Sarah L. Logan

A comparison of the clinical utility of p16INK4a immunolocalization with the presence of human papillomavirus by hybrid capture 2 for the detection of cervical dysplasia/neoplasia

Evidence suggests that overexpression of p16INK4a protein indicates infection and genomic integration of high‐risk human papillomavirus (HR HPV) and predicts progression to cervical high‐grade squamous intraepithelial lesions (HSILs) and carcinoma. The authors compared the ability of p16INK4a and HR HPV detection by Hybrid Capture 2 (HC2) to detect the presence of significant cervical disease.

High Prescription Drug Use and Associated Costs among Medicaid-Eligible Children with Autism Spectrum Disorders Identified by a Population-Based Surveillance Network

PURPOSE We assessed medication use and associated costs among 8- and 15-year-old children with autism spectrum disorders (ASD) identified by the South Carolina Autism and Developmental Disabilities Monitoring (SCADDM) Network. METHODS All Medicaid-eligible SCADDM-identified children with ASD from surveillance years 2006 and 2007 were included (n = 263). Children were classified as ASD cases when documented behaviors consistent with the DSM-IV-TR criteria for autistic disorder, Asperger disorder, or pervasive developmental disorder-not otherwise specified were present in health and education evaluation records. Medication and cost data were obtained by linking population-based and Medicaid data. RESULTS All 263 SCADDM-identified children had Medicaid data available; 56% (n = 147) had a prescription of any type, 40% (n = 105) used psychotropic medication, and 20% (n = 52) used multiple psychotropic classes during the study period. Common combinations were (1) attention deficit hyperactivity disorder medications and an antihypertensive, antidepressant or antipsychotic; and (2) antidepressants and an antipsychotic. Multiple psychotropic classes were more common among older children. Both the overall distribution of the number of prescription claims and medication costs varied significantly by age. CONCLUSIONS Results confirm that medication use in ASD, alone or in combination, is common, costly, and may increase with age.

Imaging the neural mechanisms of TMS neglect-like bias in healthy volunteers with the interleaved TMS/fMRI technique: preliminary evidence

Applying a precisely timed pulse of transcranial magnetic stimulation (TMS) over the right posterior parietal cortex (PPC) can produce temporary visuo-spatial neglect-like effects. Although the TMS is applied over PPC, it is not clear what other brain regions are involved. We applied TMS within a functional magnetic resonance imaging (fMRI) scanner to investigate brain activity during TMS induction of neglect-like bias in three healthy volunteers, while they performed a line bisection judgment task (i.e., the landmark task). Single-pulse TMS at 115% of motor threshold was applied 150 ms after the visual stimulus onset. Participants completed two different TMS/fMRI sessions while performing this task: one session while single-pulse TMS was intermittently and time-locked applied to the right PPC and a control session with TMS positioned over the vertex. Perceptual rightward bias was observed when TMS was delivered over the right PPC. During neglect-like behavior, the fMRI maps showed decreased neural activity within parieto-frontal areas, which are often lesioned or dysfunctional in patients with left neglect. Vertex TMS induced behavioral effects compatible with leftward response bias and increased BOLD signal in the left caudate (a site which has been linked to response bias). These results are discussed in relation to recent findings on neural networks subserving attention in space.

Aberrant Behaviors and Co-occurring Conditions as Predictors of Psychotropic Polypharmacy among Children with Autism Spectrum Disorders

OBJECTIVES The purpose of this study was to identify rates and predictors of psychotropic medication polypharmacy among Medicaid-eligible children in South Carolina with autism spectrum disorder (ASD) from 2000 to 2008. METHODS Population-based surveillance data were linked with state Medicaid records to obtain a detailed demographic, behavioral, educational, clinical, and diagnostic data set for all Medicaid-eligible 8-year-old children (n=629) who were identified and diagnosed with ASD using standardized criteria. Polypharmacy was defined as having interclass psychotropic medication claims overlapping for ≥30 consecutive days at any time during the 2-year study period. Multivariable logistic regression was used to model predictors of any polypharmacy, and for the three most common combinations. RESULTS Overall, 60% (n=377) used any psychotropic medication, and 41% (n=153) of those had interclass polypharmacy. Common combinations were attention-deficit/hyperactivity disorder (ADHD) medications with an antidepressant (A/AD), antipsychotic (A/AP) or a mood stabilizer (A/MS). Black children had lower odds of any polypharmacy, as did those eligible for Medicaid because of income or being foster care versus those eligible because of disability. There were no significant associations between polypharmacy and social deficits in ASD for any combination, although children with communication deficits diagnostic of ASD had lower odds of any polypharmacy and A/AP polypharmacy. Children with argumentative, aggressive, hyperactive/impulsive, or self-injurious aberrant behaviors had higher odds of polypharmacy, as did children with diagnosed co-occurring ADHD, anxiety or mood disorders, or conduct/oppositional defiant disorder (ODD) in Medicaid records. CONCLUSIONS Future research is warranted to investigate how child-level factors impact combination psychotropic medication prescribing practices and outcomes in ASD.

A RANDOMIZED CLINICAL TRIAL COMPARING EXTENSIBLE AND INEXTENSIBLE LUMBOSACRAL ORTHOSES AND STANDARD CARE ALONE IN THE MANAGEMENT OF LOWER BACK PAIN

Study Design. Single blinded, randomized clinical trial for the evaluation of lumbosacral orthoses (LSOs) in the management of lower back pain (LBP). Objective. To evaluate the effects of two types of LSOs on self-rated disability in patients with LBP. Summary of Background Data. LSOs are commonly used for the management of LBP, but their effectiveness may vary because of design. An inextensible LSO (iLSO) reduces trunk motion and increases trunk stiffness, whereas an extensible LSO (eLSO) does not. Methods. A total of 98 participants with LBP were randomized to 3 groups: (1) standard care (SC) group, which included medication and physical therapy (n = 29), (2) SC with eLSO (eLSO group) (n = 32), and (3) SC with iLSO (iLSO group) (n = 37). Outcome measures were evaluated before and after 2 weeks of treatment: modified Oswestry Disability Index (ODI), Patient Specific Activity Scale, pain ratings, and Fear Avoidance Beliefs Questionnaire. Results. There were no statistically significant differences between groups at baseline. Compared with the SC alone, iLSO group showed greater improvement on the ODI scores (P = 0.01) but not the eLSO group. The ODI scores improved by a mean of 2.4 (95% confidence interval [CI], 2.2–7.1), 8.1 (95% CI, 2.8–13.4), and 14.0 (95% CI, 8.2–19.8) points for SC, eLSO, and iLSO groups, respectively. Individuals wearing the iLSO had 4.7 times higher odds of achieving 50% or greater improvement in the ODI scores than those assigned to SC (95% CI, 1.2–18.5, P = 0.03). Both the eLSO and iLSO groups had a greater improvement in the Patient Specific Activity Scale scores than the SC group (P = .05 and P = 0.01, respectively), but the change did not meet the minimal clinically important difference. Pain ratings improved for all 3 groups, with no statistical difference between them. Finally, no significant differences across groups were found for the Fear Avoidance Beliefs Questionnaire. Conclusion. An iLSO led to greater improvement in ODI scores than SC and an eLSO. We surmise that the likely mechanism responsible for this difference in outcome was the added trunk stiffness and motion restriction by the iLSO. Level of Evidence: 2

Pilot Study and Review: Physiological Differences in BDNF, a Potential Biomarker in Males and Females with Autistic Disorder

Aims There is a need for more biologic research in autistic disorder (AD) to determine if biomarkers exist that would be useful for correlating to symptom severity and/or clinical improvement during treatment. Given the fact that AD is 4 times more common in males than females, gender differences in physiological biomarkers may be present. One potential biomarker that has begun to be studied is brain-derived neurotropic factor (BDNF), a peptide involved in the regulation of neuronal cell survival, differentiation, and plasticity, and possessing an ability to influence neurotransmitter systems by modulating gene expression. This pilot study examined whether serum BDNF differed according to gender in children with AD and whether differences were associated with a behavioral phenotype or severity of illness. Study Design Data for this investigation were collected during the participants’ baseline visit of an intervention study. Participants were males (n=29) and females (n=7), aged 5 to 12 years diagnosed with AD. Baseline serum BDNF concentration was determined for comparison to clinical ratings using an autism severity measure and the Pervasive Developmental Disorder-Behavior Inventory (PDD-BI). Results BDNF serum concentrations were higher in females (p<0.049). The baseline BDNF value corresponded significantly to hyperactivity in females (p<0.0002) but not in males. BDNF did not correlate with severity of disease in either gender. Conclusion Although this is a small study, a better understanding of the central role of BDNF may provide insight into the pathophysiology of the disease and elucidate why gender differences exist in prevalence and behavioral phenotype of AD.

Completeness of Case Ascertainment for Surveillance of Autism Spectrum Disorders Using the Autism Developmental Disabilities Monitoring Network Methodology

BACKGROUND The Autism and Developmental Disabilities Monitoring Network (ADDM), sponsored by the Centers for Disease Control and Prevention, is the largest-scale project ever undertaken to identify the prevalence of Autism Spectrum Disorders (ASD) in the United States. OBJECTIVE The objective of the present study was to examine the accuracy of the ADDM methodology in terms of completeness of case ascertainment; that is, to assess the success of the ADDM Network in identifying and accurately classifying all existing cases of ASD among 8-year-old children in the target study areas. METHODS To accomplish this objective, the ADDM methodology was applied to a selected region of South Carolina for 8-year olds in 2000 (birth year 1992) and again seven years later for the same region and birth year. RESULTS For this region and birth year, completeness of case ascertainment was high, with prevalence estimates of 7.6 per 1000 at both ages 8- and 15-years. For children common to both surveillance years, concordance in case status was also high (82%). CONCLUSIONS Given that prevalence did not change within this region and birth year, continued research is needed to better understand the changes in prevalence estimates being found by the ADDM network across surveillance groups.

Assessing drug use during follow-up: direct comparison of candidate outcome definitions in pooled analyses of addiction treatment studies

Background: Selection of appropriate outcome measures is important for clinical studies of drug addiction treatment. Researchers use various methods for collecting drug use outcomes and must consider substances to be included in a urine drug screen (UDS); accuracy of self-report; use of various instruments and procedures for collecting self-reported drug use; and timing of outcome assessments. Objectives: We sought to define a set of candidate measures to (1) assess their intercorrelation and (2) identify any differences in results. Methods: Data were combined from completed protocols in the National Institute on Drug Abuse Clinical Trials Network (CTN), with a total of 1897 participants. We defined nine outcome measures based on UDS, self-report, or a combination. Multivariable, multilevel generalized estimating equation models were used to assess subgroup differences in intervention success, controlling for baseline differences and accounting for clustering by CTN protocols. Results: There were high correlations among all candidate outcomes. All outcomes showed consistent overall results with no significant intervention impact on drug use during follow-up. However, with most UDS variables, but not with self-report or “corrected self-report,” we observed a significant gender–ethnicity interaction with benefit shown in African American women, White women, and Hispanic men. Conclusion: Despite strong associations between candidate measures, we found some important differences in results. Scientific Significance: In this study, we demonstrated the potential utility and impact of combining UDS and self-report data for drug use assessment. Our results suggest possible differences in intervention efficacy by gender and ethnicity, but highlight the need to cautiously interpret observed interactions.

Longitudinal Trends in Fall Accidents in Community Dwelling Korean Adults: The 2008–2013 Korean Community Health Survey

Objective To describe the longitudinal characteristics of unintentional fall accidents using a representative population-based sample of Korean adults. Methods We examined data from the Korean Community Health Survey from 2008 to 2013. Univariate analysis and multivariable logistic regression were used to identify the characteristics of fall accidents in adults. Results Between 2008 and 2013, the incidence rate of fall accidents requiring medical treatment increased from 1,248 to 3,423 per 100,000 people (p<0.001), while the proportion of indoor fall accidents decreased from 38.12% to 23.16% (p<0.001). Females had more annual fall accidents than males (p<0.001). The major reason for fall accidents was slippery floors (33.7% in 2011 and 36.3% in 2013). Between 2008 and 2010, variables associated with higher fall accident risk included specific months (August and September), old age, female gender, current drinker, current smoker, diabetes, osteoarthritis, osteoporosis, and depression. A high level of education and living with a partner were negatively associated with fall accident risk. In 2013, people experiencing more than 1 fall accident felt more fear of falling than those having no fall accidents (odds ratio [OR] for 1 fall, 2.12; 95% confidence interval [CI], 2.04–2.12; OR for more than 2 falls, 2.97; 95% CI, 2.83–3.10). Conclusion The occurrence of fall accidents has consistently increased in Korea from 2008 to 2013. Future intervention studies are needed to reduce the increasing incidence rates of fall accidents in community dwelling adults.

Impact of Gastrostomy Feeding Tube Placement on the 1-Year Trajectory of Care in Patients After Stroke

BACKGROUND Percutaneous endoscopic gastrostomy (PEG) feeding tubes are commonly placed in acute stroke patients with a need for enteral nutrition. However, PEG tubes are associated with medical complications and a decrease in quality of life. We compared the 1-year care trajectory of stroke patients with and without PEG tube placement to enhance knowledge about the long-term impact of PEG tube placement. METHODS We conducted a retrospective analysis of commercially insured stroke patients included in the Truven Health MarketScan Research Databases of 2011. We analyzed their index hospital stay and conducted 1-month, 3-months, 6-months, and 1-year follow-ups. We compared admissions to inpatient rehabilitation facilities, acute hospitals, skilled nursing facilities, outpatient hospital visits, and home visits for stroke patients with and without PEG tube placement using unadjusted and adjusted modelling. RESULTS Of the 8911 included stroke patients, 148 patients (1.7%) had a PEG tube placed during their index hospital stay. After controlling for age, gender, stroke severity, comorbidities, and stroke type, PEG tube placement was an independent predictor for admissions to inpatient rehabilitation facilities and skilled nursing facilities. Furthermore, PEG tube placement was an independent predictor for all-cause, unplanned hospital readmissions in a multivariable logistic model (area under the receiver operating characteristic curve was .84). CONCLUSION Stroke patients who receive a PEG tube can expect a significantly different care trajectory after being discharged from the acute hospital. Our findings can aide in predicting recovery and planning resources and identifying gaps and points for improvement in stroke care for patients with PEG tube placement.