Pediatric Providers' Knowledge, Attitudes, Practice, and Barriers to Firearms Safety Counseling.

OBJECTIVES: Firearms-related injuries and deaths are a leading cause of death in children and young adults ages 5 to 24 years. This study evaluated the counseling practices and barriers to providing safe firearms storage education by pediatricians and advance practice providers. METHODS: An online survey was sent to 296 pediatric outpatient providers in Houston, Texas. Pediatric providers were asked about demographics, knowledge, attitudes, and current practices regarding firearms safety counseling. Descriptive and comparative analyses were performed. RESULTS: Survey respondents (N = 76) were 86% women and 87% physicians. Most (86%) agree that they should discuss firearms safety with parents, whereas only 32% report routine counseling. The most frequent barrier to providing education was insufficient time (63%), followed by unfamiliarity with guns (26%). CONCLUSIONS: Pediatric providers are interested in firearms safety counseling, but few incorporate it into their practice. Addressing barriers of time and comfort level around firearms are potential first steps to curbing a leading cause of injury death among children. Further research is needed to develop counseling methods that are time efficient and culturally competent for the pediatric office.

Regorafenib in Combination with First-Line Chemotherapy for Metastatic Esophagogastric Cancer.

BACKGROUND: Angiogenesis is critical to gastroesophageal adenocarcinoma growth and metastasis. Regorafenib is a multikinase inhibitor targeting angiogenic and stromal receptor tyrosine kinases. We evaluated whether regorafenib augments the antitumor effect of first-line chemotherapy in metastatic esophagogastric cancer. MATERIALS AND METHODS: Patients with previously untreated metastatic gastroesophageal adenocarcinoma received 5-fluorouracil, leucovorin, and oxaliplatin (mFOLFOX6) every 14 days and regorafenib 160 mg daily on days 4 to 10 of each 14-day cycle. The primary endpoint was 6-month progression-free survival (PFS). To identify predictive biomarkers of outcome, we examined correlations between genomic characteristics of sequenced pretreatment tumors and PFS. RESULTS: Between August 2013 and November 2014, 36 patients with metastatic esophagogastric cancer were accrued to this single-center phase II study (NCT01913639). The most common grade 3-4 treatment-related adverse events were neutropenia (36%), leucopenia (11%) and hypertension (8%). The 6-month PFS was 53% (95% confidence interval [CI], 38%-71%), the objective response rate was 54% (95% CI, 37%-70%), and the disease control rate was 77% (95% CI, 67%-94%). Next-generation sequencing did not identify any genomic alterations significantly correlated with response, and there was no association between homologous recombination deficiency and PFS with platinum-based chemotherapy. CONCLUSION: Regorafenib (one week on-one week off schedule) is well tolerated in combination with first-line FOLFOX but does not improve 6-month PFS relative to historical control. IMPLICATIONS FOR PRACTICE: Prognosis for metastatic esophagogastric cancer remains poor despite modern systemic therapy regimens. This phase II trial indicates that the combination of regorafenib and FOLFOX is well tolerated but does not add to the efficacy of first-line chemotherapy in metastatic esophagogastric cancer. Notably, recently reported data suggest potential synergy between regorafenib and the PD-1 inhibitor nivolumab. As this study demonstrates that regorafenib plus FOLFOX is safe, and combined chemotherapy and immunotherapy show favorable toxicity profiles, future studies combining immunotherapy with regorafenib and chemotherapy may be feasible.

Improving Tracking of Postdischarge Results of Sexually Transmitted Infection Screening Tests in Hospitalized Adolescents and Young Adults: A Quality Improvement Initiative.

Hospitalizations offer chlamydia and gonorrhea screening opportunities for youth who may not seek preventive care. Tracking of screening test results still pending after hospital discharge is an important component of clinical care. This process can be improved by protocol use and enhanced by effective, automated electronic health record tools.

Nanoliposomal irinotecan with fluorouracil for the treatment of advanced pancreatic cancer, a single institution experience.

BACKGROUND: Effective treatment options for advanced pancreatic cancer are finite. NAPOLI-1, a phase III randomized trial, demonstrated the efficacy of nanoliposomal irinotecan with fluorouracil/leucovorin (nal-IRI + 5-FU/LV) for the treatment of advanced pancreatic cancer following progression on gemcitabine-based chemotherapy. There are limited additional data on the safety and efficacy of nal-IRI + 5-FU/LV following FDA approval in October 2015. We examined the post-approval safety and effectiveness of nal-IRI + 5-FU/LV in advanced pancreatic cancer patients receiving treatment at Memorial Sloan Kettering Cancer Center. METHODS: A retrospective chart review was conducted of all patients beginning treatment with nal-IRI + 5-FU/LV from October 2015 through June 2017. Using the electronic medical record and institutional database, information was extracted pertaining to demographics, performance status (ECOG), prior therapies, dose, duration of treatment, adverse events, progression free survival (PFS), overall survival (OS) and treatment response. RESULTS: Fifty six patients were identified. Median progression free survival (PFS) was 2.9 months and median overall survival (OS) was 5.3 months. Patients with prior disease progression on irinotecan experienced PFS and OS of 2.2 and 3.9 mo, respectively. Patients without prior irinotecan exposure experienced significantly longer PFS (4.8 mo, p = 0.02) and OS (7.7 mo, p = 0.002), as did patients who received prior irinotecan without disease progression (PFS, 5.7 mo, p = 0.04; OS, 9.0 mo, p = .04). Progression on prior irinotecan was associated with greater lines of prior advanced disease chemotherapy (2 vs 1). Dose reductions (DR) were most frequently due to fatigue (42%) and diarrhea (37%), but were not associated with worse outcomes. In fact, patients with ≥1 DR experienced longer PFS (5.4 v 2.6 mo, p = 0.035). Sequential therapy with nab-paclitaxel + gemcitabine (nab-P + Gem) followed by nal-IRI + 5-FU/LV (n = 25) resulted in OS of 23.0 mo. Mutations in TP53 were associated with shorter PFS. CONCLUSIONS: These data support the safety and efficacy of nal-IRI + 5-FU/LV, reinforcing results of NAPOLI-1. Patients without disease progression on prior irinotecan fared significantly better than patients with progression, when treated with nal-IRI + 5-FU/LV. Sequential therapy with nab-P + Gem followed by nal-IRI + 5-FU/LV demonstrates encouraging median OS. These findings provide guidance for patients most likely to benefit from nal-IRI + 5-FU/LV.

Increased expression of tumor proliferation genes in Hispanic women with early-stage breast cancer.

Hispanic women have higher breast cancer mortality compared to non-Hispanic whites. We evaluated for Proliferation Axis Score differences, as determined by Oncotype Dx, in Hispanic and non-Hispanic white women with newly diagnosed breast cancer. We matched 219 women, based upon age, stage, and nodal status. Compared to non-Hispanic whites, Hispanic women with hormone-sensitive, HER2-negative early-stage breast cancer had a higher Proliferation Axis Score. No differences were seen in Recurrence Score, ER, PR, or HER2 by Oncotype DX. CCNB1 and AURKA were significantly higher in Hispanic women. These tumor differences may help explain breast cancer outcome differences between the two ethnicities.

CHIPing Away at Proteomics to Find Correlations with Myeloid Neoplasms.

Plasma proteomic profiling to identify associations with myeloid neoplasm (MN) risk highlights the potential of integrating proteins and genetic biomarkers for the detection of individuals at high risk of developing MN. These proteins also offer valuable insights into biological pathways and inflammatory mechanisms involved in the progression of clonal hematopoiesis to MN. See related article by Tran et al., p. 3220.

Identifying heterogeneity using recursive partitioning: evidence from SMS nudges encouraging voluntary retirement savings in Mexico.

Individuals regularly struggle to save for retirement. Using a large-scale field experiment ( N = 97 , 149 ) in Mexico, we test the effectiveness of several behavioral interventions relative to existing policy and each other geared toward improving voluntary retirement savings contributions. We find that an intervention framing savings as a way to secure one's family future significantly improves contribution rates. We leverage recursive partitioning techniques and identify that the overall positive treatment effect masks subpopulations where the treatment is even more effective and other groups where the treatment has a significant negative effect, decreasing contribution rates. Accounting for this variation is significant for theoretical and policy development as well as firm profitability. Our work also provides a methodological framework for how to better design, scale, and deploy behavioral interventions to maximize their effectiveness.

Clinical Importance of Clonal Hematopoiesis in Metastatic Gastrointestinal Tract Cancers.

Importance: Clonal hematopoiesis (CH) has been associated with development of atherosclerosis and leukemia and worse survival among patients with cancer; however, the association with cancer therapy efficacy, in particular immune checkpoint blockade (ICB), and toxicity has not yet been established. Given the widespread use of ICB and the critical role hematopoietic stem cell-derived lymphocytes play in mediating antitumor responses, CH may be associated with therapeutic efficacy and hematologic toxicity. Objective: To determine the association between CH and outcomes, hematologic toxicity, and therapeutic efficacy in patients with metastatic gastrointestinal tract cancers being treated with systemic therapy, both in the first-line metastatic treatment setting and in ICB. Design, Setting, and Participants: This retrospective cohort study included 633 patients with stage IV colorectal (CRC) and esophagogastric (EGC) cancer who were treated with first-line chemotherapy and/or ICB at Memorial Sloan Kettering Cancer Center. Patients underwent matched tumor and peripheral blood DNA sequencing using the Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets next-generation sequencing assay between January 1, 2006, and December 31, 2020. Exposures: Clonal hematopoiesis-related genetic alterations were identified by next-generation sequencing of patients' tumor and normal blood buffy coat samples, with a subset of these CH alterations annotated as likely putative drivers (CH-PD) based upon previously established criteria. Main Outcomes and Measures: Patients with CH and CH-PD in peripheral blood samples were identified, and these findings were correlated with survival outcomes (progression-free survival [PFS] and overall survival [OS]) during first-line chemotherapy and ICB, as well as baseline white blood cell levels and the need for granulocyte colony-stimulating factor (G-CSF) support. Results: Among the 633 patients included in the study (390 men [61.6%]; median age, 58 [IQR, 48-66] years), the median age was 52 (IQR, 45-63) years in the CRC group and 61 (IQR, 53-69) years in the EGC group. In the CRC group, 161 of 301 patients (53.5%) were men, compared with 229 of 332 patients (69.0%) in the EGC group. Overall, 62 patients (9.8%) were Asian, 45 (7.1%) were Black or African American, 482 (76.1%) were White, and 44 (7.0%) were of unknown race or ethnicity. Presence of CH was identified in 115 patients with EGC (34.6%) and 83 with CRC (27.6%), with approximately half of these patients harboring CH-PD (CRC group, 44 of 83 [53.0%]; EGC group, 55 of 115 [47.8%]). Patients with EGC and CH-PD exhibited a significantly worse median OS of 16.0 (95% CI, 11.6-22.3) months compared with 21.6 (95% CI, 19.6-24.3) months for those without CH-PD (P = .01). For patients with CRC and EGC, CH and CH-PD were not associated with PFS differences in patients undergoing ICB or first-line chemotherapy. Neither CH nor CH-PD were correlated with baseline leukocyte levels or increased need for G-CSF support. Conclusions and Relevance: These findings suggest CH and CH-PD are not directly associated with the treatment course of patients with metastatic gastrointestinal tract cancer receiving cancer-directed therapy.

Physician-driven or self-directed safe firearm storage guidance: Which one is best?

BACKGROUND/PURPOSE: Access to firearms is a preventable cause of unintentional injury and suicide in children. Pediatric physicians provide injury prevention guidance, but firearm safety may not routinely be included. The purpose of this pilot study was to evaluate the effectiveness of firearm safety guidance (FSG) provided by a physician. METHODS: Prospective, randomized-controlled, trial assessing physician-delivered FSG at two pediatric clinics in Houston, Texas. Firearm-owning parents were randomized to physician guidance (PG) versus control (CG) groups. The CG received a handout with firearm safety facts and a free cable lock. The PG additionally received FSG by a physician. Pre- and post-intervention surveys were conducted. Results were analyzed using descriptive statistics and Chi square analysis. RESULTS: Thirty-two families participated; most (70%) were satisfied with the guidance. Pre-intervention safe firearm storage was high in both groups, and the intervention did not lead to improved habits in either group [PG: Pre 93% vs. Post 89%, p = 0.7 and CG: Pre 82% vs. 78%, p = 0.7].There was no difference in use of the free cable lock among groups (44% vs. 22%, p = 0.9). The PG demonstrated improved knowledge of the state child access protection law (PG: Pre 60% vs. Post 100% vs. CG: Pre 29% vs. Post 67%; p = 0.02). CONCLUSIONS: For firearm-owning parents, physician-delivered safe storage guidance may not be more effective than self-directed guidance provided by a handout. A larger trial is underway to confirm the findings of this pilot study.

Phase I/Ib study of crenolanib with ramucirumab and paclitaxel as second-line therapy for advanced esophagogastric adenocarcinoma.

PURPOSE: Paclitaxel plus ramucirumab is a standard second-line regimen for patients with advanced gastric adenocarcinoma, but clinical benefit remains modest. One potential resistance mechanism to VEGFR2 inhibition is activation of the PDGF/PDGFR pathway, which can be blocked by the selective inhibitor crenolanib. Therefore, we performed a phase I/Ib study of crenolanib in combination with paclitaxel/ramucirumab. METHODS: Patients with metastatic esophagogastric adenocarcinoma refractory to first-line therapy received escalating doses of crenolanib [60 mg twice daily (BID) to 100 mg three times daily (TID)] in combination with paclitaxel 80 mg/m2 intravenously on days 1, 8 and 15 and ramucirumab 8 mg/kg intravenously on days 1 and 15 of a 28-day cycle. The primary objective was to determine the maximally tolerated dose (MTD) of crenolanib. Additional patients were enrolled in the dose expansion cohort to assess 6-month progression-free survival (PFS) at the MTD. RESULTS: We enrolled 19 patients in the dose escalation phase and 8 patients in the dose expansion phase at the MTD of crenolanib 100 mg BID. Common grade 3/4 treatment-emergent adverse events included leukopenia (19%), anemia (11%) and neutropenia (11%). In the 14 patients treated at the MTD, 6-month PFS was 43% [95% confidence interval (CI) 23-78%] and the objective response rate (ORR) was 42% (95% CI 15-72%). The trial was terminated early due to withdrawal of crenolanib by the sponsor. CONCLUSIONS: The addition of crenolanib to paclitaxel/ramucirumab is safe and well-tolerated at a dose level up to 100 mg BID. CLINICAL TRIAL REGISTRATION: NCT03193918. June 19, 2017.

Efficacy of Combined VEGFR1-3, PDGFα/ß, and FGFR1-3 Blockade Using Nintedanib for Esophagogastric Cancer.

PURPOSE: VEGFR2-directed therapy is commonly used to treat metastatic esophagogastric cancer, but disease progresses in most patients within months. Therapeutic resistance is likely mediated in part by co-occurring amplifications of the genes for multiple oncogenic receptor tyrosine kinases (RTK). We therefore tested the efficacy of combined inhibition of VEGFR1-3, PDGFα/ß, and FGFR1-3 using nintedanib. PATIENTS AND METHODS: Patients with metastatic esophagogastric adenocarcinoma and disease progression on first-line chemotherapy were treated with nintedanib 200 mg twice daily. The primary endpoint was progression-free survival (PFS) at 6 months; secondary endpoints included tumor response and safety. Tumor biopsies were profiled by targeted capture next-generation sequencing (NGS) to identify molecular predictors of drug response. RESULTS: The study achieved its primary endpoint; 6 of 32 patients (19%) were progression-free at 6 months. With a median follow-up of 14.5 months among survivors, median overall survival (OS) was 14.2 months [95% confidence interval (CI), 10.8 months-NR]. Nintedanib was well tolerated; grade ≥ 3 toxicities were uncommon and included grade 3 hypertension (15%) and liver enzyme elevation (4%). FGFR2 alterations were identified in 18% of patients but were not predictive of clinical outcome on nintedanib therapy. Alterations in cell-cycle pathway genes were associated with worse median PFS (1.61 months for patients with cell-cycle pathway alterations vs. 2.66 months for patients without, P = 0.019). CONCLUSIONS: Nintedanib treatment resulted in modest disease stabilization in patients with metastatic esophagogastric cancer. Alterations in cell-cycle pathway genes and increased global copy-number alteration (CNA) burden warrant further study as prognostic or predictive biomarkers.

Acceptance of Routine HIV Testing by Hospitalized Adolescents and Young Adults.

BACKGROUND AND OBJECTIVES: Youth carry a disproportionate burden of new HIV infections. With our study, we aimed to characterize HIV testing experiences among adolescents and young adults admitted to a children's hospital that is located in a high HIV-prevalent community and implemented routine HIV testing for all patients ≥13 years of age. METHODS: A total of 120 patients aged 13 to 24 years old who were admitted to our hospital and had a documented offer of routine HIV testing on admission were invited to complete a self-administered survey that asked about sex, race and/or ethnicity, HIV risk behaviors, and attitudes toward routine HIV testing in the hospital. Date of birth, admission diagnosis, and verification of HIV testing and results were collected by chart review. RESULTS: Study participants (N = 99) were 17.4 ± 2.3 years old, 52% female, 47% Hispanic, and 29% African American. Additional characteristics include the following: 65% had previous sexual activity, 11% had a history of sexually transmitted infections, and 12% were worried about their risk for HIV. Forty-seven percent of participants accepted HIV testing, with older patients (P < .01) and those reporting previous sexual activity (P < .01) and a previous HIV test (P < .01) being more likely to accept testing. A total of 96% of participants agreed that the hospital is a good place to offer HIV testing. CONCLUSIONS: Our findings support offering routine HIV testing to youth admitted to children's hospital. Given the high incidence of new and undiagnosed HIV infections among youth, additional venues for HIV testing are essential.

Personalized management of elderly patients with rectal cancer: Expert recommendations of the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology, and American College of Surgeons Commission on Cancer.

With an expanding elderly population and median rectal cancer detection age of 70 years, the prevalence of rectal cancer in elderly patients is increasing. Management is based on evidence from younger patients, resulting in substandard treatments and poor outcomes. Modern management of rectal cancer in the elderly demands patient-centered treatment, assessing frailty rather than chronological age. The heterogeneity of this group, combined with the limited available data, impedes drafting evidence-based guidelines. Therefore, a multidisciplinary task force convened experts from the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology and the American College Surgeons Commission on Cancer, with the goal of identifying the best practice to promote personalized rectal cancer care in older patients. A crucial element for personalized care was recognized as the routine screening for frailty and geriatrician involvement and personalized care for frail patients. Careful patient selection and improved surgical and perioperative techniques are responsible for a substantial improvement in rectal cancer outcomes. Therefore, properly selected patients should be considered for surgical resection. Local excision can be utilized when balancing oncologic outcomes, frailty and life expectancy. Watch and wait protocols, in expert hands, are valuable for selected patients and adjuncts can be added to improve complete response rates. Functional recovery and patient-reported outcomes are as important as oncologic-specific outcomes in this age group. The above recommendations and others were made based on the best-available evidence to guide the personalized treatment of elderly patients with rectal cancer.

Kinetics and mechanisms of mercury biosorption by an exopolysaccharide producing marine isolate Bacillus licheniformis.

Eight exopolysaccharide (EPS) producing metal-removing marine bacteria were screened for mercury (Hg) sorption. Bacillus licheniformis with the highest MIC values and Hg sorption ability was selected for further study. Biosorption of Hg from aqueous solution by Bacillus licheniformis was studied with respect to the metal concentration, adsorbent concentration, pH, different contact times, and in the presence of other metal ions. Under optimum conditions, more than 70% mercury was removed by 25 mg dried biomass of Bacillus licheniformis at pH 7.0 after 1 h of contact time. Freundlich adsorption isotherm was acceptable at studied Hg concentrations as compared to Langmuir isotherm model. Pseudo-second-order kinetic model was found to be more suitable for data presentation in contrast to pseudo-first-order kinetic model. Involvement of external mass transfer was prominent as compared to intraparticle diffusion model. Desorption of Hg was more effective with acids from all the studied eluents, showing 49.36 and 33.8% eluting capacity for 0.1 N HCL and 0.1 N HNO3, respectively. Scanning electron microscopy exhibited altered cell surface morphology of the cells under the influence of mercury. The spectral images of energy dispersive spectroscopy showed the presence of metal ions on the surface of cells.

Systemic therapy of non-colorectal gastrointestinal malignancies in the elderly.

In the coming years life expectancy is expected to increase and with this the percentage of the population above age 65 will grow. Patients above 65 make up more than two thirds of those currently diagnosed with gastrointestinal malignancies. Available evidence based medicine does not focus on the average patient, above the age 70, encountered in every day practice. Most guidelines and clinical trials are not designed to take into account the special considerations needed when treating the elderly such as functional status, comorbidities, polypharmacy, life expectancy, and social support. The majority of available data is based on retrospective reviews or subset analyses of larger studies where the elderly represent a fraction of the studied population. This review focuses on the toxicities and tolerability of current standard therapies for non-colorectal gastrointestinal malignancies, including gastroesophageal, pancreatic, bile duct and hepatocellular cancers in the elderly. With careful patient selection and geriatric assessment the elderly can safely benefit from standard therapies offered to younger patients.

Working conditions and adverse pregnancy outcome: a meta-analysis.

OBJECTIVE: To evaluate the association between working conditions and adverse pregnancy outcomes by performing a meta-analysis of published studies. DATA SOURCES: We searched the English-language literature in MEDLINE through August 1999 using the terms standing, posture, work, workload, working conditions, shift, occupational exposure, occupational diseases, lifting, pregnancy complications, pregnancy, small for gestational age (SGA), fetal growth retardation (FGR), preterm, and labor. METHODS OF STUDY SELECTION: We included observational studies evaluating the effect of one or more of the following work-related exposures on adverse pregnancy outcome: physically demanding work, prolonged standing, long work hours, shift work, and cumulative work fatigue score. Outcomes of interest were preterm birth, hypertension or preeclampsia, and SGA.We conducted a meta-analysis based on 160,988 women in 29 studies to evaluate the association of physically demanding work, prolonged standing, long working hours, shift work, and cumulative work fatigue score with preterm birth. Also analyzed were the associations of physically demanding work with hypertension or preeclampsia and SGA infants. The data were analyzed using the Peto-modified Mantel-Haenszel method to estimate the pooled odds ratios (ORs) and 95% confidence intervals (CIs). TABULATION, INTEGRATION, AND RESULTS: Physically demanding work was significantly associated with preterm birth (OR 1.22, 95% CI 1.16, 1. 29), SGA (OR 1.37, 95% CI 1.30, 1.44), and hypertension or preeclampsia (OR 1.60, 95% CI 1.30, 1.96). Other occupational exposures significantly associated with preterm birth included prolonged standing (OR 1.26, 95% CI 1.13, 1.40), shift and night work (OR 1.24, 95% CI 1.06, 1.46), and high cumulative work fatigue score (OR 1.63, 95% CI 1.33, 1.98). We found no significant association between long work hours and preterm birth (OR 1.03, 95% CI 0.92, 1.16). CONCLUSION: Physically demanding work may significantly increase a woman's risk of adverse pregnancy outcome.

A competency based approach to comprehensive pregnancy care.

This paper assesses the quality and cost of a pregnancy care program based on explicit and achieved patient competencies. By using the USPHS Content of Prenatal Care (1989), key psychosocial/education elements of perinatal care were identified. The goal was a process of patient education that is competency based, integrated, and outcome oriented. Psychosocial assessment, patient education tools, criterion-based length of postpartum stay, and home nursing follow-up were implemented as part of a Comprehensive Pregnancy Program (CPP). Case-control and cohort survey methodology were used to evaluate outcome. There was a significant decrease in hospital length of stay for mothers and newborns after implementation of the CPP. Post-discharge maternal emergency room visits and/or readmits did not increase. Differences in newborn emergency room visits and/or readmits were non-significant. There was a marked reduction in hospital costs for mothers and newborns. Patient satisfaction remained high. Core competencies forming the basis of educational and assessment programs allow the focus of care to be optimal outcome, and provide a useful template against which to measure prenatal, intrapartum, and postpartum care.

Kinetics of the pituitary-thyroid axis and the peripheral thyroid hormones in 2 children with thyroxine intoxication.

Thyroxine intoxication is a benign, nonfatal condition, relatively common in the pediatric age group. We present here a detailed laboratory follow-up of all thyroidal hormones in 2 healthy girls who inadvertently ingested 2,500 micrograms of L-thyroxine. The two girls were hospitalized and treated with ipecac, gastric lavage, propranolol, prednisone, cholestyramin and propyl-thiouracil. All physical signs were normal and no symptoms were reported. All thyroidal hormones were measured 12 times from 2 h to 20 days after the ingestion. For T4, T3, rT3 and thyroglobulin (Tg) a one-compartment kinetic model was formulated and fitted to the empirical data. The kinetic data constants of production and elimination were calculated, as well as the metabolic clearance rate. All laboratory values were similar in both girls. T4 serum levels were already high 2 h after the intoxication and returned to normal values only after 13 days. Fitting the T4 serum levels with a one-compartment model resulted in absorption and degradation constants similar to those in normal adult subjects. Thyroid-stimulating hormone (TSH) levels decreased reaching their lowest concentration 14 h after the intoxication. They remained low till the 4th day, after which they rose gradually. Twenty days after the intoxication, TSH levels were still below their initial values. T3 reached its peak levels 11 h after the ingestion and decreased to normal values after 3 days. Both T3 production constants and T3 degradation constants were significantly increased. rT3 reached its peak level on the 2nd day after the intoxication and decreased to normal values on the 4th day. Its production and degradation constants were somewhat below normal levels. The T3/rT3 ratio decreased from a normal level of around 3 to as low as 1 and rose again after 13 days to extremely high levels (as high as 8). Tg serum levels dropped continuously with a half-life of 1-5 days and started rising again after 2-13 days. In conclusion, T4 intoxication in the child is combated primarily by a significant increase in T3 production and degradation, while meticulously maintaining relatively low T3 levels.