Campylobacter infection of young children in Colombia and its impact on the gastrointestinal environment.

Campylobacter infections are a leading cause of bacterial-derived gastroenteritis worldwide with particularly profound impacts on pediatric patients in low-and-middle income countries. It remains unclear how Campylobacter impacts these hosts, though it is becoming increasingly evident that it is a multifactorial process that depends on the host immune response, the gastrointestinal microbiota, various bacterial factors, and host nutritional status. Since these factors likely vary between adult and pediatric patients in different regions of the world, it is important that studies define these attributes in well characterized clinical cohorts in diverse settings. In this study, we analyzed the fecal microbiota and the metabolomic and micronutrient profiles of asymptomatic and symptomatic pediatric patients in Colombia that were either infected or uninfected with Campylobacter during a case-controlled study on acute diarrheal disease. Here, we report that the microbiome of Campylobacter- infected children only changed in their abundance of Campylobacter spp. despite the inclusion of children with or without diarrhea. In addition to increased Campylobacter, computational models were used to identify fecal metabolites that were associated with Campylobacter infection and found that glucose-6-phosphate and homovanillic acid were the strongest predictors of infection in these pediatric patients, which suggest that colonocyte metabolism are impacted during infection. Despite changes to the fecal metabolome, the concentrations of intestinal minerals and trace elements were not significantly impacted by Campylobacter infection, but were elevated in uninfected children with diarrhea. Importance: Gastrointestinal infection with pathogenic Campylobacter species has long been recognized as a significant cause of human morbidity. Recently, it has been observed that pediatric populations in low-and-middle income countries are uniquely impacted by these organisms in that infected children can be persistently colonized, develop enteric dysfunction, and exhibit reduced development and growth. While the association of Campylobacter species with these long-term effects continues to emerge, the impact of infection on the gastrointestinal environment of these children remains uncharacterized. To address this knowledge gap, our group leveraged clinical samples collected during a previous study on gastrointestinal infections in pediatric patients to examine the fecal microbiota, metabolome, and micronutrient profiles of those infected with Campylobacter species, and found that the metabolome was impacted in a way that suggests gastrointestinal cell metabolism is affected during infection, which is some of the first data indicating how gastrointestinal health in these patients may be affected.

Gaps during Pediatric to Adult Care Transfer Escalate Acute Resource Utilization in Sickle Cell Disease.

Guidelines recommend transfer to adult healthcare within six months of completing pediatric care, however this has not been studied in sickle cell (SCD). We hypothesized that longer transfer gaps are associated with increased resource utilization. Transfer gaps were defined as the time between the last pediatric and first adult visits. We estimated the association between varying transfer gaps and the rate of inpatient, emergency department (ED), and outpatient visits using negative binomial regression. Healthcare utilization was evaluated in a mid-south comprehensive program for a follow-up period of up to eight years (2012-2020) and also restricted to the first two years of adult healthcare. In total, 183 young adults (YAs) with SCD (51% male, 67% HbSS/HbSß0-thalassemia) transferred to adult healthcare between 2012-2018. YAs with transfer gaps ≥6 months compared to <2 months had 2.01 (95%CI: 1.31, 3.11) times the rate of hospitalizations in the 8-year follow-up and 1.89 (95%CI: 1.17, 3.04) when restricted to the first two years of adult healthcare. In the first two years of adult care, those with transfer gaps ≥6 months compared to <2 months, had 1.75 (95%CI: 1.10, 2.80) times the rate of ED encounters. Those with gaps ≥2 to <6 months compared to <2 months had 0.71 (95%CI: 0.53, 0.95) times the rate of outpatient visits. Among YAs with SCD, a longer transfer gap was associated with increased inpatient and decreased outpatient encounters in adult healthcare and more ED encounters in the first two years of adult healthcare. Strategies to reduce transfer gaps are needed.

Association Between mRNA Vaccination and Infection From SARS-CoV-2 During the Delta and Omicron BA.1 Waves: A Population-Level Analysis.

Introduction: COVID-19 mRNA vaccine protection against the Omicron variant of SARS-CoV-2 has been shown to be attenuated. Previous research in Shelby County, Tennessee found that vaccine effectiveness might differ by age in the Omicron surge, a finding not reported for other variants. To assess whether patterns in vaccine effectiveness by age group differed on the basis of the predominant strain of SARS-CoV2, we evaluated vaccine effectiveness in Shelby County, Tennessee by age group in the Delta wave and Omicron BA.1 (Omicron) wave. Methods: Case and vaccination statuses of residents were assessed using COVID-19 surveillance data. Age was stratified as 18-34, 35-64, and ≥65 years. Vaccination groups included unvaccinated, fully vaccinated, and fully vaccinated + booster. Person time was counted in each wave by vaccination status until the time of a positive reported COVID-19 test or until the end of the study period. Results: Incidence of COVID-19 was much higher during the Omicron wave than during the Delta wave across all vaccination groups. During the Delta wave, among adults, 79.2% fewer cases were identified in those fully vaccinated and 94.8% fewer in those fully vaccinated + booster, compared with 40.2% and 66.7%, respectively, in the Omicron wave, compared with those who were unvaccinated. Conclusions: This study found evidence that vaccine effectiveness differed by age group during the Omicron wave, where the same pattern was not prominent in the Delta wave. Further analysis investigating the influence of behavior patterns and other potential confounders on vaccine effectiveness would be useful in further understanding the relationship between age and vaccine effectiveness.

Flat-panel detector CT to assess intracranial hemorrhage immediately following mechanical thrombectomy.

BACKGROUND AND PURPOSE: The risk of symptomatic intracranial hemorrhage (ICH) approaches 5% despite mechanical thrombectomy (MT) efficacy for ischemic stroke secondary to large vessel occlusion. Flat-panel detector CT (FDCT) imaging with Syngo Dyna CT imaging (Siemens Medical Solutions, Malvern, PA) can be used immediately following MT to detect ICH. PURPOSE: To evaluate the accuracy and reliability of FDCT imaging with Dyna CT compared to conventional post-MT CT and MRI. METHODS: Head FDCT (20 second, 70 kV) was performed immediately following MT on 26 consecutive patients; postprocedural CT or MRI was obtained ∼24 hours later. Two blinded, independent neuroradiologists evaluated all imaging, identifying ICH, stroke, and presence of subarachnoid contrast. Cohen's κ statistic was used to assess interrater agreement for each imaging outcome and compared the FDCT to conventional imaging. RESULTS: FDCT for ICH demonstrated a strong degree of interrater reliability (κ = 0.896; 95% confidence interval [CI], 0.734-1.057). Negligible reliability was seen for ischemia determination on immediate post-MT FDCT (κ = 0.149; 95% CI, -0.243 to 0.541). ICH evaluation between FDCT and post-MT conventional CT revealed modest interrater reliability (κ = 0.432; 95% CI, -0.100 to 0.965), which did not reach statistical significance. There was no substantive reliability in the evaluation of ICH between FDCT and post-MT MRI (κ = 0.118, 95% CI, -0.345 to 0.580). CONCLUSION: FDCT, such as Dyna CT, immediately post-MT is a promising tool that can expedite the detection of ICH with a high degree of reliability, although the detection of ischemic parenchymal changes is limited.

Association of Radiology Findings with Etiology of Community Acquired Pneumonia among Children.

OBJECTIVE: To evaluate the association between consolidation on chest radiograph and typical bacterial etiology of childhood community acquired pneumonia (CAP) in the Etiology of Pneumonia in the Community study. STUDY DESIGN: Hospitalized children <18 years of age with CAP enrolled in the Etiology of Pneumonia in the Community study at 3 children's hospitals between January 2010 and June 2012 were included. Testing of blood and respiratory specimens used multiple modalities to identify typical and atypical bacterial, or viral infection. Study radiologists classified chest radiographs (consolidation, other infiltrates [interstitial and/or alveolar], pleural effusion) using modified World Health Organization pneumonia criteria. Infiltrate patterns were compared according to etiology of CAP. RESULTS: Among 2212 children, there were 1302 (59%) with consolidation with or without other infiltrates, 910 (41%) with other infiltrates, and 296 (13%) with pleural effusion. In 1795 children, at least 1 pathogen was detected. Among these patients, consolidation (74%) was the most frequently observed pattern (74% in typical bacterial CAP, 58% in atypical bacterial CAP, and 54% in viral CAP). Positive and negative predictive values of consolidation for typical bacterial CAP were 12% (95% CI 10%-15%) and 96% (95% CI 95%-97%) respectively. In a multivariable model, typical bacterial CAP was associated with pleural effusion (OR 7.3, 95% CI 4.7-11.2) and white blood cell ≥15 000/mL (OR 3.2, 95% CI 2.2-4.9), and absence of wheeze (OR 0.5, 95% CI 0.3-0.8) or viral detection (OR 0.2, 95% CI 0.1-0.4). CONCLUSIONS: Consolidation predicted typical bacterial CAP poorly, but its absence made typical bacterial CAP unlikely. Pleural effusion was the best predictor of typical bacterial infection, but too uncommon to aid etiology prediction.

Energy cost of walking in obese survivors of acute lymphoblastic leukemia: A report from the St. Jude Lifetime Cohort.

Purpose: Adult survivors of childhood acute lymphoblastic leukemia (ALL) have impaired adaptive physical function and poor health-related quality of life (HRQoL). Obesity may contribute to these impairments by increasing the physiological cost of walking. Due to treatment exposures during ALL therapy, survivors' cost of walking may be more impacted by obesity than the general population. Therefore, we examined associations between obesity, persistent motor neuropathy, and energy cost of walking; and examined associations between energy cost of walking, adaptive physical function, and HRQoL, in adult survivors of childhood ALL vs. community controls. Methods: Obesity was measured via body mass index (BMI) and body fat percentage. The physiological cost index (PCI) was calculated from the six-minute walk test. Adaptive physical functioning was measured using two tests: the timed up and go (TUG) test and the physical performance test. Persistent motor neuropathy was measured using the modified total neuropathy score; HRQoL was measured using the Short-Form-36 questionnaire. The associations between obesity and PCI were evaluated using multivariable linear regressions in adult survivors of childhood ALL (n = 1,166) and community controls (n = 491). Then, the associations between PCI, adaptive physical functioning and peripheral neuropathy were examined using multivariable linear regressions. Finally, to determine the association between obesity, and neuropathy on PCI, while accounting for potential lifestyle and treatment confounders, a three model, sequential linear regression was used. Results: Obese individuals (BMI > 40 kg/m2 and excess body fat percentage [males: >25%; females: >33%]) had higher PCI compared to those with normal BMI and body fat percentage (0.56 ± 0.01 vs. 0.49 ± 0.009 beats/meter p < .01; and 0.51 ± 0.007 vs. 0.48 ± .0006 beats/meter p < .01, respectively). Treatment exposures did not attenuate this association. Increased PCI was associated with longer TUG time in survivors, but not community controls (6.14 ± 0.02 s vs. 5.19 ± 0.03 s, p < .01). Survivors with PCI impairment >95th percentile of community controls had lower HRQoL compared to un-impaired ALL survivors: 46.9 ± 0.56 vs. 50.4 ± 1.08, respectively (p < .01). Conclusion: Obesity was associated with increased PCI. Survivors with high PCI had disproportionately worse adaptive physical function and HRQoL compared to controls. Survivors with increased energy costs of walking may benefit from weight loss interventions.

Real-World Association Between mRNA Vaccination and Infection From the Omicron Strain of SARS-CoV-2: A Population-Level Analysis.

Introduction: Two mRNA vaccines approved in the U.S. have high efficacy against COVID-19 disease from the original strain of SARS-CoV-2. We evaluated the population-level association between vaccination status and COVID-19 infection by age group during the initial wave of the Omicron variant in a diverse population in the Mid-South U.S. Methods: In this observational population-based cohort study, vaccination information and positive COVID-19 cases in Shelby County, Tennessee, from December 12, 2021 through January 22, 2022 were collected from surveillance data at the Shelby County Health Department (Memphis, Tennessee). Exposure groups included individuals who were unvaccinated, were fully vaccinated, and were fully vaccinated + booster. We calculated incidence rates of COVID-19 diagnosis per person-year among county adult (aged 18+ years) residents in crude form and stratified by age group. Results: In this population-based study, we identified 64.56% fewer COVID-19 infections in the fully vaccinated + booster group and 41.08% fewer in the fully vaccinated group than in the unvaccinated group. Conclusions: These results confirm and extend the findings of recent immunologic and epidemiologic studies in a racially diverse region of the Mid-South U.S. In stratified analysis, we also found evidence suggesting that vaccine protection against Omicron may increase with age.

Sickle cell disease and ventricular myocardial strain: A systematic review.

Cardiac disease is the primary cause of death in sickle cell disease (SCD). Cardiac abnormalities begin in childhood and progress throughout life. Right and left ventricular (RV, LV) myocardial strain are early markers of systolic dysfunction but are not well investigated among individuals with SCD. The objectives of this review were to (1) identify all published studies that have evaluated ventricular myocardial strain, (2) summarize their values, and (3) compare findings with those obtained from controls. From search results of four electronic databases-Medline, Embase, Scopus, and Web of Science-42 potential articles were identified, of which 18 articles and 17 studies met eligibility criteria for inclusion. The evaluated studies demonstrate that RV and LV myocardial strain are generally abnormal in individuals with SCD compared with controls, despite having normal ejection/shortening fraction. Myocardial strain has been inconsistently evaluated in this population and should be considered any time an echocardiogram is performed.

Can Pediatric Orthopaedic Surgery be Done Safely in a Freestanding Ambulatory Surgery Center? Review of 3780 Cases.

BACKGROUND: The purpose of this study was to determine the intraoperative and 30-day postoperative complication rates in a large consecutive cohort of pediatric patients who had orthopaedic surgery at a freestanding ambulatory surgery center (ASC). The authors also wanted to identify the rates of same-day, urgent hospital transfers, and 30-day hospital admissions. The authors hypothesized that pediatric orthopaedic procedures at a freestanding ASC can be done safely with a low rate of complications. METHODS: A retrospective review identified patients aged 17 years or younger who had surgery at a freestanding ASC over a 9-year period. Adverse outcomes were divided into intraoperative complications, postoperative complications, need for the secondary procedure, unexpected hospital admission on the same day of the procedure, and unexpected hospital admission within 30 days of the index procedure. Complications were graded as grade 1, the complication could be treated without additional surgery or hospitalization; grade 2, the complication resulted in an unplanned return to the operating room (OR) or hospital admission; or grade 3, the complication resulted in an unplanned return to the OR or hospitalization with a change in the overall treatment plan. RESULTS: Adequate follow-up was available for 3780 (86.1%) surgical procedures. Overall, there were 9 (0.24%) intraoperative complications, 2 (0.08%) urgent hospital transfers, 114 (3%) complications, and 16 (0.42%) readmissions. Seven of the 9 intraoperative complications resolved before leaving the OR, and 2 required return to the OR.Neither complications nor hospitalizations correlated with age, race, gender, or length or type of surgery. There was no correlation between the presence of medical comorbidities, body mass index, or American Society of Anesthesiologists score and complication or hospitalization. CONCLUSIONS: Pediatric orthopaedic surgical procedures can be performed safely in an ASC because of multiple factors that include dedicated surgical teams, single-purpose ORs, and strict preoperative screening criteria. The rates of an emergency hospital transfer, surgical complications, and 30-day readmission, even by stringent criteria, are lower than those reported for outpatient procedures performed in the hospital setting. LEVEL OF EVIDENCE: Level IV-case series.

Exposures Associated with Non-Typhoidal Salmonella Infections Caused by Newport, Javiana, and Mississippi Serotypes in Tennessee, 2013-2015: A Case-Case Analysis.

Non-typhoidal Salmonella (NTS) infection (salmonellosis) is one of the most prevalent gastrointestinal diseases throughout the world. Human infections caused by Salmonella Newport, Javiana, and Mississippi serotypes have been observed to occur at higher rates on an annual basis in western Tennessee. The reason for the increased rate of NTS infection by these three serotypes in this region is not known. We conducted a case-case analysis to identify potential risk factors associated with the three Salmonella serotypes using FoodNet data, obtained from the Tennessee Department of Health, consisting of 1578 culture-confirmed salmonellosis cases in Tennessee from 2013 through 2015. Among all the exposure variables tested (254 in total), we found contact with pet treats or chews in the seven days prior to illness was the factor that was significantly associated with these serotypes compared to other serotypes (odds ratio adjusted = 3.0 (95% confidence intervals 1.6, 5.5), P < 0.0005). This study highlights the need for further investigation of potential exposures (other than pet treats or chews), including several possible environmental sources of NTS infection in humans.

A meta-analysis of toxicities related to hydroxycarbamide dosing strategies.

Due to fear of short-term toxicities, there is nonconsensus of hydroxycarbamide dosing strategy (escalated vs fixed-dosing methods), which contributes to its suboptimal use. We performed a meta-analysis to summarize the incidence rates of toxicities associated with both dosing methods. Summarized incidence rates could not be statistically compared between dosing methods due to sparse data. Summarized neutropenia and thrombocytopenia incidence rates were slightly higher when using escalated dosing than with fixed. Summarized reticulocytopenia was comparable. Summarized hepatic and renal toxicities' incidence rates were slightly higher when using fixed doses than with escalated. We recommend diligent and transparent reporting of toxicities.

Diabetes mellitus among adult survivors of childhood acute lymphoblastic leukemia: A report from the St. Jude Lifetime Cohort Study.

BACKGROUND: Greater than one-half of children who are treated for acute lymphoblastic leukemia (ALL) develop ≥1 treatment-related medical conditions in their lifetime, many of which are known risk factors for diabetes mellitus. In the current study, the authors evaluated the prevalence and risk factors of diabetes mellitus among clinically assessed adult survivors of childhood ALL METHODS: The authors performed a retrospective evaluation of data from survivors of ALL and community controls who were enrolled in the St. Jude Lifetime Cohort Study between October 1, 2007, and June 30, 2016. Participants were adults with ≥10 years of survival of childhood ALL and community controls who completed clinical and laboratory evaluations. Data for the current analysis were abstracted from medical records. Exposures evaluated herein included chemotherapy and radiation exposures and medical history, including drug-induced diabetes mellitus. RESULTS: Of 1360 eligible adults who were ≥10-year survivors of childhood ALL, a total of 1044 completed the evaluations; these individuals had a mean age of 33.97±9.14 years and 50.86% were male. The 368 controls, 45.65% of whom were male, had a mean age of 35.33±10.21 years. Type 2 diabetes mellitus (T2DM) was found in approximately 7.47% of survivors and 3.80% of controls (odds ratio [OR], 2.07; 95% CI, 1.11-3.87). In adjusted models, among survivors, older age (OR, 1.05 for each additional year; 95% CI, 1.02-1.08), body mass index ≥30 kg/m2 (OR, 7.40; 95% CI, 2.61-20.97), and drug-induced diabetes mellitus occurring during ALL therapy (OR, 4.67; 95% CI, 2.53-8.61) were found to be associated with T2DM. CONCLUSIONS: Adult survivors of childhood ALL are at an increased risk of T2DM. Adult survivors of childhood ALL who are of older age, with an overweight or obese body mass index, and/or who developed drug-induced diabetes mellitus during treatment should be closely monitored for T2DM during long-term follow-up.

Sources of human infection by Salmonella enterica serotype Javiana: A systematic review.

Non-typhoidal Salmonella (NTS) infection is one of the major causes of diarrheal disease throughout the world. In recent years, an increase in human S. Javiana infection has been reported from the southern part of the United States. However, the sources and routes of transmission of this Salmonella serotype are not well understood. The objective of this study was to perform a systematic review of the literature to identify risk factors for human S. Javiana infection. Using PRISMA guidelines, we conducted a systematic search in Web of Science, PubMed, and the Morbidity and Mortality Weekly Report (MMWR). Searches returned 63 potential articles, of which 12 articles met all eligibility criteria and were included in this review. A review of the literature indicated that both food and non-food (such as animal contact) exposures are responsible for the transmission of S. Javiana infection to humans. Consumption of fresh produce (tomatoes and watermelons), herbs (paprika-spice), dairy products (cheese), drinking contaminated well water and animal contact were associated with human S. Javiana infections. Based on the findings of this study, control of human S. Javiana infection should include three factors, (a) consumption of drinking water after treatment, (b) safe animal contact, and (c) safe food processing and handling procedures. The risk factors of S. Javiana infections identified in the current study provide helpful insight into the major vehicles of transmission of S. Javiana. Eventually, this will help to improve the risk management of this Salmonella serotype to reduce the overall burden of NTS infection in humans.

Atherosclerotic cardiovascular disease risk assessment and predictors of statin use in Filipino-American Women.

WHAT IS KNOWN AND OBJECTIVE: Race and gender disparities in the context of appropriate treatment with lipid-lowering therapies do exist. The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines outlined four groups, three for primary prevention and one for secondary prevention, whom would benefit from statin therapy to target atherosclerotic cardiovascular disease (ASCVD). The application of these recommendations in Filipino women living in the United States is unknown; however, this population is known to have elevated cardiovascular risk. Socio-economic and clinical characteristics that predict statin utilization of this Asian American subgroup need to be explored. METHODS: This was an exploratory analysis of data collected during a cross-sectional study of Filipino-American Women (FAW). The Pooled Cohort equation was used to estimate 10-year ASCVD risk. Bivariate analysis was employed to determine the association between statin treatment and clinical and socio-economic factors. Data were analysed using SAS® 9.4; statistical significance was set at P < 0.05. RESULTS AND DISCUSSION: A total of 384 women (mean age 56.3 years) were included in the original study, and the average 10-year ASCVD risk was 3.5 ± 3.7%. Upon applying the 2013 ACC/AHA guidelines, 97 FAW were categorized into one of the primary prevention groups. Women considered to benefit from a statin based on the guideline criteria but were not prescribed a statin were considered the not statin treated group (n = 55). From the original cohort, 93 FAW reported current statin therapy use and were categorized as statin treated. The clinical characteristics associated with not being statin treated were as follows: untreated blood pressure (P = 0.012), higher diastolic blood pressure (P = 0.015), higher total cholesterol (P < 0.001), higher triglycerides (P = 0.041), higher low-density lipoprotein (P < 0.001) and higher glucose (P = 0.011). The socio-economic factor associated with not being statin treated was having two or more insurance payers (P = 0.005). Overall, this population had a waist circumference and body mass index (BMI) that exceeds guidelines for Asian women (31.5 or 80 cm). WHAT IS NEW AND CONCLUSION: Predictors of statin utilization in FAW are not well documented in the literature. These findings emphasize room for improvement for the prescribing of statins in primary prevention for this study population. Applying culturally appropriate screening strategies to identify cardiovascular risk factors early such as BMI or waist circumference may assist with quantifying patients into one of the statin benefit groups if eligible.

The Effect of Under-Dosing Prophylactic Antibiotics in the Care of Open Tibial Fractures.

OBJECTIVES: To determine the frequency and effect of under-dosing prophylactic weight-based antibiotics in patients with open tibial fractures. We hypothesized that patients who did not receive appropriate weight-based dosing of prophylactic antibiotics would have higher rates of infection. DESIGN: Retrospective cohort study. SETTING: Level 1 Trauma Center. PATIENTS/PARTICIPANTS: Patients 18 years of age or older with high-grade (Gustilo-Anderson type IIIA or IIIB) open extraarticular tibial fractures over a 5-year period. MAIN OUTCOME: The primary outcome was deep infection within one year of initial injury. Appropriate weight-based dosing of cefazolin was defined as: at least 1 g for patients <80 kg, 2 g for patients between 80 and 120 kg, and 3 g for patients >120 kg. RESULTS: Sixty-three patients met the inclusion criteria; 21 (33%) were under-dosed with cefazolin at the time of initial presentation. Among the 20 patients who subsequently developed deep infection, only 55% were appropriately dosed with cefazolin; of the patients who did not develop deep infection, 72% were appropriately dosed with cefazolin (P = 0.18). Univariate analysis revealed that hypertension was associated with infection (P = 0.049). Multivariable logistic regression analysis of infection due to all organisms did not reveal a statistically significant reduction in the odds of infection with appropriate weight-based dosing of cefazolin [Odds ratio = 0.42 (95% confidence interval, 0.12-1.48), P = 0.177]. Five of 7 (71%) of the gram positive, non-methicillin-resistant Staphylococcus aureus, infections occurred in patients who were under-dosed with cefazolin. Five (23.8%) of 21 patients who were under-dosed with cefazolin had gram-positive, non-methicillin-resistant S. aureus infections, compared to 2 (4.8%) of 42 patients who were appropriately dosed (P = 0.036). CONCLUSIONS: Under-dosing of weight-based antibiotics in the treatment of open fractures is common. Appropriate weight-based dosing of cefazolin for prophylaxis in high-grade open tibial fractures reduces the frequency of infection due to cefazolin-sensitive organisms. Interestingly, organisms not susceptible to cefazolin were responsible for the majority of infections. The effect of under-dosing of cefazolin and other weight-based antibiotics deserves further investigation in larger studies. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Behavioral symptoms and psychiatric disorders in child and adolescent long-term survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only.

BACKGROUND: Prevalence of emotional, behavioral, and psychiatric outcomes in child and adolescent survivors of childhood acute lymphoblastic leukemia treated on a chemotherapy-only protocol were not well defined. METHODS: Self- and parent-reported emotional and behavioral symptoms were assessed for 161 survivors of childhood acute lymphoblastic leukemia (51.0% female; mean [SD] age 12.1[2.6] years; 7.5[1.6] years post-diagnosis). Age- and sex-adjusted scores were calculated for standardized measures and compared with 90th percentile of norms. Frequencies of survivor psychiatric disorders from structured diagnostic interviews with parents were compared with the general population. Parent emotional distress and post-traumatic stress symptoms were assessed. Associations between child symptoms/disorders and parent distress were examined with log-binomial models, adjusting for highest parent education. RESULTS: Compared with population expectations (10%), more survivors self-reported symptoms of inattention (27.9; 95% CI, 21.0%-35.7%), hyperactivity/impulsivity (26.0%; CI, 19.2%-33.6%), and oppositional-defiant behavior (20.1%; CI, 14.1%-27.3%). Parents reported survivors with more symptoms of inattention (23.6%; CI, 17.2%-31.0%), higher frequencies of obsessive-compulsive disorder (10.3% vs 2%) and oppositional defiant disorder (16.0% vs 9.5%), but not attention-deficit/hyperactivity disorder (7.1% vs 7.8%) or generalized anxiety disorder (3.2% vs 4.1%), compared with national norms. Parent-report of child anxiety disorders was associated with parent self-reported emotional distress but not survivor self-report of anxiety. CONCLUSION: A significant minority of survivors have long-term psychiatric morbidity, multi-informant assessment is important to understand these symptom profiles and to inform selection of appropriate interventions. Interventions targeting inattention and oppositional behavior in children and emotional distress in parents are warranted in families with survivors who display behavioral problems.

Evolution of neurocognitive function in long-term survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only.

PURPOSE: The purpose of this study was to determine the evolution of neurocognitive problems from therapy completion to long-term follow-up in survivors of childhood acute lymphoblastic leukemia treated with chemotherapy only. METHODS: We evaluated whether attention problems observed at therapy completion evolve into long-term executive dysfunction in 158 survivors treated on a single institution protocol. Treatment data (high-dose intravenous methotrexate exposure [serum concentration] and triple intrathecal chemotherapy injections) were collected. Parent report of behavior and direct cognitive testing of survivors was conducted at end of therapy, and survivors completed neurocognitive testing when > 5 years post-diagnosis. RESULTS: At the end of chemotherapy, survivors (52% female; mean age 9.2 years) demonstrated higher frequency of impairment in sustained attention (38%) and parent-reported inattention (20%) compared to population expectations (10%). At long-term follow-up, survivors (mean age 13.7 years; 7.6 years post-diagnosis) demonstrated higher impairment in executive function (flexibility 24%, fluency 21%), sustained attention (15%), and processing speed (15%). Sustained attention improved from end of therapy to long-term follow-up (p < 0.001). Higher methotrexate AUC and greater number of intrathecal injections were associated with attention problems (p = 0.009, p = 0.002, respectively) at the end of chemotherapy and executive function (p < 0.001, p = 0.02, respectively) problems at long-term follow-up. Attention problems at the end of therapy were not associated with executive function problems at long-term follow-up (p's > 0.05). The direct effect of chemotherapy exposure predicted outcomes at both time points. CONCLUSIONS AND IMPLICATIONS FOR CANCER SURVIVORS: Survivors should be monitored for neurocognitive problems well into long-term survivorship, regardless of whether they show attention problems at the end of therapy. Treatment exposures are the best predictor of long-term complications.