An iPad-based intervention to improve visual-motor, visual-attention, and visual-perceptual skills in children with surgically treated hydrocephalus: A pilot study.

PURPOSE: Develop and pilot an iPad-based intervention for improving visual-motor coordination, visual-spatial processing/reasoning, and visual attention in children with surgically treated hydrocephalus (HCP). METHODS: We developed an intervention protocol targeting visual-motor coordination, visual-spatial processing/reasoning, and visual attention. Fourteen participants with HCP completed 30 h of training over 6 weeks. The primary outcome measure was the Perceptual Reasoning Index from the Wechsler Abbreviated Scale of Intelligence, Second Edition. Secondary measures included subtests from the Wechsler Intelligence Scale for Children, Fourth Edition, Developmental NEuroPSYchological Assessment, Second Edition (NEPSY-II), and Purdue Pegboard. RESULTS: Children with HCP demonstrated gains with statistical significance on the Perceptual Reasoning Index. We also observed significant improvement on a timed test of visuo-motor coordination (Wechsler Intelligence Scale for Children, Fourth Edition, Coding). CONCLUSION: Our iPad-application-based intervention may promote visual-motor coordination, visual-spatial processing/reasoning, and visual attention skills in children with HCP, offering an engaging and economical supplement to more conventional therapies.

Improved neuropsychological outcomes following proton therapy relative to X-ray therapy for pediatric brain tumor patients.

BACKGROUND: Survivors of pediatric brain tumors are at risk for impaired development in multiple neuropsychological domains. The purpose of this study was to compare neuropsychological outcomes of pediatric brain tumor patients who underwent X-ray radiotherapy (XRT) versus proton radiotherapy (PRT). METHODS: Pediatric patients who underwent either XRT or PRT and received posttreatment age-appropriate neuropsychological evaluation-including measures of intelligence (IQ), attention, memory, visuographic skills, academic skills, and parent-reported adaptive functioning-were identified. Multivariate analyses were performed to assess differences in neuropsychological outcomes and included tests for interaction between treatment cohort and follow-up time. RESULTS: Between 1998 and 2017, 125 patients with tumors located in the supratentorial (17.6%), midline (28.8%), or posterior fossa (53.6%) compartments received radiation and had posttreatment neuropsychological evaluation. Median age at treatment was 7.4 years. The PRT patient cohort had higher estimated SES and shorter median time from radiotherapy completion to last neuropsychological evaluation (6.7 vs 2.6 y, P < 0.001). On multivariable analysis, PRT was associated with higher full-scale IQ (ß = 10.6, P = 0.048) and processing speed (ß = 14.4, P = 0.007) relative to XRT, with trend toward higher verbal IQ (ß = 9.9, P = 0.06) and general adaptive functioning (ß = 11.4, P = 0.07). Planned sensitivity analyses truncating follow-up interval in the XRT cohort re-demonstrated higher verbal IQ (P = 0.01) and IQ (P = 0.04) following PRT, with trend toward improved processing speed (P = 0.09). CONCLUSIONS: PRT is associated with favorable outcomes for intelligence and processing speed. Combined with other strategies for treatment de-intensification, PRT may further reduce neuropsychological morbidity of brain tumor treatment.

Neurocognitive and Psychosocial Outcomes in Pediatric Brain Tumor Survivors.

The late neurocognitive and psychosocial effects of treatment for pediatric brain tumor (PBT) represent important areas of clinical focus and ongoing research. Neurocognitive sequelae and associated problems with learning and socioemotional development negatively impact PBT survivors' overall health-related quality of life, educational attainment and employment rates. Multiple factors including tumor features and associated complications, treatment methods, individual protective and vulnerability factors and accessibility of environmental supports contribute to the neurocognitive and psychosocial outcomes in PBT survivors. Declines in overall measured intelligence are common and may persist years after treatment. Core deficits in attention, processing speed and working memory are postulated to underlie problems with overall intellectual development, academic achievement and career attainment. Additionally, psychological problems after PBT can include depression, anxiety and psychosocial adjustment issues. Several intervention paradigms are briefly described, though to date research on innovative, specific and effective interventions for neurocognitive late effects is still in its early stages. This article reviews the existing research for understanding PBT late effects and highlights the need for innovative research to enhance neurocognitive and psychosocial outcomes in PBT survivors.

Two-year-olds can socially learn to think divergently.

This study aimed to discover whether 2-year-olds can socially learn to think divergently. Two-year-olds (N = 22) who saw an experimenter model a high level of divergent thinking on the Unusual Box Test (modelling 25 different actions, once each) went on to demonstrate a higher level of divergent thinking themselves than (N = 22) children who saw a low level of modelling (five different actions, once each), where divergent thinking was measured by the number of different actions children produced that had not been modelled by the experimenter. Additionally, all children in both High and Low Divergence conditions had higher divergent thinking than imitation scores, where imitation involved copying the experimenter's previous actions. This is the first experiment to show that 2-year-olds' divergent thinking can be increased, and that 2-year-olds do so by socially learning to think more divergently. Statement of contribution What is already known on this subject Recent research found that children as young as 1 year can think divergently, and that this is influenced by parents' own divergent thinking. What does this study add? This paper is important as it provides the first method to increase divergent thinking in toddlers. It also shows that social learning can directly affect individual learning processes, which suggests current theories of social and individual learning should be revised to be more iterative.

Implementing guidelines: Proposed definitions of neuropsychology services in pediatric oncology.

Several organizations have published guidelines for the neuropsychological care of survivors of childhood cancer. However, there is limited consensus in how these guidelines are applied. The model of neuropsychology service delivery is further complicated by the variable terminology used to describe recommended services. In an important first step to translate published guidelines into clinical practice, this paper proposes definitions for specific neuropsychological processes and services, with the goal of facilitating consistency across sites to foster future clinical program development and to clarify clinical practice guidelines.

Left hemisphere structural connectivity abnormality in pediatric hydrocephalus patients following surgery.

Neuroimaging research in surgically treated pediatric hydrocephalus patients remains challenging due to the artifact caused by programmable shunt. Our previous study has demonstrated significant alterations in the whole brain white matter structural connectivity based on diffusion tensor imaging (DTI) and graph theoretical analysis in children with hydrocephalus prior to surgery or in surgically treated children without programmable shunts. This study seeks to investigate the impact of brain injury on the topological features in the left hemisphere, contratelateral to the shunt placement, which will avoid the influence of shunt artifacts and makes further group comparisons feasible for children with programmable shunt valves. Three groups of children (34 in the control group, 12 in the 3-month post-surgery group, and 24 in the 12-month post-surgery group, age between 1 and 18 years) were included in the study. The structural connectivity data processing and analysis were performed based on DTI and graph theoretical analysis. Specific procedures were revised to include only left brain imaging data in normalization, parcellation, and fiber counting from DTI tractography. Our results showed that, when compared to controls, children with hydrocephalus in both the 3-month and 12-month post-surgery groups had significantly lower normalized clustering coefficient, lower small-worldness, and higher global efficiency (all p < 0.05, corrected). At a regional level, both patient groups showed significant alteration in one or more regional connectivity measures in a series of brain regions in the left hemisphere (8 and 10 regions in the 3-month post-surgery and the 12-month post-surgery group, respectively, all p < 0.05, corrected). No significant correlation was found between any of the global or regional measures and the contemporaneous neuropsychological outcomes [the General Adaptive Composite (GAC) from the Adaptive Behavior Assessment System, Second Edition (ABAS-II)]. However, one global network measure (global efficiency) and two regional network measures in the insula (local efficiency and between centrality) tested at 3-month post-surgery were found to correlate with GAC score tested at 12-month post-surgery with statistical significance (all p < 0.05, corrected). Our data showed that the structural connectivity analysis based on DTI and graph theory was sensitive in detecting both global and regional network abnormality when the analysis was conducted in the left hemisphere only. This approach provides a new avenue enabling the application of advanced neuroimaging analysis methods in quantifying brain damage in children with hydrocephalus surgically treated with programmable shunts.

Changes of White Matter Diffusion Anisotropy in Response to a 6-Week iPad Application-Based Occupational Therapy Intervention in Children with Surgically Treated Hydrocephalus: A Pilot Study.

Objective Our aims were (1) to test whether diffusion tensor imaging (DTI) could detect underlying white matter (WM) changes after a 6-week iPad application-based occupational therapy (OT) intervention in children with surgically treated hydrocephalus (HCP); and (2) to explore the association between WM changes and performance outcomes. Methods Five children (age range: 6.05-9.10 years) with surgically treated HCP completed an intensive iPad-based OT intervention targeting common domains of long-term deficits in children with HCP. The intervention included 6 weekly sessions in an OT clinic supplementing home-based program (1 hour/day, 4 days/week). DTI and neuropsychological assessments were performed before and after the intervention. Observation After the therapy, significant increases in fractional anisotropy (FA) and/or decreases in radial diffusivity were found in extensive WM areas. All participants demonstrated an increased perceptual reasoning index (PRI, Wechsler Abbreviated Scale of Intelligence: 2nd edition, PRI gains = 14.20 ± 7.56, p = 0.014). A significant positive correlation was found between PRI increase and the increase of FA in the right posterior limb of the internal capsule and the right external capsule (both p < 0.05). Conclusion This study provides initial evidence of DTI's sensitivity to detect subtle WM changes associated with performance improvements in response to a 6-week OT intervention in children with HCP.

Diffusion tensor imaging study of pediatric patients with congenital hydrocephalus: 1-year postsurgical outcomes.

OBJECTIVE The purpose of this study was to investigate white matter (WM) structural abnormalities using diffusion tensor imaging (DTI) in children with hydrocephalus before CSF diversionary surgery (including ventriculoperitoneal shunt insertion and endoscopic third ventriculostomy) and during the course of recovery after surgery in association with neuropsychological and behavioral outcome. METHODS This prospective study included 54 pediatric patients with congenital hydrocephalus (21 female, 33 male; age range 0.03-194.5 months) who underwent surgery and 64 normal controls (30 female, 34 male; age range 0.30-197.75 months). DTI and neurodevelopmental outcome data were collected once in the control group and 3 times (preoperatively and at 3 and 12 months postoperatively) in the patients with hydrocephalus. DTI measures, including fractional anisotropy (FA), mean diffusivity (MD), axial diffusivity (AD), and radial diffusivity (RD) values were extracted from the genu of the corpus callosum (gCC) and the posterior limb of internal capsule (PLIC). Group analysis was performed first cross-sectionally to quantify DTI abnormalities at 3 time points by comparing the data obtained in the hydrocephalus group for each of the 3 time points to data obtained in the controls. Longitudinal comparisons were conducted pairwise between different time points in patients whose data were acquired at multiple time points. Neurodevelopmental data were collected and analyzed using the Adaptive Behavior Assessment System, Second Edition, and the Bayley Scales of Infant Development, Third Edition. Correlation analyses were performed between DTI and behavioral measures. RESULTS Significant DTI abnormalities were found in the hydrocephalus patients in both the gCC (lower FA and higher MD, AD, and RD) and the PLIC (higher FA, lower AD and RD) before surgery. The DTI measures in the gCC remained mostly abnormal at 3 and 12 months after surgery. The DTI abnormalities in the PLIC were significant in FA and AD at 3 months after surgery but did not persist when tested at 12 months after surgery. Significant longitudinal DTI changes in the patients with hydrocephalus were found in the gCC when findings at 3 and 12 months after surgery were compared. In the PLIC, trend-level longitudinal changes were observed between preoperative findings and 3-month postoperative findings, as well as between 3- and 12-month postoperative findings. Significant correlation between DTI and developmental outcome was found at all 3 time points. Notably, a significant correlation was found between DTI in the PLIC at 3 months after surgery and developmental outcome at 12 months after surgery. CONCLUSIONS The data showed significant WM abnormality based on DTI in both the gCC and the PLIC in patients with congenital hydrocephalus before surgery, and the abnormalities persisted in both the gCC and the PLIC at 3 months after surgery. The DTI values remained significantly abnormal in the gCC at 12 months after surgery. Longitudinal analysis showed signs of recovery in both WM structures between different time points. Combined with the significant correlation found between DTI and neuropsychological measures, the findings of this study suggest that DTI can serve as a sensitive imaging biomarker for underlying neuroanatomical changes and postsurgical developmental outcome and even as a predictor for future outcomes.

Quality improvement initiative to increase influenza vaccination in pediatric cancer patients.

BACKGROUND: Pediatric patients with cancer face more severe complications of influenza than healthy children. Although Centers for Disease Control and Prevention guidelines recommend yearly vaccination in these patients, in our large academic center, <60% of oncology patients receiving chemotherapy were immunized at baseline. Our objective was to increase this rate through a multifaceted quality improvement initiative. METHODS: Eligible patients were >6 months old, within 1 year of receiving chemotherapy, >100 days from stem cell transplant, and had ≥ 1 outpatient oncology visit between September 1, 2012, and March 31, 2013. Five interventions were instituted concomitantly: (1) family education: influenza/vaccine handouts were provided to families in clinic waiting rooms; (2) health informatics: daily lists of outpatients due for immunization were generated from the electronic medical record and sent automatically to triage staff and nurses; (3) outpatient clinic: patients due for vaccination were given colored wristbands during triage to alert providers; (4) inpatient: vaccine order was built into admission order set; and (5) provider education: staff education was provided at conferences on screening of patients, vaccine ordering, and documentation of refusals/contraindications. RESULTS: The complete influenza immunization rate increased by 20.1% to 64.5%, and the proportion of patients receiving ≥ 1 dose of vaccination increased by 22.9% to 77.7%. Similar changes were noted across all cancer types, with highest rates of immunization in leukemia/lymphoma patients (86.8%) and lowest in patients after stem cell transplant (66.7%). CONCLUSIONS: Technology, education, and multidisciplinary clinical process changes increased influenza vaccination rates. Ongoing efforts are targeting subgroups with lowest rates of immunization.

Longitudinal comparison of diffusion tensor imaging parameters and neuropsychological measures following endoscopic third ventriculostomy for hydrocephalus.

The authors report the case of a 25-month-old boy who underwent endoscopic third ventriculostomy (ETV) for hydrocephalus resulting from aqueductal stenosis. The patient's recovery was monitored longitudinally and prospectively using MR diffusion tensor imaging (DTI) and formal neuropsychological testing. Despite minimal change in ventricle size, improvement in the DTI characteristics and neurodevelopmental trajectory was observed following ETV. These data support the use of DTI as a biomarker to assess therapeutic response in children undergoing surgical treatment for hydrocephalus. In the patient featured in this report, DTI appeared to provide more information regarding postoperative neurodevelopmental outcome than ventricle size alone.

Effectiveness of dexamethasone iontophoresis for temporomandibular joint involvement in juvenile idiopathic arthritis.

OBJECTIVE: Temporomandibular joint (TMJ) involvement is common in juvenile idiopathic arthritis (JIA). Dexamethasone iontophoresis (DIP) uses low-grade electric currents for transdermal dexamethasone delivery into deeper anatomic structures. The purpose of this study was to assess the safety and effectiveness of DIP for the treatment of TMJ involvement in JIA, and to delineate variables that are associated with improvement after DIP. METHODS: Medical records of all JIA patients who underwent DIP for TMJ involvement at a larger tertiary pediatric rheumatology center from 1997-2011 were reviewed. DIP was performed using a standard protocol. The effectiveness of DIP was assessed by comparing the maximal interincisor opening (MIO(TMJ) ) and the maximal lateral excursion (MLE(TMJ) ) before and after treatment. RESULTS: Twenty-eight patients (ages 2-21 years) who received an average of 8 DIP treatment sessions per involved TMJ were included in the analysis. Statistically significant improvement in the median MIO(TMJ) (P < 0.0001) was observed in 68%. The median MLE(TMJ) (P = 0.03) improved in 69%, and resolution of TMJ pain occurred in 73% of the patients who had TMJ pain at baseline. Side effects of DIP were transient site erythema (86%), skin blister (4%), and metallic taste (4%). Improvement in TMJ range of motion from DIP is associated with lower MIO(TMJ) , lower MLE(TMJ) , and absence of TMJ crepitus at baseline. CONCLUSION: In this pilot study, DIP appeared to be an effective and safe initial treatment of TMJ involvement in JIA, especially among patients with decreased TMJ measurements. Prospective controlled studies are needed.

An exploratory study of psychosocial risk behaviors of adolescents who are deaf or hard of hearing: comparisons and recommendations.

The study compared psychosocial risk behaviors of adolescents who were deaf or hard of hearing with those of their hearing peers in a residential treatment facility. Statistically significant differences emerged between groups. The adolescents who were deaf or hard of hearing demonstrated clinically higher scores than those of their hearing peers on the psychosocial risk behaviors of risk to others, social and adaptive functioning, need for structure, aggression toward people and animals, destruction of property, theft and deceit, and rules violations. Implications and suggestions for helping professionals are included.

Decreased connectivity and cerebellar activity in autism during motor task performance.

Although motor deficits are common in autism, the neural correlates underlying the disruption of even basic motor execution are unknown. Motor deficits may be some of the earliest identifiable signs of abnormal development and increased understanding of their neural underpinnings may provide insight into autism-associated differences in parallel systems critical for control of more complex behaviour necessary for social and communicative development. Functional magnetic resonance imaging was used to examine neural activation and connectivity during sequential, appositional finger tapping in 13 children, ages 8-12 years, with high-functioning autism (HFA) and 13 typically developing (TD), age- and sex-matched peers. Both groups showed expected primary activations in cortical and subcortical regions associated with motor execution [contralateral primary sensorimotor cortex, contralateral thalamus, ipsilateral cerebellum, supplementary motor area (SMA)]; however, the TD group showed greater activation in the ipsilateral anterior cerebellum, while the HFA group showed greater activation in the SMA. Although activation differences were limited to a subset of regions, children with HFA demonstrated diffusely decreased connectivity across the motor execution network relative to control children. The between-group dissociation of cerebral and cerebellar motor activation represents the first neuroimaging data of motor dysfunction in children with autism, providing insight into potentially abnormal circuits impacting development. Decreased cerebellar activation in the HFA group may reflect difficulty shifting motor execution from cortical regions associated with effortful control to regions associated with habitual execution. Additionally, diffusely decreased connectivity may reflect poor coordination within the circuit necessary for automating patterned motor behaviour. The findings might explain impairments in motor development in autism, as well as abnormal and delayed acquisition of gestures important for socialization and communication.

Automated bony region identification using artificial neural networks: reliability and validation measurements.

OBJECTIVE: The objective was to develop tools for automating the identification of bony structures, to assess the reliability of this technique against manual raters, and to validate the resulting regions of interest against physical surface scans obtained from the same specimen. MATERIALS AND METHODS: Artificial intelligence-based algorithms have been used for image segmentation, specifically artificial neural networks (ANNs). For this study, an ANN was created and trained to identify the phalanges of the human hand. RESULTS: The relative overlap between the ANN and a manual tracer was 0.87, 0.82, and 0.76, for the proximal, middle, and distal index phalanx bones respectively. Compared with the physical surface scans, the ANN-generated surface representations differed on average by 0.35 mm, 0.29 mm, and 0.40 mm for the proximal, middle, and distal phalanges respectively. Furthermore, the ANN proved to segment the structures in less than one-tenth of the time required by a manual rater. CONCLUSIONS: The ANN has proven to be a reliable and valid means of segmenting the phalanx bones from CT images. Employing automated methods such as the ANN for segmentation, eliminates the likelihood of rater drift and inter-rater variability. Automated methods also decrease the amount of time and manual effort required to extract the data of interest, thereby making the feasibility of patient-specific modeling a reality.

Registration and machine learning-based automated segmentation of subcortical and cerebellar brain structures.

The large amount of imaging data collected in several ongoing multi-center studies requires automated methods to delineate brain structures of interest. We have previously reported on using artificial neural networks (ANN) to define subcortical brain structures. Here we present several automated segmentation methods using multidimensional registration. A direct comparison between template, probability, artificial neural network (ANN) and support vector machine (SVM)-based automated segmentation methods is presented. Three metrics for each segmentation method are reported in the delineation of subcortical and cerebellar brain regions. Results show that the machine learning methods outperform the template and probability-based methods. Utilization of these automated segmentation methods may be as reliable as manual raters and require no rater intervention.

Quantifying metabolic asymmetry modulo structure in Alzheimer's disease.

In this paper we describe a new method for quantifying metabolic asymmetry modulo structural hemispheric differences. The study of metabolic asymmetry in Alzheimer's disease (AD) serves as a driving application. The approach is based on anatomical atlas construction by large deformation diffeomorphic metric mapping (LDDMM) first introduced in [1]. Using invariance properties of the LDDMM, we define a structurally symmetric coordinate frame in which metabolic asymmetries between the left and the right hemispheres can be studied. This structurally symmetric coordinate system of each subject provides the correspondence between left and right hemispheric structures in an individual brain. These correspondences are used for measuring metabolic asymmetry modulo structural asymmetry. Again using the atlas construction framework, we build a common symmetric coordinate system of a entire population. The metabolic asymmetry maps of individuals in a population under study are mapped into the common structurally symmetric coordinate frame, allowing for a statistical description of the populations metabolic asymmetry. In this paper we prove certain invariance properties of the LDDMM atlas construction framework that make the definition of structurally symmetric coordinate systems possible. We present results from applying the methodology to images from the Alzheimer's Disease Neuroimaging Initiative (ADNI).

Motor persistence and inhibition in autism and ADHD.

The present study compared performance of children with Attention-Deficit/Hyperactivity Disorder (ADHD) and high functioning autism (HFA) with that of controls on 4 tasks assessing 2 components of motor control: motor response inhibition and motor persistence. A total of 136 children (52 ADHD, 24 HFA, 60 controls) ages 7 to 13 years completed 2 measures of motor inhibition (Conflicting Motor Response and Contralateral Motor Response Tasks) and 2 measures of motor persistence (Lateral Gaze Fixation and NEPSY Statue). After controlling for age, IQ, gender, and basic motor speed, children with ADHD performed significantly more poorly than controls on the Conflicting Motor Response and Contralateral Motor Response Tasks, as well as on Statue. In contrast, children with HFA achieved lower scores than controls only on measures of motor persistence, with no concomitant impairment on either motor inhibition task. These results are consistent with prior research that has demonstrated relatively spared motor inhibition in autism. The findings highlight the utility of brief assessments of motor control in delineating the unique neurobehavioral phenotypes of ADHD and HFA.

Control of West Nile virus, Rhode Island, 2003.

Thanks largely to systematic larviciding by the State's 39 municipalities, and aided by the public's destruction of "backyard" mosquito habitats and adoption of personal protective measures (clothing, repellant), Rhode Island minimized the potential human burden of WNV during the 2003 mosquito season (six serious WNV cases, one death, and no reports of WNV-tainted blood donations). The potential burden of WNV on domestic animals was also reduced through immunization. Nonetheless, the State's first WNV death reminds us of the danger this disease poses for the very young, for elders, and for people of all ages who are immune-compromised. Similarly, the widespread location of birds positive for WNV signifies the ubiquity of risk. All mosquitoes must be avoided. Based on its experience with WNV control over the past few years, the State will continue and enhance its surveillance and control efforts in 2004. Once again, systematic larviciding by municipalities and continuing public education through multiple channels will form the backbone of control, supported by active surveillance for the virus in the wild, in domestic animals, and in humans. For the latter effort, the vigilance of the health care community is of signal importance to the protection of the public. Every human case is investigated thoroughly, to establish as accurately as possible the time and place of exposure. DEM and HEALTH use this information to assess potential weaknesses in WNV control efforts, and to take corrective action, as necessary. Health care providers also play an essential role in public education, reminding patients (all patients, but especially the very young, elders, and the immune-compromised) to avoid mosquito bites. Discussing the avoidance of mosquito bites with patients who engage in regular outdoor activity is especially important. School physicians and the medical directors of nursing homes are well-positioned to keep mosquito control and avoidance on the agenda of their respective institutions. Together, we can control the burden of this disease among domestic animals and humans, if we continue to pursue mosquito control and personal protection aggressively. If we don't, the potential for tragedy is tremendous, as evidenced by the recent experience of other regions of the country.

Acetaminophen as a postsurgical analgesic in rats: a practical solution to neophobia.

Acetaminophen administration is gaining popularity as a postsurgical analgesic in many rodent labs despite reports that animals may consume suboptimal doses as a result of taste neophobia. The present study evaluated the presence, duration, and extent of acetaminophen neophobia in adult male and female rats (Long Evans) with the intent of developing a protocol for administration of this analgesic in the rodent surgery lab. After a 7-day baseline period in which average water consumption, food consumption, and body weight were established for 32 rats (20 females and 12 males), cherry-flavored acetaminophen was administered (6 mg/ml) in the animals' water bottles for an additional 7 days. Fluid consumption, food consumption, and weight were monitored during this period of drug exposure. Male rats displayed a transient period (1 day) of reduced fluid consumption followed by elevated fluid consumption on subsequent days. Female animals displayed normal to elevated fluid consumption on all days of drug exposure. Both male and female animals, however, decreased their food intake after drug exposure and subsequently lost weight. Recommendations for the oral administration of acetaminophen as a postsurgical analgesic are discussed.