Search

Sparse data bias, where there is a lack of sufficient cases, is a common problem in data analysis, particularly when studying rare binary outcomes. Although a two‐step meta‐analysis approach may be used to lessen the bias by combining the summary statistics to increase the number of cases from multiple studies, this method does not completely eliminate bias in effect estimation. In this paper, we propose a one‐shot distributed algorithm for estimating relative risk using a modified Poisson regression for binary data, named ODAP‐B. We evaluate the performance of our method through both simulation studies and real‐world case analyses of postacute sequelae of SARS‐CoV‐2 infection in children using data from 184 501 children across eight national academic medical centers. Compared with the meta‐analysis method, our method provides closer estimates of the relative risk for all outcomes considered including syndromic and systemic outcomes. Our method is communication‐efficient and privacy‐preserving, requiring only aggregated data to obtain relatively unbiased effect estimates compared with two‐step meta‐analysis methods. Overall, ODAP‐B is an effective distributed learning algorithm for Poisson regression to study rare binary outcomes. The method provides inference on adjusted relative risk with a robust variance estimator. [ABSTRACT FROM AUTHOR]

Hepatitis C virus (HCV) testing is recommended for all adults 18 years and older to increase identification of those with infection and facilitate prompt referral for curative antiviral therapy. While critical to promote elimination, this strategy excludes a key demographic group who are clearly at risk of undetected HCV infection and who could benefit from early treatment: adolescents. In this paper, we review the available data on the burden of HCV and the close association with injection drug use, discuss the rationale of universal testing in adolescents and, finally, present data from a quality improvement project implementing HCV testing into routine adolescent health visits. [ABSTRACT FROM AUTHOR]

We developed a Project ECHO® module to offer prenatal providers training on engaging in shared decision-making about hepatitis C virus (HCV) treatment during pregnancy. In this pilot program, the ECHO module addressing HCV during pregnancy and the potential benefits of treatment was associated with increases in self-efficacy scores among participants. [ABSTRACT FROM AUTHOR]

The management of hepatitis B virus (HBV) in pediatrics presents many challenges, given the potential sequelae of untreated infection including hepatic fibrosis, cirrhosis, and malignancy, and a lack of clear guidance on the timing of treatment initiation. The goal of this review is to feature common clinical scenarios that occur in the evaluation and treatment of HBV infection in children. Each vignette presents an opportunity to discuss guidelines and evidence-based practices as well as review landmark studies and evolving practices. [ABSTRACT FROM AUTHOR]

The WHO recommends hepatitis B birth‐dose vaccination (HepB‐BD), but it is not routinely given in most sub‐Saharan African countries. We aimed to assess the immunogenicity of HepB‐BD in addition to the existing hepatitis B vaccine (HepB3) schedule in Kinshasa, Democratic Republic of Congo among HBV‐unexposed and HBV‐exposed infants. Using an open‐label, randomised, controlled design, HBV‐unexposed infants were randomised (1:1) to receive the standard HepB3 vaccine series (group U3), or to receive HepB‐BD in addition to HepB3 (group U4). A supplemental cohort of HBV‐exposed infants (group E4) received HepB‐BD and HepB3. We compared the proportion of infants with protective antibodies against HBV (HBV surface antibody ≥ 10 mIU/mL) between groups U3 and U4 and groups U4 and E4 at 12 months of age. Between August 20 and October 9, 2019, we enrolled 281 mother/infant dyads; 88 (31.3%) returned at 12 months. Most infants had protective antibodies against HBV at 12 months: 92.9% (75.7%–98.2%) in group U3, 85.7% (67.5%–94.5%) in group U4 and 96.9% (95% CI: 81.2%–99.6%) in group E4. Trends held in estimates adjusted for loss‐to‐follow‐up (LTFU) and baseline imbalance across groups. In this first randomised trial assessing the addition of HepB‐BD to the hepatitis B vaccine schedule in SSA, we found that HBV‐unexposed infants who received the 3‐dose and 4‐dose vaccine series had similar immunogenicity against HBV at 12 months. A high proportion of infants, and notably HBV‐exposed infants, had protective antibodies. Though extrapolation of findings may be limited by LTFU, this study adds real‐world evidence regarding HepB‐BD implementation in sub‐Saharan Africa. Trial Registration: ClinicalTrials.gov identifier: NCT03897946 [ABSTRACT FROM AUTHOR]

Background: Post‐infectious disorders of gut‐brain interaction (PI‐DGBI) have significant impact on children and adolescents. The effect of COVID‐19 on PI‐DGBI‐associated symptoms in this population, however, is unknown. Methods: We performed electronic medical record searches to identify patients 8–17 years old with a SARS‐CoV2 PCR test at Lurie Children's Hospital between November 2020 and March 2021 (cohort 1) and April–October 2021 (cohort 2). Questionnaires were administered to assess symptoms prior to and 3 months following the test. This included the Pediatric Eosinophilic Esophagitis Symptom Score (PEESS), questionnaire of pediatric gastrointestinal symptoms—Rome IV, Nausea Profile (NP), dyspepsia symptom survey (DSS), nausea severity profile (NSP), and Pediatric Quality of Life Inventory (PedsQL). We grouped patients based on the presence of symptoms prior to COVID‐19 test or the test result. Results: One hundred and ninety‐six parent(s) or guardian(s) in cohort 1 and 274 in cohort 2 completed surveys and self‐reported their child's COVID‐19 result. Cohort 1 had increased PEESS and DSS scores, lower PedsQL scores, and increased frequency of abdominal pain disorders among patients with symptoms prior to COVID‐19 testing. Both cohorts had increased NP and NSP scores among patients with symptoms prior to COVID‐19 testing that was highest among patients with a positive COVID‐19 test. Abdominal pain and diarrhea prior to COVID‐19 testing predicted higher NP scores. Conclusions: Among symptomatic COVID‐19 tested children, we found increased severity of nausea‐associated somatic, emotional, and gastrointestinal symptoms in the 3 months following the test that was most increased among patients with a positive COVID‐19 test. [ABSTRACT FROM AUTHOR]

Background Kawasaki disease (KD) is an acute febrile illness of childhood that can lead to coronary artery aneurysms (CAAs) and myocardial infarction. Intravenous immunoglobulin reduces the prevalence of CAA when given to patients with KD within 10 days of fever onset. Children with KD may undergo evaluation for other diagnoses before treatment, particularly those with incomplete KD criteria. If KD outcomes are improved with early treatment, a delay in treatment while evaluating for other causes might place these patients at risk. Methods We performed a retrospective cohort study of children treated for KD within the first 10 days of illness at our KD center from 2014 to 2021 to determine the prevalence of CAA by day of treatment. Results A total of 290 patients met the study criteria. No statistically significant difference was found in the odds of developing a maximum z score ≥2.5 for each day of delayed treatment within 10 days of fever onset (adjusted odds ratio, 0.87; 95% CI,.72–1.05; P =.13). Subgroup analyses by age, sex, and year of treatment did not reveal a significant association between treatment day and maximum z score ≥2.5, although the number of patients <6 months of age was small. Conclusions Our study supports current recommendations. We found similar odds of developing adverse coronary outcomes regardless of treatment day within 10 days from fever onset. [ABSTRACT FROM AUTHOR]

Background/Aims: The SARS-CoV-2 pandemic disproportionately impacted communities with lower access to health care in the United States, particularly before vaccines were widely available. These same communities are often underrepresented in clinical trials. Efforts to ensure equitable enrollment of participants in trials related to treatment and prevention of Covid-19 can raise concerns about exploitation if communities with lower access to health care are targeted for recruitment. Methods: To enhance equity while avoiding exploitation, our site developed and implemented a three-part recruitment strategy for pediatric Covid-19 vaccine studies. First, we publicized a registry for potentially interested participants. Next, we applied public health community and social vulnerability indices to categorize the residence of families who had signed up for the registry into three levels to reflect the relative impact of the pandemic on their community: high, medium, and low. Finally, we preferentially offered study participation to interested families living in areas categorized by these indices as having high impact of the Covid-19 pandemic on their community. Results: This approach allowed us to meet goals for study recruitment based on public health metrics related to disease burden, which contributed to a racially diverse study population that mirrored the surrounding community demographics. While this three-part recruitment strategy improved representation of minoritized groups from areas heavily impacted by the Covid-19 pandemic, important limitations were identified that would benefit from further study. Conclusion: Future use of this approach to enhance equitable access to research while avoiding exploitation should test different methods to build trust and communicate with underserved communities more effectively. [ABSTRACT FROM AUTHOR]

Advanced Practice Providers (APPs) are a rapidly growing segment of the pediatric infectious diseases workforce. APPs offer many advantages to divisions that are struggling to counter a smaller fellowship applicant pool and faculty workforce transitions as a result of the pandemic. Many divisions still have yet to incorporate APPs into their inpatient or outpatient teams. This review will discuss the diverse pool of APPs, summarize how APPs are currently being used in the field, discuss the financial considerations of hiring APPs, and highlight future needs for embracing APPs as critical members of the pediatric ID workforce. [ABSTRACT FROM AUTHOR]

Infectious diseases physicians are frequently called on to perform quality improvement and patient safety (QIPS) work. We describe a newly created faculty position at our institution that allows a faculty member with graduate training in quality and safety methodologies to address QIPS priorities at both the division and hospital levels. [ABSTRACT FROM AUTHOR]

Using electronic health record data from a national collaboration of pediatric health systems, this study examined the effectiveness of BNT162b2 vaccines for preventing COVID-19 infections and severe disease among previously uninfected children and adolescents. It found moderate effectiveness of the vaccine against the SARS-CoV-2 Omicron variant and high effectiveness against the Delta variant. Visual Abstract. Real-World Effectiveness of BNT162b2 Against Infection and Severe Diseases in Children and Adolescents: Using electronic health record data from a national collaboration of pediatric health systems, this study examined the effectiveness of BNT162b2 vaccines for preventing COVID-19 infections and severe disease among previously uninfected children and adolescents. It found moderate effectiveness of the vaccine against the SARS-CoV-2 Omicron variant and high effectiveness against the Delta variant. Background: The efficacy of the BNT162b2 vaccine in pediatrics was assessed by randomized trials before the Omicron variant's emergence. The long-term durability of vaccine protection in this population during the Omicron period remains limited. Objective: To assess the effectiveness of BNT162b2 in preventing infection and severe diseases with various strains of the SARS-CoV-2 virus in previously uninfected children and adolescents. Design: Comparative effectiveness research accounting for underreported vaccination in 3 study cohorts: adolescents (12 to 20 years) during the Delta phase and children (5 to 11 years) and adolescents (12 to 20 years) during the Omicron phase. Setting: A national collaboration of pediatric health systems (PEDSnet). Participants: 77 392 adolescents (45 007 vaccinated) during the Delta phase and 111 539 children (50 398 vaccinated) and 56 080 adolescents (21 180 vaccinated) during the Omicron phase. Intervention: First dose of the BNT162b2 vaccine versus no receipt of COVID-19 vaccine. Measurements: Outcomes of interest include documented infection, COVID-19 illness severity, admission to an intensive care unit (ICU), and cardiac complications. The effectiveness was reported as (1-relative risk)*100, with confounders balanced via propensity score stratification. Results: During the Delta period, the estimated effectiveness of the BNT162b2 vaccine was 98.4% (95% CI, 98.1% to 98.7%) against documented infection among adolescents, with no statistically significant waning after receipt of the first dose. An analysis of cardiac complications did not suggest a statistically significant difference between vaccinated and unvaccinated groups. During the Omicron period, the effectiveness against documented infection among children was estimated to be 74.3% (CI, 72.2% to 76.2%). Higher levels of effectiveness were seen against moderate or severe COVID-19 (75.5% [CI, 69.0% to 81.0%]) and ICU admission with COVID-19 (84.9% [CI, 64.8% to 93.5%]). Among adolescents, the effectiveness against documented Omicron infection was 85.5% (CI, 83.8% to 87.1%), with 84.8% (CI, 77.3% to 89.9%) against moderate or severe COVID-19, and 91.5% (CI, 69.5% to 97.6%) against ICU admission with COVID-19. The effectiveness of the BNT162b2 vaccine against the Omicron variant declined 4 months after the first dose and then stabilized. The analysis showed a lower risk for cardiac complications in the vaccinated group during the Omicron variant period. Limitation: Observational study design and potentially undocumented infection. Conclusion: This study suggests that BNT162b2 was effective for various COVID-19–related outcomes in children and adolescents during the Delta and Omicron periods, and there is some evidence of waning effectiveness over time. Primary Funding Source: National Institutes of Health. [ABSTRACT FROM AUTHOR]

Influenza is associated with significant disease burden in the US and is currently best controlled by vaccination programs. Influenza vaccine effectiveness (VE) is low and may be reduced by several factors, including egg adaptations. Although non-egg-based influenza vaccines reportedly have greater VE in egg-adapted seasons, evidence for egg adaptations' reduction of VE is indirect and dissociated, apart from two previous European consensuses. This study replicated the methodology used in a 2020 literature review and European consensus, providing an updated review and consensus opinion of 10 US experts on the evidence for a mechanistic basis for reduction of VE due to egg-based manufacturing methods. A mechanistic basis was assumed if sufficient evidence was found for underlying principles proposed to give rise to such an effect. Evidence for each principle was brought forward from the 2020 review and identified here by structured literature review and expert panel. Experts rated the strength of support for each principle and a mechanistic basis for reduction of VE due to egg-based influenza vaccine manufacture in a consensus method (consensus for strong/very strong evidence = ≥ 3.5 on 5-point Likert scale). Experts assessed 251 references (from previous study: 185; this study: 66). The majority of references for all underlying principles were rated as strong or very strong supporting evidence (52–86%). Global surveillance, WHO candidate vaccine virus selection, and manufacturing stages involving eggs were identified as most likely to impact influenza VE. After review of extensive evidence for reduction of VE due to egg-based influenza vaccine manufacture, influenza experts in the US joined those in Europe in unanimous agreement for a mechanistic basis for the effect. Vaccine providers and administrators should consider use of non-egg-based influenza vaccine manufacture to reduce the risk of egg adaptations and likely impact on VE. [ABSTRACT FROM AUTHOR]

Background Post-exposure prophylaxis (PEP) with varicella immunoglobulin is recommended to minimize risk of varicella complications for high-risk children. However, providers frequently use alternatives like acyclovir or intravenous immunoglobulin. Methods A retrospective cohort study was conducted of PEP for varicella in children from January 2009 to December 2019. Data were provided by 47 children's hospitals who participate in the Pediatric Health Information Systems database. Patients with clinical encounters for varicella exposure were reviewed. Choice of varicella PEP regimens, including differences by underlying condition and institution, and incidence of varicella disease were determined. Results A total of 1704 patients with first clinical encounters for varicella met inclusion criteria. Of these patients, 509 (29.9%) were prescribed PEP after varicella exposure, and 65 (3.8%) ultimately had a subsequent encounter for varicella disease. Of 509 patients who received PEP, acyclovir was most frequently prescribed (n  = 195, 38.3%), followed by varicella immunoglobulin (n  = 146, 28.7%), IVIG (n  = 115, 22.6%), and combination therapy (n  = 53, 10.4%). The highest proportion of varicella immunoglobulin use (10/20, 50%) was amongst children with diagnoses of rheumatological/gastrointestinal conditions. The highest proportion of acyclovir use (29/684, 4.2%) was amongst children with diagnoses of oncology/stem cell transplant conditions. The proportion of patients who subsequently had clinical encounters for varicella disease was highest for Acyclovir (30/195, 15.4%) followed by varicella immunoglobulin (5/146, 3.4%), combination therapy (2/53, 3.8%), and intravenous immunoglobulin alone (0/115) (P  < .0001). Conclusions Varicella PEP in high-risk children was highly varied among children's hospitals. In our dataset, use of acyclovir was associated with a higher rate of subsequent encounters for Varicella disease. [ABSTRACT FROM AUTHOR]

The article discusses Pneumocystis jirovecii pneumonia (PCP) as a complication in pediatric solid organ transplant recipients after discontinuation of prophylaxis. The study found that six patients developed PCP after stopping prophylaxis, requiring intensive care for respiratory failure. The authors suggest the need for better risk assessment and individualized prophylaxis strategies to prevent this serious complication in vulnerable pediatric patients. Larger studies are needed to identify reliable risk factors for guiding prophylaxis duration in this population. [Extracted from the article]

For patients with Biliary atresia, antibiotic prophylaxis after Kasai portoenterostomy is a common practice. Societal guidelines often cite one reference as supportive evidence for this practice. In this paper, we go back to review the quality of this evidence and suggest more research is required to demonstrate the efficacy of antibiotic prophylaxis in this population. [ABSTRACT FROM AUTHOR]

Multi-system inflammatory syndrome in children (MIS-C) is a severe post-acute sequela of SARS-CoV-2 infection in children, and there is a critical need to unfold its highly heterogeneous disease patterns. Our objective was to characterize the illness spectrum of MIS-C for improved recognition and management. We conducted a retrospective cohort study using data from March 1, 2020–September 30, 2022, in 8 pediatric medical centers from PEDSnet. We included 1139 children hospitalized with MIS-C and used their demographics, symptoms, conditions, laboratory values, and medications for analyses. We applied heterogeneity-adaptive latent class analyses and identified three latent classes. We further characterized the sociodemographic and clinical characteristics of the latent classes and evaluated their temporal patterns. Class 1 (47.9%) represented children with the most severe presentation, with more admission to the ICU, higher inflammatory markers, hypotension/shock/dehydration, cardiac involvement, acute kidney injury and respiratory involvement. Class 2 (23.3%) represented a moderate presentation, with 4–6 organ systems involved, and some overlapping features with acute COVID-19. Class 3 (28.8%) represented a mild presentation. Our results indicated that MIS-C has a spectrum of clinical severity ranging from mild to severe and the proportion of severe or critical MIS-C decreased over time. [ABSTRACT FROM AUTHOR]

As clinical understanding of pediatric Post-Acute Sequelae of SARS CoV-2 (PASC) develops, and hence the clinical definition evolves, it is desirable to have a method to reliably identify patients who are likely to have post-acute sequelae of SARS CoV-2 (PASC) in health systems data. In this study, we developed and validated a machine learning algorithm to classify which patients have PASC (distinguishing between Multisystem Inflammatory Syndrome in Children (MIS-C) and non-MIS-C variants) from a cohort of patients with positive SARS- CoV-2 test results in pediatric health systems within the PEDSnet EHR network. Patient features included in the model were selected from conditions, procedures, performance of diagnostic testing, and medications using a tree-based scan statistic approach. We used an XGboost model, with hyperparameters selected through cross-validated grid search, and model performance was assessed using 5-fold cross-validation. Model predictions and feature importance were evaluated using Shapley Additive exPlanation (SHAP) values. The model provides a tool for identifying patients with PASC and an approach to characterizing PASC using diagnosis, medication, laboratory, and procedure features in health systems data. Using appropriate threshold settings, the model can be used to identify PASC patients in health systems data at higher precision for inclusion in studies or at higher recall in screening for clinical trials, especially in settings where PASC diagnosis codes are used less frequently or less reliably. Analysis of how specific features contribute to the classification process may assist in gaining a better understanding of features that are associated with PASC diagnoses. [ABSTRACT FROM AUTHOR]

Background. Postacute sequelae of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (PASC) is associated with worsening diabetes trajectory. It is unknown whether PASC in children with type 1 diabetes (T1D) manifests as worsening diabetes trajectory. Objective. To explore the association between SARS-CoV-2 infection (COVID-19) and T1D-related healthcare utilization (for diabetic ketoacidosis (DKA) or severe hypoglycemia (SH)) or hemoglobin (Hb) A1c trajectory. Methods: We included children <21 years with T1D and ≥1 HbA1c prior to cohort entry, which was defined as COVID-19 (positive diagnostic test or diagnosis code for COVID-19, multisystem inflammatory syndrome in children, or PASC) or a randomly selected negative test for those who were negative throughout the study period (Broad Cohort). A subset with ≥1 HbA1c value from 28 to 275 days after cohort entry (Narrow Cohort) was included in the trajectory analysis. Propensity score-based matched cohort design followed by weighted Cox regression was used to evaluate the association of COVID-19 with healthcare utilization ≥28 days after cohort entry. Generalized estimating equation (GEE) models were used to measure change in HbA1c in the Narrow Cohort. Results. From March 01, 2020 to June 22, 2022, 2,404 and 1,221 youth met entry criteria for the Broad and Narrow Cohorts, respectively. The hazard ratio for utilization was (HR 1.45 (95% CI: 0.97, 2.16)). In the Narrow Cohort, the rate of change (slope) of HbA1c increased 91–180 days after cohort entry for those with COVID-19 (0.138 vs. −0.002, p = 0.172). Beyond 180 days, greater declines in HbA1c were observed in the positive cohort (−0.104 vs. 0.008 per month, p = 0.024). Conclusion. While a trend toward worse outcomes following COVID-19 in T1D patients was observed, these findings were not statistically significant. Continued clinical monitoring of youth with T1D following COVID-19 is warranted. [ABSTRACT FROM AUTHOR]

The article in the Journal of Infectious Diseases responds to the importance of quality measures specific to infectious diseases, particularly focusing on children. It emphasizes the need to track and improve the quality of care for pediatric populations, who face unique health challenges. The proposed guidelines center on antimicrobial stewardship, highlighting the critical importance of judicious antibiotic use in children to prevent adverse events and promote optimal health outcomes. The article suggests expanding quality improvement metrics to include children of all ages to address the diverse needs of the US population and improve health outcomes across the lifespan. [Extracted from the article]

Using electronic health record data combined with primary chart review, we identified seven children across nine participant pediatric medical centers with a diagnosis of Multisystem Inflammatory Syndrome in Children (MIS-C) managed exclusively as outpatients. These findings should raise awareness of mild presentations of MIS-C and the option of outpatient management. [ABSTRACT FROM AUTHOR]

Background: The rising prevalence of hepatitis C virus (HCV) infection and the availability of direct acting antivirals for HCV treatment has prompted a public health goal of HCV eradication. Despite the availability of treatment for HCV, treatment programs have generally excluded pregnant individuals. Our objective was to query patients and clinicians to identify barriers to including pregnant individuals in HCV treatment programs. Methods and findings: This qualitative investigation included obstetricians and previously/currently pregnant individuals with HCV. Participants completed interviews regarding knowledge of and attitudes towards HCV treatment and perceived barriers to treatment during pregnancy. Data were analyzed using the constant comparative method. Obstetricians (N = 18) and patients (N = 21) described concerns about equity, access, and cost. Both expressed uncertainty about safety and confirmed a need for clinician education. Obstetricians emphasized the lack of professional guidelines. Although some clinicians expressed concern about patient adherence and engagement, patients were largely desirous of treatment; both groups identified potential benefits of antenatal treatment. Conclusions: Both patients and obstetricians were generally receptive to HCV treatment in pregnancy and recognized pregnancy as an important window of opportunity for treatment. Our findings suggest the need for further research on maternal-fetal safety of HCV treatment as well as on interventions to ensure fair and appropriate access to HCV treatment for pregnant individuals. [ABSTRACT FROM AUTHOR]

Staphylococcus -associated glomerulonephritis (GN) is an uncommon diagnosis in pediatric patients. Empiric therapy with steroids alone could potentially worsen the underlying infectious process in these patients, leading to worse clinical outcomes. An adolescent male diagnosed with GN was subsequently found to have chronic granulomatous disease with a Staphylococcus aureus liver abscess. His GN improved with antibiotics alone. This case illustrates the need to consider chronic infection, and primary immunodeficiency, in the differential diagnosis for new-onset GN. [ABSTRACT FROM AUTHOR]

The article states that Hepatitis C virus (HCV) elimination efforts have primarily centered on amplifying screening and therapy among adults across diverse settings, with limited inclusion of subsets such as expectant mothers and minors. It focuses on research on testing timelines for infants exposed to HCV and the effectiveness of broad treatment strategies considering the higher rates of random clearance in young children.

Many problems that appear in biomedical decision‐making, such as diagnosing disease and predicting response to treatment, can be expressed as binary classification problems. The support vector machine (SVM) is a popular classification technique that is robust to model misspecification and effectively handles high‐dimensional data. The relative costs of false positives and false negatives can vary across application domains. The receiving operating characteristic (ROC) curve provides a visual representation of the trade‐off between these two types of errors. Because the SVM does not produce a predicted probability, an ROC curve cannot be constructed in the traditional way of thresholding a predicted probability. However, a sequence of weighted SVMs can be used to construct an ROC curve. Although ROC curves constructed using weighted SVMs have great potential for allowing ROC curves analyses that cannot be done by thresholding predicted probabilities, their theoretical properties have heretofore been underdeveloped. We propose a method for constructing confidence bands for the SVM ROC curve and provide the theoretical justification for the SVM ROC curve by showing that the risk function of the estimated decision rule is uniformly consistent across the weight parameter. We demonstrate the proposed confidence band method using simulation studies. We present a predictive model for treatment response in breast cancer as an illustrative example. [ABSTRACT FROM AUTHOR]

Over the last decade, Hepatitis C virus has persisted and evolved as a domestic and global health challenge for adults and children. The challenges involve both increased cases in the United States and cost of treatment both in the US and globally. [ABSTRACT FROM AUTHOR]

Recurrent urinary tract infection (rUTI) continues to challenge pediatric care providers. The diagnosis of an rUTI can be difficult, especially in young febrile children. Antibiotic resistance rates continue to rise, which limits oral treatment options. Prophylactic antibiotics are used commonly to manage rUTI, but their use increases the risk of rUTI with antibiotic-resistant strains without significantly reducing renal scarring. Alternative therapies for rUTI include probiotics and anthocyanidins (eg, cranberry extract) to reduce gut colonization by uropathogens and prevent bacterial adhesion to uroepithelia, but efficacy data for these treatments are sparse. The future of rUTI care rests in addressing the following contemporary issues: best diagnostic practices, risk factors associated with rUTI, and the prevention of recurrent infection. In this review, we summarize the state of the art for each of these issues and highlight future studies that will aim to take an alternative approach to managing rUTI. [ABSTRACT FROM AUTHOR]

We report here the first pharmacokinetic–pharmacodynamic relationship for ceftaroline in a preterm infant born at <28 weeks' gestational age who was given ceftaroline (8.5 mg/kg every 8 hours) for pneumonia attributable to methicillin-resistant Staphyloccocus aureus. This dose of ceftaroline was adequate to achieve the pharmacodynamic endpoint associated with efficacy for methicillin-resistant Staphyloccocus aureus. [ABSTRACT FROM AUTHOR]

The epidemiology of hepatitis C virus (HCV) has changed significantly over the last decade. Once most prevalent among older adults, the current burden has disproportionately affected young adults including women of childbearing age (WOCA). The Society for Maternal-Fetal Medicine recently issued guidelines that made no change in the recommendation to screen pregnant women based on risk factors. The current burden in young adults including WOCA supports a change in strategy away from risk-based screening to universal HCV screening in pregnancy. Universal screening offers several advantages that position us for a future where HCV treatment in pregnancy can happen and offers us progress toward the elimination of HCV. [ABSTRACT FROM AUTHOR]

Hepatitis B virus (HBV) is a significant public health issue that has not been adequately addressed, especially in the high-prevalence region of Africa. Despite the incorporation of HBV vaccines into the Expanded Program on Immunization, children continue to be infected with HBV through maternal-to-child transmission (MTCT). The addition of a birth dose of HBV vaccine would be a cost-effective method to reduce MTCT. Birth-dose HBV vaccine policies have been adopted in the Western Pacific region but not yet in Africa. Even better protection against HBV MTCT can be achieved by treatment of pregnant women with high HBV viral loads with tenofovir. Tenofovir is already widely used in prevention of HIV MTCT (PMTCT) programs. We suggest that existing HIV PMTCT programs could be expanded to deliver care for HBV-infected pregnant women. With appropriate adoption of birth-dose vaccination policies and expansion of PMTCT programs, elimination of HBV MTCT in Africa is achievable. [ABSTRACT FROM AUTHOR]

Purpose of Review: Increasing hepatitis C virus (HCV) cases over the past decade have raised concerns about subsequent increased cases in infants due to mother to child transmission (MTCT). Many are reminded of the early days of HIV and the rationale for using antiretroviral agents during pregnancy.Recent Findings: Direct-acting antivirals (DAAs) that are highly potent, all-oral, short-duration regimens that cure HCV have led many to consider what it would entail to use DAAs for pregnant women. Considering HIV and Hepatitis B virus (HBV) as two infections with MTCT to draw lessons from, DAA use to interrupt HCV MTCT comes with risks, costs, and many potential benefits.Summary: When considering how to effectively curb the current epidemic of HCV in the US population, using DAAs to treat pregnant women with HCV offers potential benefits to the mother immediately, to the pair in the short-term and to the child, family, and society over a lifetime. [ABSTRACT FROM AUTHOR]

Difficulty with pill-swallowing ability (PSA) is common in children, yet formal evaluation is rare. The objective of this study was to prospectively evaluate and compare PSA of inpatient and outpatient children using the Pediatric Oral Medications Screener. We identified children aged 3 to 17 years admitted to a general or subspecialty pediatric service at a university hospital or outpatient clinic. Using the Pediatric Oral Medications Screener, patients were observed swallowing 3 different-sized placebo pills (5 mm tablet, 10 mm tablet, and 22 mm capsule), and subjective measures were assessed from parents and children. We analyzed 47 inpatients and 62 outpatients. Sixteen percent of patients could not swallow any pill, 11% only swallowed the small pill, 14% swallowed up to the medium pill, and 60% swallowed all formulations. After controlling for multiple factors, inpatients had superior PSA compared with outpatients (P = .004). These results suggest targeted inpatient screening and widespread outpatient screening would likely identify children with reduced PSA. [ABSTRACT FROM AUTHOR]

Background. Postpartum hepatitis C viral (HCV) load decline followed by spontaneous clearance has been previously described. Herein we identify predictors for viral decline in a cohort of HCV-infected postpartum women. Methods. Pregnant women at Cairo University were screened for anti-HCV antibodies and HCV RNA, and viremic women were tested for quantitative HCV RNA at 3, 6, 9, and 12 months postpartum. Spontaneous clearance was defined as undetectable viremia twice at least 6-months apart. Associations between viral load and demographic, obstetrical, HCV risk factors, and interleukin- 28B gene (IL28B) polymorphism (rs12979860) were assessed. Results. Of 2514 women, 97 (3.9%) had anti-HCV antibodies, 54 (2.1%) were viremic and of those, 52 (2.1%) agreed to IL28B testing. From pregnancy until 12 months postpartum, IL28B-CC allele women had a significant viral decline (P = .009). After adjusting, the IL28B-CC allele had a near significant difference compared to the CT allele (odds ratio [OR], 0.75; 95% confidence interval [CI], 0.75,1.00; P = .05), but not the TT allele (OR, 0.91; 95% CI, 0.61,1.38; P = .64). All 14/52 (26.9%) women who subsequently cleared were among the 15 with undetectable viremia at 12 months, making that time point a strong predictor of subsequent clearance (sensitivity = 100%, specificity = 97.4%, positive predictive value = 93.3%, negative predictive value = 100%). Conclusions. In this HCV-infected cohort of postpartum women 26.9% spontaneously cleared. IL28B-CC genotype and 12-month postpartum undetectable viremia were the best predictors for viral decline and subsequent clearance. These 2 predictors should influence clinical decision making. [ABSTRACT FROM AUTHOR]

The use of empiric acyclovir for suspected neonatal herpes simplex virus (HSV) infection has been debated for years. To identify the gap in the decision to initiate empiric acyclovir, we performed a retrospective chart review and administered a survey to pediatricians to assess current practices regarding evaluation for possible HSV infection. Seventy infants received empiric acyclovir over a 1-year period; of these, 3 infants (4.3%) had positive HSV testing. Fourteen infants were identified as “high-risk” for HSV infection; of these, 13 infants had incomplete testing. Survey results revealed uncertainty in the decision to initiate acyclovir and in the composition of complete diagnostic testing. This study confirmed the clinical uncertainty in the decision to initiate empiric acyclovir. Using this chart review and survey as a baseline, future efforts will focus on a quality improvement project to reduce empiric acyclovir use in low-risk infants and to ensure complete diagnostic evaluation in high-risk infants. [ABSTRACT FROM AUTHOR]