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What's new in pediatrics
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What's new in pediatrics
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Aug 2017. | This topic last updated: Sep 14, 2017.

The following represent additions to UpToDate from the past six months that were considered by the editors and authors to be of particular interest. The most recent What's New entries are at the top of each subsection.

GENERAL PEDIATRICS AND ADOLESCENT MEDICINE

Chemical constituents released by heat-not-burn (HNB) tobacco cigarettes (August 2017)

Heat-not-burn (HNB) tobacco cigarettes use an electric blade to heat a tobacco stick to a temperature much below that at which traditional tobacco cigarettes burn. In a laboratory study, HNB tobacco cigarettes released lower amounts of harmful constituents (nicotine, polycyclic aromatic hydrocarbons, and carbon monoxide) than conventional tobacco cigarette smoke [1]. Whether this translates to lower health risks is uncertain. HNB products are not currently available in many countries, including the United States. (See "Patterns of tobacco use", section on 'Heat-not-burn tobacco cigarettes'.)

Sugar-sweetened beverage consumption in pregnancy (August 2017)

A growing body of data suggests that prenatal exposures influence susceptibility to obesity. In a prospective cohort study, higher maternal consumption of sugar-sweetened beverages during pregnancy was associated with increasing adiposity among in utero-exposed school-aged offspring [2]. The association persisted after adjustment for multiple confounding variables and was independent of the offspring's beverage intake. We advise pregnant women to avoid or limit intake of sugar-sweetened beverages because they tend to be high in calories, low in nutritive value, and may impact offspring adiposity. (See "Nutrition in pregnancy", section on 'Sugar-sweetened beverages'.)

Interpretation of blood lead levels <5 mcg/dL (0.24 micromol/L) (August 2017)

Interpretation of blood lead levels <5 mcg/dL (0.24 micromol/L) is complicated by an increased risk of specimen contamination arising from blood collection equipment (eg, needles, blood collection tubes, or cryovials) causing false positives and the inability for many laboratories to quantify low levels of blood lead resulting in false negatives [3]. However, any detectable lead <5 mcg/dL (0.24 micromol/L) warrants careful patient evaluation and an attempt at determining the source of lead exposure. (See "Childhood lead poisoning: Management", section on 'Detectable BLL <5 mcg/dL (current reference level)'.)

Targeted text messages or emails to promote safe infant sleep practices (August 2017)

In the United States, safe infant sleep practices improved during the 1990s, but have plateaued during the past decade, never reaching target levels despite public education campaigns. Now, a large trial has demonstrated benefits of using targeted electronic messaging to deliver sudden infant death syndrome (SIDS)-related education [4]. The intervention consisted of a series of health messages and short educational videos that were delivered to parents of young infants by text message or email and increased adherence to supine sleep, room-sharing without bed-sharing, no soft bedding use, and pacifier use. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'Prevention'.)

Risk of tympanic membrane perforation with topical quinolones after tympanostomy (August 2017)

An observational study reported that treatment with quinolone ear drops, with or without added topical corticosteroids, after tympanostomy tube (TT) placement was associated with increased risk of tympanic membrane (TM) perforation compared with treatment with neomycin plus hydrocortisone drops [5]. While the study raises concerns regarding the safety of quinolone ear drops, the findings should be viewed as preliminary given the observational design and source of the data (Medicaid encounter and pharmacy billing data). In addition, this study evaluated only the risk of TM perforation and did not address other adverse effects, including ototoxicity, which is a well-established side effect of neomycin (and other aminoglycosides). Until additional data are available, we continue to suggest fluoroquinolone-containing drops as our preferred treatment for uncomplicated acute TT otorrhea. (See "Tympanostomy tube otorrhea in children: Causes, prevention, and management", section on 'Uncomplicated acute TTO'.)

Low-dose ferrous sulfate for iron deficiency anemia (June 2017)

For infants and children with iron deficiency anemia, standard oral iron dosing is 3 to 6 mg/kg elemental iron per day, but the optimal dose and preparation have not been established. Now, a study reports that ferrous sulfate 3 mg/kg once daily without food was effective in most patients and was more effective than an equivalent dose of an iron polysaccharide complex formulation [6]. These findings support administering ferrous sulfate at the low end of the standard dose range as first-line treatment for nutritional iron deficiency in children. (See "Iron deficiency in infants and children <12 years: Treatment", section on 'Dose and scheduling'.)

Air mattresses/beds and sudden infant death syndrome (June 2017)

To reduce the risk for sudden infant death syndrome (SIDS), infants should sleep supine and only on a firm sleep surface designed specifically for infants. A new report emphasizes that air mattresses or air beds are not appropriate for infant sleep, even if they are firm and fully inflated, but parents often use these devices because of their low cost and portability [7,8]. This report highlights the importance of counseling parents specifically to avoid using air mattresses or air beds for infant sleep. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'Sleep position and environment'.)

Updated American Academy of Pediatrics guidelines on fruit juice for infants (June 2017)

Updated guidelines from the American Academy of Pediatrics (AAP) recommend avoiding fruit juice for infants younger than 12 months; previous guidelines recommended avoiding fruit juice for infants younger than 6 months [9]. Fruit juice provides no nutritional benefit over mashed or puréed whole fruit and may have adverse consequences, such as undernutrition, overnutrition, diarrhea, flatulence, abdominal distension, and dental caries. We agree with the AAP recommendation and now suggest mashed or puréed whole fruit rather than fruit juice for infants age 6 to 12 months. (See "Introducing solid foods and vitamin and mineral supplementation during infancy", section on 'Beverages to avoid'.)

Breastfeeding and risk of endometrial cancer (June 2017)

Breastfeeding has many maternal and infant benefits. In a meta-analysis of epidemiologic studies of women with endometrial cancer, ever-breastfeeding was associated with an 11 percent reduction in risk compared with never breastfeeding, and the greatest reduction was among those who breastfed for at least three months per child [10]. A decreased risk of endometrial cancer appears to be an additional maternal benefit of breastfeeding. (See "Endometrial carcinoma: Epidemiology and risk factors", section on 'Breastfeeding'.)

Medical use of prescription opioid medications and misuse in adolescents (May 2017)

Surveys of high school seniors in the United States over 40 years show that the use of prescription opioids is strongly correlated with misuse in adolescents and that misuse typically follows medical use by the patient [11]. Thus, health care providers should follow safe prescribing guidance for prescription opioids, including use of alternatives (eg, acetaminophen or ibuprofen) to control pain whenever possible, using the lowest effective dose and minimum quantity of prescription opioid medications when they are needed, and utilizing prescription drug monitoring programs, where available, to identify patients or caregivers who might be misusing (ie, abusing or diverting) prescription opioid medications. (See "Opioid intoxication in children and adolescents", section on 'Safe prescribing'.)

Safe storage of prescription opioids (May 2017)

Although safe storage of prescription opioid medications (eg, locked cabinet) is recommended, it infrequently occurs. In a United States nationally representative survey of over 1000 adults with prescription opioid use in the past 12 months, only 9 percent reported safe storage of their medications [12]. In further analysis of those adults with children younger than 18 years of age in the household, safe storage was reported in less than one-third of households with young children and 12 percent of households with children older than six years of age [13]. These results support the need for anticipatory guidance by health care providers, emphasizing opioid safe storage and how it may limit opioid misuse and overdose, especially in households with children and adolescents. Further research should focus on developing and implementing effective means of secure storage in households. (See "Opioid intoxication in children and adolescents", section on 'Safe storage'.)

Persistence of neurotoxicity of childhood lead poisoning into adulthood (May 2017)

Detectable blood lead levels (BLLs) are associated with irreversible neurocognitive deficits in children and a BLL lower limit for this toxicity has not been established. Previous studies had shown that this effect persists into adolescence. In a longitudinal cohort study of over 1000 patients, lead exposure, based upon BLLs obtained at 11 years of age, was associated in a dose-dependent fashion with lower intelligence quotient (IQ) and lower socioeconomic status at age 38 years after adjustment for maternal IQ, child IQ, and childhood socioeconomic status [14]. Thus, childhood lead exposure causes neurotoxicity that persists into adulthood. Primary prevention of lead exposure, including in pregnant women, can prevent these effects. (See "Childhood lead poisoning: Clinical manifestations and diagnosis", section on 'Neurologic'.)

Safety warnings issued for codeine and tramadol in breastfeeding women and children under age 12 years (April 2017)

The US Food and Drug Administration (FDA) issued a strong warning to restrict use of codeine and tramadol in breastfeeding women and children <12 years old because of increasing reports of life-threatening respiratory depression in young children exposed to these drugs [15]. Children who are ultra-rapid metabolizers metabolize these drugs faster than normal, leading to dangerously high levels of active drug. We suggest avoiding codeine and tramadol in breastfeeding women and children <12 years old. (See "Evaluation and management of pain in children", section on 'Agents not recommended'.)

Prevention of concussion in children playing hockey (April 2017)

Evidence is limited regarding specific interventions to prevent sport-related concussion. In a prospective study of the effect of a Canadian rule change on age eligibility for body checking in youth hockey, the rate of concussions decreased by 64 percent among 11- and 12-year-old hockey players after the eligible age for checking was raised to 13 years [16]. Thus, limiting types of contact until an older age appears to be an effective strategy to reduce the risk of concussion in younger players, although prior studies suggest that the risk of injuries other than concussion may be increased when players are introduced to body checking in subsequent seasons. (See "Concussion in children and adolescents: Management", section on 'Prevention'.)

IUD use does not impact human papillomavirus infection (March 2017)

A reduction in cervical cancer rates among intrauterine device (IUD) users has been observed and attributed to favorable effects of the device on human papillomavirus (HPV) clearance. However, a prospective cohort study that controlled for sexual and behavioral confounders reported no difference in HPV acquisition or clearance among women and girls with or without an IUD [17]. Thus, IUD use does not appear to impact HPV infection. (See "Intrauterine contraception: Devices, candidates, and selection", section on 'IUDs cause infection'.)

Maternal obesity and risk of cerebral palsy (March 2017)

Maternal obesity has been associated with several adverse pregnancy outcomes. Now, a population-based cohort study from Sweden has reported an increasing risk of cerebral palsy in offspring delivered at term as maternal body mass index (BMI) increases [18]. Although this observation requires confirmation, we continue to advise overweight and obese women to try to achieve a normal BMI before becoming pregnant because of established pregnancy and general health benefits. (See "Obesity in pregnancy: Complications and maternal management", section on 'Neurodevelopment'.)

Smartphone-integrated infant physiologic monitors not beneficial (March 2017)

A new class of smartphone-integrated infant physiologic monitors with sensors built into socks, clothing, or diaper clips is being marketed directly to consumers. There is no evidence that these devices have any benefit for prevention of sudden infant death syndrome (SIDS) or any other adverse outcome. Moreover, concerns have been raised that parents might feel falsely reassured by the use of such devices and fail to use established SIDS preventive practices [19]. (See "Sudden infant death syndrome: Risk factors and risk reduction strategies", section on 'No benefit from home monitors'.)

NEONATOLOGY

Voiding cystourethrogram (VCUG) in neonates with first-time febrile UTI (September 2017)

For neonates with first-time urinary tract infection (UTI), the optimal approach to evaluating for vesicoureteral reflux (VUR) is uncertain, and expert opinion differs as to whether a voiding cystourethrogram (VCUG) is necessary in all cases. A recent study of 122 young infants with first-time febrile UTI found that high-grade VUR was far less likely among infants with normal renal ultrasound and Escherichia coli infection compared with those with abnormal renal ultrasound, non-E. coli pathogen, or both abnormal ultrasound and non-E. coli pathogen (1 versus 31, 26, and 55 percent, respectively) [20]. These data suggest that a VCUG may not be necessary for all neonates with first-time UTI, and they support a strategy of "watchful waiting" for low-risk infants. However, VCUG should be performed in neonates with abnormal renal ultrasound, non-E. coli pathogen, or recurrent UTI. (See "Urinary tract infections in neonates", section on 'Voiding cystourethrogram'.)

Procalcitonin monitoring to reduce antibiotic exposure in neonatal sepsis (August 2017)

In a multicenter randomized controlled trial in neonates with suspected early-onset sepsis, a risk assessment protocol that included serial procalcitonin (PCT) measurements reduced the duration of antibiotic therapy [21]. Rates of reinfection were low in both groups, and there was only one death (in the control group). Important limitations of the study include its fairly liberal suggested antibiotic duration for infants with negative cultures and high rates of noncompliance with the treatment protocols by the treating clinicians. Despite these limitations, the results suggest that PCT may have some utility in guiding the duration of antibiotic therapy in neonates with suspected sepsis. If PCT levels are obtained, they should be used in conjunction with other clinical indicators of sepsis and should not be the sole basis of decision-making. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm infants", section on 'Other inflammatory markers'.)

Neonatal nCPAP and long-term adverse outcome (July 2017)

Nasal continuous positive airway pressure (nCPAP) is the preferred initial intervention to manage neonatal respiratory distress syndrome (RDS) versus a more invasive regimen (eg, endotracheal intubation and surfactant administration). However, an observational study of extremely preterm survivors (gestational age <28 weeks) has shown that the use of nCPAP is associated with long-term morbidity [22]. Data comparing use of respiratory support over three historical time periods showed that patients managed in the most recent period (2005) had the longest median duration of nCPAP use, the highest degree of airflow obstruction at eight years of age, and the greatest risk of bronchopulmonary dysplasia. Interpretation of these results must account for factors other than duration of nCPAP that also changed over time (decreasing use of postnatal steroids, decreasing neonatal mortality, and increasing use of nCPAP for other conditions). While these findings emphasize that clinicians need to follow the criteria for initiation and discontinuation of CPAP to avoid overuse and minimize long-term sequelae, CPAP remains the preferred intervention for the management of neonatal RDS based on evidence from clinical trials. (See "Prevention and treatment of respiratory distress syndrome in preterm infants", section on 'Long-term outcome'.)

Buprenorphine treatment of neonatal abstinence syndrome (May 2017)

Morphine and methadone are the preferred drugs for initial pharmacologic management of neonatal abstinence syndrome (NAS). However, in a single-center trial that randomly assigned 63 infants with NAS to sublingual buprenorphine or oral morphine, sublingual buprenorphine resulted in a shorter median duration of treatment and median length of hospital stay, with no difference in the use of adjunctive phenobarbital or in adverse events [23]. Until these findings are confirmed in trials with larger numbers of patients and from other centers, we continue to use either morphine or methadone for initial pharmacologic treatment of NAS. (See "Neonatal abstinence syndrome", section on 'Opioid therapy'.)

Hydrocortisone and prophylaxis for bronchopulmonary dysplasia in preterm infants (April 2017)

Although prophylactic postnatal dexamethasone therapy reduces the risk of bronchopulmonary dysplasia (BPD), its use has been restricted because of an increased risk for cerebral palsy. Hydrocortisone treatment has been studied as an alternative to dexamethasone, but data regarding efficacy and potential harms are discordant and limited by early termination of the trials. One previous trial demonstrated a reduced risk of BPD in high-risk preterm infants (gestational age <28 weeks) treated with hydrocortisone, compared with placebo, and no increase in the rate of short-term adverse events. Now, a follow-up study of these infants at a median corrected age of 22 months found no difference in neurodevelopmental outcome, including cerebral palsy, between the two groups [24]. However, before exposing a significant number of preterm infants to hydrocortisone prophylaxis, further data are needed regarding the balance between reduction of BPD and potential adverse effects of this approach. (See "Postnatal use of corticosteroids in bronchopulmonary dysplasia", section on 'Hydrocortisone'.)

Docosahexaenoic acid supplementation and bronchopulmonary dysplasia in preterm infants (April 2017)

Although previous data suggested that docosahexaenoic acid (DHA) supplementation lowered the risk of bronchopulmonary dysplasia (BPD) in preterm infants, a multicenter randomized trial in infants (gestational age <29 weeks) showed that daily DHA supplementation 60 mg/kg of body weight increased the risk of BPD compared with placebo (49 versus 44 percent) [25]. These results confirm our recommendation to not provide supplemental DHA to prevent BPD in preterm infants. (See "Prevention of bronchopulmonary dysplasia", section on 'Docosahexaenoic acid'.)

Potential predictive tool for successful discontinuation of phototherapy for neonatal hyperbilirubinemia (March 2017)

For clinicians managing neonatal jaundice, the optimal time to discontinue phototherapy to minimize need for reinitiation of therapy is unclear. A clinical tool to estimate the probability of rebound hyperbilirubinemia after inpatient phototherapy was developed using retrospective data from a large birth cohort of infants ≥35 weeks gestational age (GA) [26]. The prediction tool, which calculated a score based on three indices: GA <38 weeks, younger age at phototherapy initiation, and total bilirubin level relative to the treatment phototherapy threshold at termination, performed well in the validation data set. However, external validation is needed prior to recommending clinical use of this tool. (See "Treatment of unconjugated hyperbilirubinemia in term and late preterm infants", section on 'Rebound hyperbilirubinemia'.)

Increase in survival without impairment for periviable infants (March 2017)

For periviable infants, both overall survival and survival without neurodevelopmental impairment have increased over time. In a multicenter National Institute of Child Health and Human Development (NICHD) study of infants born at 22 to 24 weeks of gestation, survival and survival without neurodevelopmental impairment assessed at 18 to 22 months of corrected age increased across three consecutive birth-year epochs (2000 to 2003, 2004 to 2007, and 2008 to 2011) [27]. However, prognosis still remains guarded as only 36 percent of these infants survived and only 20 percent survived without neurodevelopmental impairment in the most recent epoch. (See "Periviable birth (Limit of viability)", section on 'Changes in survival rate without impairment'.)

ALLERGY, IMMUNOLOGY, AND RHEUMATOLOGY

Identification of children with low-risk past penicillin reactions (August 2017)

Many children who have mild adverse reactions to penicillins, such as maculopapular rash, hives, or gastrointestinal symptoms, are not allergic and can safely receive this class of antibiotics in the future. In a study of children presenting to an urban emergency department with histories of past penicillin reactions, nearly 600 parents/caregivers completed a questionnaire about the child’s past reaction [28]. The questionnaire included hives as a low-risk feature (for true allergy), but considered facial angioedema as a high-risk feature. One hundred of 434 patients with low-risk reactions were referred to an allergist for evaluation. Ninety-seven had negative skin tests, while three initially had positive skin tests that were negative upon later repeat testing. Ultimately, all 100 children passed oral challenge to amoxicillin. Despite these results, we consider both hives and angioedema as high-risk features and would advocate that children with past reactions involving either of these symptoms be referred to an allergy specialist to determine if penicillins can be safely used again. (See "Penicillin allergy: Delayed hypersensitivity reactions", section on 'Studies in children'.)

Data limited for probiotic plus oral immunotherapy for peanut allergy (August 2017)

Oral immunotherapy (OIT) for foods is an investigational treatment for food allergies that can lead to temporary desensitization to a food, but the ability of OIT to induce permanent tolerance to the food is less clear. Adding an immunostimulatory adjuvant, such as a probiotic, to OIT may improve sustained unresponsiveness (SU) to the food allergen. In a follow-up study four years after completion of a randomized trial and cessation of treatment, patients treated with peanut OIT plus probiotic were more likely to still be eating peanut and to have SU after eight weeks of avoidance compared with patients treated with placebo only [29]. However, there were significant flaws in the study design, and we await further data before recommending routine use of OIT (with or without an adjuvant). (See "Investigational therapies for food allergy: Oral immunotherapy", section on 'OIT plus adjuvant'.)

National Academies consensus report on food allergies (August 2017)

The National Academies of Sciences, Engineering, and Medicine consensus report on food allergies highlights a number of critical issues related to food allergy [30].

These include:

Judicious use of food allergy testing, performed and interpreted in the context of the patient's clinical history

Prompt treatment of anaphylaxis with epinephrine

Primary prevention of peanut allergy through early dietary introduction

Our approach to the diagnosis and management of food allergies is consistent with the recommendations in this report. (See "Diagnostic evaluation of food allergy", section on 'Role of allergy tests in diagnosis' and "Food-induced anaphylaxis", section on 'Epinephrine' and "Introducing highly allergenic foods to infants and children", section on 'Suggested approach'.)

Four-food elimination diet for eosinophilic esophagitis (July 2017)

The traditional six-food (cow's milk, hen's egg, soy, wheat, peanut/tree nuts, and fish/shellfish) elimination diet for eosinophilic esophagitis (EoE) results in resolution of EoE in approximately three-quarters of children but is challenging and can have negative nutritional consequences. In a prospective study of four-food elimination (milk, soy, egg, wheat) in 78 children with EoE, histologic remission was achieved in 64 percent, with decreased symptoms in 91 percent [31]. Thus, we now suggest either the four-food or six-food empiric elimination diet for most patients who opt for dietary management of EoE. (See "Dietary management of eosinophilic esophagitis", section on 'Elimination diets'.)

Outcomes in children with ANCA-associated vasculitides (July 2017)

The combination of glucocorticoids and cyclophosphamide or other remittive agents (eg, methotrexate, rituximab) has greatly improved patient outcomes for systemic vasculitis. One study of early outcomes in 105 children with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) reported a remission rate of 42 percent, an improvement rate of 92 percent, and no fatalities at 12 months [32]. This compares with the nearly universal mortality due to one form of AAV, granulomatosis with polyangiitis, prior to the regimens now in use. However, more than half of the cohort had evidence of organ damage at 12 months despite high improvement rates and aggressive treatment. (See "Vasculitis in children: Management overview", section on 'Outcomes'.)

Countering the high cost of epinephrine autoinjectors (June 2017)

Physicians and patients in the United States have been struggling with the high cost of epinephrine autoinjectors, and alternatives, as well as ways to maximize the utility of expensive devices, have begun to appear:

A prefilled syringe (Symjepi) containing 0.3 mg epinephrine per dose was approved by the US Food and Drug Administration (FDA) in June 2017 and should offer a more affordable alternative to autoinjectors [33]. It will be available in upcoming months in just one dose, labeled for use in patients weighing ≥30 kg (66 lbs). (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Prefilled syringes'.)

A study of 31 expired autoinjectors (EpiPens) found that devices as much as four years past the expiration date still contained 84 to 88 percent of the intended epinephrine dose [34]. Thus, patients should understand that expired devices retain most of their potency and that if anaphylaxis develops, using an outdated device is preferable to not injecting epinephrine at all. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Use of expired autoinjectors'.)

Introducing solids in infants with milk or soy FPIES (June 2017)

Food protein-induced enterocolitis syndrome (FPIES) is a nonimmunoglobulin E (IgE)-mediated gastrointestinal food hypersensitivity most commonly caused by cow's milk (CM) or soy protein. Recent international consensus guidelines from the American Academy of Allergy, Asthma & Immunology and the International FPIES Association advocacy group provide guidance on the introduction of solid foods in infants with CM or soy FPIES (table 1) [35]. In accordance with these guidelines, for infants with CM or soy FPIES, we suggest introduction of vegetables and then fruits, rather than cereals, at four to six months of age, to reduce the risk of reactions to rice and other grains that may occur among infants with CM or soy FPIES. (See "Food protein-induced enterocolitis syndrome (FPIES)", section on 'Introduction of new foods'.)

New guidelines for management of peanut and tree nut allergies (June 2017)

The most straightforward approach in managing any food allergy is complete avoidance of the culprit food and all similar foods, particularly for peanut and tree nuts. However, some patients may find this approach too burdensome. Reflecting a shift in clinical practice, the recent British Society of Allergy and Clinical Immunology guidelines permit, with certain restrictions, consumption of similar foods after confirming that they are safe, if the patient and family prefer this approach [36]. This guideline for the management of peanut and tree nut allergy is consistent with our approach. (See "Peanut, tree nut, and seed allergy: Management", section on 'Clinical scenarios'.)

Adalimumab for uveitis in juvenile idiopathic arthritis (May 2017)

Adalimumab, a human anti-tumor necrosis factor (TNF) alpha monoclonal antibody that is effective in adults with uveitis, has now been shown to be effective for treatment-resistant, juvenile idiopathic arthritis (JIA)-associated uveitis. In the randomized SYCAMORE trial involving 90 children, the addition of adalimumab to ongoing therapy with methotrexate and topical glucocorticoids with our without systemic glucocorticoids reduced intraocular inflammation and lowered the rate of treatment failure compared with placebo [37]. Serious adverse events were infrequent in both groups but occurred more commonly with adalimumab. Although more data are needed on long-term outcomes and safety, these results add support to the use of adalimumab in children with JIA-associated uveitis that fails to respond to glucocorticoids and methotrexate. (See "Oligoarticular juvenile idiopathic arthritis", section on 'Treatment'.)

DERMATOLOGY

Guidelines for comorbidity screening in children with psoriasis (May 2017)

The best approach for screening children with psoriasis for comorbidities has been unclear. An expert consensus document by members of the Pediatric Dermatology Research Alliance and National Psoriasis Foundation provides the first set of guidelines, including recommendations for assessment for overweight or obese status, diabetes, hyperlipidemia, hypertension, nonalcoholic fatty liver disease, psoriatic arthritis, depression, anxiety, and substance abuse [38]. Our approach to screening children with psoriasis is consistent with these guidelines. (See "Psoriasis in children: Epidemiology, clinical manifestations, and diagnosis", section on 'Additional evaluation'.)

DEVELOPMENTAL AND BEHAVIORAL PROBLEMS

Music therapy for children with autism spectrum disorder (September 2017)

In small clinical trials in children with autism spectrum disorder (ASD), music therapy was associated with improved social skills, quality of life, and parent-child interaction. Now a multicenter randomized trial in over 360 young children with ASD reported the addition of music therapy to usual care plus parent ASD counseling did not improve social skills [39], but the duration of the intervention and follow-up may have been insufficient as the trial was stopped after five months due to limited funding. Given the limitations of existing evidence, we do not specifically encourage music therapy for children with ASD but consider it an acceptable component of a comprehensive behavior program. (See "Autism spectrum disorder in children and adolescents: Complementary and alternative therapies", section on 'Music therapy'.)

EMERGENCY MEDICINE

ACCM practice parameters for management of pediatric and neonatal septic shock (August 2017)

The American College of Critical Care Medicine (ACCM) has published new practice parameters for hemodynamic support of pediatric and neonatal septic shock that continue to emphasize timely fluid administration, early initiation of broad-spectrum antibiotics, and, in patients with fluid refractory shock, prompt administration of vasoactive drug infusions (algorithm 1) [40]. After resuscitation, management is targeted to improving physiologic indicators of perfusion and vital organ function within the first six hours of care (table 2). The guidelines also recommend that each pediatric institution develop multidisciplinary approaches or "bundles" designed to increase adherence to these guidelines, decrease time to therapy, and improve outcomes in pediatric septic shock. (See "Septic shock in children: Rapid recognition and initial resuscitation (first hour)" and "Septic shock in children: Ongoing management after resuscitation".)

Home use of topical anesthesia to control pain from corneal abrasions (August 2017)

In a retrospective study of 444 patients with corneal abrasions given a 24-hour supply of topical tetracaine at the initial emergency department visit, there were no documented serious complications or uncommon adverse events [41]. However, definitive outcomes were only known for 120 patients who returned for rechecks. Patients receiving topical tetracaine were more likely to return for emergency department reevaluation compared with patients who did not receive tetracaine. Topical analgesia was prescribed inappropriately in one-third of patients, for lesions other than simple corneal abrasion (eg, large corneal abrasions, retained rust rings, herpes keratitis, anterior uveitis, and corneal erosions). Because of the possibility of overuse (ie, use beyond 24 hours) and the risk of inappropriate administration, we favor other means of pain control and discourage the prescribing of topical anesthetic agents. More evidence is needed to establish the safety of this practice in patients with simple corneal abrasions. (See "Corneal abrasions and corneal foreign bodies: Management", section on 'Pain control'.)

The Pediatric Sedation State Scale to assess pediatric procedural sedation (July 2017)

The Pediatric Sedation State Scale (PSSS) identifies six levels of sedation based on patient behavior (including patient interference with the procedure and need for restraint) and physiologic parameters (table 3). The PSSS is derived from expert opinion and has been validated, using a small sample of patients and observers, with high inter- and intra-observer agreement [42]. Scales that simply measure the depth of sedation track only one aspect of this practice and do not assess key findings that identify whether the goals of procedural sedation are met. We suggest the use of the PSSS to provide a simple and rapid means of effectively documenting and communicating the quality of pediatric sedation. (See "Procedural sedation in children outside of the operating room", section on 'Sedation state'.)

Delay of appendectomy up to 24 hours not related to appendiceal perforation in children with appendicitis (June 2017)

In the past, appendicitis has been considered a surgical emergency that requires prompt appendectomy to avoid perforation and other complications. In a multicenter, prospective observational study of 955 children 3 to 18 years of age, all of whom were treated with appendectomy for appendicitis within 24 hours of arrival to the emergency department, duration of time between initial evaluation and operation was not associated with an increase in appendiceal perforation [43]. This study adds to a growing body of evidence that suggests that adverse outcomes are not increased for children who receive timely administration of antibiotics and undergo appendectomy less than 24 hours after diagnosis. (See "Acute appendicitis in children: Management", section on 'Timing of operation'.)

Safety and efficacy of nonoperative treatment of pediatric appendicitis (March 2017)

In a systematic review of 10 studies that provided outcomes for over 400 children undergoing nonoperative treatment (NOT, antibiotics without immediate surgery) of early, uncomplicated appendicitis, initial treatment was effective in 88 to 99 percent of patients and was associated with no appendectomy at reported follow-up in 62 to 92 percent of patients [44]. Complications and total length of hospital stay appeared similar during follow-up for NOT and appendectomy. Pooled estimates were performed by the investigators but, given the underlying variation in methodology of the included studies, may be misleading, particularly given subsequent evidence suggesting that patient selection strongly influences outcomes of NOT for appendicitis [45-47]. Although appendectomy remains the treatment of choice for most children with early, uncomplicated appendicitis, NOT is an alternative for selected patients based upon caregiver preference. Additional research is needed to determine which patients are least likely to fail nonoperative treatment. (See "Acute appendicitis in children: Management", section on 'Nonoperative management'.)

ENDOCRINOLOGY

Increasing incidence of type 2 diabetes among youth (June 2017)

The incidence of type 2 diabetes mellitus (T2DM) among youth in the United States continues to rise, in parallel with the increasing rate of severe obesity. In a report from a large US dataset of youth ages 10 to 19 years, the incidence of T2DM rose by almost 5 percent annually, with the greatest annual increases among Asian/Pacific Islanders and Native Americans [48]. These findings call for ongoing efforts to mitigate the modifiable risk factors for T2DM, including obesity and access to health care, particularly among high-risk groups. (See "Epidemiology, presentation, and diagnosis of type 2 diabetes mellitus in children and adolescents", section on 'Epidemiology'.)

High risk for vascular complications in youth with type 2 diabetes (April 2017)

In a large prospective study following outcomes in youth who had been diagnosed with diabetes before age 20, those with type 2 diabetes mellitus (T2DM) had high rates of diabetic kidney disease, retinopathy, and neuropathy (20, 9, and 18 percent, respectively) after a mean diabetes duration of eight years [49]. Moreover, the risk of these complications was more than twofold higher than in those diagnosed with type 1 diabetes mellitus (T1DM), after adjustment for age, disease duration, glycemia, and obesity. These findings emphasize the need to monitor youth with either T2DM or T1DM for development of complications. (See "Comorbidities and complications of type 2 diabetes mellitus in children and adolescents", section on 'Introduction'.)

GASTROENTEROLOGY, HEPATOLOGY, AND NUTRITION

Self-administered hypnotherapy for functional abdominal pain in children and adolescents (June 2017)

Increasing evidence suggests that gut-directed hypnotherapy reduces pain frequency and intensity in children and adolescents with functional abdominal pain disorders (FAPDs). In a trial of this therapy that randomly assigned children (age 8 to 18 years) with FAPDs to a self-administered home-based approach using a compact disc or to individual therapy with a qualified therapist for three months, over 60 percent of each group had ≥50 percent reduction in pain frequency and intensity at one-year follow-up [50]. These findings suggest that self-directed hypnotherapy is a reasonable option for children and adolescents with FAPDs, particularly if trained therapists are not available. (See "Functional abdominal pain in children and adolescents: Management in primary care", section on 'Improved coping'.)

Lactate and pyruvate in pediatric acute liver failure (May 2017)

Mitochondrial disorders are increasingly recognized as an important cause of pediatric acute liver failure (PALF), especially in young infants. Data from a large registry study shows that lactic acidosis and an elevated molar ratio of lactate to pyruvate occur across all diagnostic categories in PALF, and thus are not reliable measures to identify patients with a mitochondrial disorder [51]. (See "Acute liver failure in children: Etiology and evaluation", section on 'Young infants'.)

Psychological and behavioral symptoms in young children with celiac disease (May 2017)

Untreated celiac disease in children has been associated with subtle neurologic or behavioral symptoms, but previous studies may have been confounded by the parents' knowledge of the child's celiac disease diagnosis. A new study has found that three-year-old children with persistently positive tissue transglutaminase (tTG) antibodies and not on a gluten-free diet were more likely to manifest subtle behavioral symptoms (anxiety, depression, aggressive behavior, or sleep problems) compared with those with negative tTG antibodies [52]. The parents were unaware of the child's tTG status when they reported the behavioral symptoms. These findings lend further support to an association between celiac disease and behavioral symptoms in young children. (See "Epidemiology, pathogenesis, and clinical manifestations of celiac disease in children", section on 'Neurologic disease and behavioral symptoms'.)

USPSTF statement on screening for celiac disease (April 2017)

Testing for celiac disease in the absence of suggestive signs or symptoms is controversial. A US Preventive Services Task Force report has concluded that there are insufficient data to support screening for celiac disease [53]. However, we continue to test for celiac disease in asymptomatic first-degree relatives of patients with a confirmed diagnosis of celiac disease because of their increased risk for disease. We also recommend screening asymptomatic children with several conditions associated with celiac disease, including type 1 diabetes and Down syndrome. Our recommendations are consistent with guidelines from the American College of Gastroenterology and from Pediatric Gastroenterology societies [54]. (See "Diagnosis of celiac disease in adults", section on 'Who should be tested'.)

GENETICS AND PEDIATRIC METABOLISM

Increased nuchal translucency and Noonan syndrome (August 2017)

Increased nuchal translucency on first trimester ultrasound screening has been associated with over 100 developmental and genetic syndromes. In a retrospective study in which a Noonan syndrome gene sequencing panel was obtained in 39 euploid fetuses with nuchal translucency ≥3.0 mm (median thickness 4.0 mm), 10 percent had variants consistent with Noonan syndrome [55]. It may be reasonable to offer screening for genetic mutations associated with Noonan syndrome in euploid fetuses with nuchal translucency ≥3.0 mm, but prospective studies are still needed to validate this result. (See "Cystic hygroma and increased nuchal translucency", section on 'Targeted genetic studies'.)

Genomic sequencing to identify inherited pathogenic genes in families of individuals with multiple congenital malformations (August 2017)

Next-generation sequencing, such as whole exome or whole genome sequencing, is used to aid in diagnosis of complex diseases such as severe intellectual disability or developmental delay. A study that used these techniques to evaluate patients with multiple congenital malformations and their family members identified four families with loss-of-function variants in two genes leading to nicotinamide adenine dinucleotide (NAD) deficiency (HAAO, encoding 3-hydroxyanthranilic acid 3,4-dioxygenase, and KYNU, encoding kynureninase) [56]. In a mouse model of these defects, niacin supplementation during gestation corrected the NAD deficiency and prevented abnormal embryogenesis and fetal death. (See "Birth defects: Causes", section on 'Disorders due to single gene defects' and "Principles and clinical applications of next-generation DNA sequencing", section on 'Diagnosis of complex diseases'.)

Predictive tool for sleep apnea in children with Down syndrome (March 2017)

Polysomnography or pulse oximetry monitoring during sleep is recommended in all children with Down syndrome by four years of age because of their increased risk of obstructive sleep apnea (OSA). A predictive model using a validated sleep questionnaire, medication history, patient age, anthropometric measurements, vital signs, and physical exam findings had a high negative predictive value for moderate to severe OSA [57]. If confirmed in validation studies, this tool could decrease the number of diagnostic sleep studies needed in children with Down syndrome. (See "Down syndrome: Management", section on 'Sleep apnea'.)

Revised clinical criteria for neurofibromatosis type 2 (March 2017)

Clinical criteria for neurofibromatosis type 2 (NF2), caused by mutations in the NF2 gene, have been modified to include requirement for negative LZTR1 genetic testing in patients with a unilateral vestibular schwannoma and two or more non-intradermal schwannomas [58]. Previously, these patients would have met clinical criteria for NF2. The change was prompted by recognition that the phenotypic spectrum of both NF2 and LZTR1-related schwannomatosis includes unilateral vestibular schwannoma in selected patients. (See "Neurofibromatosis type 2", section on 'Clinical criteria'.)

HEMATOLOGY AND ONCOLOGY

Updated guidelines for empiric antifungal therapy for children with fever and neutropenia (June 2017)

Updated guidelines from the International Pediatric Fever and Neutropenia Guideline Panel consider children with cancer or hematopoietic cell transplant as high risk for invasive fungal infection if they have acute myelogenous leukemia, high-risk acute lymphoblastic leukemia, relapsed acute leukemia, neutropenia for >10 days, or are receiving high-dose corticosteroids [59]. In contrast to the previous guideline, they weakly recommend against initiating empiric antifungal therapy for low-risk patients, using serial galactomannan to guide antifungal therapy, and obtaining computed tomography images of the sinuses before initiating antifungal therapy unless the patient has localizing signs or symptoms. They also now suggest abdominal imaging before initiation of antifungal therapy in high-risk patients. (See "Fever in children with chemotherapy-induced neutropenia", section on 'Antifungal therapy'.)

INFECTIOUS DISEASES AND IMMUNIZATIONS

Third dose of MMR for prevention of mumps in an outbreak setting (September 2017)

In a mumps outbreak setting, in addition to ensuring that incompletely immunized individuals receive the standard two-dose measles, mumps, and rubella (MMR) vaccine series, public health authorities may recommend a third dose of MMR under certain circumstances (eg, two-dose vaccination coverage >90 percent, intense exposure setting, high attack rate). During a mumps outbreak at a university with over 20,000 enrolled students, almost all of whom had previously received two vaccine doses, nearly 5000 students received a third MMR dose [60]. The mumps attack rate (259 cases overall) was lower among students who had received three rather than two vaccine doses (6.7 versus 14.5 cases per 1000 persons); in adjusted analysis, the third MMR dose was associated with a 78 percent lower risk of mumps. (See "Mumps", section on 'Prevention'.)

2017-2018 influenza immunization recommendations for the United States (September 2017)

The Advisory Committee on Immunization Practices (ACIP) and the American Academy of Pediatrics (AAP) have released recommendations for influenza immunization for the 2017-2018 season in the United States [61,62]. Routine influenza immunization with a licensed, age-appropriate vaccine (table 4) is recommended for all persons ≥6 months of age. Live attenuated influenza vaccine is not recommended for the 2017-2018 season. Pregnant women and persons with egg allergy of any severity can receive any licensed, age-appropriate inactivated influenza vaccine with standard immunization precautions. Although neither the ACIP nor the AAP provide a preference for a particular formulation, we favor a quadrivalent vaccine when available for adults <65 years and we recommend the high-dose vaccine for those ≥65 years. (See "Seasonal influenza in children: Prevention with vaccines", section on 'Types of vaccine' and "Seasonal influenza vaccination in adults", section on 'Choice of vaccine formulation' and "Influenza and pregnancy", section on 'Vaccination' and "Influenza vaccination in individuals with egg allergy", section on 'Safety of vaccines in patients with egg allergy'.)

Risk of congenital Zika virus syndrome (June 2017)

The magnitude of risk of birth defects resulting from in utero exposure to Zika virus is uncertain. The Centers for Disease Control and Prevention identified over 2500 pregnant women in US territories with Zika virus infection in early 2017 [63]. Maternal Zika virus infection in the first trimester was associated with an 8 percent incidence of offspring with birth defects, but fell to 4 to 5 percent with infection in the second and third trimesters. Because of study limitations, these figures likely understate the true risk of any congenital adverse outcome. Importantly, structural birth defects were seen with similar frequency in infants born to women with and without clinical signs and symptoms of Zika virus infection during pregnancy. (See "Zika virus infection: Evaluation and management of pregnant women", section on 'Risk of vertical transmission and anomalies'.)

Rising rates of HCV infection in young women in the United States (May 2017)

In parallel with the opioid and injection drug use epidemic in the United States, rates of hepatitis C virus (HCV) infection have been increasing over the past decade. In particular, the annual number of acute HCV cases among women aged 15 to 44 years rose 3.6-fold from 2006 to 2014 [64]. An estimated 29,000 women with HCV infection gave birth each year between 2011 and 2014; since the risk of vertical transmission is approximately 5.8 percent, this implies that an estimated 1700 infants were infected annually during this time. These numbers highlight the importance of screening at-risk individuals and arranging follow-up for those with HCV infection. (See "Vertical transmission of hepatitis C virus", section on 'Incidence' and "Hepatitis C virus infection in children", section on 'Epidemiology'.)

Investigational low-cost, heat-stable rotavirus vaccine for infants (May 2017)

Rotavirus gastroenteritis is an important cause of mortality in children younger than five years. Although effective vaccines are available, cost and need for refrigeration have limited vaccine uptake. Bovine rotavirus pentavalent vaccine (BRV-PV) is an investigational live, oral, heat-stable vaccine that is administered to infants at 6, 10, and 14 weeks of age. In a placebo-controlled randomized trial in more than 3500 Nigerien infants, BRV-PV was 67 percent efficacious in preventing laboratory-confirmed severe rotavirus gastroenteritis [65]. BRV-PV is less expensive than currently licensed vaccines and holds promise for vaccination programs in areas where cold-chain capacity is limited. (See "Rotavirus vaccines for infants", section on 'Other vaccines'.)

Maternal Tdap vaccination and prevention of infant pertussis (May 2017)

Immunization with the tetanus, diphtheria, and acellular pertussis (Tdap) vaccine is recommended for women during each pregnancy in order to provide passive protection against pertussis to their infants. Although passive transfer of maternal antibodies can blunt the infant's own immune response to infant doses of the diphtheria, tetanus toxoids, and acellular pertussis (DTaP) vaccine, it does not appear to interfere with clinical vaccine efficacy. In a retrospective study of nearly 150,000 infants at every level of DTaP vaccine exposure, infants exposed in utero to Tdap vaccine were better protected against pertussis during the first year of life than infants not exposed in utero [66]. (See "Immunizations during pregnancy", section on 'Rationale, efficacy, and safety'.)

Decreased susceptibility to fluoroquinolones in Shigella infection (April 2017)

When treatment for Shigella infection is indicated, susceptibility testing should be performed to guide antimicrobial selection. In the United States, an increasing proportion of Shigella isolates have minimum inhibitory concentrations (MIC) to ciprofloxacin of 0.12 to 1 mcg/mL [67]. Although these MIC values are considered susceptible and their impact on treatment outcomes in Shigella is unknown, they are associated with resistance genes that result in worse outcomes with fluoroquinolone treatment in other Enterobacteriaceae. Clinicians should request the MIC to ciprofloxacin if it is not provided with susceptibility results and avoid fluoroquinolones if the MIC is ≥0.12 mcg/mL. (See "Shigella infection: Clinical manifestations and diagnosis", section on 'Susceptibility testing' and "Shigella infection: Treatment and prevention in adults", section on 'Antibiotic selection'.)

IDSA guidelines on healthcare-associated ventriculitis and meningitis (April 2017)

The Infectious Diseases Society of America published new guidelines related to healthcare-associated ventriculitis and meningitis in March 2017 [68]. They provide guidance for clinicians on the clinical manifestations, diagnosis, treatment, and prevention of ventriculitis and meningitis in patients with central nervous system hardware, with a focus on cerebrospinal fluid shunts and drains, and in patients who have had neurosurgery or head trauma. Main concepts include the need for a low threshold of suspicion given the potentially subtle clinical findings of these infections and the importance of selecting an antimicrobial regimen that has bactericidal activity and achieves adequate concentrations in the cerebrospinal fluid. Our recommendations are generally consistent with these guidelines. (See "Infections of cerebrospinal fluid shunts and other devices", section on 'Treatment' and "Initial therapy and prognosis of bacterial meningitis in adults", section on 'Healthcare-associated meningitis' and "Gram-negative bacillary meningitis: Treatment".)

E. coli O157:H7 outbreak associated with soy nut butter (March 2017)

Escherichia coli O157:H7, which causes bloody diarrhea and is associated with the hemolytic-uremic syndrome, is typically transmitted through contaminated beef products and produce, but other foods have also been implicated in outbreaks. In the United States, a particular brand of soy nut butter (I.M. Healthy) has been linked to a multistate E. coli O157:H7 outbreak that has affected mainly children [69]. Although the soy nut butter products have been recalled, individuals should be advised to avoid and discard any remaining product, and the possibility of E. coli O157:H7 infection should be considered in exposed patients with diarrheal illnesses. Details on the outbreak can be found on the Centers for Disease Control and Prevention website. (See "Microbiology, pathogenesis, epidemiology, and prevention of enterohemorrhagic Escherichia coli (EHEC)", section on 'Other foods'.)

NEPHROLOGY AND UROLOGY

Prevention of meningococcal infection in patients receiving eculizumab (August 2017)

Eculizumab is a monoclonal antibody used for treatment of complement-mediated hemolytic uremic syndrome and paroxysmal nocturnal hemoglobinuria. It has been associated with a 1000 to 2000-fold increased incidence of meningococcal disease, including life-threatening and fatal infection. Therefore, patients should be immunized with meningococcal vaccines (both ACYW135 and serogroup B), if possible, at least two weeks prior to receiving a first dose of eculizumab. However, invasive meningococcal disease has occurred among patients receiving eculizumab despite receipt of meningococcal vaccine, including infections caused by non-typeable strains not included in the vaccines [70]. Accordingly, in addition to vaccination, we suggest daily antimicrobial prophylaxis (penicillin or, for penicillin-allergic patients, a macrolide) for prevention of meningococcal infection in all patients treated with eculizumab. In addition, patients should be monitored for signs of meningococcal infection and evaluated immediately if infection is suspected. (See "Treatment and prevention of meningococcal infection", section on 'Patients receiving eculizumab'.)

Discontinuation of eculizumab in complement-mediated hemolytic uremic syndrome (June 2017)

Eculizumab is an effective treatment for complement-mediated hemolytic uremic syndrome (HUS). Monthly intravenous maintenance administration has been the standard of care for patients attaining complete remission. Now, two case series have reported successful discontinuation of eculizumab in most patients, with successful remission after early resumption of therapy in those who relapsed [71,72]. Although these results are promising, further studies are needed to determine the optimal time to discontinue eculizumab therapy and the patient population in whom therapy can be safely discontinued. Until these data are available, the decision to withdraw eculizumab therapy should be made in conjunction with a clinician with expertise in managing patients with complement-mediated HUS. Close monitoring after withdrawal is required so eculizumab can be reinitiated if relapse occurs. (See "Complement-mediated hemolytic uremic syndrome", section on 'Discontinuation'.)

NEUROLOGY

Genetic testing in neonates with epileptic encephalopathy (August 2017)

The role of genetic testing in the clinical care of neonates with epilepsy is evolving as the number of monogenetic causes of early epileptic encephalopathy increases and specific treatments become available for some syndromes. In a prospective cohort study of over 600 consecutive newborns with seizures, 13 percent had an epilepsy syndrome, including 35 infants (6 percent) with epileptic encephalopathy [73]. Among these, the large majority had a genetic etiology identified by genetic testing, most commonly KCNQ2 encephalopathy, for which sodium channel blocking antiseizure drugs are a preferred therapy. We pursue genetic testing in neonates with epilepsy who do not have an acute symptomatic cause identified on initial history, examination, and neuroimaging. (See "Clinical features, evaluation, and diagnosis of neonatal seizures", section on 'Genetic testing'.)

Low yield of lumbar puncture after complex febrile seizure (July 2017)

After a febrile seizure, lumbar puncture to assess for infection can be avoided in most well-appearing children who have returned to their baseline, even when the febrile seizure has complex features (ie, focal onset, >15 minutes in duration, or recurrent within 24 hours). In a multicenter cohort study of more than 800 children age six months to five years presenting to a pediatric emergency department with a complex febrile seizure, rates of bacterial meningitis and herpes simplex encephalitis were 0.7 and 0 percent, respectively [74]. All five cases of infection occurred in children with a clinical examination suggestive of meningitis. (See "Clinical features and evaluation of febrile seizures", section on 'Lumbar puncture'.)

Cannabidiol in patients with Dravet syndrome and refractory epilepsy (May 2017)

Although cannabidiol (CBD), a component of cannabis, has received interest in the epilepsy community, particularly in children with Dravet syndrome (DS), controlled trials have not been available. In the first multicenter trial comparing oral CBD solution with placebo (in addition to standard antiseizure treatment) in 120 children and young adults with DS, seizure frequency was decreased at 14 weeks in the CBD group [75]. Common side effects of CBD were diarrhea, sedation, and fatigue. Further study of CBD in patients with refractory epilepsy is indicated. In the absence of an available regulated preparation of CBD, we do not advocate use of cannabis or its derivatives outside of the context of a clinical trial. (See "Dravet syndrome: Management and prognosis", section on 'Cannabinoids'.)

Consensus panel guidelines on Dravet syndrome in children and adults (April 2017)

A North American consensus panel has published guidelines on the diagnosis and management of Dravet syndrome (DS), an early-onset epileptic encephalopathy most often due to de novo mutations in the voltage-gated sodium channel, alpha-1 subunit (SCN1A) gene [76]. The document includes a description of the typical clinical presentation of DS; guidance on genetic testing and family counseling; and recommendations for first-line treatment with clobazam and/or valproic acid, avoidance of sodium channel blocking drugs, and provision of home rescue medications and an emergency seizure protocol. DS should be suspected in previously healthy infants presenting with recurrent tonic-clonic seizures, often in the setting of fever, beginning before one year of age and associated with neurodevelopmental regression after the onset of seizures. (See "Dravet syndrome: Genetics, clinical features, and diagnosis" and "Dravet syndrome: Management and prognosis".)

PULMONOLOGY

Ivacaftor for treatment of cystic fibrosis (June 2017)

Ivacaftor is an effective therapy for patients with cystic fibrosis caused by certain types of cystic fibrosis transmembrane regulator (CFTR) mutations. It is used in patients with G551D and nine other mutations. Now, the US Food and Drug Administration (FDA) has expanded the indications for ivacaftor treatment to include 23 additional mutations, based primarily on in vitro testing of responsiveness to ivacaftor [77,78]. We recommend treatment with ivacaftor for patients two years and older who carry at least one copy of G551D or another mutation listed in the table (table 5). (See "Cystic fibrosis: Overview of the treatment of lung disease", section on 'Ivacaftor for G551D, other gating mutations, and residual function mutations'.)

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