Monday, February 22, 2016

What is new in Pediatrics / Actualización en Pediatría



Bienvenido, Biblioteca Centro Medico Caracas
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What's new in pediatrics
What's new in pediatrics
Disclosures: Alison G Hoppin, MD Nothing to disclose. Melanie S Kim, MD Nothing to disclose. Elizabeth TePas, MD, MS Nothing to disclose. Mary M Torchia, MD Nothing to disclose. Carrie Armsby, MD, MPH Nothing to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence.
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All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Jan 2016. | This topic last updated: Feb 19, 2016.
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
Screening for perinatal depression (February 2016)
Up to 15 percent of pregnant women experience depression either during pregnancy or in the postpartum period. Perinatal depression is under-recognized and associated with adverse outcomes including preterm birth, impaired fetal growth, lower birth weight, and impaired maternal-infant bonding. A systematic review, comparing usual care with a program for depression screening during pregnancy (one trial) or postpartum (four trials), found that screening reduced the prevalence of depression at three- to five-month follow-up (absolute reduction 2.1 to 9.1 percent) [1,2]. We suggest routine screening for depression during pregnancy and at the six-week postpartum visit, with services available to ensure follow-up for diagnosis and treatment. The most widely used screening instrument is the 10-item Edinburgh Postnatal Depression Scale (figure 1A-B), which also can be used for prenatal depression. This approach is consistent with practice guidelines issued by the US Preventive Services Task Force, the American College of Obstetricians and Gynecologists, and the United Kingdom National Institute for Health and Care Excellence. (See "Unipolar major depression in pregnant women: Clinical features, consequences, assessment, and diagnosis" and "Postpartum blues and unipolar depression: Epidemiology, clinical features, assessment, and diagnosis".)
Evaluation of genetic testing to predict progression in adolescent idiopathic scoliosis (February 2016)
Determining the risk of progression is a crucial factor in the management of adolescent idiopathic scoliosis (AIS). Clinical factors used to predict the risk of progression include radiologic markers of skeletal maturity, age, sex, sexual maturity rating, and location and type of curve. However, accurate prediction of progression using clinical factors is limited. The AIS prognostic test (AIS-PT, marketed as ScoliScore) is an algorithm that incorporates saliva-based DNA testing to predict the risk of scoliosis progression in skeletally immature Caucasian patients with mild scoliosis. In an independent evaluation, AIS-PT scores did not differ between patients with and without curve progression [3]. Independent studies in other populations have also failed to validate the AIS-PT. Lack of validation of the AIS-PT in independent cohorts may be related to differences in the test population, genetic variability, or loss to follow-up of patients with nonprogressive scoliosis [3,4]. Until these issues are resolved, we continue to use clinical factors to predict the risk of progression in patients with AIS. (See "Adolescent idiopathic scoliosis: Management and prognosis", section on 'Genetic testing'.)
Updated guidelines for evaluation of the visual system in children (January 2016)
The American Academy of Pediatrics has issued a policy statement with updated guidelines to aid pediatricians in the assessment of the visual system in infants, children, and adolescents [5]. Changes from previous guidelines include recommendations for instrument-based screening beginning at age 12 months and preference of HOTV or LEA charts over other charts for assessment of visual acuity in young children. Our approach is consistent with these new guidelines. (See "Visual development and vision assessment in infants and children", section on 'Overview of vision assessment'.)
Outcomes of weight loss surgery for adolescents (January 2016)
Weight loss surgery is an important option for managing severe obesity in adolescents. In the past, this approach was based on outcomes in adults and on retrospective case series in adolescents. Now, a prospective study provides robust evidence for beneficial outcomes of weight loss surgery in adolescents. Among 242 adolescents with severe obesity undergoing weight loss surgery, body mass index (BMI) decreased by 27 percent at three years of follow-up [6]. Weight loss was similar for those undergoing gastric bypass compared with sleeve gastrectomy. Surgery also resulted in improved quality of life and resolution or improvement of comorbidities, including type 2 diabetes, dyslipidemia, hypertension, and abnormal kidney function. (See "Surgical management of severe obesity in adolescents", section on 'Weight loss' and "Surgical management of severe obesity in adolescents", section on 'Comorbidity improvement'.)
Cost analysis following implementation of the Low Risk Ankle Rule in children (December 2015)
Use of the Low Risk Ankle Rule (LRAR) (figure 2) in addition to routine physical examination for children 3 to 16 years of age with acute isolated ankle injuries may help determine when plain radiographs of the ankle are not required and has been associated with reduced ankle radiography. In a cost analysis of over 2100 children undergoing evaluation for ankle injuries at multiple facilities, use of the LRAR was associated with significant overall cost reductions when compared with routine clinical practice [7]. The greatest savings were due to lower radiography costs and fewer orthopedic or emergency department follow-up visits. (See "Ankle fractures in children", section on 'Low Risk Ankle Rule'.)
Prevention of positional skull flattening (deformational plagiocephaly) (October 2015)
The frequency of positional skull flattening (deformational plagiocephaly) has increased, in part because of supine sleep positioning to prevent sudden infant death syndrome. Additional risk factors include limited head rotation and decreased activity levels. In a recent trial that randomly assigned parents to receive guidance on infant positioning to prevent sudden infant death syndrome (control group) or this guidance plus detailed advice about infant environment, handling, and positioning (intervention group), infants in the intervention group had a lower rate of positional flattening and less severe asymmetry [8]. Thus, creating a nonrestrictive infant environment that encourages spontaneous physical movement and enhances symmetrical motor development can prevent or diminish the severity of positional skull flattening. (See "Overview of craniosynostosis", section on 'Positional flattening (positional plagiocephaly)'.)
Outdoor activity for prevention of myopia in children (October 2015)
The prevalence of myopia (nearsightedness) increases throughout childhood, particularly during and after puberty. Myopia often progresses as children grow older and high levels of myopia are associated with an increased risk of sight-threatening complications later in life (eg, myopic macular degeneration and retinal detachment). In a recent study, 1913 school children in China were randomized (by school) to an additional daily 40-minute outdoor class or usual activity [9]. The cumulative incidence rate of myopia over three years was lower in the intervention group compared with the control group (30 versus 40 percent). This is the first study to demonstrate an effective preventative strategy. Increasing the amount of time children spend outdoors is a simple intervention and can be discussed with patients and their families as a strategy to reduce the risk of developing myopia and/or slow its progression. (See "Refractive errors in children", section on 'Myopia'.)
Prevention of alcohol use in children and adolescents (October 2015)
Alcohol is frequently used by children and adolescents in the United States and its use is associated with death and serious injury. In August 2015, the American Academy of Pediatrics (AAP) released a clinical report encouraging pediatric clinicians to talk about the dangers of alcohol with children as young as nine years of age, when they may begin to form positive attitudes towards alcohol [10]. The AAP also recommends screening all youth for alcohol use with a structured screening instrument, either as part of more general substance use screening or, if time is limited, with an instrument that focuses on alcohol, such as the two-question screen developed in collaboration with the National Institute on Alcohol Abuse and Alcoholism (table 1). We agree with these recommendations. (See "Screening tests in children and adolescents", section on 'Alcohol and substance use'.)
E-cigarette use and use of combustible tobacco products (August 2015)
Studies have associated e-cigarette use with an increased risk of conventional cigarette smoking among youth. A new prospective study was conducted in 2530 ninth-grade students who had never used a combustible tobacco product and compared students who had ever used e-cigarettes with never users [11]. Compared with never users, ever users of e-cigarettes were more likely to report use of any combustible tobacco product at both 6-month (31 versus 8 percent) and 12-month (25 versus 9 percent) follow-up. Additionally, after adjusting for other risk factors for smoking, baseline e-cigarette use was associated with a greater likelihood of use of any combustible tobacco product (OR 2.7), including conventional cigarettes, cigars, and hookahs. (See "E-cigarettes", section on 'Effect on smoking initiation among youth'.)
NEONATOLOGY
Low target oxygen levels increase mortality in extremely preterm infants (February 2016)
The optimal range for oxygen saturation in preterm infants is controversial. The Benefits of Oxygen Saturation Targeting (BOOST II) trial evaluated outcomes of preterm infants randomly assigned to oxygen saturation targets of 85 to 89 percent versus 91 to 95 percent in the United Kingdom (UK), Australia, and New Zealand. A subsequent analysis limited to combined data from the Australia and UK study centers confirmed previous reports that in extremely preterm infants (gestational age less than 28 weeks), low target oxygen (85 to 89 percent) was associated with increased mortality compared with high target oxygen levels (91 to 95 percent) [12]. These results support our recommendation for using a targeted oxygen saturation goal between 90 and 95 percent for preterm infants. (See "Oxygen monitoring and therapy in the newborn", section on 'Clinical trials'.)
Zika virus infection in the Americas (January 2016)
Zika virus is a member of the flavivirus family that is spread via mosquito bites. Outbreaks have occurred in Africa, Southeast Asia, and the Pacific Islands; more recently Zika virus has spread to the Americas. More than 20 countries in Latin America have confirmed circulation; cases of Zika virus infection in the United States have occurred among returning travelers. The illness is usually mild; typical symptoms include fever, rash, joint pain, and conjunctivitis. However, Zika virus infection has also been associated with perinatal complications (congenital microcephaly and fetal losses) and Guillain-Barre syndrome [13]. In 2015-2016, more than 4000 cases of microcephaly were reported among newborns in Brazil; this represents a 20-fold increase in the number of cases compared with years prior to the circulation of Zika virus [14]. A number of authorities have advised that pregnant women consider postponing travel to areas with ongoing mosquito transmission of Zika virus [15]. Anecdotal reports of apparent sexual transmission have been described [16]. Although this appears to be an infrequent mechanism for Zika virus transmission, it is prudent for individuals with Zika virus infection/exposure to abstain from sexual activity (vaginal, anal, and oral sex) or use barrier protection; men who have a pregnant partner should follow such guidance for the duration of the pregnancy. Zika virus is also transmissible via blood products; deferral of blood donors for one month following Zika virus infection/exposure is advised [17]. (See "Zika virus infection", section on 'Geographic distribution'.)
Neonatal and maternal outcomes for planned out-of-hospital birth (January 2016)
In the United States (US), the safety of non-hospital births is unclear. Several studies have reported that women who deliver at home or at a birth center have equal or improved neonatal and maternal outcomes compared with those who deliver in a hospital; however, outcomes of women transferred to the hospital intrapartum or postpartum because of complications were often included with the hospital delivery group, which could have impacted results. In a US study that analyzed birth outcomes by planned birth location rather than actual delivery site, approximately 16 percent of women planning out-of-hospital births (combined home births and freestanding birth centers) required hospital transfer and their infants had higher rates of perinatal death, neonatal seizures, and neonatal ventilator support compared with infants of planned in-hospital births [18]. Mothers who planned out-of-hospital births but delivered in a hospital had fewer obstetric interventions and a higher rate of blood transfusion. For women in the United States, this study provides a more accurate understanding of the outcomes associated with planned out-of-hospital versus planned in-hospital birth. (See "Planned home birth", section on 'Retrospective studies'.)
Rapid correction of neonatal hypoglycemia and neurodevelopmental outcomes (November 2015)
When parenteral glucose administration is used to treat neonatal hypoglycemia in asymptomatic newborns, it is typically initiated with a bolus 2 mL/kg of 10 percent dextrose in water followed by a continuous infusion of 4 to 6 mg/kg/min. However, a study of asymptomatic newborns (gestational age ≥35 weeks) at risk for hypoglycemia found rapid correction of hypoglycemia was associated with poorer neurodevelopmental outcomes at two years of age [19]. These results support starting therapy with continuous glucose infusion and bypassing the initial bolus of 2 mL/kg. (See "Management and outcome of neonatal hypoglycemia", section on 'Parenteral glucose (dextrose) infusion'.)
Endotracheal suctioning does not benefit nonvigorous neonates with meconium-stained amniotic fluid (May 2015, Modified November 2015)
New American Heart Association, American Academy of Pediatrics, and International Liaison Committee on Resuscitation guidelines no longer recommend routine endotracheal suction for nonvigorous (depressed) newborns with meconium-stained amniotic fluid in the delivery room (ie, newborns with absent or depressed respirations, decreased muscle tone, or heart rate less than 100 beats/minute) [20,21]. This change was prompted by findings from a recent randomized clinical trial of endotracheal suctioning versus no suctioning in 122 nonvigorous term newborns with meconium-stained amniotic fluid [22]. No differences were observed between groups in meconium aspiration syndrome, need for mechanical ventilation, survival at nine months of age, and mental and motor developmental status at nine months of age. Our criteria for intervention for newborns with meconium-stained amniotic fluid are the same as those used for intervention in all neonates (algorithm 1). (See "Prevention and management of meconium aspiration syndrome", section on 'Neonatal care' and "Neonatal resuscitation in the delivery room", section on 'Next steps'.)
Defining neonatal hypoglycemia (October 2015)
Defining significant neonatal hypoglycemia requiring intervention based on blood glucose level remains challenging, as illustrated by a recent large prospective study of newborns delivered at ≥35 weeks and at risk for hypoglycemia (eg, maternal diabetes, large for gestational age, fetal growth restriction, prematurity) [19]. Hypoglycemic infants who were treated to maintain blood glucose above 47 mg/dL (2.61 mmol/L) had similar neurodevelopmental outcomes at two years of age as infants who did not develop hypoglycemia within 48 hours of birth. However, these findings did not provide a definitive threshold for treating neonatal hypoglycemia. We continue to use threshold goals that provide a margin of safety for infants at risk for hypoglycemia that are consistent with guidelines developed by the American Academy of Pediatrics and the Pediatric Endocrine Society. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on 'Challenge of defining neonatal hypoglycemia' and "Management and outcome of neonatal hypoglycemia", section on 'Target blood glucose levels'.)
Inhaled steroids and bronchopulmonary dysplasia (October 2015)
Systematic reviews have reported that postnatal administration of inhaled glucocorticoids (eg, budesonide) does not prevent bronchopulmonary dysplasia (BPD) in high-risk extremely preterm infants (gestational age less than 28 weeks). In contrast, a recent large randomized trial in these infants found that early administration of inhaled budesonide (within 24 hours after birth) decreased the incidence of BPD compared with placebo (28 versus 38 percent) [23]. However, a nonstatistical increase in mortality was also observed (16.9 versus 13.6 percent). The authors expressed concerns that the beneficial effect of early inhaled budesonide on BPD prevention was at the expense of increased mortality. We continue to not recommend routine use of inhaled glucocorticoids to prevent BPD until further data clearly demonstrate that this intervention is both efficacious and safe. (See "Postnatal use of glucocorticoids in bronchopulmonary dysplasia", section on 'Prevention of BPD'.)
Conjunctival icterus and bilirubin levels in newborn infants (September 2015)
Based on currently available data, the presence and extent of jaundice has not been a consistently reliable method to predict total serum or plasma bilirubin (TB) concentration for neonatal hyperbilirubinemia. However, a recent observational study of 240 term or late preterm neonates reported that conjunctival icterus may be a useful clinical marker. In this study, all infants with conjunctival icterus had TB levels that were either in the high intermediate or high risk category for severe hyperbilirubinemia (defined as TB >25 mg/dL [428 micromol/L]) using the hour-specific Bhutani nomogram (figure 3) [24]. In addition, most infants with conjunctival icterus had TB >15 mg/dL (257 micromol/L). These results suggest that TB or transcutaneous bilirubin levels should be measured in an infant with conjunctival icterus as these infants are at risk for developing severe hyperbilirubinemia. (See "Clinical manifestations of unconjugated hyperbilirubinemia in term and late preterm infants", section on 'Jaundice'.)
Filtered sunlight phototherapy for neonatal hyperbilirubinemia (September 2015)
A recent Nigerian trial confirmed results from a previous observational study that filtered sunlight using commercial window tinting films (which selectively allow the transmission of blue light and removal of significant amounts of harmful ultraviolet and infrared light rays) is a safe and efficacious method for treating neonatal hyperbilirubinemia [25]. In this trial of 447 term and late preterm infants with an elevated total serum bilirubin (TSB), filtered sunlight therapy for at least five hours a day was as effective as conventional daytime phototherapy in treating neonatal hyperbilirubinemia without adverse effects. Of note, afternoon TSB were measured in all infants, and conventional nighttime phototherapy was provided to all infants from both groups if their afternoon TSB reached a targeted level for phototherapy. These data suggest filtered sunlight phototherapy for neonatal hyperbilirubinemia may be a reasonable option in resource-limited tropical regions with limited availability of conventional phototherapy. (See "Treatment of unconjugated hyperbilirubinemia in term and late preterm infants", section on 'Sunlight exposure'.)
Prolonged hypoxia and increased late mortality and morbidity for extremely premature infants (August 2015)
A meta-analysis of several large clinical trials of extremely premature (EP) infants (gestational age <28 weeks) demonstrated low target pulse oximetry levels of hemoglobin saturation (SpO2) compared with high target SpO2 levels (85 to 89 versus 91 to 95 percent) were associated with increased mortality at hospital discharge but not mortality or morbidity at 24 months corrected age (CA). However, in a subsequent post hoc analysis of one of the included trials (Canadian Oxygen Trial), prolonged hypoxemic episodes during the first two to three months after birth were associated with late mortality or neurodevelopment impairment at 18 months CA [26]. Of note, this association was stronger for infants randomly assigned to the high SpO2 group than for those in the low SpO2 group. Nevertheless, based on currently available data, we continue to recommend an SpO2 target range between 90 to 95 percent for EP infants. (See "Oxygen monitoring and therapy in the newborn", section on 'Clinical trials'.)
Acetaminophen alone not effective in reducing neonatal pain (August 2015)
Acetaminophen (paracetamol) has been used in the management of mild to moderate procedural and postoperative neonatal pain. However, a recent systematic review of randomized trials found that acetaminophen alone was not more effective than placebo in preventing or reducing pain associated with heel lance or eye examination in newborns [27]. As a result, we do not recommend using acetaminophen as the sole agent in newborns to reduce pain from painful procedures. (See "Prevention and treatment of neonatal pain", section on 'Lack of efficacy'.)
ALLERGY, IMMUNOLOGY, AND RHEUMATOLOGY
Association between atopic eczema and anemia (January 2016)
An analysis of caregiver-reported and self-reported data on over 200,000 children and adolescents from the United States National Health Interview Survey 1997-2013 found an increased risk of anemia in children with a history of atopic disorders, including eczema, asthma, hay fever, or food allergy [28]. The risk was much higher in children with all four disorders. Using laboratory data from the National Health and Nutrition Examination Survey 2014-2015 on over 30,000 children, the authors found that children with a current history of atopic eczema or asthma had an approximately twofold increased risk of anemia, particularly microcytic anemia. Whether anemia in atopic children is related to chronic inflammation or malnutrition secondary to dietary restrictions for suspected food allergies is unknown. Further studies are needed to confirm this association and clarify the underlying mechanisms. (See "Pathogenesis, clinical manifestations, and diagnosis of atopic dermatitis (eczema)", section on 'Anemia'.)
Steroid-sparing agents for the initial treatment of juvenile dermatomyositis (January 2016)
In children with juvenile dermatomyositis (JDM), initial therapy usually includes both systemic glucocorticoids and a steroid-sparing agent to decrease the total dose and duration of glucocorticoids and thereby minimize their side effects. A randomized, unblinded, multicenter trial demonstrated improved efficacy with the addition of a steroid-sparing agent compared with prednisone alone. In this trial, 139 children with new-onset mild to moderate JDM were assigned to prednisone alone, prednisone plus methotrexate, or prednisone plus cyclosporine [29]. At six months of follow-up, the Pediatric Rheumatology International Trials Organization (PRINTO) 20 level of improvement (20 percent improvement in three of six core set variables) was higher in the two combination-therapy groups compared with prednisone alone (70 and 72 percent improvement for prednisone plus cyclosporine and prednisone plus methotrexate versus 51 percent for prednisone alone). Clinical remission was most common in the prednisone plus methotrexate group and treatment failure was most common in patients on prednisone alone. The highest rate of adverse events occurred in patients treated with prednisone plus cyclosporine. We prefer methotrexate as a steroid-sparing agent for the initial treatment of JDM, since it has lower side effects and similar efficacy compared with cyclosporine. (See "Juvenile dermatomyositis and polymyositis: Treatment, complications, and prognosis", section on 'Methotrexate'.)
Omalizumab and oral immunotherapy for food allergy (January 2016)
Investigational protocols of oral immunotherapy (OIT) for food allergy have been complicated by high rates of allergic reactions during treatment. There has been interest in co-treating patients with anti-IgE (omalizumab) to prevent these reactions, although omalizumab is expensive. Results from a randomized, multicenter trial suggest that treatment with anti-IgE before and during the build-up phase of OIT may be a more cost-effective approach than continuing anti-IgE for the duration of OIT therapy. In this trial, 57 children and adults were assigned to omalizumab or placebo for four months before and throughout the build-up and maintenance phases of open-label milk OIT [30]. The median percentages of doses per subject to cause symptoms in the omalizumab and placebo groups were 2.1 and 16.1 during build-up, and 0 and 3.4 during maintenance, respectively. There were no significant differences in the percent of patients desensitized (>70 percent) or with sustained unresponsiveness to milk (>36 percent). Thus, omalizumab treatment improved the safety, but did not impact the efficacy of OIT. Because most reactions occurred during the build-up phase, omalizumab could be limited to that phase of treatment to reduce cost. (See "Future therapies for food allergy", section on 'Oral immunotherapy combined with anti-IgE'.)
Updated guidelines for the diagnosis and management of primary immunodeficiency (November 2015)
A revised “Practice parameter for the diagnosis and management of primary immunodeficiency,” developed by the three national allergy and immunology societies in the United States, has been published to aid allergy/immunology specialists and other practitioners in the recognition, diagnosis, and general management of these disorders [31]. Highlights include screening and advanced laboratory tests for the different components of immune function, characteristic clinical manifestations and laboratory findings for a number of disorders, internet resources, antibiotic prophylaxis, and indications for hematopoietic cell transplantation or gene therapy. There are now more than 200 genetically distinct disorders of immune function that are classified using the system devised by the World Health Organization (WHO) and International Union of Immunological Societies (IUIS). Consultation with an immunology specialist with experience in diagnosing and managing primary immunodeficiencies is recommended. Our approach is consistent with that outlined in this practice parameter. (See "Approach to the child with recurrent infections" and "Laboratory evaluation of the immune system" and "Medical management of immunodeficiency".)
n-3 LCPUFA supplementation in pregnancy and allergies in offspring (November 2015)
It has been hypothesized that maternal intake of long chain polyunsaturated fatty acids (n-3 LCPUFA) during pregnancy may prevent development of allergies in offspring. However, a recent systematic review of randomized trials assessing the effect of n-3 LCPUFA supplementation during pregnancy and/or breastfeeding on allergy outcomes in offspring found supplementation did not significantly reduce childhood allergic disease (food allergy, atopic dermatitis, allergic rhinitis, asthma) at 36 months of age compared with no treatment/placebo [32]. (See "Fish consumption and omega-3 long-chain polyunsaturated fatty acid supplementation during pregnancy", section on 'Other outcomes'.)
Auvi-Q and Allerject epinephrine autoinjectors recalled by manufacturer (October 2015)
A manufacturer's recall was issued in October 2015 of all Auvi-Q epinephrine autoinjectors in the United States, as well as all Allerject devices in Canada, including both the 0.15 and 0.3 mg strengths, due to potentially inaccurate dose delivery [33,34]. Patients should be provided with a prescription for an alternate epinephrine device and return Auvi-Q and Allerject autoinjectors to their pharmacy for replacement and instruction on how to use the new device. Patients should only use Auvi-Q or Allerject if no other device is available in a severe allergic reaction and then immediately contact 9-1-1 or emergency medical services. (See "Prescribing epinephrine for anaphylaxis self-treatment", section on 'Types of autoinjectors'.)
Antibiotic use and development of juvenile idiopathic arthritis (August 2015)
A few studies have found a link between antibiotic use and the development of juvenile idiopathic arthritis (JIA). In one of these case-control studies, previous antibiotic prescriptions were compared in 152 children newly diagnosed with JIA and 1520 controls in the United Kingdom [35]. As with a previous study, this study found that any use of antibiotics was associated with a twofold increased risk of JIA. The risk was dose dependent and was greatest for antibiotic exposures that occurred within one year of diagnosis. The potential underlying mechanism is unknown, but alteration of the intestinal microbiome with subsequent immune dysregulation is postulated. Alternative explanations include the possibility that these patients develop more frequent infections due to some intrinsic abnormalities in the immune system that also predispose them to JIA. (See "Juvenile idiopathic arthritis: Epidemiology and immunopathogenesis", section on 'Antibiotics'.)
Use of azithromycin to prevent or shorten the duration of symptoms in young children with recurrent wheeze/asthma (December 2015, Modified January 2015)
The potential utility of macrolide antibiotics in the treatment of recurrent wheezing/asthma is under investigation, given their antiinflammatory properties and antimicrobial effects against Mycoplasma pneumonia and Chlamydia pneumonia.
●A multicenter trial examined whether the early use of azithromycin prevented lower respiratory tract illness (LRTI) in 607 preschool children with a history of severe recurrent wheezing [36]. Children were randomly assigned to oral azithromycin or placebo for five days in addition to albuterol. Treatment was initiated at the onset of respiratory illness in conjunction with signs/symptoms that usually preceded the development of a severe LRTI, specific to each child. The risk of progressing to severe LRTI was lower in the treatment group compared with the control, although there was no difference in urgent care utilization, emergency department visits, or hospitalizations.
●A second trail randomly assigned 72 children one to three years of age with recurrent asthma-like symptoms to three days of oral azithromycin or placebo for each episode of asthma-like symptoms lasting at least three days [37]. Treatment with azithromycin significantly decreased the duration of the episode, with a greater response seen with earlier initiation of treatment.
These studies provide some evidence for the early use of azithromycin. However, given concerns regarding antibiotic resistance and adverse effects with widespread use, further study is warranted to define subpopulations who could most benefit from preventive therapy before recommendations can be made. (See "Treatment of recurrent virus-induced wheezing in young children", section on 'Antibiotics'.)

CARDIOLOGY
Maternal hypertension and risk of congenital heart disease in offspring (November 2015)
Women with chronic hypertension, either treated or untreated, may be at increased risk of having offspring with congenital heart disease (CHD) compared with normotensive women. In a recent systematic review including 16 studies and five million subjects, the frequency of CHD in offspring of hypertensive pregnant women who received or did not receive treatment increased by 100 percent and 40 percent, respectively, compared with normotensive pregnant women [38]. The magnitude of effect was generally similar across subtypes of CHD and across the range of antihypertensive therapies. These results should be interpreted with caution, as neither a dose-response relationship between maternal hypertension medication and CHDs nor some potentially important characteristics of the population (eg, severity of hypertension) could be ascertained. We suggest avoiding antihypertensive therapy for mild hypertension in pregnancy as there is no clear maternal or fetal benefit and it may be harmful. Severe hypertension should be treated to reduce the risk of maternal stroke. (See "Management of hypertension in pregnant and postpartum women", section on 'Antihypertensive therapy'.)
Early cardiovascular disease in youth with depressive and bipolar disorders (October 2015)
The American Heart Association recently proposed that major depression and bipolar disorder in adolescents be positioned alongside other pediatric diseases that are considered moderate risk conditions for early cardiovascular disease (CVD), which include chronic inflammatory diseases (eg, systemic lupus erythematosus), HIV infection, and nephrotic syndrome [39]. There is growing evidence that major depression and bipolar disorder are associated with accelerated atherosclerosis and early CVD. In addition, traditional risk factors for CVD (eg, obesity, diabetes mellitus, sedentary lifestyle, and smoking) are more prevalent in youth with major depression and bipolar disorder. Although psychotropic medication may contribute to the elevated risk of CVD, particularly in youths with bipolar disorder, it appears that the association between depression and CVD is independent of medication effects. Management of youth with major depression and bipolar disorder should thus include monitoring and management of other CVD risk factors, including body mass index, blood pressure, lipids, and fasting glucose. (See "Diseases associated with atherosclerosis in childhood", section on 'Depressive and bipolar disorders'.)
DERMATOLOGY
Stevens-Johnson syndrome outbreak associated with M. pneumoniae (August 2015)
Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) is a rare, severe blistering mucocutaneous reaction, most commonly triggered by medications, characterized by extensive necrosis and detachment of the epidermis and mucosa. Mycoplasma pneumoniae and cytomegalovirus infections are the next most common trigger of SJS/TEN, particularly in children. Between September and November 2013, an outbreak of eight pediatric cases of M. pneumoniae-associated SJS/TEN was reported in Colorado, likely related to high levels of M. pneumoniae infection in the region [40]. All children had severe oropharyngeal mucositis; the conjunctiva was involved in seven children and the genital mucosa in five. (See "Stevens-Johnson syndrome and toxic epidermal necrolysis: Pathogenesis, clinical manifestations, and diagnosis", section on 'Infection'.)
DEVELOPMENTAL AND BEHAVIORAL PROBLEMS
Stimulant medications for ADHD not associated with new onset or worsening tics in meta-analysis (October 2015)
New onset and worsening of tics have been reported in children receiving stimulants for attention deficit hyperactivity disorder (ADHD), and stimulants are often avoided in these children if they have a personal or family history of tics. However, in a meta-analysis of 22 randomized trials of the efficacy of stimulants in the treatment of children with ADHD, the risk of tics was similar in both the stimulant and placebo groups (5.7 and 6.5 percent, respectively) [41]. For children with ADHD in whom stimulants were discontinued because of new or worsening tics, another course of stimulant therapy may be warranted, particularly if ADHD symptoms are not as well controlled with nonstimulant medications. (See "Pharmacology of drugs used to treat attention deficit hyperactivity disorder in children and adolescents", section on 'Tics'.)
Genetic testing in autism spectrum disorder (September 2015)
Genetic testing is often performed in children with autism spectrum disorder (ASD) to provide information about prognosis and recurrence. The suggested evaluation has evolved with advances in molecular diagnostic techniques. In a population-based study, the yield of genetic diagnosis with whole-exome sequencing was similar to that with chromosomal microarray (CMA): 8.4 and 9.3 percent, respectively; and 15.8 percent when both tests were performed [42]. Genetic diagnosis was achieved more often in children with higher levels of dysmorphology, suggesting that severity of dysmorphology is predictive of genetic abnormalities [43]. Pending additional studies, we continue to suggest genetic testing by CMA and DNA analysis for fragile X syndrome for all children with ASD, whether or not they have dysmorphic features. (See "Autism spectrum disorder: Diagnosis", section on 'Genetic testing'.)
EMERGENCY MEDICINE
Injuries diagnosed after ankle inversion in skeletally immature children (January 2016)
Traditionally, skeletally immature children who sustain an inversion injury of the ankle, have swelling and/or tenderness over the distal fibula, and normal bones by plain radiography are presumed to have a Salter-Harris I physeal fracture. In a multicenter, prospective, observational study of 135 such children (5 to 12 years of age), MRI demonstrated a sprain without fracture in 49 percent, a sprain with fracture in 31 percent, and isolated bone contusions in 20 percent [44]. In the overall group, 28 percent of children had avulsion fractures and just 3 percent had nondisplaced Salter-Harris I distal fibular fractures. Thus, the majority of children with inversion ankle injuries and no bony abnormality on plain radiographs appear to have sprains, and nondisplaced Salter-Harris I fractures of the distal fibula are uncommon. (See "Ankle fractures in children", section on 'Diagnosis'.)
Epinephrine for the treatment of fluid-refractory, cold septic shock in infants and children (January 2016)
The 2009 American College of Critical Care Medicine (ACCM) pediatric sepsis guidelines recommended dopamine as the first-line agent for the treatment of fluid-refractory septic shock in patients with signs of vasoconstriction or "cold" shock (eg, cold extremities and diminished peripheral pulses). However, in a single-center randomized trial of 120 infants and children (1 month to 15 years of age) undergoing treatment for fluid-refractory septic shock in a pediatric intensive care unit (88 percent with cold shock), patients who received infusions of dopamine rather than epinephrine had significantly higher mortality (21 versus 7 percent) and more healthcare-associated infections (29 versus 2 percent) [45]. Based on these findings, we now suggest that infants and children with fluid-refractory, hypotensive, cold septic shock receive infusions of epinephrine rather than dopamine. Epinephrine infusions are initiated at a dose of 0.05 to 0.1 mcg/kg/minute and titrated to response up to 1.5 mcg/kg/minute. The 2009 ACCM pediatric sepsis guidelines are undergoing review. (See "Septic shock: Rapid recognition and initial resuscitation in children", section on 'Cold shock'.)
Frequency of concussion-like symptoms during baseline testing of high school athletes (December 2015)
The lack of specificity of concussion symptoms and the broad array of alternative potential etiologies underscores the importance of baseline evaluation for pediatric athletes before sports participation. In a large observational study of almost 32,000 high school athletes with no concussion in the past six months and who underwent baseline computerized testing, 21 to 47 percent of boys with a prior history of psychiatric illness or migraines and 33 to 72 percent of girls with a prior history of substance abuse, psychiatric illness, or attention deficit disorder with hyperactivity had symptom scores that would meet international criteria for prolonged concussion [46]. Thus, neurocognitive testing before sports participation provides more information that may help clarify the etiology of symptoms in these patients if a concussion is sustained and assists with proper management. (See "Concussion in children and adolescents: Clinical manifestations and diagnosis", section on 'Preparticipation assessments'.)
Metronome use during chest compressions in children (October 2015)
The 2010 American Heart Association and International Liaison Committee on Resuscitation Cardiopulmonary Resuscitation guidelines emphasize the importance of hard, fast chest compression at an optimal rate of 100 compressions per minute. Health care providers who use a metronome are more likely to achieve this rate. In a crossover trial of 155 medical personnel who performed compressions on a pediatric manikin with or without a metronome, the mean percentage of compressions delivered at an optimal rate was achieved more often when a metronome was used (72 versus 50 percent) [47]. The rescuers tended to perform compressions too fast when a metronome was not used. (See "Pediatric basic life support for healthcare providers", section on 'Chest compressions'.)
Lower mortality for children treated in pediatric trauma centers (October 2015)
In a retrospective analysis of a national database of almost 176,000 pediatric trauma patients, the unadjusted mortality rate was lowest among patients treated in pediatric trauma centers (0.6 percent) compared with adult trauma centers (2.3 percent) and mixed trauma centers (1.8 percent) [48]. After adjustment, children treated in adult or mixed trauma centers had an estimated 57 and 45 percent increased risk of dying, respectively, when compared with patients treated in pediatric trauma centers (PTC). Because optimal outcomes occur when the critically injured child is initially resuscitated and subsequently managed in a PTC, it is preferable to provide care in such facilities from the outset, whenever possible, or to arrange transfer to a PTC for ongoing management. (See "Trauma management: Approach to the unstable child", section on 'Definitive care'.)
Contrast regimens for children requiring abdominal and pelvic computed tomography after blunt trauma (September 2015)
In a multicenter, prospective observational study of over 5000 children with blunt trauma undergoing abdominal and pelvic computed tomography (CT) with intravenous (IV) contrast, of whom 1010 also received oral contrast, the sensitivity for identifying intraabdominal injury was not significantly different with or without oral contrast (99 versus 98 percent, respectively) [49]. Patients who received oral contrast had a significantly longer delay in undergoing CT (median 12 minutes) compared with children who received IV contrast alone. Thus, oral contrast does not improve detection of intraabdominal injury in children but delays time to imaging. We suggest that hemodynamically stable children undergoing CT of the abdomen and pelvis after blunt trauma receive IV contrast alone rather than IV and oral contrast.  (See "Overview of blunt abdominal trauma in children", section on 'Use of contrast'.)
Timely administration of epinephrine improves survival following pediatric arrest (August 2015)
Epinephrine is recommended during cardiopulmonary resuscitation for children with asystole or pulseless electrical activity without ventricular fibrillation or tachycardia. In a retrospective review of registry data on 1558 children with inpatient arrest and a documented nonshockable initial rhythm, adjusted survival to discharge occurred in up to 37 percent of patients who received epinephrine one minute or less after arrest and decreased 5 percent for every additional minute delay in epinephrine administration [50]. Survival with favorable neurologic outcome at discharge occurred in approximately 16 percent of all patients and in adjusted analysis also decreased 5 percent for every additional minute of delay in epinephrine administration. Thus, timely administration of epinephrine is associated with improved outcomes after pediatric arrests with non-shockable cardiac rhythms. (See "Pediatric advanced life support (PALS)", section on 'Asystole or pulseless electrical activity'.)
ENDOCRINOLOGY
Adjunctive therapy with metformin for type 1 diabetes (December 2015)
The use of metformin as an adjunct to insulin therapy has been suggested as a means of improving diabetes control and alleviating weight gain in type 1 diabetes. In a trial of overweight adolescents with type 1 diabetes randomly assigned to metformin or placebo as an adjunct to insulin treatment, use of metformin did not improve glycemic control at six months and increased adverse gastrointestinal symptoms [51]. However, the group receiving metformin had greater reductions in total daily insulin per kg of body weight and body mass index than the placebo group. This study does not support prescribing metformin as adjunctive therapy for overweight adolescents to improve glycemic control, but it suggests that metformin may help some patients lose weight. (See "Management of type 1 diabetes mellitus in children and adolescents", section on 'Investigational therapies for type 1 diabetes'.)
Enzyme replacement therapy for hypophosphatasia (November 2015)
Hypophosphatasia is a rare, autosomal disease that is associated with low levels of alkaline phosphatase in serum and bone and the development of osteomalacia and severe periodontal disease. It may present in the perinatal period, when it is lethal; in infancy, where rachitic deformities develop by age six months; in childhood, with premature loss of deciduous teeth, delayed walking, and waddling gait; or in adulthood, where it is characterized by the presence of recurrent metatarsal stress fractures and bone pain, and an increased incidence of chondrocalcinosis. Historically, there have been few treatment options. However, enzyme replacement therapy (asfotase alfa) for perinatal, infantile, and juvenile-onset hypophosphatasia became available in October 2015, based upon the results of open-label prospective studies in 99 patients with perinatal, infantile, or juvenile-onset hypophosphatasia, in whom enzyme replacement therapy was associated with improved overall survival, ventilator-free survival, growth, and bone mineralization compared with a historic cohort [52]. (See "Clinical manifestations, diagnosis, and treatment of osteomalacia", section on 'Other causes'.)
GASTROENTEROLOGY, HEPATOLOGY, AND NUTRITION
Timing of appendectomy (January 2016)
Whether emergent appendectomy is required in all patients with early appendicitis has been debated. In many institutions, children with early appendicitis receive antibiotics and undergo appendectomy based upon operative and professional resources with a preference for performance of the procedure during daytime or evening hours. In a prospective, observational study that evaluated 230 children who underwent appendectomy, patients with symptoms greater than 48 hours had a significantly higher rate of perforation when compared with patients with symptoms ≤48 hours (46 versus 12 to 18 percent) [53]. When evaluated according to time from diagnosis, the perforation rate, length of stay, and operating time were not significantly different. Thus, limiting the total time from symptom onset to surgery rather than from diagnosis to surgery appears to be of greatest importance in preventing adverse outcomes of appendicitis. (See "Acute appendicitis in children: Management", section on 'Timing of operation'.)
Oral recombinant H. pylori vaccine (October 2015)
In a randomized phase 3 trial, 4464 H. pylori uninfected children (ages 6 to 15 years) were assigned to a three-dose oral recombinant H. pylori vaccine or placebo [54]. At one year, the incidence of H. pylori infection was significantly lower in the vaccine group. Among patients who completed extended follow-up, H. pylori acquisition continued to be lower in vaccinated as compared with unvaccinated children, but protection levels were lower in the second and third year. There were no serious adverse events related to the vaccine. Additional studies with long-term follow-up are needed to validate these results. (See "Pathophysiology of and immune response to Helicobacter pylori infection", section on 'Vaccination'.)
GENETICS AND PEDIATRIC METABOLISM
Down syndrome-specific growth charts (November 2015)
Down syndrome (DS)-specific growth charts derived from a population of patients in the United States (US) are now available and are consistent with the more contemporary charts based upon data from European populations [55]. These growth charts revealed that weight gain in children <3 years of age has improved and stature in males has increased, compared with growth chart data on DS from the 1960s. The DS-specific US growth charts will most likely supplant the US Centers for Disease Control (CDC) and World Health Organization (WHO) growth charts for assessing growth and nutritional status in children with DS. The new charts include weight-for-length and corresponding body mass index (BMI) charts that are needed to adequately assess nutritional status, although optimal weight-for-length and BMI levels for individuals with DS are not yet established. (See "Down syndrome: Management", section on 'Growth' and "Down syndrome: Clinical features and diagnosis", section on 'Growth'.)
Down syndrome disintegrative disorder (September 2015)
It is not clear if Down syndrome disintegrative disorder is one disorder or several different disorders with similar presentations [56]. The etiology is not known, but autoimmunity is suspected. There are no established diagnosis or treatment recommendations for this clinical association, although some patients respond to psychiatric care. Further research is needed in this area. (See "Down syndrome: Clinical features and diagnosis", section on 'Behavioral and psychiatric disorders'.)
Medical food supplements for organic acidemias (August 2015)
Patients with organic acidemias such as methylmalonic acidemia (MMA) are treated with a low-protein diet that is supplemented with an amino acid mixture that excludes the problematic amino acids. However, excessive consumption of this "medical food" in patients with MMA, while uncommon, can result in increased leucine intake that causes depletion of the essential amino acids valine and isoleucine [57]. These amino acid deficiencies are associated with poor growth outcomes. Patients with cobalamin C (cblC) defects, which cause combined MMA and homocystinuria, should be treated carefully with the medical food used for MMA, since this medical food is devoid of methionine and is relatively high in leucine content. Use of this medical food in patients with cblC deficiency could potentially adversely affect brain growth and development [58]. Patients with these disorders should have plasma amino acid analysis performed on a regular basis to prevent these and other complications. (See "Organic acidemias", section on 'Treatment'.)
HEMATOLOGY AND ONCOLOGY
Declining mortality among long-term survivors of childhood cancer (January 2016)
Rates of late mortality among survivors of childhood cancer have improved over time. One study evaluated late mortality among over 34,000 survivors of childhood cancer who had been treated between 1970 and 1999, with a median follow-up of 21 years [59]. Overall, mortality rates were lower in the later decades of follow-up, reflecting fewer deaths due to recurrence and long-term toxicities. Long-term treatment-related mortality decreased significantly over time among survivors of acute lymphoblastic leukemia, Hodgkin lymphoma, Wilms’ tumor, and astrocytoma, but not among survivors of other cancer subtypes. (See "Overview of the outcome of acute lymphoblastic leukemia in children and adolescents", section on 'Treatment-related mortality'.)
Genetic predisposition in pediatric cancer (December 2015)
The prevalence and spectrum of mutations predisposing to cancer are not clear in pediatric cancer patients. In a study that used next-generation sequencing to determine the contribution of known germline predisposition mutations in over 1000 children and adolescents with cancer, pathogenic or probably pathogenic mutations were identified in 8.5 percent of cases [60]. Mutations were most common in patients with adrenocortical cancers and osteosarcoma, but were also identified among patients with retinoblastoma, Ewing sarcoma, central nervous system tumors, rhabdomyosarcoma, leukemia, and neuroblastoma. Importantly, family history did not predict an underlying predisposition syndrome in most patients. (See "Clinical presentation and evaluation of adrenocortical tumors", section on 'Hereditary cancer syndromes' and "Osteosarcoma: Epidemiology, pathogenesis, clinical presentation, diagnosis, and histology", section on 'Inherited conditions'.)
Recombinant von Willebrand factor (October 2015, Modified December 2015)
Patients with von Willebrand disease (VWD) may require von Willebrand factor (VWF) replacement therapy for serious bleeding or surgery. A recombinant VWF product has now been tested in patients with VWD during bleeding episodes and found to be highly effective in restoring hemostasis [61]. Adverse effects were minor, and the half-life of the product is longer than that of plasma-derived concentrates. This product was approved by the United States Food and Drug Administration in December 2015 [62]. (See "Treatment of von Willebrand disease", section on 'VWF preparations'.)
Eltrombopag for chronic ITP in children (November 2015)
Approximately 10 to 20 percent of children who present with immune thrombocytopenia (ITP) go on to have chronic ITP with ongoing bleeding risk. In adults with refractory chronic ITP, thrombopoietin (TPO) receptor agonists increase platelet counts and reduce bleeding events, although the effect generally lasts only as long the drug is continued. A recent study found similar effects in pediatric patients. In a multicenter, randomized, double-blind trial of 92 children with chronic ITP, 40 percent of patients in the eltrombopag group achieved a sustained response in their platelet count compared with 3 percent in the placebo group [63]. Bleeding events occurred less frequently in the eltrombopag group (37 versus 55 percent). During the subsequent 24-week open-label treatment period, 81 percent of patients achieved a response. The drug was well tolerated and serious adverse events did not differ between the treatment and placebo groups. Due to cost considerations and limited pediatric experience with TPO receptor agonists in children, UpToDate reserves these agents for children with chronic ITP who fail or are ineligible for treatment with splenectomy and/or rituximab and for those requiring a high platelet count for surgery when this cannot be achieved with other therapies (eg, steroids, intravenous immune globulin). (See "Immune thrombocytopenia (ITP) in children: Management of chronic disease", section on 'Thrombopoietin receptor agonists'.)
Gardos channel mutations in hereditary stomatocytosis (October 2015)
Hereditary stomatocytosis (HSt) is a rare inherited disorder that presents with hemolytic anemia and mouth-shaped red blood cells (RBCs) known as stomatocytes. The causative genetic defect has been unclear in many affected families. Recently, three groups reported several HSt kindreds with mutations in the gene encoding the Gardos channel (KCNN4), a potassium channel in the RBC membrane [64-66]. This finding explains the anemia and suggests that one form of HSt is essentially the same as another rare condition, stomatocytic hereditary xerocytosis. Genetic testing is not yet widely available; at present diagnosis is based on clinical features and RBC testing. (See "Stomatocytosis and xerocytosis", section on 'Gardos channel'.)
INFECTIOUS DISEASES AND IMMUNIZATIONS
Azithromycin versus doxycycline for uncomplicated chlamydia (January 2016)
The first-line regimens for uncomplicated urogenital chlamydial infection are azithromycin administered as a single dose or a seven-day course of doxycycline administered twice daily. There is emerging evidence that the efficacy of doxycycline may be marginally greater than that of azithromycin, although the reasons for this are unknown. In a trial of 310 adolescents and young adults who screened positive for urogenital Chlamydia trachomatis upon entrance into a correctional facility, microbial cure rates at 28 days were high for both doxycycline and azithromycin (each administered as directly-observed therapy), but were numerically higher for doxycycline (100 versus 97 percent) [67]. Adherence is the main challenge with the doxycycline regimen, and direct observation of the full course is unrealistic in most situations; thus, it is uncertain that doxycycline would achieve a similarly superior cure rate in the community. Given the very high efficacy of azithromycin, we continue to favor directly-observed single-dose azithromycin for treatment of uncomplicated urogenital C. trachomatis infection. (See "Treatment of Chlamydia trachomatis infection", section on 'First-line agents'.)
Time to return to school following treatment for streptococcal pharyngitis (December 2015)
Traditionally, patients with streptococcal pharyngitis have been considered contagious until 24 hours following antibiotic therapy and so have not been allowed to return to daycare, school, or camp until this interval has passed. In a recent study including 111 children with a sore throat and positive streptococcal rapid antigen detection test (RADT) who were treated with single-dose amoxicillin, 91 percent had a negative follow-up RADT and throat culture the following morning (12 to 23 hours later) [68]. Based on these findings, children treated with amoxicillin for streptococcal pharyngitis by 5:00 pm are unlikely to be contagious by the next morning. When consistent with local policies, it would be reasonable to permit such children to attend school the following day if afebrile and clinically improved. (See "Treatment and prevention of streptococcal tonsillopharyngitis", section on 'Follow-up'.)
Shortened interval for postvaccination serology in infants born to HBsAg-positive mothers (October 2015)
To prevent transmission of hepatitis B infection, infants born to women who are hepatitis B surface antigen (HBsAg)-positive should receive hepatitis B immune globulin and the first dose of hepatitis B vaccine within 12 hours of birth and complete the hepatitis B vaccine series at age six months or soon thereafter. Postvaccination serology (HBsAg and antibody to HBsAg) is necessary to see if postexposure prophylaxis was successful (table 2). In agreement with updated recommendations from the Centers for Disease Control and Prevention [69], we now obtain postvaccination serology at age 9 to 12 months (or one to two months after the final dose) rather than at age 9 to 18 months as previously recommended. The shortened interval permits earlier revaccination of susceptible infants and may avoid unnecessary revaccination of infants who responded appropriately but whose antibody levels declined with time. (See "Hepatitis B virus immunization in infants, children, and adolescents", section on 'Postvaccination serology'.)
Influenza vaccination and influenza-associated pneumonia (October 2015)
Many studies have demonstrated that influenza vaccination decreases the incidence of laboratory-confirmed influenza infection, but few have evaluated the effect on the serious complications of influenza. Recent data suggest that vaccination is associated with a reduced risk of influenza pneumonia. In a case-control study of adult and pediatric patients hospitalized for community-acquired pneumonia (CAP), those with laboratory-confirmed influenza-associated pneumonia had lower odds of having received an influenza vaccine during the same influenza season compared with those with CAP not associated with influenza [70]. The estimated vaccine effectiveness for preventing influenza-associated pneumonia was 57 percent. (See "Seasonal influenza vaccination in adults", section on 'Trivalent inactivated vaccines' and "Seasonal influenza in children: Prevention with vaccines", section on 'Indications'.)
WHO recommendations on HIV treatment and prevention (October 2015)
In 2015, the World Health Organization (WHO) updated its guidelines for the prevention and treatment of HIV infection to recommend initiation of lifelong antiretroviral (ART) for all HIV-infected patients, regardless of CD4 cell count or clinical stage [71]. This recommendation was based, in part, on mounting evidence that the clinical benefit of ART extends to those with very high CD4 cell counts and data demonstrating a dramatic reduction in sexual HIV transmission to uninfected partners with successful ART. The updated guidelines also recommend pre-exposure prophylaxis (PrEP) with a tenofovir-containing regimen as part of the HIV prevention strategy for individuals at substantial risk of HIV infection (ie, those for whom the predicted incidence of infection would be >3 per 100 person years). (See "The impact of antiretroviral therapy on morbidity and mortality of HIV infection in resource-limited settings", section on 'Initiation of antiretroviral therapy' and "Pre-exposure prophylaxis against HIV infection" and "Prevention of mother-to-child HIV transmission in resource-limited settings", section on 'Recommended antiretroviral management'.)
Influenza vaccine recommendations for 2015-2016 influenza season (August 2015)
In August 2015, the Advisory Committee on Immunization Practices released recommendations for the prevention and control of influenza during the 2015-2016 influenza season in the United States. As in previous seasons, seasonal influenza vaccination is recommended for everyone ≥6 months of age [72]. Changes for the 2015-2016 season include:
●Different influenza A H3N2 and influenza B (Yamagata lineage) antigens than were in the 2014-2015 vaccines
●A simplified dosing algorithm for children six months through eight years (algorithm 2)
●Availability of a quadrivalent intradermal vaccine for adults 18 through 64 years of age (table 3)
(See "Seasonal influenza in children: Prevention with vaccines", section on 'Schedule' and "Seasonal influenza vaccination in adults", section on 'Overview'.)

NEPHROLOGY AND UROLOGY
Early volume expansion in STEC-hemolytic uremic syndrome (January 2016)
Fluid management of patients with Shiga toxin-producing Escherichia coli hemolytic uremic syndrome (STEC-HUS) has been based on assessment of intravascular volume, which can be increased or decreased. However, a prospective Italian study of 38 children with STEC-HUS from 2012 and 2014 compared with historical controls from 2006 to 2009 reported that routine early volume expansion targeted to increase body weight by 10 percent improved outcome (lower rate of renal replacement therapy, shorter hospital course, and shorter duration of intensive care) [73]. Although these results are promising, further investigation is needed due to the potential bias from the use of historical controls and the relatively small number of patients and adverse events in the study. Until confirmatory data are available, we recommend assessment of intravascular volume status and renal function, with administration of fluids to rapidly correct documented volume depletion. We recommend not routinely providing volume expansion, especially if there is evidence of increased intravascular volume. (See "Treatment and prognosis of Shiga toxin-producing Escherichia coli (STEC) hemolytic uremic syndrome (HUS) in children", section on 'Fluid management'.)
NEUROLOGY
Acute flaccid myelitis in California (January 2016)
Beginning in 2012, the first cases of a polio-like illness of unknown etiology, now termed acute flaccid myelitis (AFM), were reported in the United States. The condition predominantly affects children and young adults. In a report summarizing 59 cases from California identified through July 2015, the median age at onset was nine years [74]. Common preceding or concurrent symptoms included respiratory or gastrointestinal illness, fever, and limb myalgia. Weakness progressed rapidly, most often reaching maximum severity over the course of hours to days. Magnetic resonance imaging (MRI) of the spinal cord typically showed increased signal on T2-weighted sequences involving the central gray matter, particularly the anterior horns. In most cases, the spinal cord lesions were longitudinally extensive. Cerebrospinal fluid analysis revealed pleocytosis in most patients, but no viruses were isolated from the cerebrospinal fluid. Nonpolio enteroviruses were detected in a minority of other body samples (ie, nasopharynx swab, stool, or serum), including enterovirus D68 in nine patients. Most patients were treated with intravenous glucocorticoids, intravenous immune globulin, or plasma exchange, but acute improvement with treatment was rare. Among 45 patients with a median follow-up of nine months, persistent weakness was noted in 84 percent. (See "Polio and infectious diseases of the anterior horn", section on 'Acute flaccid myelitis'.)
School action plans for rescue medications in children with epilepsy (January 2016)
Children with epilepsy who have frequent, prolonged seizures may be prescribed benzodiazepines for use as rescue therapy in the home environment, and plans should also be in place for use in school settings where appropriate. The American Academy of Pediatrics has published a new guideline highlighting practical and legal considerations for clinicians, families, and schools when developing school-based plans [75]. In addition to parameters about when a rescue medication should be given, tailored to the child’s individual history, plans should also generally include discussion of potential adverse effects, guidance about the types of situations in which personnel should seek further medical assistance, and discussion of when a child is safe to remain in school after a seizure. (See "Seizures and epilepsy in children: Refractory seizures and prognosis", section on 'Home rescue therapy (transmucosal AEDs)'.)
Low-technology therapeutic hypothermia for neonatal encephalopathy (December 2015)
Therapeutic hypothermia, started within the first six hours after delivery, is the only effective neuroprotective therapy available for treatment of neonatal encephalopathy. The benefit was established in trials that used advanced electrical cooling systems. Low-technology therapeutic hypothermia, accomplished with cooling bags, packs, or other nonelectrical methods, also appears to be beneficial for the treatment of neonatal hypoxic-ischemic encephalopathy. In a 2015 systematic review and meta-analysis of three randomized trials with over 460 infants, the group assigned to low-technology therapeutic hypothermia had a significantly reduced mortality rate compared with the group assigned to standard therapy, both at hospital discharge and at 6 to 24 months [76]. Similarly, the rate of neurologic morbidity at 6 to 24 months in survivors was significantly lower for the group assigned to low-technology therapeutic hypothermia. (See "Clinical features, diagnosis, and treatment of neonatal encephalopathy", section on 'Randomized trials'.)
New ILAE definition of status epilepticus (November 2015)
The International League Against Epilepsy (ILAE) has published a revised definition of status epilepticus, which now incorporates two operational dimensions, t1 and t2 [77]. Specifically, status epilepticus is defined as:
●A condition resulting from either the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms which lead to abnormally prolonged seizures (after time point t1); and
●A condition that can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
For generalized convulsive status epilepticus (GCSE), the ILAE definition specifies a duration of five minutes for t1 and 30 minutes for t2. The five-minute window for GCSE is consistent with our previous recommendations for initiating urgent intervention to control seizures. (See "Convulsive status epilepticus in adults: Classification, clinical features, and diagnosis", section on 'Definition' and "Clinical features and complications of status epilepticus in children", section on 'Definition'.)

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