BACKGROUND:Rhinoconjunctivitis phenotypes are conventionally described on the basis of symptom severity, duration and seasonality, and aeroallergen sensitization. It is not known whether these phenotypes fully reflect the patterns of symptoms seen at a population level. OBJECTIVE:We sought to identify phenotypes of rhinoconjunctivitis on the basis of symptom intensity and seasonality using an unbiased approach and to compare their characteristics. METHODS:A cohort of children with asthma in low-income urban environments was prospectively followed with a rhinoconjunctivitis activity questionnaire, and their upper and lower airway disease was managed for 12 months with every 2-month visit based on standardized algorithms. We identified individual rhinoconjunctivitis symptom trajectories and clusters of those trajectories and compared the clusters focusing on atopic characteristics. RESULTS:Data obtained from 619 children yielded 5 symptom clusters: 2 had high symptoms (22.5%) but differed in seasonal pattern, 1 had medium symptoms (13.6%), 1 had medium nasal congestion only (20.4%), and 1 had low symptoms (43.6%). The latter was further split into 2 subgroups if nasal corticosteroids were frequently prescribed (23.6%) or not (20.0%). Seasonal variation was absent in the low symptom clusters. The number of allergic sensitizations and family history of allergic airway disease were higher in the high symptom clusters, but allergic sensitization did not explain differences in seasonality. CONCLUSIONS:This study identified rhinoconjunctivitis phenotypes that have not been previously reported and were not differentiated by demographics or by measures of atopy and type 2 inflammation. Factors beyond allergy need to be investigated to better understand the pathobiology of rhinoconjunctivitis.

Background: Viral wheeze is an important risk factor for asthma, which comprises several respiratory phenotypes. We sought to understand if the etiology of early life wheezing illnesses relates to childhood respiratory and asthma phenotypes. Methods: Data were collected prospectively on 429 children in the Urban Environment and Childhood Asthma (URECA) birth cohort study through age 10 years. We identified wheezing illnesses and the corresponding viral etiology (PCR testing of nasal mucus) during the first three years of life. Six phenotypes of respiratory health were identified at 10 years of age based on trajectories of wheezing, allergic sensitization, and lung function. We compared etiology of early wheezing illnesses on these respiratory phenotypes and the development of asthma. Results: In the first three years of life, at least one virus was detected in 324 (67%) of the 483 wheezing episodes documented in the study cohort. Using hierarchical partitioning we found that non-viral wheezing episodes accounted for the greatest variance on asthma diagnosed at both 7 and 10 years of age (8.0% and 5.8% respectively). Rhinovirus wheezing illnesses explained the most variance on respiratory phenotype outcome followed by non-viral wheezing episodes (4.9% and 3.9% respectively) at 10 years of age. Conclusion and Relevance: Within this high-risk urban-residing cohort early life, non-viral wheezing episodes were frequently identified and associated with asthma development. Though rhinovirus wheezing illnesses had the greatest association with phenotype outcome, the specific etiology of wheezing episode in early life provided limited information about subsequent wheezing phenotypes.

The relationship between allergic rhinitis and asthma is well established. However, it is unclear how rhinitis phenotypes are related to asthma. This study examined the association between longitudinal patterns of childhood rhinitis and diagnosis of asthma in an urban birth cohort. We analyzed rhinitis symptoms including runny nose, stuffy nose, and sneezing through age 11 in the Urban Environment and Childhood Asthma birth cohort (n=442) by latent class analysis to identify longitudinal rhinitis phenotypes. Next, we used logistic regression to compare the odds of having an asthma diagnosis at age ten amongst the rhinitis phenotypes. Four rhinitis phenotypes were identified consisting of low/minimal (N=193, 39.8%), persistent decreasing (N=102, 21%), late increasing (N=62, 12.8%), and persistent (N=128, 26.4%) groups. Rhinitis phenotypes were associated with odds of asthma diagnosis at age 10 years (p<0.0001): low/minimal (10.4%), persistent decreasing [33.3%, odds ratio (OR)=4.3, 95% Confidence Interval (CI) (2.3-8.2)], late increasing [37.1%, OR=5.1, 95%CI (2.5-10.4)], and persistent [46.3%,OR=7.5, 95% CI (4.1-13.7)]. Using the chi-square test of association, rhinitis phenotypes were related to trajectories of wheezing illnesses (p<0.0001) and aeroallergen sensitization (p=0.0037), but not lung function (FEV1/FVC, p=0.11). Rhinitis phenotypes were related to an increased prevalence of asthma in high-risk children in the URECA birth cohort, especially in children with early and persistent nasal symptoms. When features of asthma were considered separately, rhinitis was most closely related to wheezing and aeroallergen sensitivity. This relationship suggests that upper and lower airway symptoms are closely related, suggesting common pathogenic mechanisms, such as an impaired epithelial barrier.

Our objective was to identify longitudinal patterns of chronic rhinitis and their associations with early life environmental exposures in an urban birth cohort of high-risk allergic children through 11 years of age.

Background Black and Hispanic children living in urban environments in the USA have an excess burden of morbidity and mortality from asthma. Therapies directed at the eosinophilic phenotype reduce asthma exacerbations in adults, but few data are available in children and diverse populations. Furthermore, the molecular mechanisms that underlie exacerbations either being prevented by, or persisting despite, immune-based therapies are not well understood. We aimed to determine whether mepolizumab, added to guidelines-based care, reduced the number of asthma exacerbations during a 52-week period compared with guidelines-based care alone. Methods This is a randomised, double-blind, placebo-controlled, parallel-group trial done at nine urban medical centres in the USA. Children and adolescents aged 6-17 years, who lived in socioeconomically disadvantaged neighbourhoods and had exacerbation-prone asthma (defined as >= two exacerbations in the previous year) and blood eosinophils of at least 150 cells per mu L were randomly assigned 1:1 to mepolizumab (6-11 years: 40 mg; 12-17 years: 100 mg) or placebo injections once every 4 weeks, plus guideline-based care, for 52 weeks. Randomisation was done using a validated automated system. Participants, investigators, and the research staff who collected outcome measures remained masked to group assignments. The primary outcome was the number of asthma exacerbations that were treated with systemic corticosteroids during 52 weeks in the intention-to-treat population. The mechanisms of treatment response were assessed by study investigators using nasal transcriptomic modular analysis. Safety was assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT03292588. Findings Between Nov 1, 2017, and Mar 12, 2020, we recruited 585 children and adolescents. We screened 390 individuals, of whom 335 met the inclusion criteria and were enrolled. 290 met the randomisation criteria, were randomly assigned to mepolizumab (n=146) or placebo (n=144), and were included in the intention-to-treat analysis. 248 completed the study. The mean number of asthma exacerbations within the 52-week study period was 0.96 (95% CI 0.78-1.17) with mepolizumab and 1.30 (1.08-1.57) with placebo (rate ratio 0.73; 0.56-0.96; p=0.027). Treatment-emergent adverse events occurred in 42 (29%) of 146 participants in the mepolizumab group versus 16 (11%) of 144 participants in the placebo group. No deaths were attributed to mepolizumab. Interpretation Phenotype-directed therapy with mepolizumab in urban children with exacerbation-prone eosinophilic asthma reduced the number of exacerbations. Copyright (C) 2022 Elsevier Ltd. All rights reserved.

BACKGROUND: Perennial aeroallergen sensitization is associated with greater asthma morbidity and is required for treatment with omalizumab. OBJECTIVE: To investigate the predictive relationship between the number of aeroallergen sensitizations, total serum IgE, and serum eosinophil count, and response to omalizumab in children and adolescents with asthma treated during the fall season. METHODS: This analysis includes inner-city patients with persistent asthma and recent exacerbations aged 6-20 years comprising the placebo- and omalizumab-treated groups in 2 completed randomized clinical trials, the Inner-City Anti-IgE Therapy for Asthma study and the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations study. Logistic regression modeled the relationship between greater degrees of markers of allergic inflammation and the primary outcome of fall season asthma exacerbations. RESULTS: The analysis included 761 participants who were 62% male and 59% African American with a median age of 10 years. Fall asthma exacerbations were significantly higher in children with greater numbers of aeroallergen-specific sensitizations in the placebo group (odds ratio [OR], 1.33; 95% confidence interval [CI], 1.11-1.60; P < .01), but not in the omalizumab-treated children (OR, 1.08; 95% CI, 0.91-1.28; P = .37), indicating a significant differential effect (P < .01). Likewise, there was a differential effect of omalizumab treatment in children with greater baseline total serum IgE levels (P < .01) or greater baseline serum eosinophil counts (P <. 01). Multiple aeroallergen sensitization was the best predictor of response to omalizumab; treated participants sensitized to >= 4 different groups of aeroallergens had a 51% reduction in the odds of a fall exacerbation (OR, 0.49; 95% CI, 0.30-0.81; P <.01). CONCLUSIONS: In preventing fall season asthma exacerbations, treatment with omalizumab was most beneficial in children with a greater degree of allergic inflammation. (C) 2020 American Academy of Allergy, Asthma & Immunology.

Background: Rhinitis and asthma are linked, but substantial knowledge gaps in this relationship exist. Objective: We sought to determine the prevalence of rhinitis and its phenotypes in children and adolescents with asthma, assess symptom severity and medication requirements for rhinitis control, and investigate associations between rhinitis and asthma. Methods: Seven hundred forty-nine children with asthma participating in the Asthma Phenotypes in the Inner-City study received baseline evaluations and were managed for 1 year with algorithm-based treatments for rhinitis and asthma. Rhinitis was diagnosed by using a questionnaire focusing on individual symptoms, and predefined phenotypes were determined by combining symptom patterns with skin tests and measurement of serum specific IgE levels. Results: Analyses were done on 619 children with asthma who completed at least 4 of 6 visits. Rhinitis was present in 93.5%, and phenotypes identified at baseline were confirmed during the observation/management year. Perennial allergic rhinitis with seasonal exacerbations was most common (34.2%) and severe. Nonallergic rhinitis was least common (11.3%) and least severe. The majority of children remained symptomatic despite use of nasal corticosteroids with or without oral antihistamines. Rhinitis was worse in patients with difficult-to-control versus easy-to-control asthma, and its seasonal patterns partially corresponded to those of difficult-to-control asthma. Conclusion: Rhinitis is almost ubiquitous in urban children with asthma, and its activity tracks that of lower airway disease. Perennial allergic rhinitis with seasonal exacerbations is the most severe phenotype and most likely to be associated with difficult-to-control asthma. This study offers strong support to the concept that rhinitis and asthma represent the manifestations of 1 disease in 2 parts of the airways.

Background: A Seasonal Asthma Exacerbation Predictive Index (saEPI) was previously reported based on 2 prior National Institute of Allergy and Infectious Diseases Inner City Asthma Consortium trials. Objective: This study sought to validate the saEPI in a separate trial designed to prevent fall exacerbations with omalizumab therapy. Methods: The saEPI and its components were analyzed to characterize those who had an asthma exacerbation during the Preventative Omalizumab or Step-Up Therapy for Fall Exacerbations (PROSE) study. We characterized those inner-city children with and without asthma exacerbations in the fall period treated with guidelines-based therapy (GBT) in the absence and presence of omalizumab. Results: A higher saEPI was associated with anexacerbation in both the GBT alone (P < .001; area under the curve, 0.76) and the GBT1 omalizumab group (P < .01; area under the curve, 0.65). In the GBT group, younger age at recruitment, higher total IgE, higher blood eosinophil percentage and number, and higher treatment step were associated with thosewho had an exacerbation compared with those who did not. In the GBT + omalizumab group, younger age at recruitment, increased eosinophil number, recent exacerbation, and higher treatment step were also associated with those who had an exacerbation. The saEPI was associated with a high negative predictive value in both groups. Conclusions: An exacerbation in children treated with GBT with or without omalizumab was associated with a higher saEPI along with higher markers of allergic inflammation, treatment step, and a recent exacerbation. Those that exacerbated on omalizumab had similar features with the exception of some markers of allergic sensitization, indicating a need to develop better markers to predict poor response to omalizumab therapy and alternative treatment strategies for children with these risk factors. The saEPI was able to reliably predict those children unlikely to have an asthma exacerbation in both groups.

Background: Pathway analyses can be used to determine how host and environmental factors contribute to asthma severity.Objective: To investigate pathways explaining asthma severity in inner-city children.Methods: On the basis of medical evidence in the published literature, we developed a conceptual model to describe how 8 risk-factor domains (allergen sensitization, allergic inflammation, pulmonary physiology, stress, obesity, vitamin D, environmental tobacco smoke [ETS] exposure, and rhinitis severity) are linked to asthma severity. To estimate the relative magnitude and significance of hypothesized relationships among these domains and asthma severity, we applied a causal network analysis to test our model in an Inner-City Asthma Consortium study. Participants comprised 6- to 17-year-old children (n = 561) with asthma and rhinitis from 9 US inner cities who were evaluated every 2 months for 1 year. Asthma severity was measured by a longitudinal composite assessment of day and night symptoms, exacerbations, and controller usage.Results: Our conceptual model explained 53.4% of the variance in asthma severity. An allergy pathway (linking allergen sensitization, allergic inflammation, pulmonary physiology, and rhinitis severity domains to asthma severity) and the ETS exposure pathway (linking ETS exposure and pulmonary physiology domains to asthma severity) exerted significant effects on asthma severity. Among the domains, pulmonary physiology and rhinitis severity had the largest significant standardized total effects on asthma severity (-0.51 and 0.48, respectively), followed by ETS exposure (0.30) and allergic inflammation (0.22). Although vitamin D had modest but significant indirect effects on asthma severity, its total effect was insignificant (0.01).Conclusions: The standardized effect sizes generated by a causal network analysis quantify the relative contributions of different domains and can be used to prioritize interventions to address asthma severity.

OBJECTIVES:To use the children's sleep habits questionnaire (CSHQ) to characterize sleep problems in a group of 5- to 6-year-old minority children living in urban communities and to compare our findings with data from 5- to 6-year-old children in the original CSHQ validation study.METHODS:A cross-sectional study design was used to collect sleep data from parents using the CSHQ.RESULTS:The CSHQ was completed by 160 parents; 150 (94%) scored ≥41, indicating a sleep problem. The prevalence of having sleep problems for our minority community sample was significantly higher than the original community sample (94% vs. 23%, P < .001). The minority sample also had significantly higher mean total CSHQ scores (51.5 vs 37.9, P < .001) and higher scores across all 8 subscales of the CSHQ (P < .001 for all comparisons).CONCLUSIONS:The results suggest that sleep problems may be more prevalent in urban, early-school-aged minority children than previously reported.

905 Letter to the Editor—Freedman et al The following is a letter to the editor on the Task Force report on the Treatment of Adult CSA and the response to the comments contained in the letter. The format used below lists the comment with the corresponding response immediately following it. With the exception of the initial comment and response, the comments and responses are numbered to aid the reader.

An important update in the recommendation about the use of rotigotine for the treatment of signs and symptoms associated with moderate-to-severe primary restless legs syndrome (RLS) is included in a letter to the editor that was published after the American Academy of Sleep Medicine (AASM) Board of Directors approved the practice parameters. This letter to the editor is an essential supplement to the practice parameters document:

A systematic literature review and meta-analyses (where appropriate) were performed to update the previous AASM practice parameters on the treatments, both dopaminergic and other, of RLS and PLMD. A considerable amount of literature has been published since these previous reviews were performed, necessitating an update of the corresponding practice parameters. Therapies with a STANDARD level of recommendation include pramipexole and ropinirole. Therapies with a GUIDELINE level of recommendation include levodopa with dopa decarboxylase inhibitor, opioids, gabapentin enacarbil, and cabergoline (which has additional caveats for use). Therapies with an OPTION level of recommendation include carbamazepine, gabapentin, pregabalin, clonidine, and for patients with low ferritin levels, iron supplementation. The committee recommends a STANDARD AGAINST the use of pergolide because of the risks of heart valve damage. Therapies for RLS secondary to ESRD, neuropathy, and superficial venous insufficiency are discussed. Lastly, therapies for PLMD are reviewed. However, it should be mentioned that because PLMD therapy typically mimics RLS therapy, the primary focus of this review is therapy for idiopathic RLS.

We thank Dr. Thomas for his comments, questions, and concerns regarding the practice parameter paper on the management of central sleep apnea syndrome (CSAS). 1 We agree that the practice parameter paper did not address all aspects of complex sleep disordered breathing, and we did not intend to do so.Specifically, he has raised several issues, which we would like to address.1. Complex sleep disordered breathing is an important problem and was not addressed.We did not address positive airway pressure (PAP)-emergent central sleep apnea (or complex sleep apnea) for several reasons.Specifically, we followed current CSAS classification as outlined in the ICSD-2 to maintain consistency in our reporting. 2While we recognize the potential significance of PAP-emergent central apnea, we were mindful of the lack of consensus regarding the definition, pathophysiology or optimal management.In addition, the natural history from available literature indicates that the entity in question resolves in 99% of patients on a follow-up study. 3Regardless, we agree that due importance should be given to this entity in the future when more robust evidence is available.We hope that further research will allow this question to be addressed on a future parameter, guideline, or best practice paper.2. CPAP should be rejected as a treatment for CSA in CHF patients.We recognize that CPAP alone may not be sufficient to correct central sleep disordered breathing in all CHF patients.However, available evidence taken together supports the use of CPAP before trying other PAP treatment modalities.Other modalities are available if CPAP fails to control the sleep disordered breathing.This is well outlined and clearly emphasized in the last sentence of our parameter 4.2.1.a. 1 3. CPAP is not harmless, particularly if not effective.CPAP is effective in many, although not in all patients with CSA based on the available evidence that we have presented.Potential "harm" with CPAP for treatment of CSA is theoretical and unproven.Since CPAP is more affordable and accessible, it should be preferred over other more expensive PAP modalities or complicated treatment plans.Conversely, if CSA persists on CPAP, alternative modalities presented should be considered.

BACKGROUND There has been marked expansion in the literature and practice of pediatric sleep medicine; however, no recent evidence-based practice parameters have been reported. These practice parameters are the first of 2 papers that assess indications for polysomnography in children. This paper addresses indications for polysomnography in children with suspected sleep related breathing disorders. These recommendations were reviewed and approved by the Board of Directors of the American Academy of Sleep Medicine. METHODS A systematic review of the literature was performed, and the American Academy of Neurology grading system was used to assess the quality of evidence. RECOMMENDATIONS FOR PSG USE: 1. Polysomnography in children should be performed and interpreted in accordance with the recommendations of the AASM Manual for the Scoring of Sleep and Associated Events. (Standard) 2. Polysomnography is indicated when the clinical assessment suggests the diagnosis of obstructive sleep apnea syndrome (OSAS) in children. (Standard) 3. Children with mild OSAS preoperatively should have clinical evaluation following adenotonsillectomy to assess for residual symptoms. If there are residual symptoms of OSAS, polysomnography should be performed. (Standard) 4. Polysomnography is indicated following adenotonsillectomy to assess for residual OSAS in children with preoperative evidence for moderate to severe OSAS, obesity, craniofacial anomalies that obstruct the upper airway, and neurologic disorders (e.g., Down syndrome, Prader-Willi syndrome, and myelomeningocele). (Standard) 5. Polysomnography is indicated for positive airway pressure (PAP) titration in children with obstructive sleep apnea syndrome. (Standard) 6. Polysomnography is indicated when the clinical assessment suggests the diagnosis of congenital central alveolar hypoventilation syndrome or sleep related hypoventilation due to neuromuscular disorders or chest wall deformities. It is indicated in selected cases of primary sleep apnea of infancy. (Guideline) 7. Polysomnography is indicated when there is clinical evidence of a sleep related breathing disorder in infants who have experienced an apparent life-threatening event (ALTE). (Guideline) 8. Polysomnography is indicated in children being considered for adenotonsillectomy to treat obstructive sleep apnea syndrome. (Guideline) 9. Follow-up PSG in children on chronic PAP support is indicated to determine whether pressure requirements have changed as a result of the child's growth and development, if symptoms recur while on PAP, or if additional or alternate treatment is instituted. (Guideline) 10. Polysomnography is indicated after treatment of children for OSAS with rapid maxillary expansion to assess for the level of residual disease and to determine whether additional treatment is necessary. (Option) 11. Children with OSAS treated with an oral appliance should have clinical follow-up and polysomnography to assess response to treatment. (Option) 12. Polysomnography is indicated for noninvasive positive pressure ventilation (NIPPV) titration in children with other sleep related breathing disorders. (Option) 13. Children treated with mechanical ventilation may benefit from periodic evaluation with polysomnography to adjust ventilator settings. (Option) 14. Children treated with tracheostomy for sleep related breathing disorders benefit from polysomnography as part of the evaluation prior to decannulation. These children should be followed clinically after decannulation to assess for recurrence of symptoms of sleep related breathing disorders. (Option) 15. Polysomnography is indicated in the following respiratory disorders only if there is a clinical suspicion for an accompanying sleep related breathing disorder: chronic asthma, cystic fibrosis, pulmonary hypertension, bronchopulmonary dysplasia, or chest wall abnormality such as kyphoscoliosis. (Option) RECOMMENDATIONS AGAINST PSG USE: 16. Nap (abbreviated) polysomnography is not recommended for the evaluation of obstructive sleep apnea syndrome in children. (Option) 17. Children considered for treatment with supplemental oxygen do not routinely require polysomnography for management of oxygen therapy. (Option) CONCLUSIONS Current evidence in the field of pediatric sleep medicine indicates that PSG has clinical utility in the diagnosis and management of sleep related breathing disorders. The accurate diagnosis of SRBD in the pediatric population is best accomplished by integration of polysomnographic findings with clinical evaluation.

Background. The risk of developing childhood asthma has been linked to the severity and etiology of viral respiratory illnesses in early childhood. Since inner-city infants have unique environmental exposures, we hypothesized that patterns of respiratory viral infections would also be distinct.Methods. We compared the viral etiology of respiratory illnesses in 2 groups: a cohort of 515 infants from 4 inner-city areas and a cohort of 285 infants from mainly suburban Madison, Wisconsin. Nasal secretions were sampled during periods of respiratory illness and at 1 year of age and were analyzed for viral pathogens by multiplex polymerase chain reaction.Results. Overall, inner-city infants had lower rates of viral detection. Considering specific viruses, sick urban infants had lower rates of detectable rhinovirus or respiratory syncytial virus infection and higher rates of adenovirus infection. Every urban site had a higher proportion of adenovirus-positive samples associated with illnesses (10%-21%), compared with Madison (6%).Conclusions. These findings provide evidence that inner-city babies have different patterns of viral respiratory illnesses than babies who grow up in a more suburban location. These findings raise important questions about the etiology of virus-negative illnesses in urban infants and the possibility of long-term consequences of early life infections with adenovirus in this population.

The International Classification of Sleep Disorders, Second Edition (ICSD-2) distinguishes 5 subtypes of central sleep apnea syndromes (CSAS) in adults. Review of the literature suggests that there are two basic mechanisms that trigger central respiratory events: (1) post-hyperventilation central apnea, which may be triggered by a variety of clinical conditions, and (2) central apnea secondary to hypoventilation, which has been described with opioid use. The preponderance of evidence on the treatment of CSAS supports the use of continuous positive airway pressure (CPAP). Much of the evidence comes from investigations on CSAS related to congestive heart failure (CHF), but other subtypes of CSAS appear to respond to CPAP as well. Limited evidence is available to support alternative therapies in CSAS subtypes. The recommendations for treatment of CSAS are summarized as follows: CPAP therapy targeted to normalize the apnea-hypopnea index (AHI) is indicated for the initial treatment of CSAS related to CHF. (STANDARD)Nocturnal oxygen therapy is indicated for the treatment of CSAS related to CHF. (STANDARD)Adaptive Servo-Ventilation (ASV) targeted to normalize the apnea-hypopnea index (AHI) is indicated for the treatment of CSAS related to CHF. (STANDARD)BPAP therapy in a spontaneous timed (ST) mode targeted to normalize the apnea-hypopnea index (AHI) may be considered for the treatment of CSAS related to CHF only if there is no response to adequate trials of CPAP, ASV, and oxygen therapies. (OPTION)The following therapies have limited supporting evidence but may be considered for the treatment of CSAS related to CHF after optimization of standard medical therapy, if PAP therapy is not tolerated, and if accompanied by close clinical follow-up: acetazolamide and theophylline. (OPTION)Positive airway pressure therapy may be considered for the treatment of primary CSAS. (OPTION)Acetazolamide has limited supporting evidence but may be considered for the treatment of primary CSAS. (OPTION)The use of zolpidem and triazolam may be considered for the treatment of primary CSAS only if the patient does not have underlying risk factors for respiratory depression. (OPTION)The following possible treatment options for CSAS related to end-stage renal disease may be considered: CPAP, supplemental oxygen, bicarbonate buffer use during dialysis, and nocturnal dialysis. (OPTION) .

Free AccessNightmare DisorderRevisiting Evidence-Based Guidelines: Not Such a Nightmare Standards of Practice Committee:, R. Nisha Aurora, M.D., Rochelle S. Zak, M.D., Sanford H. Auerbach, M.D., Kenneth R. Casey, M.D., Susmita Chowdhuri, M.D., Anoop Karippot, M.D., Rama K. Maganti, M.D., Kannan Ramar, M.D., David A. Kristo, M.D., Sabin R. Bista, M.D., Carin I. Lamm, M.D., Timothy I. Morgenthaler, M.D. Standards of Practice Committee: Search for more papers by this author , R. Nisha Aurora, M.D. Johns Hopkins University, Department of Medicine, Baltimore, MD Search for more papers by this author , Rochelle S. Zak, M.D. Sleep Disorders Center, University of California, San Francisco, San Francisco, CA Search for more papers by this author , Sanford H. Auerbach, M.D. Boston University School of Medicine, Boston, MA Search for more papers by this author , Kenneth R. Casey, M.D. Cincinnati Veterans Affairs Medical Center, Cincinnati, OH Search for more papers by this author , Susmita Chowdhuri, M.D. Sleep Medicine Section, John D. Dingell VA Medical Center, Detroit, MI Search for more papers by this author , Anoop Karippot, M.D. Penn State University Hershey Medical Center, Hershey, PA and University of Louisville School of Medicine, Louisville, KY Search for more papers by this author , Rama K. Maganti, M.D. Barrow Neurological Institute at Saint Joseph's, Phoenix, AZ Search for more papers by this author , Kannan Ramar, M.D. Mayo Clinic, Rochester, MN Search for more papers by this author , David A. Kristo, M.D. University of Pittsburgh, Pittsburgh, PA Search for more papers by this author , Sabin R. Bista, M.D. University of Nebraska Medical Center, Omaha, NE Search for more papers by this author , Carin I. Lamm, M.D. Children's Hospital of NY – Presbyterian, Columbia University Medical Center, New York, NY Search for more papers by this author , Timothy I. Morgenthaler, M.D. Mayo Clinic, Rochester, MN Search for more papers by this author Published Online:October 15, 2011https://doi.org/10.5664/JCSM.1332SectionsPDF ShareShare onFacebookTwitterLinkedInRedditEmail ToolsAdd to favoritesDownload CitationsTrack Citations AboutINTRODUCTIONDr. Cranston and colleagues should be commended for the thorough job they did expanding upon the foundation of the article, “Best Practice Guide for the Treatment of Nightmare Disorder in Adults.”1 The authors have 3 criticisms of the article: (1) the methodology was used inconsistently at updated time points; (2) the article was missing references that were within the search criteria and therefore not reported; and (3) the search database used was insufficient. In the following sections, these concerns are addressed.Our initial search was conducted in December 2007 and then updated in March 2009 to include all articles indexed and available at that time. Since the cut-off date was March 2009, a number of articles that Cranston and colleagues found missing from our paper were not included. In response to one of our external reviewer's comments, another electronic search was conducted in February 2010 using the keywords “anxiety dreams.” The results yielded 19 articles, which were manually refined to evaluate all inclusion criteria and limits, including discussion of a treatment or therapy. However, there were no additional papers that met all of the inclusion criteria. Thus, the search was in fact conducted consistently at updated time points.Table 1 lists the articles cited by Cranston et al., along with the reasons for not including them in our review. One article was in our database but inadvertently omitted from the analysis (Davis and Wright 20072); Krakow et al. (19953) was superseded by another publication by the same research group on the same subjects (Krakow et al. 19964), so it was discussed but not included in the tally of supporting evidence; two did not have keywords used in our search criteria (Thompson et al. 2008,5 Aukst-Margetic et al. 20046); four were published after the cut-off date of March 2009 (Fraser 2009,7 Lu et al. 2009,8 Harb et al. 2009,9 Swanson et al. 200910); one was excluded because it was a letter to the editor (Moore and Krakow 200711); and three (Fraser 2009,7 Harb et al. 2009,9 Ginsberg 200312) were not in PubMed (of which two (Fraser 2009,7 Harb et al. 20099) were published after the cut-off date).Table 1ArticleTreatmentLevelReason for ExclusionThompson 2008Prazosin4Not found using the keyword searchGinsberg 2003Prazosin4Not in PubMedAukst-Margetic 2004Levomepromazine4Not found using the keyword searchFraser 2009Nabilone4Not in PubMed; published after date cut-offKrakow 1995IRT2Was cited in the paper as a level 2 study; it was not cited in the first paragraph as it was superseded by Krakow 1996, a level 3 paper but it was included in the discussion of the level 3 paperLu 2009IRT4Published after date cut-offMoore 2007IRTNALetter to the EditorHarb 2009IRT4Not in PubMed and published after the cut-off dateDavis 2007ERRT2Inadvertently excludedSwanson 2009ERRT4Published after cut-off dateTable 2TermLevelEvidence LevelsExplanationRecommended / Not recommendedA1 or 2Assessment supported by a substantial amount of high quality (Level I or II) evidence and/or based on a consensus of clinical judgmentSuggested / Not SuggestedB1 or 2—few studies3 or 4—many studies and expert consensusAssessment supported by sparse high grade (Level I or II) data or a substantial amount of low-grade (Level III or IV) data and/or clinical consensus by the task forceMay be considered / Probably should not be consideredC3 or 4Assessment supported by low grade data without the volume to recommend more highly and likely subject to revision with further studiesOf the three articles from Table 1 that could have resulted in a recommendation change, only one was incorrectly omitted. Davis and Wright was in our evidence table, graded and extracted, but was inadvertently missed in the analysis (Davis and Wright 2007).2 We agree with the authors that it should have been included. This oversight on our part had the greatest effect, as the recommendation for Exposure, Relaxation, and Rescripting Therapy (ERRT) would likely have been increased from a Level C to a Level B. We regret this omission and believe that a correction should be issued to address this error.The other two papers were not included in our final analysis for the following reasons. Aukst-Margetic et al. 20046 was not found using our keyword search. Had this paper been included, there may have been a Level C recommendation based on the use of levomepromazine. The other paper (Fraser 20097), which discusses nabilone, was published after the March 2009 cut-off date. This latter paper was not in PubMed, but would have been picked up by using PsycINFO, if the search had been performed at a later date.There were 3 articles that were not in PubMed, but were picked up by other search databases. In terms of our paper's conclusions, however, one article would have been excluded because it was published after March 2009 (Harb et al. 20099), and it did not affect the level of recommendation; one would have been included (Ginsberg 200312) but did not affect the level of recommendation; and the other, as mentioned above, may have supported the use of nabilone, but would not have been included as it was published after the cut-off date (Fraser 20097). This information does not justify using only one database but merely points out that the fundamental conclusions of our paper would not have been substantially altered by including the additional database given the cut-off date. Nonetheless, we would have added a discussion of nabilone, had the cut-off been later and we would like to thank Cranston et al. for pointing this out.In addition, Cranston et al., commented that we “clustered treatment evidence” for PTSD-associated and idiopathic nightmares. In each recommendation, we included the type of nightmare disorder studied and only used “nightmare disorder” in the instances in which the study populations were noted either to have both PTSD-associated and idiopathic nightmares or the type of nightmare disorder was not specified. We agree that the two disorders may be preferentially responsive to different types of treatment. We also recognize that at times it is clinically difficult to differentiate between the two.Interestingly, Cranston et al. used the search methodology described in our paper and, with the exceptions noted above, formed the same evidence tables that we did. To some extent, this is perhaps remarkable when one considers that the final evidence tables contained only 4% of those returned by the computerized search, and that the two lists were 98% homologous. The AGREE instrument13 for appraising guidelines suggests that “The criteria for selecting the evidence are clearly described.” We seem to have hit the mark on this item. On the other hand, a recent task force commissioned by the Institute of Medicine recommended that when performing systematic reviews one should “access an array of information sources that provide both published and unpublished research reports.”14 In this regard, we agree that searching more databases is a desirable strategy that should be targeted. However, a balance must be struck between allocating additional resources and the gains attained with searching additional databases. With respect to this best practice paper, adding the additional database would not have changed our conclusions substantially.In summary, the approach utilized by Cranston and colleagues would have resulted in an increase in the level of recommendation only for ERRT from a Level C to a Level B. Nonetheless, we appreciate the time, effort, and commitment devoted by the authors in replicating and expanding the search and analyses for “Best Practice Guide for the Treatment of Nightmare Disorder in Adults.” The excellent work by Cranston and colleagues gave us the opportunity to reevaluate our process and methods.DISCLOSURE STATEMENTThe Standards of Practice Committee members have indicated no financial conflicts of interest.REFERENCES1 Aurora RNZak RSAuerbach SA, et al.Best practice guide for the treatment of nightmare disorder in adultsJ Clin Sleep Med20106389401, 20726290LinkGoogle Scholar2 Davis JWright DRandomized clinical trial for treatment of chronic nightmares in trauma-exposed adultsJ Trauma Stress20072012333, 17427914CrossrefGoogle Scholar3 Krakow BKellner RPathak DLambert LImagery reharsal treatment for chronic nightmaresBehav Res Ther19953383743, 7677723CrossrefGoogle Scholar4 Krakow BKellner RPathak DLambert LLong term reduction of nightmares with imagery rehearsal treatmentBehav Cogn Psychother19962413548CrossrefGoogle Scholar5 Thompson CETaylor FBMcFall MEBarnes RFRaskind MANonnightmare distressed awakenings in veterans wiht posttraumatic stress disorder: response to prazosinJ Trauma Stress20082141720, 18720392CrossrefGoogle Scholar6 Aukst-Margetic BMargetic BTosic GBillc-Prcic ALevomepromazine helps reduce sleep problems in patients with PTSDEur Psychiatry2004192356, 15196608CrossrefGoogle Scholar7 Fraser GAThe use of a synthetic cannabinoid in the management of treatment-resistant nightmares in posttraumatic stress disorder (PTSD)CNS Neurosci Ther200915848, 19228182CrossrefGoogle Scholar8 Lu MWagner AVan Male LWhitehead ABoehnlein JImagery rehearsal therapy for posttraumatic nightmares in U.S. veteransJ Trauma Stress2009222369, 19444882CrossrefGoogle Scholar9 Harb GCCook JMGehrman PRGamble GMRoss RJPost-traumatic stress disorder nightmares and sleep disturbance in Iraq war veterans: a feasible and promising treatment combinationJ Aggress Maltreat Trauma20091851631CrossrefGoogle Scholar10 Swanson LMFavorite TKHorin EAmedt JTImagery rehearsal therapy for posttraumatic nightmares in U.S. veteransJ Trauma Stress2009222369, 19444882CrossrefGoogle Scholar11 Moore BAKrakow BImagery rehearsal therapy for acute posttraumatic nightmares among combat soldiers in IraqAm J Psychiatry20071646834, 17403990CrossrefGoogle Scholar12 Ginsberg DLPrazosin reduces nightmares in posttraumatic stress disorderPrim Psychiatry20031024Google Scholar13 The AGREE CollaborationAppraisal of Guidelines for Research – Evaluation (AGREE) Instrument2001 www.agreecollaboration.orgGoogle Scholar14 IOM (Institute of Medicine)Finding What Works in Health Care: Standards for Systematic Reviews2011Washington, DCThe National Academies PressGoogle Scholar Previous article Next article FiguresReferencesRelatedDetails Volume 07 • Issue 05 • October 15, 2011ISSN (print): 1550-9389ISSN (online): 1550-9397Frequency: Monthly Metrics History Submitted for publicationAugust 1, 2011Accepted for publicationAugust 1, 2011Published onlineOctober 15, 2011 Information© 2011 American Academy of Sleep MedicinePDF download