by by ranked innineclinicalspecialties andnationally of Medicine University ofPittsburgh School Pittsburgh isaffiliated withthe UPMC Children’s Hospitalof Spring 2019 •  •  •  •  •  In This Issue U.S. News&World Report for Physicians Podcast Series Division Faculty Evaluation Center New CMECourses Available New Pediatric Research Recent Publications From About thePediatric Sleep All Sleepiness IsNottheSame Pediatric Insights .

symptoms, specificallytheinability to wake upinthemorning, continued to a worsen with AB worked diligently withthesleeppsychologist to improve hissleepschedule. However, his Evaluation Center. sleep timeonweekdays, hewas referred to oneofthesleeppsychologists inthePediatric Sleep As theinitialpicture was consistent withdelayed sleepphasesyndrome withinadequate total by more thanthree hours. in thefirst week andnine to 10hours inthesecond week, withdelayed wake timeon weekends obstructive sleepapnea.Hisinitialactigraphy showed anaverage dailysleeptimeofeighthours AB hadanormalneurology evaluation andanormalvideoEEG. Polysomnography didnotreveal examination was unremarkable. AB didnothave ahistory ofviral illnesses, headtrauma, ornew medications.Hisoverall physical REM-related (rapid eye movement) phenomena,orrestless legs.Hedidreport consistent snoring. normal range. Hereported occasional sleepparalysis butnocataplexy, hypnagogic hallucinations, sleepiness; hisEpworth sleepiness scale(ESS) score of5(<10considered normal) was inthe duration thatwas interfering withhisability to complete schoolwork. Hedidnothave daytime symptoms coincided withtheonset ofpubertyandwere accompanied by aprolongation ofsleep school nightswith>13hours ofcatch-up sleepwithalate wake-up timeonweekends. These arouse himuntilhe“woke up” ontheway to school.The patientreported eighthours ofsleep on responsive uponawakening andalsowas unableto walk. Hedidnotremember any effortsto difficulty waking up for schoolandthe exhibition offloppiness upon awakening. AB wasbarely Pediatric SleepEvaluation Center by hispediatricianandneurologist becauseoftheonset AB isa16-year-old boy withoutany significantpastmedicalhistory who was referred to the Summary ofCase the patientledt an inability to wake upontimefor school.Asubsequentcomprehensive workup of of Pittsburgh Pediatric SleepEvaluation Center withacommon sleepcomplaint — We describethecaseofabrightstudentwhopresented to theUPMC Children’s Hospital Case Report All Sleepiness IsNotthe Same o therevelation ofanunusualand poorlyunderstood sleepproblem. An Update From theDivisionofPediatric Pulmonology Division ofPediatric Pulmonology Visiting Associate Professor ofPediatrics, Co-Director, Pediatric SleepEvaluation Center Deepa Burman,MD Division ofPediatric Pulmonology Associate Professor ofPediatrics, Director, Pediatric SleepEvaluation Center Hiren Muzumdar, MD

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2 Pediatric Insights: Pulmonology Spring 2019

All Sleepiness Is Not the Same Continued from Page 1

concomitant increase in sleep duration. His father was now taking two or more hours to get him out of bed. The father had a video of AB sitting on the stairs and sleeping while his father attempted to take him to the car to drive him to school. Three hours after awakening, he “woke up” and did not feel the need to sleep anymore during the day. He did not report daytime sleepiness, felt refreshed after sleep, and his ESS had not changed. His total sleep time had increased further to 10.5 hours on weekdays and 12 hours on weekends confirmed by a sleep diary and actigraphy testing (Figures 1 and 2). He still had delayed wake times on weekends by two hours, which was somewhat of an improvement from the previous time of three hours.

Polysomnography with multiple sleep latency Figure 1. Sleep diary. testing (MSLT) to evaluate sleepiness showed an overnight sleep time of 433 minutes and Physiologic Sleep Requirements Hypersomnia sleep efficiency of 86 percent with an arousal index of 15 per hour; apnea-hypopnea index Adequate duration and quality of sleep are Excessive sleepiness or hypersomnolence (AHI) 0.8 per hour; and oxygen saturation important for health and well-being. Short is a common sleep complaint that refers to above 90 percent for 100 percent of the night. sleep duration is associated with a wide range the inability to stay awake during major wake The sleep study was terminated at 6 a.m. per of negative health outcomes including periods of the day resulting in an excessive protocol. Upon awakening from the overnight accidents, poor work performance, obesity, need for sleep, unscheduled periods of study, the patient reported that he could not and increased risk of self-harm or suicidal drowsiness, or sleep present despite normal move his legs and was not alert for some time thoughts. The length of nocturnal sleep quality and timing of nocturnal sleep.2 It is after the lights came on. During the MSLT, depends on multiple factors including important not to confuse symptoms of fatigue/ AB only slept on the first nap and had a mean intrinsic/genetic determinants and volitional tiredness with those of true sleepiness.­ sleep latency (MSL) of 19 minutes without control.1 While sleep restriction is generally Chronic fatigue syndrome has persistent any REM sleep. regarded as detrimental to health, optimal fatigue and a subjective report of tiredness sleep duration is not clearly understood. that does not resolve with sleep or rest. Discussion There are several competing sets of The third edition of the International recommendations for the optimal duration of In summary, AB had new-onset excessive Classification of Sleep Disorders sleep, and a commonly cited reference is from sleep inertia or “sleep drunkenness” (with (ICSD) classifies central disorders of the National Sleep Foundation (NSF), which confirmed prolonged sleep duration) in hypersomno­lence into eight subtypes2: conjunction with normal subjective sleepiness also is endorsed by the American Academy of during the day and normal nap latency without Pediatrics (https://www.sleepfoundation.org/ • Narcolepsy type 1 and 2 (NT1 and NT2) press-release/national-sleep-foundation- REM periods. This new-onset constellation of • Idiopathic hypersomnia (IH) symptoms with progression of sleep needs recommends-new-sleep-times). These was felt to be most consistent with idiopathic consensus guidelines developed by sleep • Kleine-Levin syndrome experts recommend eight to 10 hours of sleep hypersomnia (IH), with the exceptions that • Hypersomnia due to medications AB found sleep refreshing and did not feel for teenagers, with less than seven hours and • Hypersomnia due to a medical disorder sleepy during the day. We discuss our more than 11 hours “not recommended.” Of note, sleep requirements steadily decrease reasoning in the context of physiological • Hypersomnia in relation to a from 14 to 17 hours during infancy to seven to sleep requirements and central disorders psychiatric disorder of hypersomnolence. nine hours in adulthood. • Insufficient sleep syndrome and normal variant — long sleeper (physiological long sleeper) UPMCPhysicianResources.com/Pediatrics 3

In addition to the presence of episodes of childhood, feel fully rested with sleep, are: 1) periods of daytime lapses into sleep; rapid onset uncontrollable daytime sleepiness, and do not have any sleepiness if they 2) absence of cataplexy; 3) fewer than two NT1 is characterized by cataplexy and/or are able to satisfy their sleep requirements. SOREMPs during MSLT; and 4) symptoms hypocretin deficiency and MSL≤ 8 minutes Hypersom­nia associated with medical or not explained by other causes including and two or more sleep onset REM periods psychiatric disorders or medication occurs insufficient sleep. Additionally, one or both (SOREMP). NT2 has polysomnographic and in conjunction with relevant triggers. of the following should be present: 1) MSL of MSLT features of NT1 without cataplexy eight minutes or less during the MSLT, and/or or low levels of hypocretin.2 Klein-Levin Idiopathic Hypersomnia 2) 11 hours or more of sleep per day (either in syndrome is defined as episodes of recurrent, a 24-hour sleep study or in a week of at-home Compared to narcolepsy, which was first time-limited hypersomnia (two days to monitoring). Sleep drunkenness and long described in 1877, the identification of IH is five weeks) associated with cognitive or unrefreshing naps are supportive features.2 very recent and, in fact, the term itself was perceptual dysfunction, disinhibition, or coined as late as 1976.4 Since then, there have IH is an uncommon disorder that affects disordered eating with a return to normal been several variations in the definition of the mostly young subjects with an uncertain baseline between events.3 Insufficient disease, including the newly released ICSD 3, prevalence with estimates of 0.002% to sleep syndrome is completely reversed by which revised the diagnostic criteria and 0.02% of the population. In comparison, normalizing sleep time. Physiological long simplified the definition of IH as supported by the prevalence of excessive daytime sleepers have long sleep periods from early underlying data. The current ICSD 3 IH criteria sleepiness in the general population ranges from 4% to 30%. The average age of onset of IH is reported from 16.6 to 21.2 years, and the disorder is generally stable and persistent though spontaneous remission Actogram: has been reported.

12:00 PM 8:00 PM 12:00 AM 6:00 AM 12:00 PM Debilitating daytime sleepiness is a feature of IH though it is reported to be less irresistible than Tuesday 10/2/2018 with narcolepsy (See Table 1 on Page 4). Naps Day 1 tend to be longer and unrefreshing in 48% to 78% of patients with IH, and self-reported Wednesday sleep duration is 10 hours or more in 30% of 10/3/2018 Day 2 patients. Sleep efficiency on poly­somnography is usually high (90% to 94%).

Thursday Sleep inertia refers to the transitional state 10/4/2018 Day 3 between sleep and wake on awakening, marked by impaired performance, reduced

Friday vigilance, and a desire to return to sleep. 10/5/2018 Some sleep inertia is a normal phenomenon Day 4 but can have dangerous ramifications, e.g., in health care workers5 or military personnel Saturday 10/6/2018 who are woken abruptly in the night and Day 5 required to make cognitively taxing decisions.6

Pronounced sleep inertia or sleep drunkenness Sunday 10/7/2018 is defined as a prolonged difficulty in awakening Day 6 with repeated returns to sleep, irritability, automatic behaviors, and confusion. It is a Monday core supportive feature of IH with symptoms 10/8/2018 Day 7 lasting up to four hours. It can be more

12:00 PM 8:00 PM 12:00 AM 6:00 AM 12:00 PM problematic than daytime sleepiness with Legend: Activity White Light Red Light Green Light Blue Light some patients requiring the assistance of Rest Sleep Excluded Custom Sleep/Wake Off Wrist Marker another person to be able to wake up. Sleep Activity Scale: 1645/0, White Light Scale: 48891.3/0.1, Color Light Scale: 9.252E+04/1.000E-02 drunkenness is present in 1% of the general population compared to 36% to 66% of patients with IH.7

Figure 2. Actigraphy. Continued on Page 4 4 Pediatric Insights: Pulmonology Spring 2019

All Sleepiness Is Not the Same Continued from Page 3

Delayed sleep phase has been demonstrated Table 1. Clinical Features of Narcolepsy, Idiopathic Hypersomnia, in IH but it is not clear if this is coincidental and Physiological Long Sleepers or causal. Regardless, the combination of the two can be very detrimental to social and NT1 NT2 NT1 IH Physiological Long Sleeper academic life with consequent mental health Excessive sleepiness +++ +++ ++ +/- implications, as was apparent in our patient.

The etiology of IH is poorly understood. The Sleep paralysis +++ +++ +/- +/- accumulation of unspecified neurochemical­ Cataplexy - + - - compounds, some genetic markers, immunologic mechanisms, and alteration Difficulty staying asleep + + - - in circadian molecular mechanisms all at night have been implicated in the genesis Refreshing sleep after night of IH. IH possibly is a cluster of disorders + + +/- + with differing etiologies and natural time sleep and naps progressions. Regarding sleep inertia, Sleep drunkenness +/- +/- +++++ - it has been hypothesized­ that it occurs when awakening occurs before adenosine, NT = narcolepsy type, IH = idiopathic hypersomnia a neuronal metabolite correlated with sleepiness, is fully cleared. The decay of Table 2. Therapeutic Options for Treating Hypersomnia subjective sleepiness after awakening closely parallels the time courses of both Treatment Key Features extremity cooling and the cortisol awakening response, suggesting possible links of both Stimulants including Sympathomimetic medications and hence improve daytime thermoregulation and the hypothalamic- Modafinil sleepiness. Potential adverse psychiatric and cardiovascular effects. Two recent randomized, double-blind, placebo-controlled pituitary-adrenal axis to sleep inertia. trials demonstrated that Modafinil improves EDS in IH.8 In our case, though AB did not have sleepiness on MSLT or debilitating daytime Sodium Oxybate Sodium salt of gamma hydroxybutyrate (GHB), an endogenous sleepiness, he had new onset of prolonged cerebral inhibitory neurotransmitter, which activates its receptors sleep time (in contrast with physiological and possibly modulates the GABAB receptors. Promotes deep sleep and improves daytime sleepiness.9 sleep requirements that progressively decrease with age) with extreme sleep inertia that is consistent with IH. AB’s main symptom was Newer Treatments Still Under Investigation sleep drunkenness, particularly on school days and especially when he did not get Pitolisant Histamine-3 receptor inverse agonist stimulates histamine 11 to 12 hours of sleep. release. Used with some success in treatment-refractory IH.

Management Flumazenil Antagonist of GABAA receptor has been shown to improve psychomotor vigilance and subjective alertness. The main goal of treating patients with central

disorders of hypersomnolence is to relieve Clarithromycin Negative allosteric modulator of GABAA receptors. Still pending EDS and improve quality of life, and, in the randomized, placebo-controlled trial results. case of IH, to also mitigate sleep inertia.8 Compared to the treatment of narcolepsy, JZP-258 Investigational oxybate mixed-salts oral solution with 90 percent less sodium than a sodium oxybate oral solution. Currently in treatment for other hypersomnolence Phase 3 clinical trials for treatment of IH. disorders is more challenging and less codified. No medication is currently approved by the tDCS Noninvasive brain stimulation technique that creates temporary United States Food and Drug Administration changes in the excitability of the cortex — the outermost part of (FDA) to treat IH; consequently, medications the brain, which is responsible for executive function. Because approved for narcolepsy are often used of positive results of tDCS on sleep deprivation, Arnulf et al. are off-label to treat IH. investigating its effect on IH. Seven of the eight participants (87.5%) reported improvement in their daytime sleepiness, The therapeutic options for the treatment of including for up to two weeks after the end of the study. hypersomnia are outlined in Table 2. UPMCPhysicianResources.com/Pediatrics 5

In AB’s case, the most distressing symptom sleep disorders. Sleep psychologists and References was sleep inertia. Since stimulants have therapists play a critical role in identifying 1 Sehgal A, Mignot E. Genetics of Sleep and Sleep been reported to be helpful for some patients mental health difficulties that may be Disorders. Cell. 2011; 146(2): 194–207. with IH, AB was prescribed methylphenidate secondary to a sleep disorder or may be 2 Medicine AAOS. International Classification of Sleep 30 minutes before scheduled wake time and associated with a sleep disorder and help Disorders — Third Edition (ICSD-3). Darien; 2014. had tangible improvement in sleep inertia. patients cope with these difficulties. Overall, 3 Arnulf I, Groos E, Dodet P. Kleine-Levin However, this was discontinued because of the importance of these associated issues Syndrome: A Neuropsychiatric Disorder. Rev Neurol (Paris). 2018; 174(4): 216–227. tachycardia, hypertension, and weight loss. cannot be understated in the management 4 Modafinil did not improve his sleep inertia of patients with sleep-related illnesses. Roth B. Narcolepsy and Hypersomnia: Review and Classification of 642 Personally Observed Cases. and was associated with confusion. Sodium Schweiz Arch Neurol Neurochir Psychiatr. 1976; oxybate has been shown to improve sleep Conclusion and Summary 119(1): 31–41. inertia in patients with IH, possibly through AB’s case is unique in that he does not fit 5 Smith-Coggins R, Howard SK, Mac DT, et al. consolidation of overnight sleep. AB has had Improving Alertness and Performance in in a well-defined “box.” His case illustrates difficulty obtaining sodium oxybate because Emergency Department Physicians and Nurses: the continuum of sleep disorders and the of insurance coverage issues. The Use of Planned Naps. Ann Emerg Med. 2006; difficulty many patients encounter in obtaining 48(5): 596–604. In addition to medications, management a diagnosis. A diagnosis of IH should only be 6 Horne J, Moseley R. Sudden Early-morning by behavioral therapy can be critical for made after carefully ruling out other causes of Awakening Impairs Immediate Tactical Planning patients to learn sleep-wake management EDS. IH causes daytime sleepiness and sleep in a Changing “Emergency” Scenario. J Sleep Res. skills needed to cope with IH. AB reported inertia that can have a tremendous impact on 2011; 20(2): 275–278. improvement in quality of life with behavioral quality of life, especially when associated with 7 Roth B, Nevsímalová S, Ságová V, Paroubková D, Horáková A. Neurological, Psychological and therapy, particularly management of delayed delayed sleep phase. Pharmacologic treatment Polygraphic Findings in Sleep Drunkenness. sleep phase that was induced by waking up combined with nonpharmacologic intervention Schweiz Arch Neurol Neurochir Psychiatr. 1981; later on weekends. This phase delay was offers the best chance of improving quality 129(2): 209–222. associated with later sleep onset and greater of life in patients with IH. Although recent 8 Billiard M, Sonka K. Idiopathic Hypersomnia. sleep inertia on school days. A common work has provided clinicians with some Sleep Med Rev. 2016; 29: 3–33. aspect of the difficulties faced by patients direction in terms of pharmacologic and 9 Leu-Semenescu S, Louis P, Arnulf I. Benefits and with sleep disorders is the mental distress nonpharmaco­logic strategies, much work Risk of Sodium Oxybate in Idiopathic Hyper­somnia secondary to the lack of public awareness of remains to be done. Versus Narcolepsy Type 1: A Chart Review. Sleep Med. 2016; 17: 38–44.

About the Pediatric Sleep Evaluation Center

The Pediatric Sleep Evaluation Center at team of sleep technologists led by Craig To contact a physician or refer a patient for UPMC Children’s Hospital of Pittsburgh is Halper, RPSGT. The program conducts consultation, please call Melisa Kennedy, a multidisciplinary program dedicated to approximately 1,700 to 1,800 attended administrative coordinator, at 412-692-8736. diagnosing and treating all sleep disorders in-laboratory-based sleep studies on in children, from birth to 21 years of age. patients from infancy to young adulthood. The Center provides care to children with The Center provides training in pediatric Pediatric Sleep Evaluation complex issues including craniofacial sleep medicine to fellows from the Sleep Center Staff abnormalities, Down syndrome, ventilator- Medicine Fellowship at UPMC, which over Hiren Muzumdar, MD dependent children, and Prader–Willi the last 10 years has trained more than Director syndrome. The Center has two behavioral 20 sleep fellows from varied medical Deepa Burman, MD psychologists embedded in the program, specialties, including adult and pediatric Co-Director Ryan Anderson, PhD, and Hannah Ford, pulmonology, adult and pediatric neurology, PhD, allowing comprehensive care for mask family medicine, pediatrics, internal Ryan Anderson, PhD desensitization, insomnia, parasomnias, medicine, psychiatry, and otolaryngology. Hannah Ford, PhD hypersomnia, sleep disruption due to The Pediatric Sleep Evaluation Center Craig Halper, RPSGT mental/psychiatric disorders, and circadian works closely with other specialties, Frank Boyd, RPSGT rhythm disorders. The American Academy including pediatric otolaryngology, plastic Nancy Popovich, RRT, RPSGT of Sleep Medicine-accredited sleep lab at surgery, pediatric­ neurosurgery, and UPMC Children’s has eight beds with a pediatric neurology. 6 Pediatric Insights: Pulmonology Spring 2019

Recent Publications From Division Faculty

Forno E, Wang T, Qi C, Yan Q, Xu CJ, Boutaoui N, Han YY, Forno E, Boutaoui N, Canino G, Celedón Ravindra A, and Kurland G. The Pediatric Han YY, Weeks DE, Jiang Y, Rosser F, Vonk JM, JC. Vitamin D Insufficiency, TH2 Cytokines, and Pulmonologist and the Infant or Child Before Brouwer S, Acosta-Perez E, Colón-Semidey A, Allergy Markers in Puerto Rican Children With Lung Transplantation: Pretransplant Evaluation Alvarez M, Canino G, Koppelman GH, Chen W, Asthma. Ann Allergy Asthma Immunol. 2018 Oct; and Care of the Potential Pediatric Lung Celedón JC. DNA Methylation in Nasal 121(4): 497-498. Recipient. In: Dunn SP and Horslen S (Eds.) Epithelium, Atopy, and Atopic Asthma in Solid Organ Transplantation in Infants and Children: A Genome-Wide Study. Lancet Respir Han YY, Forno E, Celedón JC. Anxiety and Children. Springer, 2018. Med. 2018 Dec 21. Epub ahead of print. Noneosinophilic Asthma Among Adults in A genome-wide study of DNA methylation in nasal the United States. J Allergy Clin Immunol Pract. Roman J, Viegi G, Schenker M, Ojeda V, epithelium, atopy, and atopic asthma. This is the first 2018 Nov 3. Epub ahead of print. Perez-Stable E, Nemery B, Annesi-Maesano I, large-scale study of nasal respiratory epithelium, a Patel S, La Grutta S, Holguin F, Moughrabieh A, proxy for bronchial epithelium that identified loci Han YY, Forno E, Canino G, Celedón JC. Bime C, Lindberg A, Migliori G, de Vries G, previously not associated with asthma in genome- Psychosocial Risk Factors and Asthma Among Ramirez J, Aliberti S, Feldman C, Celedón JC. wide studies. The study built a 30-marker panel Adults in Puerto Rico. J Asthma. 2018 May; 8: 1-9. An American Thoracic Society and European that accurately classified children according to atopy Respiratory Society Workshop Report: Research or atopic asthma status. The study suggests that Han YY, Rosser F, Forno E, Celedón JC. Exposure Needs on Respiratory Health in Migrant and nasal methylation profiling could be of clinical utility to Polycyclic Aromatic Hydrocarbons, Vitamin D, Refugee Populations. Annals Am Thorac Soc. in the prediction of asthma and asthma-related and Lung Function in Children With Asthma. 2018; 15: 1247-55. outcomes. Pediatr Pulmonol. 2018 Oct; 53(10): 1362-1368. Rosser F, Han YY, Forno E, Celedón JC. Urinary Sommerfeld C, Nowalk A, Larkin A, Weiner DJ. Hernandez-Pacheco N, Farzan N, Francis B, Polycyclic Aromatic Hydrocarbons and Allergic Hypersensitivity Pneumonitis and Acute Karimi L, Repnik K, Vijverberg SJ, Soares P, Sensitization in a Nationwide Study of Children Respiratory Distress Syndrome from E-Cigarette Schieck M, Gorenjak M, Forno E, Eng C, S Oh S, and Adults in the U.S. J Allergy Clin Immunol. Use. Pediatrics. 2018 Jun; 141(6). Epub ahead Pérez-Méndez L, Berce V, Tavendale R, Samedy 2018; 142: 1641-3. of print. LA, Hunstman S, Hu D, Meade K, Farber HJ, Avila PC, Serebrisky D, Thyne SM, Brigino- Spahr J, Weiner DJ, Stokes DC, Kurland G. This is the first reported case of hypersensitivity Buenaventura E, Rodriguez-Cintron W, Sen S, Pulmonary Disease in the Pediatric Patient with pneumonitis and acute respiratory distress Kumar R, Lenoir M, Rodriguez-Santana JR, Acquired Immunodeficiency States. In: Wilmott syndrome as a risk of e-cigarette use. Celedón JC, Mukhopadhyay S, Poto˘cnik U, RW, Deterding R, Li A, Ratjen F, Sly P, Zar HJ, Pirmohamed M, Verhamme KM, Kabesch M, and Bush A. (editors) Kendig’s Disorders of the Han YY, Forno E, Celedón JC. Health Risk Palmer CNA, Hawcutt DB, Flores C, van der Zee Respiratory Tract in Children. 9th Edition; Elsevier, Behaviors, Violence Exposure, and Current AHM, Burchard EG, Pino-Yanes M. Genome- Philadelphia, 2019; Chapter 64, pp. 923-943. Asthma Among Adolescents in the United wide Association Study of Inhaled Corticosteroid States. Pediatr Pulmonol. 2019 Mar; 54(3): Response in Admixed Children With Asthma. Szentpetery S, Weiner DJ, and Kurland G. 237-244. Clin Exp Allergy. 2019 Jan 29. Epub ahead of print. Pulmonary Complications of Solid Organ Victimization is associated with current asthma in a Transplantation. In: Koumbourlis AC and Nevin national sample of adolescents, mediated through Mendy A, Forno E, Niyonsenga T, Carnahan R, MA (editors) Pulmonary Complications of feeling sad or hopeless and any suicidal behavior. Gasana J. Prevalence and Features of Asthma- Non-Pulmonary Pediatric Disorders. Humana COPD Overlap in the United States 2007-2012. Press; Springer Nature, Cham, Switzerland. Chavez LM, Shrout PE, García P, Forno E, Clin Respir J. 2018 Aug; 12(8): 2369-2377. 2018; pp. 281-295. Celedón JC. Measurement Invariance of the Adolescent Quality of Life-Mental Health Mendy A, Gopal R, Alcorn JF, Forno E. Reduced Yang G, Han YY, Forno E, Acosta-Pérez E, Scale (AQOL-MHS) Across Gender, Age and Mortality From Lower Respiratory Tract Disease Colón-Semidey A, Alvarez M, Canino G, Chen Treatment Context. J Child Fam Stud. 2018 in Adult Diabetic Patients Treated With W, Celedón JC. Under-diagnosis of Atopic Oct; 27(10): 3176-3184. Metformin. Respirology. 2019 Feb 13. Epub Dermatitis in Puerto Rican Children. World ahead of print. Allergy Org J. 2019. Epub ahead of print. Forno E, Abraham N, Winger DG, Rosas-Salazar C, Kurland G, and Weiner DJ. Perception of Newman B and Kurland G. Tools for Diagnosis Zemanick ET, Wagner BD, Robertson CE, Pulmonary Function in Children With Asthma and Management of Respiratory Disease. In: Ahrens RC, Chmiel JF, Clancy JP, Gibson RL, and Cystic Fibrosis. Ped Allergy, Immunology, Kline M W (Chief Ed.) Rudolph’s Pediatrics, Harris WT, Kurland G, Laguna TA, McColley SM, and Pulmonology. 2018 Sep 1; 31(3): 139-145. 23rd Edition. McGraw Hill; New York. 2018; McCoy K, Retsch-Bogart G, Sobush KT, Zeitlin PL, Chapter 499, pp. 2377-2386. Stevens MJ, Accurso FJ, Sagel SD, Harris JK. Guglani L, Kasi A, Starks M, Pedersen KE, Airway Microbiota Across Age and Disease Nielsen JG, Weiner DJ. Difference Between Okoniewski W, Lu KD, Forno E. Weight Loss for Spectrum in Cystic Fibrosis. Eur Resp J. 2017; 50 SF6 and N2 Multiple Breath Washout Kinetics Children and Adults With Obesity and Asthma: (5). Epub ahead of print. Is Due to N2 Back Diffusion and Error in N2 A Systematic Review of Randomized Controlled Offset. J Appl Physiol (1985). 2018 Jul 26. Trials. Ann Am Thorac Soc. 2019 Jan 3. Epub Epub ahead of print. ahead of print. UPMCPhysicianResources.com/Pediatrics 7

UPMC Children’s Hospital of Pittsburgh Launches New Pediatric Research Podcast Series

UPMC Children’s Hospital of Pittsburgh has launched a new medical podcast series for physicians, scientists, and other health care professionals featuring the hospital’s leading researchers and clinicians.

Episodes of “That’s Pediatrics” will include UPMC Children’s Hospital “Mysteries That Affect Our compelling interviews with scientists at UPMC “Neonatal Cardiovascular Children” with Terence Children’s Hospital who are performing Research” with Thomas Dermody, MD, Vira I. Heinz innovative basic, translational, and clinical Diacovo, MD, chief, UPMC Professor and chair, research. New episodes will be released Newborn Medicine Program, Department of Pediatrics; every two weeks. and director of Neonatal Physician-in-Chief and Cardiovascular Research, Heart Institute Scientific Director, UPMC Children’s Hospital. “Going back to the polio at UPMC Children’s Hospital vaccine, Pittsburgh has always In addition to Dr. Williams, been a hub of very innovative “In Pursuit of the Self-Healing Heart” with “That’s Pediatrics” hosts are: research, and in recent years Bernhard Kühn, MD, associate director, really has become a nexus for Richard King Mellon Foundation Institute for Carolyn Coyne, PhD, director, Center some groundbreaking research Pediatric Research, and director, Research in for Microbial Pathogenesis, UPMC in pediatric medicine,” said John Williams, MD, Cardiology at UPMC Children’s Hospital Children’s Hospital chief of the Division of Pediatric Infectious Diseases at UPMC Children’s and one of the “A History of Pediatric Liver Stephanie Dewar, MD, director, Pediatric podcast hosts. “There is a spirit of collabora­ ­ Transplantation” with George Residency Training Program, UPMC tion here in Pittsburgh that makes it somewhat Mazariegos, MD, chief, Children’s Hospital unique nationally and we really want to Pediatric Transplantation Brian Martin, DMD, vice president, Medical explore the research that is happening here Affairs, UPMC Children’s Hospital and how we have a real opportunity to change the way pediatric medicine is practiced “A Passion for Pediatric Emergency Medicine” around the world.” with Mioara Manole, MD, president, Children’s Community Pediatrics, and chief, Current episodes of Division of General Academic Pediatrics “That’s Pediatrics” include: “Let’s Talk About Ears” with Alejandro “Gene Therapy” with George Gittes, MD, Hoberman, MD director of the Richard King Mellon Foundation­ Institute for Pediatric Research and co-scientific “From the U.S. Navy to UTIs” with Tim Shope, director, UPMC Children’s Hospital MD, MPH, professor of pediatrics

“All About Acute Flaccid Myelitis” with “The First Handshake” with Tim Hand, PhD John Williams, MD, chief, Division of Pediatric Subscribe to “That’s Pediatrics” in iTunes or Infectious Diseases “Beyond Corn and Carrots: The Future of Pediatric Diabetes” Google Play Music to have new episodes automatically download to your phone for “Don’t Rule Out Brain Injuries” with Radhika Muzumdar, MD, free when they become available. with Rachel Berger, MD, MPH, chief, Division of Pediatric chief, Child Advocacy Center, Endocrinology, Diabetes, and UPMC Children’s Hospital Metabolism 4401 Penn Ave. Pittsburgh, PA 15224

New CME Courses Available for Physicians

Visit UPMCPhysicianResources.com/Pediatrics for the latest CME courses and videos available for physicians, including:

CME Courses Video Rounds

Solving the Puzzle of Asthma Disparities Video Rounds is a series of short, informative, and educational videos Presented by Juan Celedón, MD, DrPH created for physicians and cover a variety of medical and surgical disciplines. The following Video Rounds in Pediatric Pulmonary Medicine Dr. Celedón discusses risk factors for health disparities are available by visiting UPMCPhysicianResources.com/Pediatrics. in childhood asthma, and reviews genetic and epigenetic studies to help develop personalized medicine for asthma. Studying the Correlation Between Vitamin D Levels and Dr. Celedón’s presentation explores the evidence to Asthma in Children support the role of vitamin D, psychosocial stress, and Presented by Juan Celedón, MD, DrPH obesity in asthma pathogenesis. He also discusses which major racial and ethnic groups have the greatest Pulmonary Function Testing in the Pediatric Population burden from asthma in the United States. Presented by Daniel Weiner, MD

This course is accredited for 1.0 AMA PRA Category 1 Credits™. Cystic Fibrosis Presented by Daniel Weiner, MD

About UPMC Children’s Hospital of Pittsburgh Regionally, nationally, and globally, UPMC Children’s Hospital of Pittsburgh is a leader in the treatment of childhood conditions and diseases, a pioneer in the development of new and improved therapies, and a top educator of the next generation of pediatricians and pediatric subspecialists. With generous community support, UPMC Children’s Hospital has fulfilled this mission since its founding in 1890. UPMC Children’s is recognized consistently for its clinical, research, educational, and advocacy-related accomplishments, including ranking 15th among children’s hospitals and schools of medicine in funding for pediatric research provided by the National Institutes of Health (FY2018).

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