highest likelihood of hospital readmission.

Study Design and Setting

We conducted a national, retrospective cohort study of index hospitalizations for children ages 3 to 21 years who were discharged from January 1, 2013, to November 30, 2013, in the Agency for Healthcare Research and Quality’s (AHRQ) Nationwide Readmissions Database (NRD). Admissions occurring in December 2013 were excluded because they did not have a 30-day timeframe available for readmission measurement. The 2013 NRD includes administrative data for a nationally representative sample of 14 million hospitalizations in 21 states, accounting for 49% of all US hospitalizations and weighted to represent 35.6 million hospitalizations. The database includes deidentified, verified patient linkage numbers so that patients can be tracked across multiple hospitalizations at the same institution or different institutions within a state. The NRD includes hospital information, patient demographic information, and the International Classification of Diseases, 9th Revision-Clinical Modification (ICD-9-CM) discharge diagnoses and procedures, with 1 primary diagnosis and up to 24 additional fields for comorbid diagnoses. This study was approved for exemption by the Children’s Hospital of Philadelphia Institutional Review Board.

Index Admissions

We used the methods described below to create a study cohort of the 10 medical and 10 procedure index admissions associated with the highest volume (ie, the greatest absolute number) of 30-day hospital readmissions. Conditions with a high volume of readmissions were chosen in an effort to identify conditions in which readmission-prevention interventions had the greatest potential to reduce the absolute number of readmissions. We first categorized index hospitalizations for medical and procedure conditions by using the All Patient Refined Diagnosis Related Groups (APR-DRGs; 3M Health Information Systems, Wallingford, CT).²⁷ APR-DRGs use all diagnosis and/or procedure ICD-9-CM codes registered for a hospital discharge to assign 1 reason that best explains the need for hospitalization. We then excluded obstetric hospitalizations, psychiatric hospitalizations, and hospitalizations resulting in death or transfer from being considered as index admissions. Afterwards, we ranked each APR-DRG index hospitalization by the total number of 30-day hospital readmissions that occurred afterward and selected the 10 medical and 10 procedure index admissions with the highest number of readmissions. The APR-DRG index admissions are listed in Figures 1 and 2. For the APR-DRG “digestive system diagnoses,” the most common diagnosis was constipation, and we refer to that category as “constipation.” The most common diagnosis for the APR-DRG called “other operating room procedure for neoplasm” was tumor biopsy, and we refer to that category as “tumor biopsy.”

Main Outcome Measure

The primary study outcome was unplanned, all-cause readmission to any hospital within 30 days of index hospitalization. All-cause readmissions include any hospitalization for the same or different condition as the index admission, including conditions not eligible to be considered as index admissions (obstetric, psychiatric, and hospitalizations resulting in death or transfer). Planned readmissions, identified by using pediatric-specific measure specifications endorsed by AHRQ and the National Quality Forum,²⁸ were excluded from measurement. For index admissions with multiple 30-day readmissions, only the first readmission was counted. Each readmission was treated as an index admission.

Main Independent Variable

The main independent variable was the presence of an MHC documented during the index hospitalization. MHCs were identified and classified into diagnosis categories derived from the AHRQ Chronic Condition Indicator system by using ICD-9-CM codes.²⁹ MHC categories included anxiety disorders, attention-deficit/hyperactivity disorder (ADHD), autism, depression, and substance abuse. Less common MHCs included bipolar disorder, schizophrenia, disruptive behavior disorders, somatoform disorders, and eating disorders. These conditions are included in the group with any MHC, but we did not calculate the adjusted odds ratios (AORs) of readmission for these conditions. Children were identified as having multiple MHCs if they had more than 1 MHC.

Other Characteristics of Index Hospitalizations

A priori, we selected for analysis the known demographic, clinical, and hospital factors associated with the risk of readmission.^20-24 The demographic characteristics included patient age, gender, payer category, urban or rural residence, and the median income quartile for a patient’s ZIP code. The hospital characteristics included location, ownership, and teaching hospital designation. The clinical characteristics included the number of chronic conditions³⁰ and indicators for the presence of a complex chronic condition in each of 12 organ systems.³¹

Statistical Analysis

We calculated descriptive summary statistics for the characteristics of index hospitalizations. We compared characteristics in index admissions of children with versus without MHC by using Wilcoxon Rank-Sum tests for continuous variables and Wald χ² tests for categorical variables. In the multivariable analysis, we derived logistic regression models to assess the relationship of 30-day hospital readmission with each type of MHC, adjusting for index admission demographic, hospital, and clinical characteristics. MHCs were modeled as binary indicator variables with the presence of any MHC, more than 1 MHC, or each of 5 MHC categories (anxiety disorders, ADHD, autism, depression, substance abuse) compared with no MHC. Four types of logistic regression models were derived (1) for the combined sample of all 10 index medical admissions with each MHC category versus no MHC as a primary predictor, (2) for each medical index admission with any MHC versus no MHC as the primary predictor, (3) for the combined sample of all 10 index procedure admissions with each MHC category versus no MHC as a primary predictor, and (4) for each procedure index admission with any MHC versus no MHC as the primary predictor. All analyses were weighted to achieve national estimates and clustered by hospital by using AHRQ-recommended survey procedures. SAS version 9.4 (SAS Institute, Cary, NC) was used for all analyses. All tests were two-sided, and a P < .05 was
considered statistically significant.

Study Population

Across all index admissions, 16.3% were for children with an MHC. Overall, children with MHCs were older and more likely to have a chronic³⁰ or complex chronic³¹ physical health condition than children with no MHCs (Table).

Index Medical Admissions, Mental Health Conditions, and Hospital Readmission

The 10 index medical hospitalizations with the most readmissions for children ages 3 to 20 years were asthma, chemotherapy, constipation, diabetes, gastroenteritis, inflammatory bowel disease, neutropenia, pneumonia, seizure, and sickle cell crisis. Across all index medical hospitalizations, 17.5% were for patients with an MHC (Figure 1). Of index medical admissions with any MHC, 26.3% had ADHD, 22.9% had an anxiety disorder, 14.9% had autism, 18.3% had depression, and 30.9% had substance abuse. Among all admissions with MHCs, 28.9% had 2 or more MHCs.

Index Medical Admissions Combined

For all index medical hospitalizations combined, 17.0% (n = 59,138) had an unplanned, 30-day hospital readmission. The rate of 30-day hospital readmissions was higher with versus without an MHC (17.5 vs 16.8%; P < .001). In a multivariable analysis, presence of an MHC was associated with a higher likelihood of hospital readmission following an index medical admission (AOR, 1.23; 95% confidence interval [CI], 1.19-1.26); Figure 1). All MHCs except autism and ADHD had a higher likelihood of readmission (Figure 3). 

Specific Index Medical Admissions

Index Procedure Admissions, Mental Health Conditions, and Hospital Readmission

Index Procedure Admissions Combined

Specific Index Procedure Admissions

For specific index procedure admissions, the rate of 30-day hospital readmission ranged from 2.2% for knee procedures to 33.6% for tumor biopsy. For 3 (ie, urinary tract, ventricular shunt, and bowel procedures) of the 10 specific index procedure hospitalizations, having an MHC was associated with higher adjusted odds of 30-day readmission (AOR range, 1.38-2.27; Figure 2).

In total, adjusting for sociodemographic, clinical, and hospital characteristics, MHCs were associated with an additional 2501 medical readmissions and 217 procedure readmissions beyond what would have been expected if MHCs were not associated with readmissions.

MHCs are common among pediatric hospitalizations with the highest volume of readmissions; MHCs were present in approximately 1 in 5 medical and 1 in 7 procedure index hospitalizations. Across medical and procedure admissions, the adjusted likelihood of unplanned, all-cause 30-day readmission was 25% higher for children with versus without an MHC. The readmission likelihood varied by the type of medical or procedure admission and by the type of MHC. MHCs had the strongest associations with readmissions following hospitalization for diabetes and urinary tract procedures. The MHC categories associated with the highest readmission likelihood were depression, substance abuse, and multiple MHCs.

The current study complements existing literature by helping establish MHCs as a prevalent and important risk factor for hospital readmission in children. Estimates of the prevalence of MHCs in hospitalized children are between 10% and 25%,^10,11,32 and prevalence has increased by as much as 160% over the last 10 years.²⁹ Prior investigations have found that children with an MHC tend to stay longer in the hospital compared with children with no MHC.³² Results from the present study suggest that children with MHCs also experience more inpatient days because of rehospitalizations. Subsequent investigations should strive to understand the mechanisms in the hospital, community, and family environment that are responsible for the increased inpatient utilization in children with MHCs. Understanding how the receipt of mental health services before, during, and after hospitalization influences readmissions could help identify opportunities for practice improvement. Families report the need for better coordination of their child’s medical and mental health care,³³ and opportunities exist to improve attendance at mental health visits after acute care encounters.³⁴ Among adults, interventions that address posthospital access to mental healthcare have prevented readmissions.³⁵

Depression was associated with an increased risk of readmission in medical and procedure hospitalizations. As a well-known risk factor for readmission in adult patients,²¹ depression can adversely affect and exacerbate the physical health recovery of patients experiencing acute and chronic illnesses.^14,36,37 Depression is considered a modifiable contributor that, when controlled, may help lower readmission risk. Optimal adherence with behavior and medication treatment for depression is associated with a lower risk of unplanned 30-day readmissions.^14-16,19 Emerging evidence demonstrates how multifaceted, psychosocial approaches can improve patients’ adherence with depression treatment plans.³⁸ Increased attention to depression in hospitalized children may uncover new ways to manage symptoms as children transition from hospital to home.

Other MHCs were associated with a different risk of readmission among medical and procedure hospitalizations. For example, ADHD or autism documented during index hospitalization was associated with an increased risk of readmission following procedure hospitalizations and a decreased risk following medical hospitalizations. Perhaps children with ADHD or autism who exhibit hyperactive, impulsive, or repetitive behaviors^39,40 are at risk for disrupting their postprocedure wound healing, nutrition recovery, or pain tolerance, which might contribute to increased readmission risk.

MHCs were associated with different readmission risks across specific types of medical or procedure hospitalizations. For example, among medical conditions, the association of readmissions with MHCs was highest for diabetes, which is consistent with prior research.²⁶ Factors that might mediate this relationship include changes in diet and appetite, difficulty with diabetes care plan adherence, and intentional nonadherence as a form of self-harm. Similarly, a higher risk of readmission in chronic medical conditions like asthma, constipation, and sickle cell disease might be mediated by difficulty adhering to medical plans or managing exacerbations at home. In contrast, MHCs had no association with readmission following chemotherapy. In our clinical experience, readmissions following chemotherapy are driven by physiologic problems, such as thrombocytopenia, fever, and/or neutropenia. MHCs might have limited influence over those health issues. For procedure hospitalizations, MHCs had 1 of the strongest associations with ventricular shunt procedures. We hypothesize that MHCs might lead some children to experience general health symptoms that might be associated with shunt malfunction (eg, fatigue, headache, behavior change), which could lead to an increased risk of readmission to evaluate for shunt malfunction. Conversely, we found no relationship between MHCs and readmissions following appendectomy. For appendectomy, MHCs might have limited influence over the development of postsurgical complications (eg, wound infection or ileus). Future research to better elucidate mediators of increased risk of readmission associated with MHCs in certain medical and procedure conditions could help explain these relationships and identify possible future intervention targets to prevent readmissions.

This study has several limitations. The administrative data are not positioned to discover the mechanisms by which MHCs are associated with a higher likelihood of readmission. We used hospital ICD-9-CM codes to identify patients with MHCs. Other methods using more clinically rich data (eg, chart review, prescription medications, etc.) may be preferable to identify patients with MHCs. Although the use of ICD-9-CM codes may have sufficient specificity, some hospitalized children may have an MHC that is not coded. Patients identified by using diagnosis codes could represent patients with a higher severity of illness, patients using medications, or patients whose outpatient records are accessible to make the hospital team aware of the MHC. If documentation of MHCs during hospitalization represents a higher severity of illness, findings may not extrapolate to lower-severity MHCs. As hospitals transition from ICD-9 -CM to ICD-10 coding, and health systems develop more integrated inpatient and outpatient EHRs, diagnostic specificity may improve. We could not analyze the relationships with several potential confounders and explanatory variables that may be related both to the likelihood of having an MHC and the risk of readmission, including medication administration, psychiatric consultation, and parent mental health. Postdischarge health services, including access to a medical home or a usual source of mental healthcare and measures of medication adherence, were not available in the NRD.

Despite these limitations, the current study underscores the importance of MHCs in hospitalized children upon discharge. As subsequent investigations uncover the key drivers explaining the influence of MHCs on hospital readmission risk, hospitals and their local outpatient and community practices may find it useful to consider MHCs when (1) developing contingency plans and establishing follow-up care at discharge,⁴¹ (2) exploring opportunities of care integration between mental and physical health care professionals, and (3) devising strategies to reduce hospital readmissions among populations of children.

MHCs are prevalent in hospitalized children and are associated with an increased risk of 30-day, unplanned hospital readmission. Future readmission prevention efforts may uncover new ways to improve children’s transitions from hospital to home by investigating strategies to address their MHCs.

Acknowledgments

The authors thank Donjo Lau and Troy Richardson for their assistance with the analysis.

Disclosures

Dr. Doupnik was supported by a Ruth L. Kirschstein National Research Service Award institutional training grant (T32-HP010026), funded by the National Institutes of Health. Dr. Zima was supported by the Behavioral Health Centers of Excellence for California (SB852). Dr. Bardach was supported by the National Institute of Child Health and Human Development (K23-HD065836). Dr. Berry was supported by the Agency for Healthcare Research and Quality (R21 HS023092-01). The authors have no financial relationships relevant to this article to disclose. The authors have no potential conflicts of interest to disclose. Dr. Doupnik led the study design and analysis and drafted the initial manuscript. Mr. Lawlor performed the data analysis. Dr. Hall provided statistical consultation. All authors participated in the design of the study, interpretation of the data, revised the manuscript for key intellectual content, and all authors read and approved the final manuscript.

NEW ORLEANS – It’s a widespread misconception among internists: Implementing an office-based adult immunization program is a potential financial sinkhole and just isn’t worth the hassle.

That’s utterly wrong, Jason M. Goldman, MD, declared at the annual meeting of the American College of Physicians.

Bruce Jancin/MDedge News

Why implement adult immunization?

Many internists send patients off to a pharmacy for their vaccinations. That’s simply not good medical care, Dr. Goldman said.

“We are the primary care doctors,” he said. “We are the ones who should be vaccinating our patients, for several reasons: It’s the standard of care. It’s good medical practice.”

And Dr. Goldman frequently doesn’t receive any reports from the pharmacies. That means patients come to his office and have no idea what vaccines they received.

“That’s not good documentation,” he cautioned. “And when patients go into the hospital, they all get Pneumovax every single week because the hospital isn’t keeping documentation.”

The bottom line with vaccinating: “Whether you’re in a small group, a solo practitioner, or in a large health system, the vaccine programs work. They prevent disease and save lives. It’s easy to incorporate into your practice. And it is profitable.”

How profitable?

Dr. Goldman has the answer. For a great many different vaccines, he has calculated his average cost for the needle, syringe, medical assistant, time in the room, and other factors involved in running his practice. He also knows from experience the average purchase price paid for a given vaccine, the typical reimbursement for that vaccine, plus the reimbursement for its administration, which is a separate yet necessary coding/billing item.

The typical net profit ranges from $21.50 for high-dose influenza vaccine to, at the top end, $47.41 for meningococcal group B vaccine (Bexsero) and $49.58 for recombinant human papillomavirus 9-valent vaccine (Gardasil-9).
 

Purchasing and storage considerations

Always buy vaccines directly from the manufacturer; it’s a better deal than going through a middleman, who’ll invariably take a cut out of what should be the physician’s profit.

Each of the major vaccine makers has a dedicated vaccine purchase website where a physician can sign up for an account and order the company’s vaccines. These include Merck (www.merckvaccines.com), Aventis (www.vaccineshoppe.com), Pfizer (www.pfizerprime.com), and GlaxoSmithKline (www.gskdirect.com).

You’ll get a discount by buying multiple different vaccines on the same order.

“You can defer payment of your invoice for several months,” Dr. Goldman explained. “You purchase the vaccines now, but you don’t have to pay for them until 3-4 months later. By then, hopefully, you’ll have received reimbursement. So, your cost is covered, and you have profit on the side.”

For paying promptly on the due date, the manufacturer will provide an additional discount. The easiest way to do that is to have the money automatically charged to a credit card on that date.

Also, the vaccine manufacturers’ staff are happy to provide reliably expert reimbursement guidance.

With a little experience, it’s easy to predict how many vaccines will be used per month, Dr. Goldman said. Order what’s needed, so there aren’t a bunch of vaccines expiring in the office.

“However, even if that does happen, all is not lost,” he noted. “You can call up the manufacturer, and many of them will take back unused or even expired vaccines for full credit to the account. So, again, you really can’t lose money.”

With regard to vaccine storage, don’t skimp on the refrigerator and/or freezer. Get a professional model. And follow the best practices as described in the Centers for Disease Control and Prevention toolkit.

“It’s really common sense: Don’t use a dorm-type refrigerator; don’t put food or beverages in there; make sure the vaccines are appropriately stored; check the temperature every day; make sure if you lose power, your building has a backup generator,” he explained. “If you train your staff the right way, they’ll be able to handle it so you don’t have to worry about it. You just have to look at the logs and make sure they’re doing it.”


 

Use standing orders

Studies show that standing orders result in higher vaccination rates.

“You’re empowering the nurses or other staff members to act within the full extent of their license,” Dr. Goldman said. “It takes the burden off the physician to have to do anything that can be delegated to other individuals to make sure patients get vaccinated.”
 

Coding and billing for commercially insured patients

All vaccines have the same ICD-10 diagnostic code: Z23. And each vaccine has its own CPT code. For example, 90750 for Shingrix, the new herpes zoster vaccine; 90715 for Tdap; and 90686 for quadrivalent influenza.

But there are two components to the CPT code for a vaccination: the individual vaccine code and the administration code.

If you give one vaccination to a non-Medicare patient, the administration code is 90471. If you give a second vaccination during the same visit, its administration code is 90472. If you give a patient, say, four vaccines during one visit, you would bill the first using the administration code 90471, and the others as 90472 times three units.

If the vaccines are being given during a legitimate office visit, the physician can bill for both by employing modifiers 25 and 59. Modifier 25 goes with the appropriate E/M code for the office visit; it serves to tell the coding system that other things are going on in addition to the billable office visit. Modifier 59 needs to be attached to both the specific vaccine code and the vaccine administration code for reimbursement to occur.

Billing for vaccines for all commercially insured patients go through the office’s normal claims process.
 

Immunizing Medicare patients

For patients under Medicare Part B, vaccines for influenza, pneumonia, and hepatitis B have their own individual G codes: G0008 for influenza, G0009 for a pneumonia vaccine, and G0010 for hepatitis B. If a Medicare patient also gets an additional vaccine other than one of those three during the visit, administration code 90472 is applied to it. Those G-code bills are also submitted through the office’s normal claims process.

Under Medicare, vaccines for herpes zoster, hepatitis A, and Tdap are a special case. They are considered drugs and are covered under Medicare Part D.

“To bill that, you have to tell Medicare that you’re acting as a pharmacy,” Dr. Goldman explained. “You go to www.mytransactRX.com. You request there to be seen as a pharmacy billing for a drug. You will then be able to receive direct payment into your bank account from your Medicare payer. It will also allow you to check out patient coverage, print out proof of coverage, and submit the claim through the portal.”

If the Medicare patient doesn’t have a drug plan for those vaccines, or if the information in the system isn’t up to date, it’s a good idea to download the Advanced Beneficiary Notice of Noncoverage from the Medicare website and have the patient sign it. It spells out what the patient’s financial responsibility could be.

“The ABN also protects you as a provider, because it shows you’re not trying to balance-bill the patient,” he noted.

Dr. Goldman implored his internist colleagues to stand up and become the stewards of adult immunization.

“Remember: Keep calm and vaccinate,” he urged.

He reported having no relevant financial conflicts.

[email protected]

NEW ORLEANS – It’s a widespread misconception among internists: Implementing an office-based adult immunization program is a potential financial sinkhole and just isn’t worth the hassle.

That’s utterly wrong, Jason M. Goldman, MD, declared at the annual meeting of the American College of Physicians.

Bruce Jancin/MDedge News

Why implement adult immunization?

Many internists send patients off to a pharmacy for their vaccinations. That’s simply not good medical care, Dr. Goldman said.

“We are the primary care doctors,” he said. “We are the ones who should be vaccinating our patients, for several reasons: It’s the standard of care. It’s good medical practice.”

And Dr. Goldman frequently doesn’t receive any reports from the pharmacies. That means patients come to his office and have no idea what vaccines they received.

“That’s not good documentation,” he cautioned. “And when patients go into the hospital, they all get Pneumovax every single week because the hospital isn’t keeping documentation.”

The bottom line with vaccinating: “Whether you’re in a small group, a solo practitioner, or in a large health system, the vaccine programs work. They prevent disease and save lives. It’s easy to incorporate into your practice. And it is profitable.”

How profitable?

Dr. Goldman has the answer. For a great many different vaccines, he has calculated his average cost for the needle, syringe, medical assistant, time in the room, and other factors involved in running his practice. He also knows from experience the average purchase price paid for a given vaccine, the typical reimbursement for that vaccine, plus the reimbursement for its administration, which is a separate yet necessary coding/billing item.

The typical net profit ranges from $21.50 for high-dose influenza vaccine to, at the top end, $47.41 for meningococcal group B vaccine (Bexsero) and $49.58 for recombinant human papillomavirus 9-valent vaccine (Gardasil-9).
 

Purchasing and storage considerations

Always buy vaccines directly from the manufacturer; it’s a better deal than going through a middleman, who’ll invariably take a cut out of what should be the physician’s profit.

Each of the major vaccine makers has a dedicated vaccine purchase website where a physician can sign up for an account and order the company’s vaccines. These include Merck (www.merckvaccines.com), Aventis (www.vaccineshoppe.com), Pfizer (www.pfizerprime.com), and GlaxoSmithKline (www.gskdirect.com).

You’ll get a discount by buying multiple different vaccines on the same order.

“You can defer payment of your invoice for several months,” Dr. Goldman explained. “You purchase the vaccines now, but you don’t have to pay for them until 3-4 months later. By then, hopefully, you’ll have received reimbursement. So, your cost is covered, and you have profit on the side.”

For paying promptly on the due date, the manufacturer will provide an additional discount. The easiest way to do that is to have the money automatically charged to a credit card on that date.

Also, the vaccine manufacturers’ staff are happy to provide reliably expert reimbursement guidance.

With a little experience, it’s easy to predict how many vaccines will be used per month, Dr. Goldman said. Order what’s needed, so there aren’t a bunch of vaccines expiring in the office.

“However, even if that does happen, all is not lost,” he noted. “You can call up the manufacturer, and many of them will take back unused or even expired vaccines for full credit to the account. So, again, you really can’t lose money.”

With regard to vaccine storage, don’t skimp on the refrigerator and/or freezer. Get a professional model. And follow the best practices as described in the Centers for Disease Control and Prevention toolkit.

“It’s really common sense: Don’t use a dorm-type refrigerator; don’t put food or beverages in there; make sure the vaccines are appropriately stored; check the temperature every day; make sure if you lose power, your building has a backup generator,” he explained. “If you train your staff the right way, they’ll be able to handle it so you don’t have to worry about it. You just have to look at the logs and make sure they’re doing it.”


 

Use standing orders

Studies show that standing orders result in higher vaccination rates.

“You’re empowering the nurses or other staff members to act within the full extent of their license,” Dr. Goldman said. “It takes the burden off the physician to have to do anything that can be delegated to other individuals to make sure patients get vaccinated.”
 

Coding and billing for commercially insured patients

All vaccines have the same ICD-10 diagnostic code: Z23. And each vaccine has its own CPT code. For example, 90750 for Shingrix, the new herpes zoster vaccine; 90715 for Tdap; and 90686 for quadrivalent influenza.

But there are two components to the CPT code for a vaccination: the individual vaccine code and the administration code.

If you give one vaccination to a non-Medicare patient, the administration code is 90471. If you give a second vaccination during the same visit, its administration code is 90472. If you give a patient, say, four vaccines during one visit, you would bill the first using the administration code 90471, and the others as 90472 times three units.

If the vaccines are being given during a legitimate office visit, the physician can bill for both by employing modifiers 25 and 59. Modifier 25 goes with the appropriate E/M code for the office visit; it serves to tell the coding system that other things are going on in addition to the billable office visit. Modifier 59 needs to be attached to both the specific vaccine code and the vaccine administration code for reimbursement to occur.

Billing for vaccines for all commercially insured patients go through the office’s normal claims process.
 

Immunizing Medicare patients

For patients under Medicare Part B, vaccines for influenza, pneumonia, and hepatitis B have their own individual G codes: G0008 for influenza, G0009 for a pneumonia vaccine, and G0010 for hepatitis B. If a Medicare patient also gets an additional vaccine other than one of those three during the visit, administration code 90472 is applied to it. Those G-code bills are also submitted through the office’s normal claims process.

Under Medicare, vaccines for herpes zoster, hepatitis A, and Tdap are a special case. They are considered drugs and are covered under Medicare Part D.

“To bill that, you have to tell Medicare that you’re acting as a pharmacy,” Dr. Goldman explained. “You go to www.mytransactRX.com. You request there to be seen as a pharmacy billing for a drug. You will then be able to receive direct payment into your bank account from your Medicare payer. It will also allow you to check out patient coverage, print out proof of coverage, and submit the claim through the portal.”

If the Medicare patient doesn’t have a drug plan for those vaccines, or if the information in the system isn’t up to date, it’s a good idea to download the Advanced Beneficiary Notice of Noncoverage from the Medicare website and have the patient sign it. It spells out what the patient’s financial responsibility could be.

“The ABN also protects you as a provider, because it shows you’re not trying to balance-bill the patient,” he noted.

Dr. Goldman implored his internist colleagues to stand up and become the stewards of adult immunization.

“Remember: Keep calm and vaccinate,” he urged.

He reported having no relevant financial conflicts.

[email protected]

NEW ORLEANS – It’s a widespread misconception among internists: Implementing an office-based adult immunization program is a potential financial sinkhole and just isn’t worth the hassle.

That’s utterly wrong, Jason M. Goldman, MD, declared at the annual meeting of the American College of Physicians.

Bruce Jancin/MDedge News

Why implement adult immunization?

Many internists send patients off to a pharmacy for their vaccinations. That’s simply not good medical care, Dr. Goldman said.

“We are the primary care doctors,” he said. “We are the ones who should be vaccinating our patients, for several reasons: It’s the standard of care. It’s good medical practice.”

And Dr. Goldman frequently doesn’t receive any reports from the pharmacies. That means patients come to his office and have no idea what vaccines they received.

“That’s not good documentation,” he cautioned. “And when patients go into the hospital, they all get Pneumovax every single week because the hospital isn’t keeping documentation.”

The bottom line with vaccinating: “Whether you’re in a small group, a solo practitioner, or in a large health system, the vaccine programs work. They prevent disease and save lives. It’s easy to incorporate into your practice. And it is profitable.”

How profitable?

Dr. Goldman has the answer. For a great many different vaccines, he has calculated his average cost for the needle, syringe, medical assistant, time in the room, and other factors involved in running his practice. He also knows from experience the average purchase price paid for a given vaccine, the typical reimbursement for that vaccine, plus the reimbursement for its administration, which is a separate yet necessary coding/billing item.

The typical net profit ranges from $21.50 for high-dose influenza vaccine to, at the top end, $47.41 for meningococcal group B vaccine (Bexsero) and $49.58 for recombinant human papillomavirus 9-valent vaccine (Gardasil-9).
 

Purchasing and storage considerations

Always buy vaccines directly from the manufacturer; it’s a better deal than going through a middleman, who’ll invariably take a cut out of what should be the physician’s profit.

Each of the major vaccine makers has a dedicated vaccine purchase website where a physician can sign up for an account and order the company’s vaccines. These include Merck (www.merckvaccines.com), Aventis (www.vaccineshoppe.com), Pfizer (www.pfizerprime.com), and GlaxoSmithKline (www.gskdirect.com).

You’ll get a discount by buying multiple different vaccines on the same order.

“You can defer payment of your invoice for several months,” Dr. Goldman explained. “You purchase the vaccines now, but you don’t have to pay for them until 3-4 months later. By then, hopefully, you’ll have received reimbursement. So, your cost is covered, and you have profit on the side.”

For paying promptly on the due date, the manufacturer will provide an additional discount. The easiest way to do that is to have the money automatically charged to a credit card on that date.

Also, the vaccine manufacturers’ staff are happy to provide reliably expert reimbursement guidance.

With a little experience, it’s easy to predict how many vaccines will be used per month, Dr. Goldman said. Order what’s needed, so there aren’t a bunch of vaccines expiring in the office.

“However, even if that does happen, all is not lost,” he noted. “You can call up the manufacturer, and many of them will take back unused or even expired vaccines for full credit to the account. So, again, you really can’t lose money.”

With regard to vaccine storage, don’t skimp on the refrigerator and/or freezer. Get a professional model. And follow the best practices as described in the Centers for Disease Control and Prevention toolkit.

“It’s really common sense: Don’t use a dorm-type refrigerator; don’t put food or beverages in there; make sure the vaccines are appropriately stored; check the temperature every day; make sure if you lose power, your building has a backup generator,” he explained. “If you train your staff the right way, they’ll be able to handle it so you don’t have to worry about it. You just have to look at the logs and make sure they’re doing it.”


 

Use standing orders

Studies show that standing orders result in higher vaccination rates.

“You’re empowering the nurses or other staff members to act within the full extent of their license,” Dr. Goldman said. “It takes the burden off the physician to have to do anything that can be delegated to other individuals to make sure patients get vaccinated.”
 

Coding and billing for commercially insured patients

All vaccines have the same ICD-10 diagnostic code: Z23. And each vaccine has its own CPT code. For example, 90750 for Shingrix, the new herpes zoster vaccine; 90715 for Tdap; and 90686 for quadrivalent influenza.

But there are two components to the CPT code for a vaccination: the individual vaccine code and the administration code.

If you give one vaccination to a non-Medicare patient, the administration code is 90471. If you give a second vaccination during the same visit, its administration code is 90472. If you give a patient, say, four vaccines during one visit, you would bill the first using the administration code 90471, and the others as 90472 times three units.

If the vaccines are being given during a legitimate office visit, the physician can bill for both by employing modifiers 25 and 59. Modifier 25 goes with the appropriate E/M code for the office visit; it serves to tell the coding system that other things are going on in addition to the billable office visit. Modifier 59 needs to be attached to both the specific vaccine code and the vaccine administration code for reimbursement to occur.

Billing for vaccines for all commercially insured patients go through the office’s normal claims process.
 

Immunizing Medicare patients

For patients under Medicare Part B, vaccines for influenza, pneumonia, and hepatitis B have their own individual G codes: G0008 for influenza, G0009 for a pneumonia vaccine, and G0010 for hepatitis B. If a Medicare patient also gets an additional vaccine other than one of those three during the visit, administration code 90472 is applied to it. Those G-code bills are also submitted through the office’s normal claims process.

Under Medicare, vaccines for herpes zoster, hepatitis A, and Tdap are a special case. They are considered drugs and are covered under Medicare Part D.

“To bill that, you have to tell Medicare that you’re acting as a pharmacy,” Dr. Goldman explained. “You go to www.mytransactRX.com. You request there to be seen as a pharmacy billing for a drug. You will then be able to receive direct payment into your bank account from your Medicare payer. It will also allow you to check out patient coverage, print out proof of coverage, and submit the claim through the portal.”

If the Medicare patient doesn’t have a drug plan for those vaccines, or if the information in the system isn’t up to date, it’s a good idea to download the Advanced Beneficiary Notice of Noncoverage from the Medicare website and have the patient sign it. It spells out what the patient’s financial responsibility could be.

“The ABN also protects you as a provider, because it shows you’re not trying to balance-bill the patient,” he noted.

Dr. Goldman implored his internist colleagues to stand up and become the stewards of adult immunization.

“Remember: Keep calm and vaccinate,” he urged.

He reported having no relevant financial conflicts.

[email protected]

The National Institutes of Health is canning a large study on the potential health benefits of moderate alcohol consumption after an advisory committee agreed with reporting by the New York Times that NIH employees and scientists solicited study funds from the alcoholic beverage industry.

NIH Francis Collins, MD, said the ethical violations resulted in a fundamentally flawed study that could not proceed.

“NIH has strong policies that detail the standards of conduct for NIH employees, including prohibiting the solicitation of gifts and promoting fairness in grant competitions. We take very seriously any violations of these standards,” Dr. Collins said in a statement, which added that the agency will take appropriate personnel actions.

While testifying before the Senate Appropriations Committee in mid-May on NIH’s budget request for 2019, Dr. Collins vowed not only to appropriately close the Moderate Alcohol and Cardiovascular Health (MACH) study, but to investigate whether other potential conflicts exist in other NIH-funded studies.

The story broke in mid-March, when The New York Times reported that scientists and officials from the National Institute on Alcohol Abuse and Alcoholism who were working on the MACH trial met at informational sessions with five liquor and beer companies in 2013 and 2014. The officials suggested that “the research might reflect favorably on moderate drinking, while institute officials pressed the groups for support,” according to documents obtained by the Times.

In all, the Times reported, the alcohol companies agreed to foot $67 million of the trial’s total $100 million bill. Such action violates NIH policy. An NIH report named those companies as Anheuser-Busch InBev, Carlsberg Breweries A/S, Diageo plc, Heineken, and Pernod Ricard USA LLC.

The MACH study was a multicenter, randomized clinical trial to determine the effects of one serving of alcohol (approximately 15 grams) daily, compared to no alcohol intake, on the rate of new cases of cardiovascular disease and the rate of new cases of diabetes among participants free of diabetes at baseline.

“The study was launched because some epidemiological studies have shown that moderate alcohol consumption has health benefits by reducing risk for coronary artery disease, type 2 diabetes, and rheumatoid arthritis,” according to the NIH statement. “The study aimed to enroll 7,800 participants. After a planning phase, it began enrollment on Feb. 5, 2018, and was suspended on May 10, 2018, at which time there were 105 participants enrolled.”

The trial was being led by researchers at Beth Israel Deaconess Medical Center, Boston.

In response to the public disclosure of the study’s funding, NIH convened a working group to ascertain:

• the circumstances that led to securing private funding for MACH trial
• the scientific premise of and planning for the MACH trial
• the process used to decide to support the MACH trial
• program development and oversight once funding was secured by the secured by the Foundation for NIH (FNIH)
• a review of the NIAAA portfolio prior to and during the leadership of the current NIAAA Director to assess what programmatic shifts, if any, could be discerned.

While noting that public-private partnerships are key to advancing science, the committee found that soliciting funds from alcoholic beverage companies for a study that could prove such beverages are beneficial, crossed the “firewall” between public funds and private resources. The committee recommended terminating the study.

The committee also recommended an expanded investigation into measures that would prevent NIH staff from soliciting external funds to support research programs.

The committee uncovered an email trail strongly suggesting that the solicitation of funds was planned and intended to be secretive.

According to the working group report, there was “frequent email correspondence among members of NIAAA senior staff, select extramural investigators (including the eventual PI of the MACH trial), and industry representatives occurred prior to involvement of the FNIH and the development of the NIH funding opportunity announcement for a multi-site clinical trial on moderate drinking and cardiovascular health. These communications appear to be an attempt to persuade industry to provide funding for the MACH trial. Moreover, these senior members of NIAAA staff appear to have purposefully kept other key members of NIAAA staff and the FNIH ignorant of these efforts. For example, correspondence between NIAAA staff draws attention to a February 2014 wine industry blog that reports that FNIH is initiating a search for industry funding to support a major clinical study on the health effects of moderate alcohol consumption. One senior staff member at NIAAA is unaware of any such potential planning, asking another senior staff member about the article. ‘... Anything seem broken here?’ even though such a trial to test moderate drinking effects on cardiovascular health should very likely involve the programmatic division to which this senior staff member belongs. In response to receiving the forwarded discussion, NIAAA senior leadership communicates among one other, ‘Best not to respond right now but we can’t keep him totally in the dark.’ "

The trial was also funded in part by NIAAA, which expected to commit $20 million to the overall project over 10 years, of which $4 million has been spent.

“The integrity of the NIH grants administrative process, peer review, and the quality of NIH-supported research must always be above reproach,” Dr. Collins said in the statement. “When any problems are uncovered, however, efforts to correct them must be swift and comprehensive.”

[email protected]

The National Institutes of Health is canning a large study on the potential health benefits of moderate alcohol consumption after an advisory committee agreed with reporting by the New York Times that NIH employees and scientists solicited study funds from the alcoholic beverage industry.

NIH Francis Collins, MD, said the ethical violations resulted in a fundamentally flawed study that could not proceed.

“NIH has strong policies that detail the standards of conduct for NIH employees, including prohibiting the solicitation of gifts and promoting fairness in grant competitions. We take very seriously any violations of these standards,” Dr. Collins said in a statement, which added that the agency will take appropriate personnel actions.

While testifying before the Senate Appropriations Committee in mid-May on NIH’s budget request for 2019, Dr. Collins vowed not only to appropriately close the Moderate Alcohol and Cardiovascular Health (MACH) study, but to investigate whether other potential conflicts exist in other NIH-funded studies.

The story broke in mid-March, when The New York Times reported that scientists and officials from the National Institute on Alcohol Abuse and Alcoholism who were working on the MACH trial met at informational sessions with five liquor and beer companies in 2013 and 2014. The officials suggested that “the research might reflect favorably on moderate drinking, while institute officials pressed the groups for support,” according to documents obtained by the Times.

In all, the Times reported, the alcohol companies agreed to foot $67 million of the trial’s total $100 million bill. Such action violates NIH policy. An NIH report named those companies as Anheuser-Busch InBev, Carlsberg Breweries A/S, Diageo plc, Heineken, and Pernod Ricard USA LLC.

The MACH study was a multicenter, randomized clinical trial to determine the effects of one serving of alcohol (approximately 15 grams) daily, compared to no alcohol intake, on the rate of new cases of cardiovascular disease and the rate of new cases of diabetes among participants free of diabetes at baseline.

“The study was launched because some epidemiological studies have shown that moderate alcohol consumption has health benefits by reducing risk for coronary artery disease, type 2 diabetes, and rheumatoid arthritis,” according to the NIH statement. “The study aimed to enroll 7,800 participants. After a planning phase, it began enrollment on Feb. 5, 2018, and was suspended on May 10, 2018, at which time there were 105 participants enrolled.”

The trial was being led by researchers at Beth Israel Deaconess Medical Center, Boston.

In response to the public disclosure of the study’s funding, NIH convened a working group to ascertain:

• the circumstances that led to securing private funding for MACH trial
• the scientific premise of and planning for the MACH trial
• the process used to decide to support the MACH trial
• program development and oversight once funding was secured by the secured by the Foundation for NIH (FNIH)
• a review of the NIAAA portfolio prior to and during the leadership of the current NIAAA Director to assess what programmatic shifts, if any, could be discerned.

While noting that public-private partnerships are key to advancing science, the committee found that soliciting funds from alcoholic beverage companies for a study that could prove such beverages are beneficial, crossed the “firewall” between public funds and private resources. The committee recommended terminating the study.

The committee also recommended an expanded investigation into measures that would prevent NIH staff from soliciting external funds to support research programs.

The committee uncovered an email trail strongly suggesting that the solicitation of funds was planned and intended to be secretive.

According to the working group report, there was “frequent email correspondence among members of NIAAA senior staff, select extramural investigators (including the eventual PI of the MACH trial), and industry representatives occurred prior to involvement of the FNIH and the development of the NIH funding opportunity announcement for a multi-site clinical trial on moderate drinking and cardiovascular health. These communications appear to be an attempt to persuade industry to provide funding for the MACH trial. Moreover, these senior members of NIAAA staff appear to have purposefully kept other key members of NIAAA staff and the FNIH ignorant of these efforts. For example, correspondence between NIAAA staff draws attention to a February 2014 wine industry blog that reports that FNIH is initiating a search for industry funding to support a major clinical study on the health effects of moderate alcohol consumption. One senior staff member at NIAAA is unaware of any such potential planning, asking another senior staff member about the article. ‘... Anything seem broken here?’ even though such a trial to test moderate drinking effects on cardiovascular health should very likely involve the programmatic division to which this senior staff member belongs. In response to receiving the forwarded discussion, NIAAA senior leadership communicates among one other, ‘Best not to respond right now but we can’t keep him totally in the dark.’ "

The trial was also funded in part by NIAAA, which expected to commit $20 million to the overall project over 10 years, of which $4 million has been spent.

“The integrity of the NIH grants administrative process, peer review, and the quality of NIH-supported research must always be above reproach,” Dr. Collins said in the statement. “When any problems are uncovered, however, efforts to correct them must be swift and comprehensive.”

[email protected]

The National Institutes of Health is canning a large study on the potential health benefits of moderate alcohol consumption after an advisory committee agreed with reporting by the New York Times that NIH employees and scientists solicited study funds from the alcoholic beverage industry.

NIH Francis Collins, MD, said the ethical violations resulted in a fundamentally flawed study that could not proceed.

“NIH has strong policies that detail the standards of conduct for NIH employees, including prohibiting the solicitation of gifts and promoting fairness in grant competitions. We take very seriously any violations of these standards,” Dr. Collins said in a statement, which added that the agency will take appropriate personnel actions.

While testifying before the Senate Appropriations Committee in mid-May on NIH’s budget request for 2019, Dr. Collins vowed not only to appropriately close the Moderate Alcohol and Cardiovascular Health (MACH) study, but to investigate whether other potential conflicts exist in other NIH-funded studies.

The story broke in mid-March, when The New York Times reported that scientists and officials from the National Institute on Alcohol Abuse and Alcoholism who were working on the MACH trial met at informational sessions with five liquor and beer companies in 2013 and 2014. The officials suggested that “the research might reflect favorably on moderate drinking, while institute officials pressed the groups for support,” according to documents obtained by the Times.

In all, the Times reported, the alcohol companies agreed to foot $67 million of the trial’s total $100 million bill. Such action violates NIH policy. An NIH report named those companies as Anheuser-Busch InBev, Carlsberg Breweries A/S, Diageo plc, Heineken, and Pernod Ricard USA LLC.

The MACH study was a multicenter, randomized clinical trial to determine the effects of one serving of alcohol (approximately 15 grams) daily, compared to no alcohol intake, on the rate of new cases of cardiovascular disease and the rate of new cases of diabetes among participants free of diabetes at baseline.

“The study was launched because some epidemiological studies have shown that moderate alcohol consumption has health benefits by reducing risk for coronary artery disease, type 2 diabetes, and rheumatoid arthritis,” according to the NIH statement. “The study aimed to enroll 7,800 participants. After a planning phase, it began enrollment on Feb. 5, 2018, and was suspended on May 10, 2018, at which time there were 105 participants enrolled.”

The trial was being led by researchers at Beth Israel Deaconess Medical Center, Boston.

In response to the public disclosure of the study’s funding, NIH convened a working group to ascertain:

• the circumstances that led to securing private funding for MACH trial
• the scientific premise of and planning for the MACH trial
• the process used to decide to support the MACH trial
• program development and oversight once funding was secured by the secured by the Foundation for NIH (FNIH)
• a review of the NIAAA portfolio prior to and during the leadership of the current NIAAA Director to assess what programmatic shifts, if any, could be discerned.

While noting that public-private partnerships are key to advancing science, the committee found that soliciting funds from alcoholic beverage companies for a study that could prove such beverages are beneficial, crossed the “firewall” between public funds and private resources. The committee recommended terminating the study.

The committee also recommended an expanded investigation into measures that would prevent NIH staff from soliciting external funds to support research programs.

The committee uncovered an email trail strongly suggesting that the solicitation of funds was planned and intended to be secretive.

According to the working group report, there was “frequent email correspondence among members of NIAAA senior staff, select extramural investigators (including the eventual PI of the MACH trial), and industry representatives occurred prior to involvement of the FNIH and the development of the NIH funding opportunity announcement for a multi-site clinical trial on moderate drinking and cardiovascular health. These communications appear to be an attempt to persuade industry to provide funding for the MACH trial. Moreover, these senior members of NIAAA staff appear to have purposefully kept other key members of NIAAA staff and the FNIH ignorant of these efforts. For example, correspondence between NIAAA staff draws attention to a February 2014 wine industry blog that reports that FNIH is initiating a search for industry funding to support a major clinical study on the health effects of moderate alcohol consumption. One senior staff member at NIAAA is unaware of any such potential planning, asking another senior staff member about the article. ‘... Anything seem broken here?’ even though such a trial to test moderate drinking effects on cardiovascular health should very likely involve the programmatic division to which this senior staff member belongs. In response to receiving the forwarded discussion, NIAAA senior leadership communicates among one other, ‘Best not to respond right now but we can’t keep him totally in the dark.’ "

The trial was also funded in part by NIAAA, which expected to commit $20 million to the overall project over 10 years, of which $4 million has been spent.

“The integrity of the NIH grants administrative process, peer review, and the quality of NIH-supported research must always be above reproach,” Dr. Collins said in the statement. “When any problems are uncovered, however, efforts to correct them must be swift and comprehensive.”

[email protected]

WASHINGTON – Less than a quarter of patients with heartburn that appears refractory to proton pump inhibitor treatment truly have reflux-related, drug-refractory heartburn with a high symptom–related probability, but patients who fall into this select subgroup often have significant symptom relief from surgical fundoplication, based on results from a randomized, multicenter, Department of Veterans Affairs study with 78 patients.

Although laparoscopic Nissen fundoplication relieved the heartburn symptoms of just two-thirds of patients who met the study’s definition of having true proton pump inhibitor (PPI)–refractory heartburn, this level of efficacy far exceeded the impact of drug therapy with baclofen or desipramine, which was little better than placebo, Stuart J. Spechler, MD, said at the annual Digestive Disease Week^®.

Mitchel L. Zoler/MDedge News

“Fundoplication fell out of favor because of the success of PPI treatment, and because of complications from the surgery, but what our results show is that there is a subgroup of patients who can benefit from fundoplication. The challenge is identifying them,” said Dr. Spechler, a gastroenterologist and professor of medicine at the University of Texas, Dallas. “If you go through a careful work-up you will find the patients who have true PPI-refractory acid reflux and heartburn, and in the end we don’t have good medical treatments for these patients,” leaving fundoplication as their best hope for symptom relief.

The study he ran included 366 patients seen at about 30 VA Medical Centers across the United States who had been referred to his center because of presumed PPI-refractory heartburn. The careful work-up that Dr. Spechler and his associates ran included a closely supervised, 2-week trial of a standardized PPI regimen with omeprazole, careful symptom scoring on this treatment with a reflux-specific, health-related quality of life questionnaire, endoscopic esophageal manometry, and esophageal pH monitoring while on omeprazole.

This process placed patients into several distinct subgroups: About 19% dropped out of the study during this assessment, and another 15% left the study because of their intolerance of various stages of the work-up. Nearly 12% of patients wound up being responsive to the PPI regimen, about 6% had organic disorders not related to gastroesophageal reflux disease, and 27% had functional heartburn with a normal level of acid reflux, which left 78 patients (21%) who demonstrated true reflux-related, PPI-refractory heartburn symptoms.

The researchers then randomized this 78-patient subgroup into three treatment arms, with one group of 27 underwent fundoplication surgery. A group of 25 underwent active medical therapy with 20 mg omeprazole b.i.d. plus baclofen, which was started at 5 mg t.i.d. and increased to 20 mg t.i.d. In baclofen-intolerant or nonresponding patients, this treatment was followed up with desipramine, increasing from a starting dosage of 25 mg/day to 100 mg/day. A third group of 26 control patients received active omeprazole at the same dosage but placebo in place of the baclofen and desipramine. These three subgroups showed no statistically significant differences at baseline for all demographic and clinical parameters recorded.

The study’s primary endpoint was the percentage of patients in each treatment arm who had a “successful” outcome, defined as at least a 50% improvement in their gastroesophageal reflux health-related quality of life score (J Gastrointest Surg. 1998 Mar-Apr;2[2]:141-5) after 1 year on treatment, which occurred in 67% of the fundoplication patients, 28% in the active medical arm, and 12% in the control arm. The fundoplication-treated patients had a significantly higher rate of a successful outcome, compared with patients in each of the other two treatment groups, while the success rates among patients in the active medical group and the control group did not differ significantly, Dr. Spechler said.

Dr. Spechler had no disclosures to report.

[email protected]

WASHINGTON – Less than a quarter of patients with heartburn that appears refractory to proton pump inhibitor treatment truly have reflux-related, drug-refractory heartburn with a high symptom–related probability, but patients who fall into this select subgroup often have significant symptom relief from surgical fundoplication, based on results from a randomized, multicenter, Department of Veterans Affairs study with 78 patients.

Although laparoscopic Nissen fundoplication relieved the heartburn symptoms of just two-thirds of patients who met the study’s definition of having true proton pump inhibitor (PPI)–refractory heartburn, this level of efficacy far exceeded the impact of drug therapy with baclofen or desipramine, which was little better than placebo, Stuart J. Spechler, MD, said at the annual Digestive Disease Week^®.

Mitchel L. Zoler/MDedge News

“Fundoplication fell out of favor because of the success of PPI treatment, and because of complications from the surgery, but what our results show is that there is a subgroup of patients who can benefit from fundoplication. The challenge is identifying them,” said Dr. Spechler, a gastroenterologist and professor of medicine at the University of Texas, Dallas. “If you go through a careful work-up you will find the patients who have true PPI-refractory acid reflux and heartburn, and in the end we don’t have good medical treatments for these patients,” leaving fundoplication as their best hope for symptom relief.

The study he ran included 366 patients seen at about 30 VA Medical Centers across the United States who had been referred to his center because of presumed PPI-refractory heartburn. The careful work-up that Dr. Spechler and his associates ran included a closely supervised, 2-week trial of a standardized PPI regimen with omeprazole, careful symptom scoring on this treatment with a reflux-specific, health-related quality of life questionnaire, endoscopic esophageal manometry, and esophageal pH monitoring while on omeprazole.

This process placed patients into several distinct subgroups: About 19% dropped out of the study during this assessment, and another 15% left the study because of their intolerance of various stages of the work-up. Nearly 12% of patients wound up being responsive to the PPI regimen, about 6% had organic disorders not related to gastroesophageal reflux disease, and 27% had functional heartburn with a normal level of acid reflux, which left 78 patients (21%) who demonstrated true reflux-related, PPI-refractory heartburn symptoms.

The researchers then randomized this 78-patient subgroup into three treatment arms, with one group of 27 underwent fundoplication surgery. A group of 25 underwent active medical therapy with 20 mg omeprazole b.i.d. plus baclofen, which was started at 5 mg t.i.d. and increased to 20 mg t.i.d. In baclofen-intolerant or nonresponding patients, this treatment was followed up with desipramine, increasing from a starting dosage of 25 mg/day to 100 mg/day. A third group of 26 control patients received active omeprazole at the same dosage but placebo in place of the baclofen and desipramine. These three subgroups showed no statistically significant differences at baseline for all demographic and clinical parameters recorded.

The study’s primary endpoint was the percentage of patients in each treatment arm who had a “successful” outcome, defined as at least a 50% improvement in their gastroesophageal reflux health-related quality of life score (J Gastrointest Surg. 1998 Mar-Apr;2[2]:141-5) after 1 year on treatment, which occurred in 67% of the fundoplication patients, 28% in the active medical arm, and 12% in the control arm. The fundoplication-treated patients had a significantly higher rate of a successful outcome, compared with patients in each of the other two treatment groups, while the success rates among patients in the active medical group and the control group did not differ significantly, Dr. Spechler said.

Dr. Spechler had no disclosures to report.

[email protected]

WASHINGTON – Less than a quarter of patients with heartburn that appears refractory to proton pump inhibitor treatment truly have reflux-related, drug-refractory heartburn with a high symptom–related probability, but patients who fall into this select subgroup often have significant symptom relief from surgical fundoplication, based on results from a randomized, multicenter, Department of Veterans Affairs study with 78 patients.

Although laparoscopic Nissen fundoplication relieved the heartburn symptoms of just two-thirds of patients who met the study’s definition of having true proton pump inhibitor (PPI)–refractory heartburn, this level of efficacy far exceeded the impact of drug therapy with baclofen or desipramine, which was little better than placebo, Stuart J. Spechler, MD, said at the annual Digestive Disease Week^®.

Mitchel L. Zoler/MDedge News

“Fundoplication fell out of favor because of the success of PPI treatment, and because of complications from the surgery, but what our results show is that there is a subgroup of patients who can benefit from fundoplication. The challenge is identifying them,” said Dr. Spechler, a gastroenterologist and professor of medicine at the University of Texas, Dallas. “If you go through a careful work-up you will find the patients who have true PPI-refractory acid reflux and heartburn, and in the end we don’t have good medical treatments for these patients,” leaving fundoplication as their best hope for symptom relief.

The study he ran included 366 patients seen at about 30 VA Medical Centers across the United States who had been referred to his center because of presumed PPI-refractory heartburn. The careful work-up that Dr. Spechler and his associates ran included a closely supervised, 2-week trial of a standardized PPI regimen with omeprazole, careful symptom scoring on this treatment with a reflux-specific, health-related quality of life questionnaire, endoscopic esophageal manometry, and esophageal pH monitoring while on omeprazole.

This process placed patients into several distinct subgroups: About 19% dropped out of the study during this assessment, and another 15% left the study because of their intolerance of various stages of the work-up. Nearly 12% of patients wound up being responsive to the PPI regimen, about 6% had organic disorders not related to gastroesophageal reflux disease, and 27% had functional heartburn with a normal level of acid reflux, which left 78 patients (21%) who demonstrated true reflux-related, PPI-refractory heartburn symptoms.

The researchers then randomized this 78-patient subgroup into three treatment arms, with one group of 27 underwent fundoplication surgery. A group of 25 underwent active medical therapy with 20 mg omeprazole b.i.d. plus baclofen, which was started at 5 mg t.i.d. and increased to 20 mg t.i.d. In baclofen-intolerant or nonresponding patients, this treatment was followed up with desipramine, increasing from a starting dosage of 25 mg/day to 100 mg/day. A third group of 26 control patients received active omeprazole at the same dosage but placebo in place of the baclofen and desipramine. These three subgroups showed no statistically significant differences at baseline for all demographic and clinical parameters recorded.

The study’s primary endpoint was the percentage of patients in each treatment arm who had a “successful” outcome, defined as at least a 50% improvement in their gastroesophageal reflux health-related quality of life score (J Gastrointest Surg. 1998 Mar-Apr;2[2]:141-5) after 1 year on treatment, which occurred in 67% of the fundoplication patients, 28% in the active medical arm, and 12% in the control arm. The fundoplication-treated patients had a significantly higher rate of a successful outcome, compared with patients in each of the other two treatment groups, while the success rates among patients in the active medical group and the control group did not differ significantly, Dr. Spechler said.

Dr. Spechler had no disclosures to report.

[email protected]

Enteroviruses cause most summer colds. The enteroviruses include echoviruses, coxsackieviruses, numbered enteroviruses, and the polioviruses. Most summer colds seen in private practice are self limited, presenting with fever alone or clinically distinctive pictures such as hand-foot-and-mouth disease (HFMD), herpangina, or pleurodynia. However, enteroviruses also cause serious illnesses such as meningitis, myocarditis, encephalitis, and neonatal sepsis. Enterovirus infections often are confused with bacterial infections and treated unnecessarily with antibiotics.

Enteroviral infections spread predominantly by the fecal-oral route. Contaminated swimming pools also may serve as a source of transmission. Enteroviruses colonize the respiratory and the gastrointestinal tract. The infection spreads to the lymph nodes, where the virus replicates and an initial viremia occurs on approximately the third postexposure day. The viremia results in subsequent spread to the throat (herpangina), and/or hands and feet (HFMD), lungs (pleurodynia), heart (myocarditis) or meninges (viral meningitis). Infection at the secondary sites corresponds to the onset of clinical symptoms 4-6 days after exposure. The clinical manifestations of enteroviral infections result from the damage caused by the virus at the secondary sites of infection.

Lpettet/Getty Images

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He reported having no conflicts of interest. Email him at [email protected].

Enteroviruses cause most summer colds. The enteroviruses include echoviruses, coxsackieviruses, numbered enteroviruses, and the polioviruses. Most summer colds seen in private practice are self limited, presenting with fever alone or clinically distinctive pictures such as hand-foot-and-mouth disease (HFMD), herpangina, or pleurodynia. However, enteroviruses also cause serious illnesses such as meningitis, myocarditis, encephalitis, and neonatal sepsis. Enterovirus infections often are confused with bacterial infections and treated unnecessarily with antibiotics.

Enteroviral infections spread predominantly by the fecal-oral route. Contaminated swimming pools also may serve as a source of transmission. Enteroviruses colonize the respiratory and the gastrointestinal tract. The infection spreads to the lymph nodes, where the virus replicates and an initial viremia occurs on approximately the third postexposure day. The viremia results in subsequent spread to the throat (herpangina), and/or hands and feet (HFMD), lungs (pleurodynia), heart (myocarditis) or meninges (viral meningitis). Infection at the secondary sites corresponds to the onset of clinical symptoms 4-6 days after exposure. The clinical manifestations of enteroviral infections result from the damage caused by the virus at the secondary sites of infection.

Lpettet/Getty Images

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He reported having no conflicts of interest. Email him at [email protected].

Enteroviruses cause most summer colds. The enteroviruses include echoviruses, coxsackieviruses, numbered enteroviruses, and the polioviruses. Most summer colds seen in private practice are self limited, presenting with fever alone or clinically distinctive pictures such as hand-foot-and-mouth disease (HFMD), herpangina, or pleurodynia. However, enteroviruses also cause serious illnesses such as meningitis, myocarditis, encephalitis, and neonatal sepsis. Enterovirus infections often are confused with bacterial infections and treated unnecessarily with antibiotics.

Enteroviral infections spread predominantly by the fecal-oral route. Contaminated swimming pools also may serve as a source of transmission. Enteroviruses colonize the respiratory and the gastrointestinal tract. The infection spreads to the lymph nodes, where the virus replicates and an initial viremia occurs on approximately the third postexposure day. The viremia results in subsequent spread to the throat (herpangina), and/or hands and feet (HFMD), lungs (pleurodynia), heart (myocarditis) or meninges (viral meningitis). Infection at the secondary sites corresponds to the onset of clinical symptoms 4-6 days after exposure. The clinical manifestations of enteroviral infections result from the damage caused by the virus at the secondary sites of infection.

Lpettet/Getty Images

Dr. Pichichero is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He reported having no conflicts of interest. Email him at [email protected].

Immunohistochemical panels used in the diagnosis of mantle cell lymphoma should include cyclin D1 and SOX11 immunostaining, according to a good practice paper from the British Society of Haematology.

Pamela McKay, MD, of the Beatson West of Scotland Cancer Centre, Glasgow, and her colleagues provided updated recommendations on diagnosis and staging of mantle cell lymphoma (MCL) based on a review of literature from 1980 to 2017. The good practice paper aims to offer best practice advice based on consensus where the evidence is limited. Specifically, the paper incorporates new information on molecular pathology and the use of positron emission tomography/computed tomography (PET/CT) scanning in staging of disease.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The top recommendations related to MCL diagnosis include performing lymph node excision or adequate core biopsy for diagnosis of nodal MCL. For non-nodal presentation, a tissue biopsy or peripheral blood can be used. Additionally, immunohistochemical panels should include cyclin D1 and SOX11 immunostaining.

In cases of atypical morphology, aberrant immunophenotype, equivocal cyclin D1 positivity, or unusual clinical presentation, the authors recommended fluorescence in situ hybridization (FISH) to demonstrate the presence of the t(11;14) translocation. They also recommended recording the Ki67 Proliferation Index at baseline, with an index of greater than 30% being indicative of a poorer outcome.

In terms of staging disease, Dr. McKay and her associates recommended that patients undergo staging with CT of the neck, chest, abdomen, and pelvis. They recommended against routine use of fluorodeoxyglucose PET for MCL staging, but said it could be considered if radical radiotherapy is being proposed for early-stage disease.

For cases with suspicion of central nervous system involvement, lumbar puncture with cytospin and immunophenotyping is recommended.

They recommended that all MCL patients have either their simplified or combined MCL international prognostic index score recorded at baseline.

All the authors made a declaration of interest to the British Society of Haematology and task force chairs, which may be viewed on request.

[email protected]

SOURCE: McKay P et al. Br J Haematol. 2018 Jun 8. doi: 10.1111/bjh.15281.

Immunohistochemical panels used in the diagnosis of mantle cell lymphoma should include cyclin D1 and SOX11 immunostaining, according to a good practice paper from the British Society of Haematology.

Pamela McKay, MD, of the Beatson West of Scotland Cancer Centre, Glasgow, and her colleagues provided updated recommendations on diagnosis and staging of mantle cell lymphoma (MCL) based on a review of literature from 1980 to 2017. The good practice paper aims to offer best practice advice based on consensus where the evidence is limited. Specifically, the paper incorporates new information on molecular pathology and the use of positron emission tomography/computed tomography (PET/CT) scanning in staging of disease.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The top recommendations related to MCL diagnosis include performing lymph node excision or adequate core biopsy for diagnosis of nodal MCL. For non-nodal presentation, a tissue biopsy or peripheral blood can be used. Additionally, immunohistochemical panels should include cyclin D1 and SOX11 immunostaining.

In cases of atypical morphology, aberrant immunophenotype, equivocal cyclin D1 positivity, or unusual clinical presentation, the authors recommended fluorescence in situ hybridization (FISH) to demonstrate the presence of the t(11;14) translocation. They also recommended recording the Ki67 Proliferation Index at baseline, with an index of greater than 30% being indicative of a poorer outcome.

In terms of staging disease, Dr. McKay and her associates recommended that patients undergo staging with CT of the neck, chest, abdomen, and pelvis. They recommended against routine use of fluorodeoxyglucose PET for MCL staging, but said it could be considered if radical radiotherapy is being proposed for early-stage disease.

For cases with suspicion of central nervous system involvement, lumbar puncture with cytospin and immunophenotyping is recommended.

They recommended that all MCL patients have either their simplified or combined MCL international prognostic index score recorded at baseline.

All the authors made a declaration of interest to the British Society of Haematology and task force chairs, which may be viewed on request.

[email protected]

SOURCE: McKay P et al. Br J Haematol. 2018 Jun 8. doi: 10.1111/bjh.15281.

Immunohistochemical panels used in the diagnosis of mantle cell lymphoma should include cyclin D1 and SOX11 immunostaining, according to a good practice paper from the British Society of Haematology.

Pamela McKay, MD, of the Beatson West of Scotland Cancer Centre, Glasgow, and her colleagues provided updated recommendations on diagnosis and staging of mantle cell lymphoma (MCL) based on a review of literature from 1980 to 2017. The good practice paper aims to offer best practice advice based on consensus where the evidence is limited. Specifically, the paper incorporates new information on molecular pathology and the use of positron emission tomography/computed tomography (PET/CT) scanning in staging of disease.

Wikimedia Commons/TexasPathologistMSW/CC-ASA 4.0 International

The top recommendations related to MCL diagnosis include performing lymph node excision or adequate core biopsy for diagnosis of nodal MCL. For non-nodal presentation, a tissue biopsy or peripheral blood can be used. Additionally, immunohistochemical panels should include cyclin D1 and SOX11 immunostaining.

In cases of atypical morphology, aberrant immunophenotype, equivocal cyclin D1 positivity, or unusual clinical presentation, the authors recommended fluorescence in situ hybridization (FISH) to demonstrate the presence of the t(11;14) translocation. They also recommended recording the Ki67 Proliferation Index at baseline, with an index of greater than 30% being indicative of a poorer outcome.

In terms of staging disease, Dr. McKay and her associates recommended that patients undergo staging with CT of the neck, chest, abdomen, and pelvis. They recommended against routine use of fluorodeoxyglucose PET for MCL staging, but said it could be considered if radical radiotherapy is being proposed for early-stage disease.

For cases with suspicion of central nervous system involvement, lumbar puncture with cytospin and immunophenotyping is recommended.

They recommended that all MCL patients have either their simplified or combined MCL international prognostic index score recorded at baseline.

All the authors made a declaration of interest to the British Society of Haematology and task force chairs, which may be viewed on request.

[email protected]

SOURCE: McKay P et al. Br J Haematol. 2018 Jun 8. doi: 10.1111/bjh.15281.

AMSTERDAM – Mining of the Food and Drug Administration adverse events database revealed a more substantial risk of rheumatic and musculoskeletal events on checkpoint inhibitor therapy than has been previously reported, according to Xerxes N. Pundole, PhD, an instructor in the research faculty at the University of Texas MD Anderson Cancer Center, Houston.

In a video interview, Dr. Pundole summarized data he presented at the European Congress of Rheumatology.

So far, according to Dr. Pundole, there have been a relatively limited number of reports in the medical literature of inflammatory rheumatic or musculoskeletal events from checkpoint inhibitors. However, other inflammatory conditions, such as colitis and pneumonitis, are known to occur commonly with these agents. The FDA adverse event database provided an opportunity to evaluate how often rheumatic and musculoskeletal events are reported in the real world.

In this interview, Dr. Pundole explained that rheumatic and musculoskeletal events do occur at higher rates than would be expected in patients not treated with a checkpoint inhibitor. With data from more than 30,000 unique patients, the relative risks of some of these adverse events, such as polymyositis, were more than doubled, although the event rates were not evenly distributed.

Specifically, rheumatic and musculoskeletal adverse events were far less common with the cytotoxic T-lymphocyte antigen 4 checkpoint inhibitor ipilimumab (Yervoy) relative to programmed cell death protein 1 inhibitors, particularly nivolumab (Opdivo).

In another notable finding, a demographic stratification of the FDA database found elderly men to be overrepresented among patients developing adverse events related to musculoskeletal inflammation.

Overall, his data do support a relationship between checkpoint inhibitors and a greater risk of rheumatic and musculoskeletal adverse events than has been previously reported, but he noted that these data provide no specific guidance for those who already have RA or another inflammatory condition.

“Can you identify these adverse events early on to keep the patients on immune checkpoint inhibitor therapy and not have to stop their cancer treatment? That’s a question,” Dr. Pundole said. However, he suggested that the FDA data support clinician awareness of the problem and the studies that will establish strategies for preserving the benefit-to-risk ratio of checkpoint inhibitors in patients who are at greater risk of adverse events relative to immune function because of a preexisting inflammatory condition.

SOURCE: Pundole XN et al. Ann Rheum Dis. 2018;77(Suppl 2):147-148. Abstract OP0197.

AMSTERDAM – Mining of the Food and Drug Administration adverse events database revealed a more substantial risk of rheumatic and musculoskeletal events on checkpoint inhibitor therapy than has been previously reported, according to Xerxes N. Pundole, PhD, an instructor in the research faculty at the University of Texas MD Anderson Cancer Center, Houston.

In a video interview, Dr. Pundole summarized data he presented at the European Congress of Rheumatology.

So far, according to Dr. Pundole, there have been a relatively limited number of reports in the medical literature of inflammatory rheumatic or musculoskeletal events from checkpoint inhibitors. However, other inflammatory conditions, such as colitis and pneumonitis, are known to occur commonly with these agents. The FDA adverse event database provided an opportunity to evaluate how often rheumatic and musculoskeletal events are reported in the real world.

In this interview, Dr. Pundole explained that rheumatic and musculoskeletal events do occur at higher rates than would be expected in patients not treated with a checkpoint inhibitor. With data from more than 30,000 unique patients, the relative risks of some of these adverse events, such as polymyositis, were more than doubled, although the event rates were not evenly distributed.

Specifically, rheumatic and musculoskeletal adverse events were far less common with the cytotoxic T-lymphocyte antigen 4 checkpoint inhibitor ipilimumab (Yervoy) relative to programmed cell death protein 1 inhibitors, particularly nivolumab (Opdivo).

In another notable finding, a demographic stratification of the FDA database found elderly men to be overrepresented among patients developing adverse events related to musculoskeletal inflammation.

Overall, his data do support a relationship between checkpoint inhibitors and a greater risk of rheumatic and musculoskeletal adverse events than has been previously reported, but he noted that these data provide no specific guidance for those who already have RA or another inflammatory condition.

“Can you identify these adverse events early on to keep the patients on immune checkpoint inhibitor therapy and not have to stop their cancer treatment? That’s a question,” Dr. Pundole said. However, he suggested that the FDA data support clinician awareness of the problem and the studies that will establish strategies for preserving the benefit-to-risk ratio of checkpoint inhibitors in patients who are at greater risk of adverse events relative to immune function because of a preexisting inflammatory condition.

SOURCE: Pundole XN et al. Ann Rheum Dis. 2018;77(Suppl 2):147-148. Abstract OP0197.

AMSTERDAM – Mining of the Food and Drug Administration adverse events database revealed a more substantial risk of rheumatic and musculoskeletal events on checkpoint inhibitor therapy than has been previously reported, according to Xerxes N. Pundole, PhD, an instructor in the research faculty at the University of Texas MD Anderson Cancer Center, Houston.

In a video interview, Dr. Pundole summarized data he presented at the European Congress of Rheumatology.

So far, according to Dr. Pundole, there have been a relatively limited number of reports in the medical literature of inflammatory rheumatic or musculoskeletal events from checkpoint inhibitors. However, other inflammatory conditions, such as colitis and pneumonitis, are known to occur commonly with these agents. The FDA adverse event database provided an opportunity to evaluate how often rheumatic and musculoskeletal events are reported in the real world.

In this interview, Dr. Pundole explained that rheumatic and musculoskeletal events do occur at higher rates than would be expected in patients not treated with a checkpoint inhibitor. With data from more than 30,000 unique patients, the relative risks of some of these adverse events, such as polymyositis, were more than doubled, although the event rates were not evenly distributed.

Specifically, rheumatic and musculoskeletal adverse events were far less common with the cytotoxic T-lymphocyte antigen 4 checkpoint inhibitor ipilimumab (Yervoy) relative to programmed cell death protein 1 inhibitors, particularly nivolumab (Opdivo).

In another notable finding, a demographic stratification of the FDA database found elderly men to be overrepresented among patients developing adverse events related to musculoskeletal inflammation.

Overall, his data do support a relationship between checkpoint inhibitors and a greater risk of rheumatic and musculoskeletal adverse events than has been previously reported, but he noted that these data provide no specific guidance for those who already have RA or another inflammatory condition.

“Can you identify these adverse events early on to keep the patients on immune checkpoint inhibitor therapy and not have to stop their cancer treatment? That’s a question,” Dr. Pundole said. However, he suggested that the FDA data support clinician awareness of the problem and the studies that will establish strategies for preserving the benefit-to-risk ratio of checkpoint inhibitors in patients who are at greater risk of adverse events relative to immune function because of a preexisting inflammatory condition.

SOURCE: Pundole XN et al. Ann Rheum Dis. 2018;77(Suppl 2):147-148. Abstract OP0197.

The Food and Drug Administration has approved the first generic versions of Suboxone (buprenorphine and naloxone) sublingual film for the medication-assisted treatment of opioid dependence.

Medication-assisted treatment (MAT) combines approved medication, such as methadone, buprenorphine, or naltrexone, with counseling and other behavioral therapies to treat opioid use disorders. Suboxone adherence reduces opioid withdrawal symptoms, the desire to use opioid, and the pleasurable effects of opioid use. Patients who receive MAT reduce their risk of death from all causes by about 50%.

Wikimedia Commons/FitzColinGerald/Creative Commons License

“The FDA is taking new steps to advance the development of improved treatments for opioid use disorder and to make sure these medicines are accessible to the patients who need them. That includes promoting the development of better drugs and also facilitating market entry of generic versions of approved drugs to help ensure broader access,” FDA Commissioner Scott Gottlieb, MD, said in the June 14 press release.

The approval to market Suboxone generics, at multiple strengths, has been granted to Mylan Technologies and Dr. Reddy’s Laboratories.

The agency said data from the Substance Abuse and Mental Health Services Administration show that patients who receive MAT as an intervention for opioid use reduce their risk of death from all causes by 50%.

Common adverse events associated with Suboxone include oral hypoesthesia, glossodynia, oral mucosal erythema, headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, pain, and peripheral edema.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration has approved the first generic versions of Suboxone (buprenorphine and naloxone) sublingual film for the medication-assisted treatment of opioid dependence.

Medication-assisted treatment (MAT) combines approved medication, such as methadone, buprenorphine, or naltrexone, with counseling and other behavioral therapies to treat opioid use disorders. Suboxone adherence reduces opioid withdrawal symptoms, the desire to use opioid, and the pleasurable effects of opioid use. Patients who receive MAT reduce their risk of death from all causes by about 50%.

Wikimedia Commons/FitzColinGerald/Creative Commons License

“The FDA is taking new steps to advance the development of improved treatments for opioid use disorder and to make sure these medicines are accessible to the patients who need them. That includes promoting the development of better drugs and also facilitating market entry of generic versions of approved drugs to help ensure broader access,” FDA Commissioner Scott Gottlieb, MD, said in the June 14 press release.

The approval to market Suboxone generics, at multiple strengths, has been granted to Mylan Technologies and Dr. Reddy’s Laboratories.

The agency said data from the Substance Abuse and Mental Health Services Administration show that patients who receive MAT as an intervention for opioid use reduce their risk of death from all causes by 50%.

Common adverse events associated with Suboxone include oral hypoesthesia, glossodynia, oral mucosal erythema, headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, pain, and peripheral edema.

Find the full press release on the FDA website.

[email protected]

The Food and Drug Administration has approved the first generic versions of Suboxone (buprenorphine and naloxone) sublingual film for the medication-assisted treatment of opioid dependence.

Medication-assisted treatment (MAT) combines approved medication, such as methadone, buprenorphine, or naltrexone, with counseling and other behavioral therapies to treat opioid use disorders. Suboxone adherence reduces opioid withdrawal symptoms, the desire to use opioid, and the pleasurable effects of opioid use. Patients who receive MAT reduce their risk of death from all causes by about 50%.

Wikimedia Commons/FitzColinGerald/Creative Commons License

“The FDA is taking new steps to advance the development of improved treatments for opioid use disorder and to make sure these medicines are accessible to the patients who need them. That includes promoting the development of better drugs and also facilitating market entry of generic versions of approved drugs to help ensure broader access,” FDA Commissioner Scott Gottlieb, MD, said in the June 14 press release.

The approval to market Suboxone generics, at multiple strengths, has been granted to Mylan Technologies and Dr. Reddy’s Laboratories.

The agency said data from the Substance Abuse and Mental Health Services Administration show that patients who receive MAT as an intervention for opioid use reduce their risk of death from all causes by 50%.

Common adverse events associated with Suboxone include oral hypoesthesia, glossodynia, oral mucosal erythema, headache, nausea, vomiting, hyperhidrosis, constipation, signs and symptoms of withdrawal, insomnia, pain, and peripheral edema.

Find the full press release on the FDA website.

[email protected]