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Inhaled Steroids May Suppress Growth in Children with Asthma
Inhaled corticosteroids may suppress growth in the first year of treatment in children with asthma, but lower doses may minimize the effects, according to findings of 2 systematic reviews published online July 17 in the Cochrane Library.
Inhaled corticosteroids are the most effective drugs for asthma control, reducing asthma mortality, hospital visits, and exacerbations while improving quality of life. Although they are generally considered first-line treatment for persistent asthma, their potential effect on childhood growth was previously undefined, and the potential for growth retardation and other systemic adverse effects continues to be a matter of concern.
Of the 7 inhaled corticosteroids currently available worldwide (beclomethasone, budesonide, ciclesonide, flunisolide, fluticasone, mometasone, and triamcinolone), ciclesonide, fluticasone, and mometasone are newer and are thought to have a better safety profile.
"The evidence we reviewed suggests that children treated daily with inhaled corticosteroids may grow approximately half a centimetre less during the first year of treatment," lead author of the first article, Linjie Zhang, MD, PhD, from the Faculty of Medicine, Federal University of Rio Grande in Brazil, said in a Cochrane news release. "But this effect is less pronounced in subsequent years, is not cumulative, and seems minor compared to the known benefits of the drugs for controlling asthma and ensuring full lung growth."
Dr. Zhang and colleagues searched the Cochrane Airways Group Specialised Register of trials, respiratory journals, meeting abstracts, ClinicalTrials.gov, and manufacturers' clinical trial databases in January 2014 for pertinent parallel-group randomized controlled trials.
They included 25 trials in their review. The trials enrolled a total of 8471 participants aged 18 years or younger who had mild to moderate persistent asthma treated with any of the available inhaled corticosteroids except for triamcinolone. Fourteen of these trials, enrolling a total of 5717 children, reported on growth over the course of a year.
Compared with placebo or nonsteroidal drugs, inhaled corticosteroids as a group suppressed growth rates, with those in the treatment group growing an average of 0.5 cm less than the average for the control group.
Compared with placebo or nonsteroidal drugs, inhaled corticosteroids were associated with a statistically significant reduction in linear growth velocity (−0.48 cm/year; 95% confidence interval, −0.65 to −0.30 cm/year; P < .0001) and in the change from baseline in height (mean difference, −0.61 cm/year; 95% confidence interval, −0.83 to −0.38) during a 1-year treatment period.
However, there was no statistically significant difference in linear growth velocity between participants treated with inhaled corticosteroids and controls during the second year of treatment.
The effect size of inhaled corticosteroids on linear growth velocity appeared to be associated more strongly with the specific drug than with the device or dose.
Lower Doses May Minimize Growth Suppression
The second article, by Aniela I. Pruteanu, MD, from the Research Centre, Centre HospitalierUniversitaire Sainte-Justine, and the Department of Pediatrics, University of Montreal, Québec, Canada, and colleagues included 22 trials of low or medium doses of inhaled corticosteroids in children, with data on different doses of all drugs except triamcinolone and flunisolide. Of 3 trials reporting follow-up for at least 1 year in a total of 728 children, 1 tested 3 different dosing regimens.
"Only 14% of the trials we looked at monitored growth in a systematic way for over a year," said senior author Francine Ducharme, MD, also from the Department of Pediatrics, in the news release. "This is a matter of major concern, given the importance of this topic."
The 3 trials showed that reducing the inhaled corticosteroid dose by about 1 puff per day was associated with improved growth by a quarter centimeter at 1 year.
"We recommend that the minimal effective dose be used in children with asthma until further data on doses becomes available," Dr. Ducharme said. "Growth should be carefully documented in all children treated with inhaled corticosteroids, as well in all future trials testing inhaled corticosteroids in children."
Growth suppression varied across studies, which could in part be because of use of specific drugs and/or other factors affecting growth.
"Conclusions about the superiority of 1 drug over another should be confirmed by further trials that directly compare the drugs," said Dr. Zhang, who was also a coauthor on the second review.
The investigators also recommend additional long-term trials and trials comparing different doses, particularly in children with more severe asthma requiring higher doses of inhaled corticosteroids.
"In prepubescent school-aged children with mild to moderate persistent asthma, a small but statistically significant group difference in growth velocity was observed between low doses of [inhaled corticosteroids] and low to medium doses of [hydrofluoroalkane]-beclomethasone equivalent, favouring the use of low-dose ICS," Dr. Pruteanu and colleagues conclude. "No apparent difference in the magnitude of effect was associated with three molecules reporting one-year growth velocity, namely, mometasone, ciclesonide and fluticasone. In view of prevailing parents' and physicians' concerns about the growth suppressive effect of [inhaled corticosteroids], lack of or incomplete reporting of growth velocity in more than 86% (19/22) of eligible paediatric trials, including those using beclomethasone and budesonide, is a matter of concern."
These reviews received no external funding. The authors have disclosed no relevant financial relationships.
(Laurie Barclay, MD in Medscape Pediatrics, July 18 2014)
Combination of Praziquantel plus Albendazole Superior to Albendazole Alone for Neurocysticercosis
Neurocysticercosis causes a substantial burden of seizure disorders worldwide. Treatment with either praziquantel or albendazole has suboptimum efficacy. We aimed to establish whether combination of these drugswould increase cysticidalefficacy and whether complete cyst resolution results in fewer seizures. We added anincreased dose albendazole group to establish a potential effect of increased albendazole concentrations.
Methods In this double-blind, placebo-controlled, phase 3 trial, patients with viable intraparenchymalneurocysticercosis were randomly assigned to receive 10 days of combined albendazole (15 mg/kg per day) plus praziquantel (50 mg/kg per day), standard albendazole (15 mg/kg per day), or increased dose albendazole (22.5 mg/kg per day).
Randomization was done with a computer generated schedule balanced within four strata based on number of cystsand concomitant antiepileptic drug. Patients and investigators were masked to group assignment. The primary outcome was complete cyst resolution on 6-month MRI. Enrolment was stopped after interim analysis because of parasiticidal superiority of one treatment group. Analysis excluded patients lost to follow-up before the 6-month MRI. This trial is registered with ClinicalTrials.gov, number NCT00441285.
Findings Between March 3, 2010 and Nov 14, 2011, 124 patients were randomly assigned to study groups (41 to receive combined albendazole plus praziquantel [39 analysed], 43 standard albendazole [41 analysed], and 40 increased albendazole [38 analysed]). 25 (64%) of 39 patients in the combined treatment group had complete resolution of brain cysts compared with 15 (37%) of 41 patients in the standard albendazole group (rate ratio [RR] 1.75, 95% CI 1.10–2.79, p=0.014). 20 (53%) of 38 patients in the increased albendazole group had complete cyst resolution at 6-month MRI compared with 15 (37%) of 41 patients in the standard albendazole group (RR 1.44, 95% CI 0.87–2.38, p=0.151). No significant differences in adverse events were reported between treatment groups (18 in combined treatment group, 11 in standard albendazole group, and 19 in increased albendazole group).
Interpretation Combination of albendazole plus praziquantel increases the parasiticidal effect in patients with multiple brain cysticercosis cysts without increased side-effects. A more efficacious parasiticidal regime without increased treatment-associated side-effects should improve the treatment and long term prognosis of patients with neurocysticercosis.
(Hector H Garcia, Isidro Gonzales, et al. Lancet Infect Dis 2014; 14: 687–95)
Preterm Birth Complications, Pneumonia Are Leading Causes of Death in Children
Complications from preterm births and pneumonia are now the leading causes of death in children aged younger than 5 years, together responsible for nearly 2 million deaths in 2013, according to the latest estimates published today in The Lancet.
Robert Black, MD, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, and colleagues used the latest available data and modelling methods to examine what caused an estimated 6.3 million deaths of newborn babies and children aged younger than 5 years in 2013.
They found that complications from preterm birth were the largest single cause, responsible for 965,000 deaths in children aged younger than 5 years, with pneumonia responsible for a further 935,000 deaths, and complications from childbirth the next leading cause, responsible for 662,000 deaths.
More than half (51.8%) of children died from infectious causes, including pneumonia, diarrhoea, and malaria. India, Nigeria, Pakistan, Democratic Republic of Congo, and China had the highest numbers of child deaths, together contributing to around half of all child and neonatal deaths globally in 2013.
The results are published as the 2015 deadline for the Millennium Development Goals (MDGs) approaches, with MDG4 (to reduce by two thirds, between 1990 and 2015, the under-5 mortality rate) unlikely to be achieved by more than a handful of countries.
“Despite remarkable progress at the level of global averages, at national level, MDG 4 will not be achieved in most countries in 2015,” the authors wrote. “As we enter the final 500 days of the MDG era, our analysis underlines a major transition for child survival symbolised by the fact that preterm birth complications are now the leading cause of under-5 deaths globally, not just of deaths in the neonatal period.”
Although rates of child deaths reduced dramatically -- from 77.4 to 45.6 per 1000 live births -- between 2000 and 2013, the authors’ projections show that, if current trends continue, in 2030, 4.4 million children aged younger than 5 years will still die, and 60% of these deaths will occur in sub-Saharan Africa. However, the authors pointed out that with increased commitment to preventing the most important causes of child deaths, this number could be nearly halved, with just 2.8 million child deaths in 2030.
“Although great progress has been made in child survival in the past two decades, with most of this progress in the past decade, it has not been enough,” the authors wrote. “Millions of children are still dying of preventable causes at a time when we have the means to deliver cost-effective interventions. Through the MDG effort, we have learned that substantial progress can be achieved but is not guaranteed, that good-quality data are crucial for tracking of progress, and that long-term targets are useful not only for planning and coordination, but also for rallying countries and the global health community.”
SOURCE: The Lancet
Azithromycin Use in Infants Directly Linked to Pyloric Stenosis
Oral administration of the macrolide antibiotic azithromycin in the first 90 days of life has been conclusively linked with the development of infantile hypertrophic pyloric stenosis (IHPS), in which thickening of the pylorus muscle leads to gastric-outlet obstruction, according to results of a retrospective study presented September 7 at the 54th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC).
“Ingestion of oral azithromycin places young infants at increased risk of developing pyloric stenosis,” stated Matthew Eberly, MD, Uniformed Services University of the Health Sciences, Bethesda, Maryland. The association is strongest if the exposure occurred within the first 2 weeks of life (8-fold increase in the odds). The association persisted, but was less strong, in children 2 to 6 weeks of age (2- to 3-fold increase in the odds).
The use of azithromycin in infants, particularly against pertussis, was prompted when it was proven that oral administration of erythromycin in the first few weeks of life increases the risk of developing IHPS. The results of the current trial prove that these concerns affect azithromycin users as well.
Dr. Eberly and colleagues conducted a cohort study of early azithromycin use involving 1,078,430 children born between June 2001 and April 2012. The team used the TRICARE Management Activity military health-system database to identify infants <90 days of age who had IHPS (n = 2,466, 51.5% male). Identification was based on specific diagnostic and procedural codes corresponding to congenital hypertrophic pyloric stenosis, acquired hypertrophic pyloric stenosis, and pylorospasm.
The records then were combed for outpatient prescription data concerning oral erythromycin (1,902 infants) or azithromycin (4,875 infants) during the first 90 days of life. IHPS developed in 17 (14 males) erythromycin recipients (8.94 per 1,000) and 8 (8 male) azithromycin recipients (1.64 per 1,000).
The median (interquartile range [IQR]) age at the time of IHPS for the 2,756 infants was 34 days (26 to 45 days). Of those, the median (IQR) age of infants prescribed erythromycin and azithromycin was 49 days (23 to 70 days) and 68 days (50 to 80 days), respectively. The age difference according to prescription was significant (P< .001).
The time between first dose of erythromycin or azithromycin and pyloromyotomy, the corrective surgical procedure for IHPS, was 13 days (range: 2 to 40 days; IQR 8 to 25 days) and 29.5 days (range: 9 to 45 days; IQR 20.5 to 38.5 days), respectively. The time difference was significant (P = .08).
Of the 148 infants exposed to azithromycin in the first 14 days of life, 3 (1.84%) developed IHPS (OR 8.18; 95% CI, 2.60 to 25.80; P< .001). Of the 729 infants who first received azithromycin at days 15 to 42 of life, 5 subsequently developed IHPS (OR 2.94; 95% CI, 1.21 to 7.11; P = .015). Of 1,076 infants aged 43 to 90 days exposed to azithromycin, 3 developed IHPS.
Of the 291 infants exposed to erythromycin in the first 14 days of life, 9 (2.88%) developed IHPS (odds ratio [OR] 13.40; 95% CI, 6.86 to 26.10; P< .001). During days 15 to 42 days of life, 729 infants received erythromycin, and 5 developed IHPS (OR 4.13; 95% CI, 1.71 to 10.00; P = .002). A total of 3,998 infants received erythromycin during days 43 to 90 of life; none developed IHPS (OR 1.22; 95% CI, 0.39 to 3.76; P = .76).
“Practitioners must carefully weigh the risk and benefits when prescribing azithromycin, particularly to male infants in the first few weeks of life. These infants should be monitored for signs and symptoms of pyloric stenosis for 6 weeks following treatment with azithromycin,” the researchers cautioned.
[Presentation title: Association of Azithromycin in Early Infancy With Development of Pyloric Stenosis. Abstract G-993, the 54th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). ]
Be Careful About Dosage While Prescribing Liquid Medicines
Study Summary
This study employed a cross-sectional approach, evaluating the dose-measuring abilities of the parents of children who received prescriptions for liquid medications in 2 pediatric emergency departments (EDs) during 2010 and 2011. The focus of the study was to determine whether provider strategies such as advanced counseling (asking the parent to teach-back medication information or use of graphical teaching aids for dosage) or provision of a standardized dosing instrument (such as a syringe or measuring cup) were associated with improved ability to appropriately measure a standard dose of a medication.
Participants were parents of children younger than 9 years old who received a prescription for a liquid medication to be administered for less than 2 weeks. The patients were followed by phone as well as in person for a final visit, which took place about 8 weeks after completing the prescribed medication. During the follow-up visit, data were obtained by interview and by direct observation. For the direct observation exercise, the parents were asked to demonstrate preparation of a dose of acetaminophen, with an error being classified as preparing plus or minus 20% of the expected dose. ED encounters were classified as any counseling (if the family received any medication directions in the ED); advanced counseling (if the parent reported verbal teach-back, graphical instruments, demonstration, or show-back of medication administration); and instrument provision (if the parent received a measuring instrument at either the ED or the pharmacy). The analyses also accounted for language concordance between the ED providers and the parent. Study Findings
There were 287 parents in the study; the overwhelming majority were mothers (90%) and from low socioeconomic backgrounds (83%). More than 80% of the medications prescribed during the ED visits were antibiotics, and 17% were corticosteroids. A dosing error was made by 41.1% of the parents during the observation visit; the majority (81.4%) wereunderdosing errors, and the remaining 18.6% were overdose errors. One in 3 parents received advanced counseling in the ED, and 74.6% of the parents received a dosing instrument. In bivariate analyses, receipt of at least 1 advanced counseling strategy was associated with lower errors by the parents (30.5% vs 40.4% among parents who did not receive advanced counseling strategies). Provision of any dosing instrument in the ED was associated with reduced frequency of errors but not if parents received the dosing instrument from a pharmacy. Only 15% of parents received both advanced counseling and a dosing instrument. However, the receipt of both strategies was associated with a much lower error frequency (20.9%) compared with those who received neither strategy (47.8%). Provision of only advanced counseling or a dosing instrument was not associated with frequency of errors in multivariate analyses that adjusted for parental age, race/ethnicity, language, country of birth, socioeconomic status, education, health literacy, child age, the presence of a child chronic disease, and the ED site. Unlike in the bivariate analyses, only the receipt of both strategies was associated with a lower dosing error frequency. The adjusted odds ratio for a dosing error among those who received both strategies was 0.30 (95% confidence interval, 0.1-0.7). The study authors concluded that the use of advanced counseling strategies coupled with provision of a standardized dosing instrument was associated with a lower frequency of dosing errors in this population. Viewpoint
The biggest take-home point of this study for pediatric providers is to be aware of how challenging it can be for parents to appropriately dose liquid medications. Other studies have demonstrated the value of advanced counseling strategies alone as well as the value of standardized dosing instruments, including marked syringes that result in the most accurate dosing. Although it is reassuring in some ways to see that underdosing was more prevalent than overdosing, the fact that most of the prescriptions were either for antibiotics or steroids suggests that underdosing may be just as clinically relevant as overdosing and should also be a subject of our consideration.
(Yin HS, Dreyer BP, Moreira HA, et al. AcadPediatr 2014; 14:262-270 & William T. Basco. Medscape. Aug 08, 2014.)
Levofloxacin Shows No Evidence of Cartilage Toxicity in Kids
Levofloxacin, a fluoroquinolone antibiotic, was not linked to joint cartilage injuries in a nonblinded study that followed-up children for 5 years after they took the drug. As the first long-term follow-up (LTFU) study on levofloxacin's effects on the joints of growing children, one expert says the study provides reassurance for pediatricians who use the drug, especially with regard to multidrug-resistant infections for which there are few treatment options.
Joint injuries resulting from fluoroquinolone use have been observed in animal studies, leading to caution about using these drugs in children.
"If long-term injury occurs with levofloxacin, the rate of these events is low," John S. Bradley, MD, from the University of California, San Diego, School of Medicine, and colleagues write in an article published online June 2 in Pediatrics.
The study included 124 children who had taken levofloxacin and 83 children who had taken a nonfluoroquinolone drug, all of whom had been identified during a 12-month surveillance phase follow-up study as having more than 1 of the following: growth impairment or possible growth impairment 12 months posttreatment, abnormal bone or joint symptoms during the 12 months after treatment, musculoskeletal adverse events that persisted at the end of the 12-month study, or concerns about joint toxicity. Participants were not randomized at the time of entry into the LTFU study, and parents were not blinded.
The researchers asked patients to return for annual examinations, during which they gave them a questionnaire about musculoskeletal injuries and measured their height to assess growth. However, many children did not return for all of the follow-up visits or visited outside the requested window for each visit.
The investigators considered a wide range of musculoskeletal injuries, including arthritis, arthralgia, gait abnormality, tendinopathy, and growth impairment caused by damage to an epiphyseal plate.
At the beginning of the LTFU study, 1 year after taking the drug, 29 children in the levofloxacin group (2% of those exposed) and 10 children in the comparator group (1%) were judged to have a "possible" drug-related injury. After 5 years, 1 child in each group had ongoing concerns about possible joint toxicity, although the Data Safety and Monitoring Committee did not consider these "likely" to be drug-related.
In total, 30% of the levofloxacin group and 35% of the comparator group were lost to follow-up, and only 49% of patients completed the study.
This is "one of the biggest limitations" of the study, Jennifer L. Goldman, MD, a pediatric infectious disease physician at Children's Mercy Hospital in Kansas City, Missouri, told Medscape Medical News. Dr. Goldman, who was not involved in the current study, also noted that the investigators excluded children who did not develop injuries in the first year after taking the drug.
Still, the study provides additional reassurance, she said, to pediatricians who must weigh the benefits and risks of the drug on a case-by-case basis, consistent with American Academy of Pediatrics' guidelines on fluoroquinolones, which recommend the drugs when there is no safe and effective alternative; for example, in the case of multidrug-resistant infections.
This study was funded by Janssen Research and Development (JRD). Dr. Bradley reports work as an unpaid scientific advisor to JRD, and consulting services were contracted by the Regents of the University of California to JRD, for which Dr. Bradley’s department received funding to support research and other university activities. Three coauthors are currently employees of Johnson & Johnson/JRD. The other authors and Dr. Goldman have disclosed no relevant financial relationships.
(http://www.medscape.com/viewarticle/826024?nlid=58685_2046&src=wnl_edit_medn_peds&spon=9)
Rituximab for Complicated, Childhood-onset Refractory NephroticSyndrome
Rituximab could be an effective treatment for childhood-onset, complicated, frequently relapsing nephrotic syndrome (FRNS) and steroid-dependent nephrotic syndrome (SDNS). We investigated the efficacy and safety of rituximab in patients with high disease activity.
Method
We did a multicentre, double-blind, randomised, placebo-controlled trial at nine centres in Japan. We screened patients aged 2 years or older experiencing a relapse of FRNS or SDNS, which had originally been diagnosed as nephrotic syndrome when aged 1-18 years. Patients with complicated FRNS or SDNS who met all other criteria were eligible for inclusion after remission of the relapse at screening. We used a computer-generated sequence to randomly assign patients (1:1) to receive rituximab (375 mg/m2) or placebo once weekly for 4 weeks, with age, institution, treatment history, and the intervals between the previous three relapses as adjustment factors. Patients, guardians, caregivers, physicians, and individuals assessing outcomes were masked to assignments. All patients received standard steroid treatment for the relapse at screening and stopped taking immunosuppressive agents by 169 days after randomisation. Patients were followed up for 1 year. The primary endpoint was the relapse-free period. Safety endpoints were frequency and severity of adverse events. Patients who received their assigned intervention were included in analyses. This trial is registered with the University Hospital Medical Information Network clinical trials registry, number UMIN000001405.
Finding
Patients were centrally registered between Nov 13, 2008, and May 19, 2010. Of 52 patients who underwent randomisation, 48 received the assigned intervention (24 were given rituximab and 24 placebo). The median relapse-free period was significantly longer in the rituximab group (267 days, 95% CI 223-374) than in the placebo group (101 days, 70-155; hazard ratio: 0•27, 0•14-0•53; p<0•0001). Ten patients (42%) in the rituximabgroup and six (25%) in the placebo group had at least one serious adverse event (p=0•36).
Interpretation
Rituximab is an effective and safe treatment for childhood-onset, complicated FRNS and SDNS.
(Iijima K1,et al. Lancet. 2014 Jun 20. pii: S0140-6736(14)60541-9. doi: 10.1016/S0140-6736(14)60541-9. [Epub ahead of print]
Certain factors predicative of renal scarring after first UTI
Children with a urinary tract infection who have abnormal renal ultrasonographic results or a high fever and an etiological organism other than Escherichia coli have a high risk for renal scarring.
Nader Shaikh, MD, MPH, of the University of Pittsburgh School of Medicine in Pittsburgh, and colleagues conducted a meta-analysis of patient data from cohort studies of children who underwent renal scanning with technetium Tc 99m succimer (dimercaptosuccinic acid) at least 5 months after their first urinary tract infection (UTI). Studies with positive urine culture results were included, those with neonatal cohorts were excluded. Nine studies were included in the analysis, yielding a study cohort of 1,280 children.
Most of study participants were younger than 24 months. Approximately 48% had a temperature of at least 39°C and 8.4% of infections were from an organism other than E. coli, according to the study data.
An estimated 20% of children had an abnormal renal ultrasonographic; 29.1% of children had vesicoureteral reflux (VUR); and 4.1% had VUR of grades IV to V.
Of the 199 children (15.5%) with renal scarring, 100 (50.3%) had VUR. The proportion of children with renal scarring increased as the grade of VUR increased.
Risk factors for renal scarring, listed in descending significance, includeed grade IV or V VUR; abnormal ultrasonographic finding; grade III VUR; C-reactive protein level of more than 40 mg/L; temperature of at least 39°C; organism other than E. coli; and grade I or II VUR.
To identify variables predictive of renal scarring through univariate analysis, researchers developed and compared three increasingly invasive strategies for evaluating a first-diagnosed UTI in children. Model 1 included routinely collected information, including history, exam results, and renal ultrasonographic findings. Model 2 included all information in model 1 plus serum inflammatory markers. Model 3 included everything in model 2 plus information on the presence and degree of VUR.
A model 1 score of 2 or more had a sensitivity of 44.9% and specificity of 82.4%. A model 1 score of 2 or more predicted 68.2% of patients with a grade IV or V VUR. Subanalysis of models 2 and 3 was limited due to small sample size, but in general appeared less significant than model one, according to researchers.
“Because we included studies that were conducted at a time when [voiding cystourethrogram] was routinely recommended, we were able to assess the additional predictive ability of three increasingly invasive models. We found that using a simple model with only three clinical variables provided a reasonable screening strategy…. Early identification of children at risk for renal scarring using the prediction rules developed in this study could help clinicians deliver specific treatment and follow-up for this small subgroup in the future,” the researchers concluded.
(Citation: Shaikh N. JAMA Pediatr. 2014;10.1001/jamapediatrics.2014.637.)
Comments:
Ellen R. Wald
Urinary tract infection (UTI) is the most common serious bacterial infection in young children. This report by Shaikh and colleagues is an important study designed to inform the primary care provider regarding the risk of renal scarring in children of any age who experience their first UTI. The authors developed a simple predictive model using basic clinical, laboratory (microbiologic results of urine culture) and ultrasonographic data. In this model, a temperature ≥39°C earns 1 point, an organism other than Escherichia coli earns 1 point and an abnormal renal ultrasound (RUS) earns 2 points. A score of 2 or greater (present in 21.7 % of children) predicts renal scarring in 30.7% (about twice the baseline risk). This simple model does not require the performance of either blood tests (thereby avoiding venipuncture) or a voiding cystourethrogram.
RUSs performed on children aged 2 and 24 months experiencing their first febrile UTI can be expected to be abnormal in 12% to 15% of children. Most of these abnormalities are not “actionable,” ie, do not require an intervention (eg, double collecting system, calculus). Unfortunately, there were no data in this study on the precise nature of the abnormalities found on RUS. It is quite likely, that some findings (the 1% to 3% of actionable [eg, moderate hydronephrosis] findings) are much more predictive of renal scarring than others.
In the meanwhile, children with temperature ≥39°C and an organism other than E. coli, or those with “actionable” finds on RUS should be considered at high risk of renal scarring. When children are at high risk, it is critical to do close follow-up to insure comprehensive evaluation of all unexplained fevers so as to favor early detection of recurrent UTI.
(Ellen R. Wald, MD; Infectious Diseases in Children. Available from: http://www.healio.com/pediatrics/emerging-diseases/news/online/%7B26e2cbcd-d26f-4ca7-a688-ea421a9412e1%7D/certain-factors-predicative-of-renal-scarring-after-first-uti )
Viral Infection May Trigger Childhood Diabetes in Utero
A study published in the journal Diabetic Medicine suggests that diabetes is initiated in utero.
According to the research, women who contract a viral infection during pregnancy transmit viruses to their genetically susceptible fetuses, sparking the development of type 1 diabetes.
“We knew that type 1 diabetes was associated with other autoimmune diseases like Hashimoto Thyroiditis, celiac disease, and multiple sclerosis, so we investigated the seasonality of birth months for these respective diseases in Israel and other countries,” explained ZviLaron, MD, Tel Aviv University, and Schneider Children's Medical Center of Israel, Tel Aviv, Israel.
“We found that the seasonality of the birth of children who went on to develop these diseases did indeed differ from that of the general public. In further studies, we found evidence that viral infections of the mother during pregnancy induced damage to the pancreas of the mother and/or the fetus, evidenced by specific antibodies including those affecting the pancreatic cells producing insulin.”
For the study, researchers conducted blood tests of 107 healthy pregnant women, testing for islet cell auto-antibodies -- evidence of diabetes that appears years before initial symptoms do. They also tested for anti-rotavirus and anti-CoxB3 antibodies.
The researchers found a striking difference between women tested in different seasons, suggesting a link to winter epidemics. The concurrent presence of GAD65 antibodies in cord blood and their mothers indicated autoimmune damage to islet cells during gestation, possibly caused by cross-placental transmission of viral infections and/or antivirus antibodies. In other words, during viral epidemics of winter months, ten percent of the healthy pregnant women who had no family background of autoimmune diseases tested positive for damaging antibodies.
In addition, the cord blood antibody concentrations that exceeded those of the corresponding maternal sample, or antibody-positive cord blood samples with antibody-negative maternal samples, implied an in utero immune response by the fetus.
“If our hypothesis can be verified, then preventive vaccine before conception would be useful in stopping the increasing incidence of type 1 diabetes and other autoimmune diseases,” said Dr. Laron. “There is no cure for this diabetes, so true intervention would be important not only medically but also psychologically and financially, as the costs of the lifelong treatment of this chronic disease and other autoimmune diseases are great.”
>(Source: Tel Aviv University)