The patient perspective on dose optimization for anticancer treatments: A new era of cancer drug dosing-Challenging the "more is better" dogma.

The Patient-Centered Dosing Initiative, a patient-led effort advocating for a paradigm shift in determining cancer drug dosing strategies, pioneers a departure from traditional oncology drug dosing practices. Historically, oncology drug dosing relies on identifying the maximum tolerated dose through phase 1 dose escalation methodology, favoring higher dosing for greater efficacy, often leading to higher toxicity. However, this approach is not universally applicable, especially for newer treatments like targeted therapies and immunotherapies. Patient-Centered Dosing Initiative challenges this "more is better" ethos, particularly as metastatic breast cancer patients themselves, as they not only seek longevity but also a high quality of life since most metastatic breast cancer patients stay on treatment for the rest of their lives. Surveying 1221 metastatic breast cancer patients and 119 oncologists revealed an evident need for flexible dosing strategies, advocating personalized care discussions based on patient attributes. The survey results also demonstrated an openness toward flexible dosing and a willingness from both patients and clinicians to discuss dosing as part of their care. Patient-centered dosing emphasizes dialogue between clinicians and patients, delving into treatment efficacy-toxicity trade-offs. Similarly, clinical trial advocacy for multiple dosing regimens encourages adaptive strategies, moving away from strict adherence to maximum tolerated dose, supported by recent research in optimizing drug dosages. Recognizing the efficacy-effectiveness gap between clinical trials and real-world practice, Patient-Centered Dosing Initiative underscores the necessity for patient-centered dosing strategies. A focus on individual patient attributes aligns with initiatives like Project Optimus and Project Renewal, aiming to optimize drug dosages for improved treatment outcomes at both the pre- and post-approval phases. Patient-Centered Dosing Initiative's efforts extend to patient education, providing tools to initiate dosage-related conversations with physicians. In addition, it emphasizes physician-patient dialogues and post-marketing studies as essential in determining optimal dosing and refining drug regimens. A dose-finding paradigm prioritizing drug safety, tolerability, and efficacy benefits all stakeholders, reducing emergency care needs and missed treatments for patients, aligning with oncologists' and patients' shared goals. Importantly, it represents a win-win scenario across healthcare sectors. In summary, the Patient-Centered Dosing Initiative drives transformative changes in cancer drug dosing, emphasizing patient well-being and personalized care, aiming to enhance treatment outcomes and optimize oncology drug delivery.

A novel clinical risk scoring system for neurodevelopmental outcomes among survivors of neonatal hypoxic-ischemic encephalopathy (HIE).

OBJECTIVE: We aimed to develop a risk scoring system as a predictor of 24-month neurodevelopmental outcomes (cognitive, language, and motor) for neonates treated with therapeutic hypothermia for hypoxic-ischemic encephalopathy (HIE). METHODS: This was a chart review of infants with HIE treated with therapeutic hypothermia who were admitted to the Neonatal Intensive Care Unit (NICU) at the University of Michigan between 2009 and 2019 and followed in the neonatal developmental clinic until 24 months of age. We examined bivariate associations between the neonatal characteristics and Bayley-III scores. We then performed stepwise logistic regression. To create the risk scores, a participant was given one point for each of the factors included in the final model. RESULTS: Fifty-five infants were included. The final model for Bayley cognitive abnormality included abnormal neonatal neurologic exam (p < 0.0001), white matter/watershed MRI abnormality (p = 0.01), 5-min Apgar score (p = 0.02), and EEG-confirmed seizures (p = 0.04). The model for language abnormality included abnormal neurologic exam (p = 0.0002), seizures (p = 0.007), clinical severity of HIE (p = 0.06), and basal ganglia/thalamus MRI abnormality (p = 0.17). The model for motor abnormality included seizures (p = 0.03), abnormal neurologic exam (p = 0.06) and basal ganglia/thalamus MRI abnormality (p = 0.02). The positive predictive values for the risk scores were 60 %, 85 % and 71 %, respectively, for the Bayley-III cognitive, language and motor domains. CONCLUSION: Our study identifies early clinical features that differentially predict domains of neurodevelopmental outcome and associated risk scores that may be of value to both clinicians and families. This novel scoring system should next be validated in a larger, prospective study.

Patient perceptions of altering chemotherapy treatment due to peripheral neuropathy.

PURPOSE: Clinical practice guidelines recommend altering neurotoxic chemotherapy treatment in patients experiencing intolerable chemotherapy-induced peripheral neuropathy (CIPN). The primary objective of this survey was to understand patient's perspectives on altering neurotoxic chemotherapy treatment, including their perceptions of the benefits of preventing irreversible CIPN and the risks of reducing treatment efficacy. METHODS: A cross-sectional online survey was distributed via social networks to patients who were currently receiving or had previously received neurotoxic chemotherapy for cancer. Survey results were analyzed using descriptive statistics and qualitative analysis. RESULTS: Following data cleaning, 447 participants were included in the analysis. The median age was 57 years, 93% were white, and most were from the UK (53%) or USA (38%). Most participants who were currently or recently treated expected some CIPN symptom resolution (86%), but 45% of those who had completed treatment more than a year ago reported experiencing no symptom resolution. Participants reported that they would discontinue chemotherapy treatment for less severe CIPN if they knew their symptoms would be permanent than if symptoms would disappear after treatment. Most patients stated that the decision to alter chemotherapy or not was usually made collaboratively between the patient and their treating clinician (61%). The most common reason participants were reluctant to talk with their clinician about CIPN was fear that treatment would be altered. Participants noted a need for improved understanding of CIPN symptoms and their permanence, better patient education relating to CIPN prior to and after treatment, and greater clinician understanding and empathy around CIPN. CONCLUSIONS: This survey highlights the importance of shared decision-making, including a consideration of both the long-term benefits and risks of altering neurotoxic chemotherapy treatment due to CIPN. Additional work is needed to develop decision aids and other communication tools that can be used to improve shared decision making and help patients with cancer achieve their treatment goals.

Patient-centered dosing: oncologists' perspectives about treatment-related side effects and individualized dosing for patients with metastatic breast cancer (MBC).

PURPOSE: Although metastatic breast cancer (MBC) is treatable, it is not curable and most patients remain on treatment indefinitely. While oncologists commonly prescribe the recommended starting dose (RSD) from the FDA-approved label, patient tolerance may differ from that seen in clinical trials. We report on a survey of medical oncologists' perspectives about treatment-related toxicity and willingness to discuss flexible dosing with patients. METHODS: We disseminated a confidential survey via social media/email in Spring 2021. Eligible respondents needed to be US-based medical oncologists with experience treating patients with MBC. RESULTS: Of 131 responses, 119 were eligible. Physicians estimated that 47% of their patients reported distressing treatment-related side effects; of these, 15% visited the Emergency Room/hospital and 37% missed treatment. 74% (n = 87) of doctors reported improvement of patient symptoms after dose reduction. 87% (n = 104) indicated that they had ever, if appropriate, initiated treatment at lower doses. Most (85%, n = 101) respondents did not believe that the RSD is always more effective than a lower dose and 97% (n = 115) were willing to discuss individualized dosing with patients. CONCLUSION: Treatment-related side effects are prevalent among patients with MBC, resulting in missed treatments and acute care visits. To help patients tolerate treatment, oncologists may decrease initial and/or subsequent doses. The majority of oncologists reject the premise that a higher dose is always superior and are willing to discuss individualized dosing with patients. Given potential improvements regarding quality of life and clinical care, dose modifications should be part of routine shared decision-making between patients and oncologists.

Improving the odds together: a framework for breast cancer research scientists to include patient advocates in their research.

Including patient advocates in basic cancer research ensures that breast cancer research is intentional, supports effective communication with broader audiences, and directly connects researchers with those who they are striving to help. Despite this utility, many cancer research scientists do not work with patient advocates. To understand barriers to engagement and build a framework for enhanced interactions in the future, we hosted a workshop with patient advocates and researchers who do engage, then discussed findings at an international metastatic breast cancer conference to solicit additional feedback and suggestions. Findings demonstrate that researchers are uncertain about how to initiate and maintain relationships with advocates. We offer actionable steps to support researchers working with patient advocates to improve cancer research and accomplish our collective goal of improving lives of those who have been diagnosed with breast cancer. We hope that this initiative will facilitate such collaborative efforts.

Webinar as an Informational Resource on Trastuzumab Biosimilars: Planning, Promotion, Execution, and Evaluation.

Despite the incorporation of trastuzumab biosimilars (to treat HER2-positive breast cancer) in clinical practice guidelines, gaps remain such as patient and clinician education. We hosted a webinar comprised of a panel of biosimilars experts, oncologists, pharmacist, infusion nurse, and a patient advocate. The outcomes of the webinar include audience responses to pre- and post-webinar questionnaires, educational benefits, real-time opportunities to ask questions, and a recording. Education needs to be tailored to the needs of both, patients and clinicians.

Characterizing experiences of non-medical switching to trastuzumab biosimilars using data from internet-based surveys with US-based oncologists and breast cancer patients.

PURPOSE: To characterize current experiences with communication and decision-making practices when non-medical switching to a biosimilar trastuzumab is proposed or required by cancer center or insurer. METHODS: We developed and launched 60- and 51-item internet surveys to elicit US breast cancer patient and medical oncologist lived experiences with trastuzumab biosimilars and patient information needs and seeking practices. We recruited participants using social media and administered via REDCap in 2020-2021. RESULTS: 143 breast cancer patients and 33 medical oncologists completed the surveys. 63.9% patients reported having switched to a trastuzumab biosimilar and 40.8% reported receiving no prior notification about switching. 44% of patients reported learning about biosimilars primarily through self-directed learning and 41% wanting more time to discuss with oncologist. None of the oncologists reported that the decision to switch a patient to a biosimilar was initiated by them, but rather more frequently by the insurer (45.2%). About 54.8% reported not receiving any pharmaceutical manufacturer material related to the selected biosimilar. Patients and oncologists diverged in their responses to items regarding patient opportunities to ask questions, adequacy of resources, effectiveness of treatment, patient worry, and magnitude of change. CONCLUSION: There is a need for tailored and effective patient and oncologist information and education on trastuzumab biosimilars, along with improved healthcare communication regarding switching. The discrepancy between patient-reported experiences and oncologist perceptions of the patient experience, suggests a lack of adequate information that may be a challenge not only to the uptake of trastuzumab biosimilars, but to the patient-oncologist relationship.

Lateralized neonatal EEG coherence during sleep predicts language outcome.

BACKGROUND: Enriched language exposure may benefit infants in the neonatal intensive care unit. We hypothesized that changes in neonatal electroencephalogram (EEG) coherence during sleep, in response to maternal voice exposure, predict language development. METHODS: Convalescent neonates underwent 12-h polysomnography. A recording of the mother's voice was randomized to continuous playback in the first or second 6 h. We calculated the imaginary coherence (ICOH-a measure of functional connectivity) between EEG leads. Spearman correlations were computed between ICOH and 18-month Bayley-III language scores. RESULTS: Thirty-five neonates were included (N = 18 33-to-<35 weeks gestation; N = 17 ≥ 35 weeks). Predictive value of ICOH during neonatal non-rapid eye movement (NREM) sleep was left lateralized, and varied with gestational age and voice playback. ICOH in the left-hemispheric (C3-Cz; T3-Cz) channels across multiple EEG frequency bands was associated with 18-month language scores (rho = -0.34 to -0.48). The association was driven by neonates born at 33-34 weeks gestation, and a trend suggested a possible effect of maternal voice at some EEG frequencies. Right hemisphere ICOH (C4-Cz; T4-Cz) was not associated with language outcome. CONCLUSIONS: Left-hemispheric EEG functional connectivity during neonatal NREM sleep shows early signs of physiologic asymmetry that may predict language development. We speculate that sleep analyses could have unique prognostic value. IMPACT: During neonatal NREM sleep, EEG functional connectivity predicts future language development. Left temporal and central EEG coherence-specifically the imaginary component of coherence-is predictive, whereas the same analysis from the right hemisphere is not. These results appear to vary according to the infant's gestational age, and a trend suggests they may be enhanced by measuring functional connectivity during exposure to the mother's voice. These findings identify early evidence of physiologic differentiation within the cerebral hemispheres and raise the possibility that neonatal NREM sleep has a role to play in language development.

Thrombocytopenia in pediatric patients on concurrent cannabidiol and valproic acid.

In January 2019, a new plant-derived purified cannabidiol preparation, approved by the US Food and Drug Administration, became commercially available for patients ≥2 years old with Lennox-Gastaut syndrome or Dravet syndrome. Among our patients who were prescribed the new cannabidiol formulation, we observed several cases of thrombocytopenia and therefore embarked on this study. We conducted a single-center systematic chart review of all pediatric patients (<21 years old) who were prescribed cannabidiol from January to August 2019. We evaluated salient features of the patients' epilepsy syndrome, age, concurrent medications, and surveillance laboratory results before and after cannabidiol initiation. Among 87 patients, nine (10%) developed thrombocytopenia (platelet nadir range = 17 000-108 000) following initiation of cannabidiol. Each of these nine children was on combination therapy of cannabidiol with valproic acid. Whereas no children on cannabidiol without valproic acid (0/57) developed thrombocytopenia, nine of 23 treated with combination valproic acid and cannabidiol developed platelets < 110 000/µL (P < .0001). We report a novel and clinically important side effect of thrombocytopenia in one-third of patients treated concurrently with cannabidiol and valproic acid. If this finding is confirmed, clinicians should perform close monitoring for thrombocytopenia when adding cannabidiol to a regimen that includes valproic acid.

Differential Diagnosis of Autism Spectrum Disorder Versus Language Disorder in Children Ages 2 to 5 Years: Contributions of Parent-Reported Development and Behavior.

Early diagnosis of autism spectrum disorder (ASD) has focused on differentiating children with ASD from neurotypical children. However, many children presenting with concern for ASD are ultimately diagnosed with language disorder (LD). This study aimed to identify differences in parent-rated development and behavior among children ages 2 to 5 years presenting with concern for ASD who were diagnosed with either ASD or LD. Children with ASD were rated as more socially withdrawn and more delayed in social development and self-help skills than those with LD. Parent-rated developmental delays were positively correlated with scores on an autism screening measure and with social withdrawal and pervasive developmental problems among children with ASD. Among those with LD, parent-rated social and self-help development were positively correlated with social withdrawal and attention problems. Thus, parent ratings of social withdrawal and development of social and self-help skills may facilitate differential diagnosis of ASD and LD in children ages 2 to 5 years.

Sleep-disordered breathing is common among term and near term infants in the NICU.

OBJECTIVE: Among older infants and children, sleep-disordered breathing (SDB) has negative neurocognitive consequences. We evaluated the frequency and potential impact of SDB among newborns who require intensive care. STUDY DESIGN: Term and near-term newborns at risk for seizures underwent 12-h attended polysomnography in the neonatal intensive care unit (NICU). Bayley Scales of Infant Development, third edition (Bayley-III) were administered at 18-22 months. RESULT: The 48 newborns (EGA 39.3 ± 1.6) had a median pediatric apnea-hypopnea index (AHI) of 10.1 (3.3-18.5) and most events were central (vs obstructive). Maternal and prenatal factors were not associated with AHI. Moreover, neonatal PSG results were not associated with Bayley-III scores (P > 0.05). CONCLUSION: SDB is common among term and near-term newborns at risk for seizures. Follow-up at ages when more nuanced testing can be performed may be necessary to establish whether neonatal SDB is associated with long-term neurodevelopmental disability.

Neurodevelopmental and Behavioral Outcomes in Extremely Premature Neonates With Ventriculomegaly in the Absence of Periventricular-Intraventricular Hemorrhage.

Importance: Studies of cranial ultrasonography and early childhood outcomes among cohorts of extremely preterm neonates have linked periventricular-intraventricular hemorrhage and cystic periventricular leukomalacia with adverse neurodevelopmental outcomes. However, the association between nonhemorrhagic ventriculomegaly and neurodevelopmental and behavioral outcomes is not fully understood. Objective: To characterize the outcomes of extremely preterm neonates younger than 27 weeks' gestational age who experienced nonhemorrhagic ventriculomegaly that was detected prior to 36 weeks' postmenstrual age. Design, Setting, and Participants: This longitudinal observational study was conducted at 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants born prior to 27 weeks' gestational age in any network facility between July 1, 2006, and June 30, 2011, were included if they had a cranial ultrasonogram performed prior to 36 weeks' postmenstrual age. Comparisons were made between those with ventriculomegaly and those with normal cranial sonograms. Data analysis was completed from August 2013 to August 2017. Main Outcomes and Measures: The main outcome was neurodevelopmental impairment, defined as a Bayley Scales of Infant and Toddler Development III cognitive score less than 70, moderate/severe cerebral palsy, a Gross Motor Function Classification System score of level 2 or more, vision impairment, or hearing impairment. Secondary outcomes included Bayley Scales of Infant and Toddler Development III subscores, components of neurodevelopmental impairment, behavioral outcomes, and death/neurodevelopmental impairment. Logistic regression was used to evaluate the association of ventriculomegaly with adverse outcomes while controlling for potentially confounding variables and center differences as a random effect. Linear regression was used similarly for continuous outcomes. Results: Of 4193 neonates with ultrasonography data, 300 had nonhemorrhagic ventriculomegaly (7%); 3045 had normal cranial ultrasonograms (73%), 775 had periventricular-intraventricular hemorrhage (18.5%), and 73 had cystic periventricular leukomalacia (1.7%). Outcomes were available for 3008 of 3345 neonates with ventriculomegaly or normal scans (90%). Compared with normal cranial ultrasonograms, ventriculomegaly was associated with lower gestational age, male sex, and bronchopulmonary dysplasia, late-onset sepsis, meningitis, necrotizing enterocolitis, and stage 3 retinopathy of prematurity. After adjustment, neonates with ventriculomegaly had higher odds of neurodevelopmental impairment (odds ratio [OR], 3.07; 95% CI, 2.13-4.43), cognitive impairment (OR, 3.23; 95% CI, 2.09-4.99), moderate/severe cerebral palsy (OR, 3.68; 95% CI, 2.08-6.51), death/neurodevelopmental impairment (OR, 2.17; 95% CI, 1.62-2.91), but not death alone (OR, 1.09; 95% CI, 0.76-1.57). Behavioral outcomes did not differ. Conclusions and Relevance: Nonhemorrhagic ventriculomegaly is associated with increased odds of neurodevelopmental impairment among extremely preterm neonates.

Neonatal Sleep-Wake Analyses Predict 18-month Neurodevelopmental Outcomes.

Objectives: The neurological examination of critically ill neonates is largely limited to reflexive behavior. The exam often ignores sleep-wake physiology that may reflect brain integrity and influence long-term outcomes. We assessed whether polysomnography and concurrent cerebral near-infrared spectroscopy (NIRS) might improve prediction of 18-month neurodevelopmental outcomes. Methods: Term newborns with suspected seizures underwent standardized neurologic examinations to generate Thompson scores and had 12-hour bedside polysomnography with concurrent cerebral NIRS. For each infant, the distribution of sleep-wake stages and electroencephalogram delta power were computed. NIRS-derived fractional tissue oxygen extraction (FTOE) was calculated across sleep-wake stages. At age 18-22 months, surviving participants were evaluated with Bayley Scales of Infant Development (Bayley-III), 3rd edition. Results: Twenty-nine participants completed Bayley-III. Increased newborn time in quiet sleep predicted worse 18-month cognitive and motor scores (robust regression models, adjusted r2 = 0.22, p = .007, and 0.27, .004, respectively). Decreased 0.5-2 Hz electroencephalograph (EEG) power during quiet sleep predicted worse 18-month language and motor scores (adjusted r2 = 0.25, p = .0005, and 0.33, .001, respectively). Predictive values remained significant after adjustment for neonatal Thompson scores or exposure to phenobarbital. Similarly, an attenuated difference in FTOE, between neonatal wakefulness and quiet sleep, predicted worse 18-month cognitive, language, and motor scores in adjusted analyses (each p < .05). Conclusions: These prospective, longitudinal data suggest that inefficient neonatal sleep-as quantified by increased time in quiet sleep, lower electroencephalogram delta power during that stage, and muted differences in FTOE between quiet sleep and wakefulness-may improve prediction of adverse long-term outcomes for newborns with neurological dysfunction.

Whole Exome Sequencing in Pediatric Neurology Patients: Clinical Implications and Estimated Cost Analysis.

Genetic heterogeneity in neurologic disorders has been an obstacle to phenotype-based diagnostic testing. The authors hypothesized that information compiled via whole exome sequencing will improve clinical diagnosis and management of pediatric neurology patients. The authors performed a retrospective chart review of patients evaluated in the University of Michigan Pediatric Neurology clinic between 6/2011 and 6/2015. The authors recorded previous diagnostic testing, indications for whole exome sequencing, and whole exome sequencing results. Whole exome sequencing was recommended for 135 patients and obtained in 53 patients. Insurance barriers often precluded whole exome sequencing. The most common indication for whole exome sequencing was neurodevelopmental disorders. Whole exome sequencing improved the presumptive diagnostic rate in the patient cohort from 25% to 48%. Clinical implications included family planning, medication selection, and systemic investigation. Compared to current second tier testing, whole exome sequencing can result in lower long-term charges and more timely diagnosis. Overcoming barriers related to whole exome sequencing insurance authorization could allow for more efficient and fruitful diagnostic neurological evaluations.

Cognitive outcomes in febrile infection-related epilepsy syndrome treated with the ketogenic diet.

Febrile infection-related epilepsy syndrome (FIRES) is a newly recognized epileptic encephalopathy in which previously healthy school-aged children present with prolonged treatment-resistant status epilepticus (SE). Survivors are typically left with pharmacoresistant epilepsy and severe cognitive impairment. Various treatment regimens have been reported, all with limited success. The ketogenic diet (KD) is an alternative treatment of epilepsy and may be an appropriate choice for children with refractory SE. We report 2 previously healthy children who presented with FIRES and were placed on the KD during the acute phase of their illness. Both children experienced resolution of SE and were maintained on the KD, along with other anticonvulsant medications, for several months. Both were able to return to school, with some academic accommodations. These cases highlight the potential value of the KD as a preferred treatment in FIRES, not only in the acute setting but also for long-term management. Early KD treatment might optimize both seizure control and cognitive outcome after FIRES.

Acute unilateral ophthalmoplegia as the presenting sign of acute myeloid leukemia in a 15-month-old girl.

Central nervous system manifestations of acute myeloid leukemia are rare at presentation. Acute cranial nerve findings on neurologic examination can be indications for brain imaging. Magnetic resonance imaging can highlight cranial nerves emerging from the brainstem, particularly if they are gadolinium-enhanced or thickened. We describe a 15-month-old girl with acute unilateral ophthalmoplegia as the presenting sign of acute myeloid leukemia. Her presentation emphasizes the importance of appropriate laboratory and radiographic evaluation in a toddler with new-onset strabismus, which may be discounted as a previously unrecognized or benign finding.

Treatment of Wilson's disease with tetrathiomolybdate: V. Control of free copper by tetrathiomolybdate and a comparison with trientine.

It has become clear that serum "free" copper (the copper not bound to ceruloplasmin in the blood) is the copper causing copper toxicity in Wilson's disease. But up until now, free copper has not been closely followed during initiation of anticopper therapy in neurologically presenting patients. During this period of initial therapy, the future fate of these patients hangs in the balance-if they worsen neurologically as often happens with penicillamine or trientine therapy, many never recover. We hypothesize that free copper levels are a biological marker of clinical outcome in these patients. In this article, we evaluate the control of free copper in 3 studies of initial anticopper treatment in neurologically presenting Wilson's disease patients. The first (study 1) is a 55-patient open-label trial of tetrathiomolybdate, the second (study 2) is a 48-patient double-blind trial comparing tetrathiomolybdate and trientine, and the third (study 3) is a 40-patient double-blind comparison of 2 disease regimens of tetrathiomolybdate. Free copper levels were determined by subtracting ceruloplasmin and tetrathiomolybdate bound copper from total serum copper. Tetrathiomolybdate showed very strong control of free copper levels over the 8 weeks of treatment in the 55-patient open-label study (study 1), reducing it to a mean value of about one fourth, or less, of baseline. In the tetrathiomolybdate/trientine double blind (study 2), tetrathiomolybdate again showed good control of free copper levels over 8 weeks of treatment, which is significantly better than trientine. In the trientine arm of study 2, mean free copper levels actually went up during trientine therapy. The 5 patients who neurologically worsened on trientine therapy over 8 weeks of treatment showed significant spikes in serum free copper levels associated in time with their neurologic worsening. Patients who did not worsen neurologically generally did not show significant spikes in free copper. Tetrathiomolybdate controlled copper less well in the dose regimen study (study 3) than in the previous 2 studies of tetrathiomolybdate treatment, probably because of a change in the way "away from food" tetrathiomolybdate was given.

Prevalence and etiology of intracranial hemorrhage in term children under the age of two years: a retrospective study of computerized tomographic imaging and clinical outcome in 798 children.

RATIONALE AND OBJECTIVES: The purposes of this study were to retrospectively identify various etiologies underlying intracranial hemorrhages (ICHs) in term infants aged <2 years and their respective prevalence in this population and to describe the long-term clinical outcomes in these patients. MATERIALS AND METHODS: A retrospective review of the medical records and computed tomographic studies of the head in 798 term infants aged 0 to 24 months with suspected or known ICHs was conducted. RESULTS: ICHs were present in 195 of the 798 infants (24%). More than one type of ICH was present in 32%. Subdural hemorrhage was the most frequent type of ICH, occurring in 63% of the infants. Good clinical outcomes were present in 49% of the infants but varied depending on the location, etiology, and timing of the ICH. CONCLUSION: The incidence of various etiologies of ICH depended on the ages of the infants. The overall clinical outcomes were good, with no long-term sequelae in half of the infants presenting with ICHs. In infants aged >4 weeks presenting with ICHs, special attention should be given to the possibility of nonaccidental trauma etiology, because this is common and has worse long-term outcomes.