Search

The Society of Nuclear Medicine and Molecular Imaging (SNMMI), founded in 1954, is an international scientific and professional organization with a purpose to promote the science, technology, and practical application of nuclear medicine. The European Association of Nuclear Medicine (EANM), founded in 1985, is a nonprofit professional medical association with a purpose to facilitate international communication among individuals in nuclear medicine pursuing clinical and academic excellence. Members of the SNMMI and EANM are physicians, technologists, and scientists who specialize in the research and practice of nuclear medicine. The SNMMI and EANM will periodically publish new guidelines for nuclear medicine practice to further advance the science of nuclear medicine and improve patient care. Existing standards/guidelines will be reviewed for revision or renewal, as appropriate. Each standard/guideline, representing a policy statement by the SNMMI/EANM, has undergone a thorough review, and represents an expert consensus. The SNMMI and EANM recognize that the safe and effective use of diagnostic nuclear medicine imaging requires specific training and skills, as described in each document. These standards/guidelines are educational resources designed to assist practitioners in providing appropriate nuclear medicine care for patients. They are consensus documents, and are not mandatory provisions or requirements of practice. They are not intended, nor should they be used, to establish a legal standard of care. For these reasons and those set forth below, the SNMMI and the EANM cautions against the use of these standards/guidelines in litigation procedures that call into question the clinical decisions of a practitioner. The ultimate judgment regarding the appropriateness and propriety of any specific procedure or course of action must be made by medical professionals, taking into account the unique context of each case. Thus, there is no implication that action differing from what is detailed in these standards/guidelines, on its own, is below the standard of care. On the contrary, a conscientious practitioner may responsibly adopt a course of action different from that set forth in the standards/guidelines when, based on the reasonable judgment of the practitioner, such course of action is warranted based on the condition of the patient, limitations of available resources, or advances in knowledge or technology subsequent to publication of the standards/guidelines. Practicing medicine involves not only the science, but also the art of dealing with the prevention, detection, diagnosis, and treatment of disease. The variety and complexity of human conditions make it impossible for general guidelines to consistently allow for an accurate diagnosis to be reached or a specific treatment response to be predicted. Therefore, it should be recognized that adhering to these standards/guidelines does not ensure a successful outcome. All that should be expected is that a practitioner follows a reasonable course of action based on their level of training, the current landscape of knowledge, the resources at their disposal, and the needs/context of the particular patient being treated. The purpose of this document is to provide nuclear medicine physicians, radiologists, and other clinicians with guidelines for the recommendation, performance and interpretation of 99mTc-dimercaptosuccinic acid renal cortical scintigraphy ([99mTc] Tc-DMSA scintigraphy) in pediatric patients. These recommendations represent the expert opinions of experienced leaders in this field, and these recommendations are not all supported by a high level of evidence. Further studies are required to have evidence-based recommendations for the application of [99mTc] Tc-DMSA renal cortical scintigraphy in pediatrics. This guideline summarizes the views of the SNMMI Renal Cortical Scintigraphy in Children Working Group and the EANM Pediatrics Committee. It reflects recommendations for which the SNMMI and EANM cannot be held responsible. The recommendations should be taken into context of good practice of nuclear medicine and do not substitute for national and international legal or regulatory provisions.

Dating back to 2011, practice guidelines considered Black race a factor associated with lower risk of urinary tract infection (UTI). Race-based clinical decisions raise concerns about potential treatment disparities. We investigate urine testing (urinalysis and/or urine culture) among young febrile children in the emergency department (ED), revisits, and potential missed diagnoses by race/ethnicity. We performed a multicenter retrospective cohort study of children 2–24 months evaluated in 26 US EDs from 2009 to 2019 with a fever diagnosis. We evaluated longitudinal testing trends, constructed a generalized linear mixed-effects model to identify the association of race/ethnicity with testing, and characterized UTI diagnoses and ≤ 7-day revisits. Of 734,730 included patients, 24.1% were Black. Variation in urine testing was observed by patient race/ethnicity (23.4% Black, 31.7% White, 33.9% Hispanic, 30.0% other race). Relative differences in testing persisted over time. Black patients had lower adjusted odds of testing (0.70, 95% confidence interval [CI] 0.69–0.71). Among patients with urine testing, 2.4% (95% CI 2.3–2.6%) of Black and 3.3% (95% CI 3.1–3.4%) of White patients were diagnosed with UTI. Among Black patients with urine testing on the index visit, 8.5% (95% CI 8.2–8.8%) had return visits compared to 7.6% (95% CI 7.5–7.8%) among those without urine testing on index visit. Among patients with urine testing on revisit, UTI diagnosis was similar by race/ethnicity. Black patients had lower rates of urine testing and UTI diagnoses relative to other racial/ethnic groups. This was not associated with higher rates of missed diagnoses or unscheduled return visits.

The bacterial components of the urobiome have been described in children, both with and without urinary tract infections (UTI). However, less is known about the pediatric uromycobiome: the community of fungi in the urine. The objectives of this study were to describe the uromycobiome in children and determine whether the uromycobiome differs between children with and without UTI.This was a cross-sectional study of febrile children less than 3 years of age who presented to the Emergency Department and had a catheterized urine sample sent as part of clinical care. We obtained residual urine for use in this study and identified components of the uromyobiome through amplification and sequencing of the fungal ITS2 region. We then compared the uromycobiome between those with and without UTI.We included 374 children in this study (UTI = 50, no UTI = 324). Fungi were isolated from urine samples of 310 (83%) children. Fungi were identified in a higher proportion of children with UTI, compared to those without UTI (96% vs. 81%, p = 0.01). Shannon diversity index was higher in children with UTI, compared to those without (p = 0.04). Although there were differences in the most abundant taxa between children with and without UTI, there was no significant difference in beta diversity between groups.Fungi were detected in the majority of catheterized urine samples from children. While a higher proportion of children with UTI had fungi in their urine, compared to children without UTI, there was no difference in the composition of these groups. A higher resolution version of the Graphical abstract is available as Supplementary information.

The microbial ecosystem within the bladder that can be measured within the urine, or urobiome, is an emerging field of study with little published data regarding children. However, investigations into urobiome research have the potential to significantly impact the understanding of the pathophysiology of genitourinary conditions, as well as potentially identify novel therapeutics. Therefore, both researchers and clinicians should be aware of pediatric urobiome research. The purpose of this review is to highlight the literature around urobiome research in urinary tract infections, nephrolithiasis, and neurogenic bladder; comment on pediatric-specific considerations when reading and interpreting the urobiome literature; and to identify new potential areas of research.

To evaluate the cost-effectiveness of tympanostomy tube placement vs. nonsurgical medical management, with the option of tympanostomy tube placement in the event of treatment failure, in children with recurrent acute otitis media (AOM).A Markov decision model compared management strategies in children ages 6 to 35 months, using patient-level data from a recently completed, multicenter, randomized clinical trial of tympanostomy tube placement vs. medical management. The model ran over a two-year time horizon using a societal perspective. Probabilities, including risk of AOM symptoms, were derived from prospectively collected patient diaries. Costs and quality-of-life measures were derived from the literature. We performed one-way and probabilistic sensitivity analyses, and secondary analyses in predetermined low- and high-risk subgroups. The primary outcome was incremental cost per quality-adjusted life-year gained.Tympanostomy tubes cost $989 more per child than medical management. Children managed with tympanostomy tubes gained 0.69 more quality-adjusted life-days than children managed medically, corresponding to $520,855 per quality-adjusted life-year gained. Results were sensitive to the costs of oral antibiotics, missed work, special childcare, the societal cost of antibiotic resistance, and the quality of life associated with AOM. In probabilistic sensitivity analyses, medical management was favored in 66% of model iterations at a willingness-to-pay threshold of $100,000/quality-adjusted life-year. Medical management was preferred in secondary analyses of low- and high-risk subgroups.For young children with recurrent AOM, the additional cost associated with tympanostomy tube placement outweighs the small improvement in quality of life. Medical management for these children is an economically reasonable strategy.

To compare clinical history and measurements of fecal load on abdominal radiography (AR) in the prediction of urinary tract infection (UTI) recurrence in children. We combined data from two multicenter longitudinal studies in which children less than 6 years of age with a first or second UTI were followed for recurrence of UTI. Two radiologists reviewed the scout abdominal radiographs of initial voiding cystourethrograms obtained at enrollment from children at two participating sites and measured stool visible in various parts of the colon. We examined how well clinical variables (e.g., voiding and bowel history, use of laxatives at enrollment) and measurements of fecal load predicted recurrence of UTI within 12 months of enrollment. One hundred and ninety-two children were included. On univariate analyses, age, vesicoureteral reflux (VUR), cecal diameter, rectal diameter, and total stool length on AR were associated with recurrence of UTI. After controlling for age, the odds of recurrent UTI in children with VUR at baseline was 3.85 (95% CI: 1.62, 9.14) higher than in children without VUR. Recurrent UTI was 2.57 (95% CI: 1.01, 6.55) times more likely in children with cecal diameter > 3.10 cm than children with lower cecal diameters; time to first recurrent UTI was shorter in children with elevated cecal diameters (p = 0.0023). Cecal diameter on abdominal radiographs predicts UTI recurrence in children with a previous UTI. However, its accuracy is suboptimal to serve as a screening test. Accordingly, its routine use for this indication is not supported. If cecal diameter on an AR ordered for another indication is > 3.10 cm, then management of constipation could be considered.

IMPORTANCE: A previously reported prediction model included a child’s race to estimate risk of urinary tract infection (UTI), but race-conscious medicine encourages investigating how race is likely to be a proxy for other factors that should instead be used for risk prediction. OBJECTIVES: To systematically review the available literature to evaluate the robustness of the association between race and UTI and to assess whether other variables could replace race as a variable in a previously developed prediction tool without adversely affecting its accuracy. DATA SOURCE: MEDLINE was searched through May 28, 2021. STUDY SELECTION: English-language studies that reported data on the prevalence of UTI according to race for children younger than 18 years were included. DATA EXTRACTION AND SYNTHESIS: Two independent reviewers assessed studies for risk of bias and abstracted data. Random-effects models were used to pool odds ratios, and meta-regression was used to explore heterogeneity. MAIN OUTCOMES AND MEASURES: Odds of UTI among non-Black children vs Black children. RESULTS: Sixteen studies (17 845 children) were included. In the primary analysis, which included 11 studies, the pooled odds ratio of UTI among non-Black children was 2.44-fold higher (95% CI, 1.87-3.20) than among Black children. The corresponding odds ratio in studies with low or very low risk of bias was 4.84-fold higher (95% CI, 3.16-7.41; I(2) = 0%) among non-Black children than among Black children. Replacing race with history of UTI and duration of fever resulted in a model with similar accuracy (training cohort: overall sensitivity, 96% [95% CI, 94%-98%]; overall specificity, 35% [95%, 32%-38%]; overall area under the receiver operating characteristic curve, 0.80 [95% CI, 0.77-0.82]; validation cohort: overall sensitivity, 97% [95% CI, 90%-100%]; overall specificity, 32% [95% CI, 26%-37%]; overall area under the receiver operating characteristic curve, 0.84 [95% CI, 0.77-0.92]). CONCLUSIONS AND RELEVANCE: Although previous studies suggested that an association between race and UTI exists, because of the issues associated with the inclusion of race in decision models, we replaced the variable of race with history of UTI and duration of fever in a previously developed risk prediction model and found similar accuracy.

Background Little is known regarding parents’ experiences caring for children with acute otitis media (AOM). This study aimed to explore parents’ experiences caring for their child with AOM, identifying symptoms they observed, their thoughts and feelings about those symptoms, how they managed the episode, and what factors caused them to seek medical evaluation. Methods From October 2019 to February 2020, we conducted 24 semi-structured cross-sectional interviews with parents of children 3 to 36 months of age with AOM diagnosed at primary care offices associated with the Children’s Hospital of Pittsburgh regarding (1) symptoms and behaviors that led parents to believe their child might have AOM; (2) symptoms that were most bothersome to parent and child; (3) what parents did in response to these symptoms; (4) motivations for seeking clinical care; and (5) parents’ expectations regarding AOM resolution. Data were analyzed using template analysis, resulting in a hybrid inductive/deductive analytic process. Results We interviewed 24 parents within 72 h of diagnosis of AOM. Parents frequently believed ear tugging was the symptom most indicative of AOM, despite its presence in only half of the children in this sample. Parents consistently sought medical care when their child had an elevated temperature or lack of sleep, or when symptoms worsened or were unresponsive to home remedies. Parents of children with history of recurrent AOM had less difficulty identifying symptoms of AOM than parents of children with their first ear infection. Conclusions Our findings provide insight into symptoms of AOM that cause parents concern and motivate the use of healthcare services. Parents differed in their abilities to observe and report symptoms of AOM. Thus, when interviewing parents who are concerned their preverbal child has AOM, rather than focusing on ear tugging and fever alone, providers should ascertain all unusual behaviors observed by the parent.

To identify risk factors for febrile recurrence of urinary tract infections (UTIs) in children with a history of UTI.We included 500 children aged 2-72 months with a history of UTI who were followed prospectively for approximately 2 years in the context of 2 previously conducted studies (Randomized Intervention for Children with Vesicoureteral Reflux and Careful Urinary Tract Infection Evaluation). We identified significant risk factors for febrile recurrences among children not receiving antimicrobial prophylaxis using univariate and multivariate logistic regression.On univariate analysis, non-Black race, febrile index UTI, bowel-bladder dysfunction, grade IV vesicoureteral reflux, renal scarring at baseline, and renal-bladder ultrasound abnormalities were associated with febrile recurrence. On multivariate analysis, the following variables independently increased the odds of febrile recurrences (OR; 95% CI): non-Black race (7.1; 1.5-127.9), bowel-bladder dysfunction (2.6; 1.1-5.3), febrile index UTI (2.5; 1.1-6.9), abnormalities on renal-bladder ultrasound scan (2.6; 1.2-5.6), grade IV vesicoureteral reflux (3.9; 1.4-10.5), and renal scarring at baseline (4.7; 1.2-19.1).Non-Black race and grade IV vesicoureteral reflux increased the odds of febrile recurrence of UTI. Although our findings should stimulate other studies to further explore the relationship between race and UTIs, given that the link between race and UTI recurrence is unclear, race should not be used to make decisions regarding management of children with a UTI.

BACKGROUND Acute otitis media (AOM) is the most frequent reason for children to be prescribed antimicrobial treatment. Surfactants are naturally occurring substances that may restore the eustachian tube’s function and potentially enhance resolution of AOM. METHODS This was a phase 2a, single-center, double-blind, randomized, placebo-controlled, parallel group clinical trial to assess safety, tolerability, and efficacy of 20 mg per day intranasal OP0201 as an adjunct therapy to oral antimicrobial agents for treating AOM in young children. We randomly assigned 103 children aged 6 to 24 months with AOM to receive either OP0201 or placebo twice daily for 10 days. All children received amoxicillin-clavulanate 90/6.4 mg/kg per day in 2 divided doses for 10 days. Participants were managed for up to 1 month. Postrandomization visits occurred between days 4 and 6 (visit 2), days 12 and 14 (visit 3), and days 26 and 30 (visit 4). Primary efficacy endpoints were resolution of a bulging tympanic membrane at visit 2 and resolution of middle-ear effusion at visit 3. RESULTS No clinically meaningful differences between treatment groups were apparent for primary or secondary endpoints. There were no safety concerns identified. CONCLUSIONS In young children with AOM, intranasally administered surfactant (OP0201) did not improve clinical outcomes. Further research may be warranted among children with persistent middle-ear effusion.

Objective: Children with no pathogenic bacteria in the nasopharynx are unlikely to have acute bacterial sinusitis. We evaluated whether information on clinical presentation, viral co-detection, and mucosal cytokine levels could be used to predict presence of bacteria in the nasopharynx.Method: We obtained nasopharyngeal (NP) swabs from children diagnosed with acute sinusitis. NP swabs were processed for bacterial culture, viral PCR testing, and cytokine expression. We examined whether results of the bacterial culture could be predicted based on the presence of clinical information, presence of viruses or mucosal cytokine levels.Results: We enrolled 174 children; 123 (71%) had a positive culture for potentially pathogenic bacteria and 51 (29%) had normal flora. 122/174 (70%) tested positive for one or more viruses. Compared to children with normal flora, children with pathogenic bacteria were more likely to have viruses (p < 0.01), but this relationship disappeared when we adjusted for age. Children with pathogenic bacteria in their nasopharynx and children with normal flora had similar levels of nasal cytokines.Conclusion: In children with clinically diagnosed acute sinusitis, clinical presentation, levels of nasal cytokines, and presence of viruses do not differentiate children with and without pathogenic bacteria in their nasopharynx.

Urinary tract infections in children can lead to permanent renal scarring in approximately 15% of cases. Technetium-99m ((99m)Tc)-dimercaptosuccinic acid (DMSA) scintigraphy is the gold standard for identifying renal scarring. Using data and scans from children enrolled at our center in a 2-year prospective clinical trial (RIVUR study), we included children with radiologically confirmed pyelonephritis who exhibited renal scarring on their 1 and/or 2-year follow-up scans and asked 3 blinded pediatric nuclear medicine physicians to reexamine the renal contours in these scans. Five girls met all eligibility criteria (each had two late (99m)Tc-DMSA scans 1 and 2 years after index UTI). Of the 20 kidneys imaged, 10 exhibited renal scarring and of these, 7 exhibited renal contour abnormalities. These findings suggest that the presence of abnormalities of the renal contour is not necessary for diagnosis of renal scarring.

Dating back to 2011, practice guidelines considered Black race a factor associated with lower risk of urinary tract infection (UTI). Race-based clinical decisions raise concerns about potential treatment disparities. We investigate urine testing (urinalysis and/or urine culture) among young febrile children in the emergency department (ED), revisits, and potential missed diagnoses by race/ethnicity.We performed a multicenter retrospective cohort study of children 2-24 months evaluated in 26 US EDs from 2009 to 2019 with a fever diagnosis. We evaluated longitudinal testing trends, constructed a generalized linear mixed-effects model to identify the association of race/ethnicity with testing, and characterized UTI diagnoses and ≤ 7-day revisits.Of 734,730 included patients, 24.1% were Black. Variation in urine testing was observed by patient race/ethnicity (23.4% Black, 31.7% White, 33.9% Hispanic, 30.0% other race). Relative differences in testing persisted over time. Black patients had lower adjusted odds of testing (0.70, 95% confidence interval [CI] 0.69-0.71). Among patients with urine testing, 2.4% (95% CI 2.3-2.6%) of Black and 3.3% (95% CI 3.1-3.4%) of White patients were diagnosed with UTI. Among Black patients with urine testing on the index visit, 8.5% (95% CI 8.2-8.8%) had return visits compared to 7.6% (95% CI 7.5-7.8%) among those without urine testing on index visit. Among patients with urine testing on revisit, UTI diagnosis was similar by race/ethnicity.Black patients had lower rates of urine testing and UTI diagnoses relative to other racial/ethnic groups. This was not associated with higher rates of missed diagnoses or unscheduled return visits.

* Abbreviations: CI — : confidence interval COVID-19 — : coronavirus disease 2019 PCR — : polymerase chain reaction SARS-CoV-2 — : severe acute respiratory syndrome coronavirus 2 Abbott BinaxNOW (a bedside lateral flow immunoassay intended for the qualitative detection of nucleocapsid protein antigen) is widely available under US Food and Drug Administration emergency use authorization for the detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in symptomatic patients within 7 days of symptom onset. Its diagnostic performance in symptomatic children has not been evaluated. Cross-sectional study of symptomatic children ≤20 years presenting for care to 1 of 2 primary care practices in December 2020, during which time coronavirus disease 2019 (COVID-19) rates were … Address correspondence to Nader Shaikh, MD, MPH, University of Pittsburgh Medical Center, Children’s Hospital of Pittsburgh, 1 Children’s Hospital Dr, 4401 Penn Ave, Pittsburgh, PA 15224. E-mail: nader.shaikh{at}chp.edu

BACKGROUND: Official recommendations differ regarding tympanostomy-tube placement for children with recurrent acute otitis media. METHODS: We randomly assigned children 6 to 35 months of age who had had at least three episodes of acute otitis media within 6 months, or at least four episodes within 12 months with at least one episode within the preceding 6 months, to either undergo tympanostomy-tube placement or receive medical management involving episodic antimicrobial treatment. The primary outcome was the mean number of episodes of acute otitis media per child-year (rate) during a 2-year period. RESULTS: In our main, intention-to-treat analysis, the rate (±SE) of episodes of acute otitis media per child-year during a 2-year period was 1.48±0.08 in the tympanostomy-tube group and 1.56±0.08 in the medical-management group (P = 0.66). Because 10% of the children in the tympanostomy-tube group did not undergo tympanostomy-tube placement and 16% of the children in the medical-management group underwent tympanostomy-tube placement at parental request, we conducted a per-protocol analysis, which gave corresponding episode rates of 1.47±0.08 and 1.72±0.11, respectively. Among secondary outcomes in the main analysis, results were mixed. Favoring tympanostomy-tube placement were the time to a first episode of acute otitis media, various episode-related clinical findings, and the percentage of children meeting specified criteria for treatment failure. Favoring medical management was children’s cumulative number of days with otorrhea. Outcomes that did not show substantial differences included the frequency distribution of episodes of acute otitis media, the percentage of episodes considered to be severe, and antimicrobial resistance among respiratory isolates. Trial-related adverse events were limited to those included among the secondary outcomes of the trial. CONCLUSIONS: Among children 6 to 35 months of age with recurrent acute otitis media, the rate of episodes of acute otitis media during a 2-year period was not significantly lower with tympanostomy-tube placement than with medical management. (Funded by the National Institute on Deafness and Other Communication Disorders and others; ClinicalTrials.gov number, NCT02567825.)

Objective To modify a parent-reported scale we developed to follow symptoms of young children with acute otitis media (AOM-SOS) with the aim of improving its psychometric properties. Study design We modified version 4.0 of the scale by increasing the number of response options from 3 to 6. We compared the distribution of scores, internal reliability, construct validity, and responsiveness of versions 4.0 and 5.0 in children diagnosed with acute otitis media (AOM) in 2 studies. For Version 5.0, we also estimated the minimal important difference (MID) and assessed its construct validity. Results 291 and 70 children were enrolled in the studies evaluating version 4.0 and 5.0, respectively. Version 5.0 had fewer items at the ceiling and better psychometric properties (responsiveness, internal reliability, and test-retest reliability). Changes in the score for Version 5.0 corresponded to changes in clinical status. Factor analysis supported a one-factor solution. Children whose parents reported only a small degree of improvement on the diary (compared to the day before) had a mean decrease in AOM-SOS score of approximately 20%. This value can be used as the MID for this version of the scale. Conclusions Modification of the AOM-SOS improved its psychometric properties. Data presented here support the use of Version 5.0 of the AOM-SOS as a measure of change in symptom burden in clinical trials of children with acute otitis media.

The sensitivity and specificity of the leukocyte esterase test for the diagnosis of urinary tract infection (UTI) are suboptimal. Recent studies have identified markers that appear to more accurately differentiate children with and without UTI. The objective of this study was to determine the accuracy of these markers, which included CCL3, IL-8, CXCL1, TNF-alpha, IL-6, IFN-gamma, IL-17, IL-9, IL-2, and NGAL, in the diagnosis of UTI.This was a prospective cross-sectional study to compare inflammatory proteins between urine samples from febrile children with a UTI, matched febrile controls without a UTI, and asymptomatic healthy controls.We included 192 children (75 with febrile UTI, 69 febrile controls, and 48 asymptomatic healthy controls). Urinary proteins that best discriminated between febrile children with and without UTI were NGAL, a protein that exerts a local bacteriostatic role in the urinary tract through iron chelation; CCL3, a chemokine involved in leukocyte recruitment; and IL-8, a cytokine involved in neutrophil recruitment. Levels of these proteins were generally undetectable in asymptomatic healthy children.NGAL, CCL3, and IL-8 may be useful in the early diagnosis of UTI.ClinicalTrials.gov (NCT01391793) A higher resolution version of the Graphical abstract is available as Supplementary information.

BACKGROUND: In children with urinary tract infection (UTI), only those with pyelonephritis (and not cystitis) are at risk for developing long‐term renal sequelae. If non‐invasive biomarkers could accurately differentiate children with cystitis from children with pyelonephritis, treatment and follow‐up could potentially be individualized. This is an update of a review first published in 2015. OBJECTIVES: The objectives of this review were to 1) determine whether procalcitonin (PCT), C‐reactive protein (CRP), erythrocyte sedimentation rate (ESR) can replace the acute DMSA scan in the diagnostic evaluation of children with UTI; 2) assess the influence of patient and study characteristics on the diagnostic accuracy of these tests, and 3) compare the performance of the three tests to each other. SEARCH METHODS: We searched MEDLINE, EMBASE, DARE, Web of Science, and BIOSIS Previews through to 17th December 2019 for this review. The reference lists of all included articles and relevant systematic reviews were searched to identify additional studies not found through the electronic search. SELECTION CRITERIA: We only considered published studies that evaluated the results of an index test (PCT, CRP, ESR) against the results of an acute‐phase (99)Tc‐dimercaptosuccinic acid (DMSA) scan (conducted within 30 days of the UTI) in children aged 0 to 18 years with a culture‐confirmed episode of UTI. The following cut‐off values were used for the primary analysis: 0.5 ng/mL for procalcitonin, 20 mg/L for CRP and 30 mm/hour for ESR. DATA COLLECTION AND ANALYSIS: Two authors independently applied the selection criteria to all citations and independently abstracted data. We used the bivariate model to calculate pooled random‐effects pooled sensitivity and specificity values. MAIN RESULTS: A total of 36 studies met our inclusion criteria. Twenty‐five studies provided data for the primary analysis: 12 studies (1000 children) included data on PCT, 16 studies (1895 children) included data on CRP, and eight studies (1910 children) included data on ESR (some studies had data on more than one test). The summary sensitivity estimates (95% CI) for the PCT, CRP, ESR tests at the aforementioned cut‐offs were 0.81 (0.67 to 0.90), 0.93 (0.86 to 0.96), and 0.83 (0.71 to 0.91), respectively. The summary specificity values for PCT, CRP, and ESR tests at these cut‐offs were 0.76 (0.66 to 0.84), 0.37 (0.24 to 0.53), and 0.57 (0.41 to 0.72), respectively. AUTHORS' CONCLUSIONS: The ESR test does not appear to be sufficiently accurate to be helpful in differentiating children with cystitis from children with pyelonephritis. A low CRP value (< 20 mg/L) appears to be somewhat useful in ruling out pyelonephritis (decreasing the probability of pyelonephritis to < 20%), but unexplained heterogeneity in the data prevents us from making recommendations at this time. The procalcitonin test seems better suited for ruling in pyelonephritis, but the limited number of studies and the marked heterogeneity between studies prevents us from reaching definitive conclusions. Thus, at present, we do not find any compelling evidence to recommend the routine use of any of these tests in clinical practice.

A state-of-the art review of current literature on UTI in children, with a particular focus on its diagnosis and management by general pediatricians. Urinary tract infection (UTI) is common in children, and girls are at a significantly higher risk, as compared to boys, except in early infancy. Most cases are caused by Escherichia coli. Collection of an uncontaminated urine specimen is essential for accurate diagnosis. Oral antibiotic therapy for 7 to 10 days is adequate for uncomplicated cases that respond well to the treatment. A renal ultrasound examination is advised in all young children with first febrile UTI and in older children with recurrent UTI. Most children with first febrile UTI do not need a voiding cystourethrogram; it may be considered after the first UTI in children with abnormal renal and bladder ultrasound examination or a UTI caused by atypical pathogen, complex clinical course, or known renal scarring. Long-term antibiotic prophylaxis is used selectively in high-risk patients. Few patients diagnosed with vesicoureteral reflux after a UTI need surgical correction. The most consequential long-term complication of acute pyelonephritis is renal scarring, which may increase the risk of hypertension or chronic kidney disease later in life. Treatment of acute pyelonephritis with an appropriate antibiotic within 48 hours of fever onset and prevention of recurrent UTI lowers the risk of renal scarring. Pathogens causing UTI are increasingly becoming resistant to commonly used antibiotics, and their indiscriminate use in doubtful cases of UTI must be discouraged.

Objective: Antimicrobial prophylaxis for children with vesicoureteral reflux (VUR) reduces recurrences of urinary tract infection (UTI) but requires daily antimicrobials for extended periods. We used a cost-utility model to evaluate whether the benefits of antimicrobial prophylaxis outweigh its risks and, if so, to investigate whether the benefits and risks vary according to grade of VUR. Methods: We compared the cost per quality-adjusted life-year (QALY) gained in four treatment strategies in children aged

Limiting the duration of antimicrobial treatment constitutes a potential strategy to reduce the risk of antimicrobial resistance among children with acute otitis media.We assigned 520 children, 6 to 23 months of age, with acute otitis media to receive amoxicillin-clavulanate either for a standard duration of 10 days or for a reduced duration of 5 days followed by placebo for 5 days. We measured rates of clinical response (in a systematic fashion, on the basis of signs and symptomatic response), recurrence, and nasopharyngeal colonization, and we analyzed episode outcomes using a noninferiority approach. Symptom scores ranged from 0 to 14, with higher numbers indicating more severe symptoms.Children who were treated with amoxicillin-clavulanate for 5 days were more likely than those who were treated for 10 days to have clinical failure (77 of 229 children [34%] vs. 39 of 238 [16%]; difference, 17 percentage points [based on unrounded data]; 95% confidence interval, 9 to 25). The mean symptom scores over the period from day 6 to day 14 were 1.61 in the 5-day group and 1.34 in the 10-day group (P=0.07); the mean scores at the day-12-to-14 assessment were 1.89 versus 1.20 (P=0.001). The percentage of children whose symptom scores decreased more than 50% (indicating less severe symptoms) from baseline to the end of treatment was lower in the 5-day group than in the 10-day group (181 of 227 children [80%] vs. 211 of 233 [91%], P=0.003). We found no significant between-group differences in rates of recurrence, adverse events, or nasopharyngeal colonization with penicillin-nonsusceptible pathogens. Clinical-failure rates were greater among children who had been exposed to three or more children for 10 or more hours per week than among those with less exposure (P=0.02) and were also greater among children with infection in both ears than among those with infection in one ear (P0.001).Among children 6 to 23 months of age with acute otitis media, reduced-duration antimicrobial treatment resulted in less favorable outcomes than standard-duration treatment; in addition, neither the rate of adverse events nor the rate of emergence of antimicrobial resistance was lower with the shorter regimen. (Funded by the National Institute of Allergy and Infectious Diseases and the National Center for Research Resources; ClinicalTrials.gov number, NCT01511107 .).

BACKGROUND: A recent study in young infants found that different cutoffs maximized the accuracy of the urine white blood cell count in dilute versus concentrated urine samples. We aimed to confirm this finding and to determine its impact on clinical care. METHODS: We conducted a retrospective analysis of data gathered on consecutive children RESULTS: We included 10 078 children. The ability to rule in UTI (as measured by the positive likelihood ratio [LR]) was similar in dilute and concentrated urine for the leukocyte esterase test (11.76 vs 10.71, respectively). The positive LR for urine white blood cell count per high-powered field was higher in dilute urine (9.83 vs 6.12). In contrast, the positive LR for the nitrite test was lower in dilute urine (20.54 vs 47.44). Despite these differences, we found little change in the number of children treated with antibiotics in predictive models that took urine SG into consideration. CONCLUSIONS: Although we found that urine SG influences the accuracy of some components of the urinalysis, its inclusion in the decision-making process had negligible effect on the clinical care of children with UTI.

Vesicoureteral reflux (VUR) is a complex, heritable disorder. Genome-wide linkage analyses of families affected by VUR have revealed multiple genomic loci linked to VUR. These loci normally harbor a number of genes whose biologically functional variant is yet to be identified. DNA copy number variations (CNVs) have not been extensively studied at high resolution in VUR patients. In this study, we performed array comparative genomic hybridization (aCGH) on a cohort of patients with a history of both VUR and urinary tract infection (UTI) with the objective of identifying genetic variations responsible for VUR and/or UTI susceptibility. UTI/VUR-associated CNVs were identified by aCGH results from the 192 Randomized Intervention for Children With Vesicoureteral Reflux (RIVUR) patients compared to 683 controls. Rare, large CNVs that are likely pathogenic and lead to VUR development were identified using stringent analysis criteria. Because UTI is a common affliction with multiple risk factors, we utilized standard analysis to identify potential disease-modifying CNVs that can contribute to UTI risk. Gene ontology analysis identified that CNVs in innate immunity and development genes were enriched in RIVUR patients. CNVs affecting innate immune genes may contribute to UTI susceptibility in VUR patients and may provide the first step in assisting clinical medicine in determining adverse outcome risk in children with VUR.

Urinary tract infections (UTIs) in children are among the most common bacterial infections in childhood. They are equally common in boys and girls during the first year of life and become more common in girls after the first year of life. Dividing UTIs into three categories; febrile upper UTI (acute pyelonephritis), lower UTI (cystitis), and asymptomatic bacteriuria, is useful for numerous reasons, mainly because it helps to understand the pathophysiology of the infection. A single episode of febrile UTI is often caused by a virulent Escherichia coli strain, whereas recurrent infections and asymptomatic bacteriuria commonly result from urinary tract malformations or bladder disturbances. Treatment of an upper UTI needs to be broad and last for 10 days, a lower UTI only needs to be treated for 3 days, often with a narrow-spectrum antibiotic, and asymptomatic bacteriuria is best left untreated. Investigations of atypical and recurrent episodes of febrile UTI should focus on urinary tract abnormalities, whereas in cases of cystitis and asymptomatic bacteriuria the focus should be on bladder function.

Objectives: To gather preliminary data on the effectiveness and feasibility of cerumen removal using three irrigation methods and a metal curette in young children. Study design: Pilot study conducted as a randomized clinical trial of well and ill children age 6 months to 6 years with ≥25% cerumen occlusion in at least one ear. Children were stratified by age and randomized to one of four methods of cerumen removal: syringe with attached angiocath tubing, Elephant Ear Washer Bottle System®, OtoClear® Spray Wash Kit, or metal curette. Clinicians, blinded from treatment assignment, assessed the degree of cerumen occlusion before and after the procedure. Outcomes included reduction in cerumen occlusion, successful removal, time until completion and parental satisfaction. Rules for stopping procedures were established a priori. Results: Thirty-eight children underwent procedures (59 ears). There were no significant differences in reduction in cerumen and successful removal among the methods. Overall, 36 (61%) of 59 of procedures were successful. The syringe with angiocath tubing took the most time (P = 0.04) and resulted in the most stopped procedures (P < 0.01). Parental satisfaction scores were not significantly different. Conclusions: Irrigation methods performed comparably to cerumen removal with curette; the SA method had drawbacks. Irrigation can be performed by non-clinicians, which is potentially a significant advantage. (Clinical trial registration: http://www.isrctn.com/ISRCTN74402562).

Objective To develop a method to perform multiple tests on single nasopharyngeal (NP) swab. Study design We collected a NP swab on children aged 2–12 years with acute sinusitis and processed it for bacterial culture, viruses, cytokine expression, and 16S ribosomal RNA gene sequencing analysis. During the course of the study, we expand the scope of evaluation to include RNA sequencing, which we accomplished by cutting the tip of the swab. Results Of the 174 children enrolled, 126 (72.4%) had a positive bacterial culture and 121(69.5%) tested positive for a virus. Cytokine measurement, as judged by the adequate levels of a housekeeping enzyme (GAPDH), appeared successful. From the samples used for 16S ribosomal sequencing we recovered, on average, 16,000 sequences per sample, accounting for a total of 2,646 operational taxonomic units across all samples sequenced. Samples used for RNA sequencing had a mean RNA Integrity number of 6.0. Cutting the tip of the swab did not affect the recovery yield for viruses or bacteria, nor did it affect species richness in microbiome analysis. Conclusion We describe a minimally invasive sample collection protocol that allows for multiple diagnostic and research investigations in young children.