Original Article
Optimizing Care With a Standardized Management Protocol for Patients With Infantile Spasms
Journal of Child Neurology 1-3 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073814562251 jcn.sagepub.com
Erin M. Fedak, DO1, Anup D. Patel, MD1, Geoffrey L. Heyer, MD1, Eric G. Wood, MBA2, and John R. Mytinger, MD1
Abstract The primary aim of this quality improvement initiative was to increase the number of patients receiving first-line therapy (adrenocorticotropic hormone, corticosteroids, vigabatrin) as the initial treatment for infantile spasms. We implemented a standardized management protocol for infantile spasms based on the best available data and expert consensus. To assess the impact of this intervention, we compared the 3-month remission rates between prestandardization (January 2009 to August 2012) and poststandardization (September 2012 to May 2014) cohorts. We found that the percentage of patients receiving first-line therapy as the initial treatment was 57% (31/54) in the prestandardization cohort and 100% (35/35) in the poststandardization cohort (P < .001). The rate of infantile spasms remission was higher poststandardization compared to prestandardization (78.8% vs 30.6%, P < .001). Management standardization led to all patients receiving first-line therapy as the initial treatment and was associated with a significantly improved rate of infantile spasms remission 3 months after diagnosis. Keywords quality improvement, standardization, infantile spasms, West syndrome Received June 01, 2014. Received revised October 06, 2014. Accepted for publication November 09, 2014.
Infantile spasms are seizures that frequently occur in the setting of West syndrome—a severe infantile epileptic encephalopathy typically affecting infants 3 to 12 months of age. Developmental outcome is largely dependent on the underlying etiology for seizures as well as the timing of diagnosis and the effectiveness of treatment.1,2 Although data are limited, the 3 treatments with greater than Class IV evidence to support their use for infantile spasms are adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin.3,4 A 2012 survey about the treatment of infantile spasms found that ACTH was the most commonly used initial therapy for infantile spasms, not due to tuberous sclerosis complex.5 Other commonly used treatments were oral corticosteroids, vigabatrin, and topiramate.5 As part of a quality improvement initiative, we implemented a standardized management protocol for the treatment of infantile spasms based on the best available data and expert consensus.3,4,6 The primary aim of this project was to assure that all patients receive first-line therapy as the initial treatment for infantile spasms. To further assess the impact of this intervention, we compared the rate of infantile spasms remission 3 months after diagnosis between pre- and poststandardization cohorts. Our secondary aim was to reduce the diagnostic admission length of stay through early diagnosis and treatment.
Methods We incorporated SQUIRE (Standards for Quality Improvement Reporting Excellence) guidelines7 in the construction of this manuscript. This study included all patients diagnosed and treated for infantile spasms at Nationwide Children’s Hospital from January 2009 to May 2014. Subjects were identified using an EEG database (search terms: hypsarrhythmia and infantile spasms) and hospital discharge codes (345.60, 345.61). The diagnosis was confirmed after independent retrospective chart review by 2 of the authors (EMF, JRM). Patients were grouped into prestandardization (January 2009 to August 2012) and poststandardization (September 2012 to May 2014) cohorts. Patients who were initially treated at an outside hospital were excluded. All patients who were admitted to our hospital at the time of diagnosis were included in the length of stay analysis. Clinical remission was assigned if the patient was free of infantile spasms
1
Department of Pediatrics, Division of Pediatric Neurology, The Ohio State University, Nationwide Children’s Hospital 2 Department of Quality Improvement Services, Nationwide Children’s Hospital Corresponding Author: John R. Mytinger, MD, Ohio State University, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA. Email: [email protected]
Downloaded from jcn.sagepub.com at TULANE UNIV on December 29, 2014
2
Journal of Child Neurology
Table 1. Initial Treatment Allocations as a Function of Standardization.a Prestandardization cohort (n ¼ 54) ACTH Corticosteroids Vigabatrin Topiramate Levetiracetam Topiramate and levetiracetam Zonisamide Oxcarbazepine
21 7 3 11 8 2
(38.9) (13) (5.6) (20.4) (14.8) (3.7)
1 (1.8) 1 (1.8)
Table 2. Median LOS as a Function of Cohort and Initial Treatment. LOS all LOS LOS Prestandardization Poststandardization patients (median d) (median d) (median d)
Poststandardization cohort (n ¼ 35) 17 (48.6) 6 (17.1) 12 (34.3) 0 0 0 0 0
All treatments ACTH Corticosteroids Vigabatrin Other
3.6 5.2 1.9 2.5 2
4 5 2.8 2.2 n/a
3.9 5.1 2.2 2.4 2
Abbreviations: ACTH, adrenocorticotropic hormone; LOS, length of stay; d, days; n/a, not applicable.
the median length of stay for oral corticosteroids was lower than the length of stay for ACTH (2.2 days vs 5.1 days, P < .001) despite similar monitoring and caregiver education.
Abbreviation: ACTH, adrenocorticotropic hormone. a Data are n (%).
for at least the previous 28 days leading up to a time point 3 months after diagnosis. Given that ACTH, corticosteroids, and vigabatrin are the only 3 therapies for infantile spasms with greater than Class IV evidence to support their use, our standardized management protocol included a recommendation for 1 of these treatments as initial therapy. Vigabatrin was recommended for infantile spasms due to tuberous sclerosis complex. For children without tuberous sclerosis complex, families were offered any 1 of these ‘‘first-line’’ therapies.
Statistical Analysis Categorical variables were compared using the Pearson chi-square test; continuous variables were compared using the Mann-Whitney U test. Statistical significance was set at 5%. All statistics were performed using SPSS Version 21 (SPSS Inc, Chicago, IL).
Results Four patients who were initially treated at an outside institution were excluded from the analysis, leaving 89 patients (54 prestandardization and 35 poststandardization) with initial treatment decisions analyzed. Patients were grouped by pre- or poststandardization and by initial treatment: ACTH, corticosteroids, vigabatrin, or other. Initial treatment allocation is seen in Table 1. The percentage of patients receiving first-line therapy as initial treatment was 57% (31/54) prestandardization and 100% (35/35) poststandardization (P < .001). Remission of infantile spasms could not be determined from chart review in 7 patients. Of those remaining, remission rates were higher in the poststandardization cohort (26/33, 78.8%) compared to the prestandardization cohort (15/49, 30.6%; P < .001). There was no significant difference in the median diagnostic admission length of stay between pre- and poststandardization cohorts even when analyzed by treatment type (data not shown). Length of stay by cohort and treatment allocation is seen in Table 2. The longest length of stay in both groups occurred in patients treated with ACTH and management standardization did not reduce length of stay. For the entire cohort,
Discussion This quality improvement initiative was successful insofar as the implementation of a standardized management protocol for infantile spasms improved the percentage of patients receiving first-line therapy from 57% to 100%. The initial use of first-line therapies may have contributed to the significantly improved rate of infantile spasms remission 3 months after diagnosis (78.8% poststandardization vs 30.6% prestandardization). However, our management protocol includes other features that also likely improved remission rates. For example, our protocol emphasizes early (eg, 2 weeks) changes in treatment if a therapy is deemed ineffective. A patient in the poststandardization protocol could receive up to 3 treatments in less than 8 weeks. Thus, our reported remission rate may not reflect the response to the initial treatment but instead reflects management over a 3-month period. Challenges to the implementation of a standardized management protocol include the education and the support of colleagues within a practice. This can be a daunting task given the variability in the treatment of infantile spasms. However, in our large practice of 20 child neurologists and 6 nurse practitioners, we were able to achieve agreement on this initiative. Despite the implementation of our management protocol, we did not reduce the diagnostic admission length of stay. This may relate to our small sample size and the already relatively low prestandardization length of stay. We noted that ACTH admissions had the longest length of stay. Despite similar monitoring and education with corticosteroids, the median ACTH admission length of stay (5.1 days) was nearly 3 days longer than the median corticosteroid admission length of stay (2.2 days). We attribute this discrepancy to the requirement for ACTH insurance authorization prior to hospital discharge, which is consistent with the findings from a small retrospective study that reported a longer length of stay after the ACTH price increase in 2007.8 Our project has several limitations. In many circumstances, we were unable to document the clinical reasoning behind the choice of initial treatment in the prestandardization cohort.
Downloaded from jcn.sagepub.com at TULANE UNIV on December 29, 2014
Fedak et al
3
Some families may have feared the possible side effects associated with ACTH, corticosteroids, or vigabatrin and may have requested an alternative treatment. Counseling families after protocol implementation likely influenced decisions about treatment. For example, that we designated vigabatrin as a first-line treatment option may explain why it was used more often in the poststandardization cohort. Differences between the 2004 and the 2012 infantile spasms practice parameters from the American Academy of Neurology and the Child Neurology Society could have also influenced treatment decisions. However, the only change relevant to our manuscript was the addition of Class III evidence for the use of higher-dose oral corticosteroids in the 2012 update.4 This change would not explain the frequent use of non-first-line therapy in the prestandardization cohort. In regard to our assessment of infantile spasms remission, we were unable to confirm the presence or absence of infantile spasms remission in 7 patients secondary to either insufficient documentation or ongoing spells of uncertain significance. Our inability to confirm electrographic improvement in the prestandardization cohort is also a study limitation. In contrast, all patients in the poststandardization cohort had adequate EEG data. Of the 26 patients in the poststandardization cohort in clinical remission at 3 months, 24 had electrographic remission as well. Twenty of 26 had posttreatment EEG monitoring that extended overnight. Overnight EEG to confirm electroclinical remission was not available for 5 patients in the poststandardization cohort because we did not introduce this practice to our management protocol until March of 2013. Since that time, only 1 additional patient with electroclinical remission (based on caregiver reporting and a 60-minute EEG with sleep) did not receive an overnight EEG for other clinical reasons. Our standardized infantile spasms management protocol increased the percentage of patients who received first-line therapy as the initial treatment of infantile spasms, was associated with an improved remission rate 3 months after diagnosis, but did not reduce the diagnostic admission length of stay. Diagnostic admissions in which ACTH was chosen were associated with a longer median length of stay than with corticosteroids, which is likely explained by the need for ACTH insurance approval prior to hospital discharge. Future quality improvement initiatives should target length of stay optimization with ACTH treatment. Acknowledgments This work was performed at Nationwide Children’s Hospital in Columbus Ohio.
Author Contributions EMF wrote the initial manuscript draft. EMF, ADP, and JRM were responsible for project conception/design. EMF, EW, and JRM acquired the data. GLH performed statistical analysis and JRM was responsible for project mentorship. All study authors analyzed and interpreted the data and revised the manuscript.
Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval The internal review board at Nationwide Children’s Hospital does not require approval for quality improvement projects.
References 1. Riikonen R. Long-term outcome of patients with West syndrome. Brain Dev. 2001;23:683-687. 2. Kivity S, Lerman P, Ariel R, et al. Long-term cognitive outcomes of a cohort of children with cryptogenic infantile spasms treated with high-dose adrenocorticotropic hormone. Epilepsia. 2004;45: 255-262. 3. Mackay MT, Weiss SK, Adams-Webber T, et al. Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology. 2004;62:1668-1681. 4. Go CY, Mackay MT, Weiss SK, et al. Evidence-based guideline update: medical treatment of infantile spasms. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2012;78:1974-1980. 5. Mytinger JR, Joshi S, Pediatric Epilepsy Research Consortium, Section on Infantile Spasms. The current evaluation and treatment of infantile spasms among members of the Child Neurology Society. J Child Neurol. 2012;27:1289-1294. 6. Pellock JM, Hrachovy R, Shinnar S, et al. Infantile spasms: a U.S. consensus report. Epilepsia. 2010;51:2175-2189. 7. Davidoff F, Batalden P, Stevens D, et al. Publication guidelines for quality improvement studies in health care: evolution of the SQUIRE project. BMJ. 2009;338:a3152. 8. Wray CD, Benke TA. Effect of price increase of adrenocorticotropic hormone on treatment practices of infantile spasms. Pediatr Neurol. 2010;43:163-166.
Downloaded from jcn.sagepub.com at TULANE UNIV on December 29, 2014
Optimizing Care With a Standardized Management Protocol for Patients With Infantile Spasms
Journal of Child Neurology 1-3 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0883073814562251 jcn.sagepub.com
Erin M. Fedak, DO1, Anup D. Patel, MD1, Geoffrey L. Heyer, MD1, Eric G. Wood, MBA2, and John R. Mytinger, MD1
Abstract The primary aim of this quality improvement initiative was to increase the number of patients receiving first-line therapy (adrenocorticotropic hormone, corticosteroids, vigabatrin) as the initial treatment for infantile spasms. We implemented a standardized management protocol for infantile spasms based on the best available data and expert consensus. To assess the impact of this intervention, we compared the 3-month remission rates between prestandardization (January 2009 to August 2012) and poststandardization (September 2012 to May 2014) cohorts. We found that the percentage of patients receiving first-line therapy as the initial treatment was 57% (31/54) in the prestandardization cohort and 100% (35/35) in the poststandardization cohort (P < .001). The rate of infantile spasms remission was higher poststandardization compared to prestandardization (78.8% vs 30.6%, P < .001). Management standardization led to all patients receiving first-line therapy as the initial treatment and was associated with a significantly improved rate of infantile spasms remission 3 months after diagnosis. Keywords quality improvement, standardization, infantile spasms, West syndrome Received June 01, 2014. Received revised October 06, 2014. Accepted for publication November 09, 2014.
Infantile spasms are seizures that frequently occur in the setting of West syndrome—a severe infantile epileptic encephalopathy typically affecting infants 3 to 12 months of age. Developmental outcome is largely dependent on the underlying etiology for seizures as well as the timing of diagnosis and the effectiveness of treatment.1,2 Although data are limited, the 3 treatments with greater than Class IV evidence to support their use for infantile spasms are adrenocorticotropic hormone (ACTH), oral corticosteroids, and vigabatrin.3,4 A 2012 survey about the treatment of infantile spasms found that ACTH was the most commonly used initial therapy for infantile spasms, not due to tuberous sclerosis complex.5 Other commonly used treatments were oral corticosteroids, vigabatrin, and topiramate.5 As part of a quality improvement initiative, we implemented a standardized management protocol for the treatment of infantile spasms based on the best available data and expert consensus.3,4,6 The primary aim of this project was to assure that all patients receive first-line therapy as the initial treatment for infantile spasms. To further assess the impact of this intervention, we compared the rate of infantile spasms remission 3 months after diagnosis between pre- and poststandardization cohorts. Our secondary aim was to reduce the diagnostic admission length of stay through early diagnosis and treatment.
Methods We incorporated SQUIRE (Standards for Quality Improvement Reporting Excellence) guidelines7 in the construction of this manuscript. This study included all patients diagnosed and treated for infantile spasms at Nationwide Children’s Hospital from January 2009 to May 2014. Subjects were identified using an EEG database (search terms: hypsarrhythmia and infantile spasms) and hospital discharge codes (345.60, 345.61). The diagnosis was confirmed after independent retrospective chart review by 2 of the authors (EMF, JRM). Patients were grouped into prestandardization (January 2009 to August 2012) and poststandardization (September 2012 to May 2014) cohorts. Patients who were initially treated at an outside hospital were excluded. All patients who were admitted to our hospital at the time of diagnosis were included in the length of stay analysis. Clinical remission was assigned if the patient was free of infantile spasms
1
Department of Pediatrics, Division of Pediatric Neurology, The Ohio State University, Nationwide Children’s Hospital 2 Department of Quality Improvement Services, Nationwide Children’s Hospital Corresponding Author: John R. Mytinger, MD, Ohio State University, Nationwide Children’s Hospital, 700 Children’s Drive, Columbus, OH 43205, USA. Email: [email protected]
Downloaded from jcn.sagepub.com at TULANE UNIV on December 29, 2014
2
Journal of Child Neurology
Table 1. Initial Treatment Allocations as a Function of Standardization.a Prestandardization cohort (n ¼ 54) ACTH Corticosteroids Vigabatrin Topiramate Levetiracetam Topiramate and levetiracetam Zonisamide Oxcarbazepine
21 7 3 11 8 2
(38.9) (13) (5.6) (20.4) (14.8) (3.7)
1 (1.8) 1 (1.8)
Table 2. Median LOS as a Function of Cohort and Initial Treatment. LOS all LOS LOS Prestandardization Poststandardization patients (median d) (median d) (median d)
Poststandardization cohort (n ¼ 35) 17 (48.6) 6 (17.1) 12 (34.3) 0 0 0 0 0
All treatments ACTH Corticosteroids Vigabatrin Other
3.6 5.2 1.9 2.5 2
4 5 2.8 2.2 n/a
3.9 5.1 2.2 2.4 2
Abbreviations: ACTH, adrenocorticotropic hormone; LOS, length of stay; d, days; n/a, not applicable.
the median length of stay for oral corticosteroids was lower than the length of stay for ACTH (2.2 days vs 5.1 days, P < .001) despite similar monitoring and caregiver education.
Abbreviation: ACTH, adrenocorticotropic hormone. a Data are n (%).
for at least the previous 28 days leading up to a time point 3 months after diagnosis. Given that ACTH, corticosteroids, and vigabatrin are the only 3 therapies for infantile spasms with greater than Class IV evidence to support their use, our standardized management protocol included a recommendation for 1 of these treatments as initial therapy. Vigabatrin was recommended for infantile spasms due to tuberous sclerosis complex. For children without tuberous sclerosis complex, families were offered any 1 of these ‘‘first-line’’ therapies.
Statistical Analysis Categorical variables were compared using the Pearson chi-square test; continuous variables were compared using the Mann-Whitney U test. Statistical significance was set at 5%. All statistics were performed using SPSS Version 21 (SPSS Inc, Chicago, IL).
Results Four patients who were initially treated at an outside institution were excluded from the analysis, leaving 89 patients (54 prestandardization and 35 poststandardization) with initial treatment decisions analyzed. Patients were grouped by pre- or poststandardization and by initial treatment: ACTH, corticosteroids, vigabatrin, or other. Initial treatment allocation is seen in Table 1. The percentage of patients receiving first-line therapy as initial treatment was 57% (31/54) prestandardization and 100% (35/35) poststandardization (P < .001). Remission of infantile spasms could not be determined from chart review in 7 patients. Of those remaining, remission rates were higher in the poststandardization cohort (26/33, 78.8%) compared to the prestandardization cohort (15/49, 30.6%; P < .001). There was no significant difference in the median diagnostic admission length of stay between pre- and poststandardization cohorts even when analyzed by treatment type (data not shown). Length of stay by cohort and treatment allocation is seen in Table 2. The longest length of stay in both groups occurred in patients treated with ACTH and management standardization did not reduce length of stay. For the entire cohort,
Discussion This quality improvement initiative was successful insofar as the implementation of a standardized management protocol for infantile spasms improved the percentage of patients receiving first-line therapy from 57% to 100%. The initial use of first-line therapies may have contributed to the significantly improved rate of infantile spasms remission 3 months after diagnosis (78.8% poststandardization vs 30.6% prestandardization). However, our management protocol includes other features that also likely improved remission rates. For example, our protocol emphasizes early (eg, 2 weeks) changes in treatment if a therapy is deemed ineffective. A patient in the poststandardization protocol could receive up to 3 treatments in less than 8 weeks. Thus, our reported remission rate may not reflect the response to the initial treatment but instead reflects management over a 3-month period. Challenges to the implementation of a standardized management protocol include the education and the support of colleagues within a practice. This can be a daunting task given the variability in the treatment of infantile spasms. However, in our large practice of 20 child neurologists and 6 nurse practitioners, we were able to achieve agreement on this initiative. Despite the implementation of our management protocol, we did not reduce the diagnostic admission length of stay. This may relate to our small sample size and the already relatively low prestandardization length of stay. We noted that ACTH admissions had the longest length of stay. Despite similar monitoring and education with corticosteroids, the median ACTH admission length of stay (5.1 days) was nearly 3 days longer than the median corticosteroid admission length of stay (2.2 days). We attribute this discrepancy to the requirement for ACTH insurance authorization prior to hospital discharge, which is consistent with the findings from a small retrospective study that reported a longer length of stay after the ACTH price increase in 2007.8 Our project has several limitations. In many circumstances, we were unable to document the clinical reasoning behind the choice of initial treatment in the prestandardization cohort.
Downloaded from jcn.sagepub.com at TULANE UNIV on December 29, 2014
Fedak et al
3
Some families may have feared the possible side effects associated with ACTH, corticosteroids, or vigabatrin and may have requested an alternative treatment. Counseling families after protocol implementation likely influenced decisions about treatment. For example, that we designated vigabatrin as a first-line treatment option may explain why it was used more often in the poststandardization cohort. Differences between the 2004 and the 2012 infantile spasms practice parameters from the American Academy of Neurology and the Child Neurology Society could have also influenced treatment decisions. However, the only change relevant to our manuscript was the addition of Class III evidence for the use of higher-dose oral corticosteroids in the 2012 update.4 This change would not explain the frequent use of non-first-line therapy in the prestandardization cohort. In regard to our assessment of infantile spasms remission, we were unable to confirm the presence or absence of infantile spasms remission in 7 patients secondary to either insufficient documentation or ongoing spells of uncertain significance. Our inability to confirm electrographic improvement in the prestandardization cohort is also a study limitation. In contrast, all patients in the poststandardization cohort had adequate EEG data. Of the 26 patients in the poststandardization cohort in clinical remission at 3 months, 24 had electrographic remission as well. Twenty of 26 had posttreatment EEG monitoring that extended overnight. Overnight EEG to confirm electroclinical remission was not available for 5 patients in the poststandardization cohort because we did not introduce this practice to our management protocol until March of 2013. Since that time, only 1 additional patient with electroclinical remission (based on caregiver reporting and a 60-minute EEG with sleep) did not receive an overnight EEG for other clinical reasons. Our standardized infantile spasms management protocol increased the percentage of patients who received first-line therapy as the initial treatment of infantile spasms, was associated with an improved remission rate 3 months after diagnosis, but did not reduce the diagnostic admission length of stay. Diagnostic admissions in which ACTH was chosen were associated with a longer median length of stay than with corticosteroids, which is likely explained by the need for ACTH insurance approval prior to hospital discharge. Future quality improvement initiatives should target length of stay optimization with ACTH treatment. Acknowledgments This work was performed at Nationwide Children’s Hospital in Columbus Ohio.
Author Contributions EMF wrote the initial manuscript draft. EMF, ADP, and JRM were responsible for project conception/design. EMF, EW, and JRM acquired the data. GLH performed statistical analysis and JRM was responsible for project mentorship. All study authors analyzed and interpreted the data and revised the manuscript.
Declaration of Conflicting Interests The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The authors received no financial support for the research, authorship, and/or publication of this article.
Ethical Approval The internal review board at Nationwide Children’s Hospital does not require approval for quality improvement projects.
References 1. Riikonen R. Long-term outcome of patients with West syndrome. Brain Dev. 2001;23:683-687. 2. Kivity S, Lerman P, Ariel R, et al. Long-term cognitive outcomes of a cohort of children with cryptogenic infantile spasms treated with high-dose adrenocorticotropic hormone. Epilepsia. 2004;45: 255-262. 3. Mackay MT, Weiss SK, Adams-Webber T, et al. Practice parameter: medical treatment of infantile spasms: report of the American Academy of Neurology and the Child Neurology Society. Neurology. 2004;62:1668-1681. 4. Go CY, Mackay MT, Weiss SK, et al. Evidence-based guideline update: medical treatment of infantile spasms. Report of the Guideline Development Subcommittee of the American Academy of Neurology and the Practice Committee of the Child Neurology Society. Neurology. 2012;78:1974-1980. 5. Mytinger JR, Joshi S, Pediatric Epilepsy Research Consortium, Section on Infantile Spasms. The current evaluation and treatment of infantile spasms among members of the Child Neurology Society. J Child Neurol. 2012;27:1289-1294. 6. Pellock JM, Hrachovy R, Shinnar S, et al. Infantile spasms: a U.S. consensus report. Epilepsia. 2010;51:2175-2189. 7. Davidoff F, Batalden P, Stevens D, et al. Publication guidelines for quality improvement studies in health care: evolution of the SQUIRE project. BMJ. 2009;338:a3152. 8. Wray CD, Benke TA. Effect of price increase of adrenocorticotropic hormone on treatment practices of infantile spasms. Pediatr Neurol. 2010;43:163-166.
Downloaded from jcn.sagepub.com at TULANE UNIV on December 29, 2014
