Anthony Fabio

A systematic review of the effects of postnatal maternal anxiety on children

Several decades of research have focused on the impact of exposure to postnatal depression on children, while anxiety has been largely overlooked. Estimates of the prevalence of postnatal maternal anxiety (PMA) range from 3% to 43%, suggesting PMA may be an important risk factor for adverse outcomes in children. This review summarizes what is known about the effects of PMA exposure on children and makes recommendations for future research. A systematic search of Ovid MEDLINE® and PsychINFO® through 2008 identified 18 studies that evaluated child outcomes associated with PMA exposure. Identified studies covered three domains: somatic, developmental, and psychological outcomes. The strongest evidence for an adverse effect of PMA exposure is in somatic and psychological outcomes; the evidence for an effect of PMA on child development is inconclusive. Methodological differences among the studies make comparisons difficult and there are a number of common limitations that challenge the validity of these studies.

Levetiracetam versus phenytoin for seizure prophylaxis in severe traumatic brain injury

OBJECT Current standard of care for patients with severe traumatic brain injury (TBI) is prophylactic treatment with phenytoin for 7 days to decrease the risk of early posttraumatic seizures. Phenytoin alters drug metabolism, induces fever, and requires therapeutic-level monitoring. Alternatively, levetiracetam (Keppra) does not require serum monitoring or have significant pharmacokinetic interactions. In the current study, the authors compare the EEG findings in patients receiving phenytoin with those receiving levetiracetam monotherapy for seizure prophylaxis following severe TBI. METHODS Data were prospectively collected in 32 cases in which patients received levetiracetam for the first 7 days after severe TBI and compared with data from a historical cohort of 41 cases in which patients received phenytoin monotherapy. Patients underwent 1-hour electroencephalographic (EEG) monitoring if they displayed persistent coma, decreased mental status, or clinical signs of seizures. The EEG results were grouped into normal and abnormal findings, with abnormal EEG findings further categorized as seizure activity or seizure tendency. RESULTS Fifteen of 32 patients in the levetiracetam group warranted EEG monitoring. In 7 of these 15 cases the results were normal and in 8 abnormal; 1 patient had seizure activity, whereas 7 had seizure tendency. Twelve of 41 patients in the phenytoin group received EEG monitoring, with all results being normal. Patients treated with levetiracetam and phenytoin had equivalent incidence of seizure activity (p = 0.556). Patients receiving levetiracetam had a higher incidence of abnormal EEG findings (p = 0.003). CONCLUSIONS Levetiracetam is as effective as phenytoin in preventing early posttraumatic seizures but is associated with an increased seizure tendency on EEG analysis.

Abusive Head Trauma During a Time of Increased Unemployment: A Multicenter Analysis

OBJECTIVE: To evaluate the rate of abusive head trauma (AHT) in 3 regions of the United States before and during an economic recession and assess whether there is a relationship between the rate of AHT and county-level unemployment rates. METHODS: Clinical data were collected for AHT cases diagnosed in children younger than 5 years from January 1, 2004 until June 30, 2009, by hospital-based child protection teams within 3 geographic regions. The recession was defined as December 1, 2007 through June 30, 2009. Quarterly unemployment rates were collected for every county in which an AHT case occurred. RESULTS: During the 5½-year study period, a total of 422 children were diagnosed with AHT in a 74-county region. The overall rate of AHT increased from 8.9 in 100 000 (95% confidence interval [CI]: 7.8–10.0) before the recession to 14.7 in 100 000 (95% CI: 12.5–16.9) during the recession (P < .001). There was no difference in the clinical characteristics of subjects in the prerecession versus recession period. There was no relationship between the rate of AHT and county-level unemployment rates. CONCLUSIONS: The rate of AHT increased significantly in 3 distinct geographic regions during the 19 months of an economic recession compared with the 47 months before the recession. This finding is consistent with our understanding of the effect of stress on violence. Given the high morbidity and mortality rates for children with AHT, these results are concerning and suggest that prevention efforts might need to be increased significantly during times of economic hardship.

Acute Serum Hormone Levels: Characterization and Prognosis after Severe Traumatic Brain Injury

Experimental traumatic brain injury (TBI) studies report the neuroprotective effects of female sex steroids on multiple mechanisms of injury, with the clinical assumption that women have hormonally mediated neuroprotection because of the endogenous presence of these hormones. Other literature indicates that testosterone may exacerbate injury. Further, stress hormone abnormalities that accompany critical illness may both amplify or blunt sex steroid levels. To better understand the role of sex steroid exposure in mediating TBI, we 1) characterized temporal profiles of serum gonadal and stress hormones in a population with severe TBI during the acute phases of their injury; and 2) used a biological systems approach to evaluate these hormones as biomarkers predicting global outcome. The study population was 117 adults (28 women; 89 men) with severe TBI. Serum samples (n=536) were collected for 7 days post-TBI for cortisol, progesterone, testosterone, estradiol, luteinizing hormone (LH), and follicle-stimulating hormone (FSH). Hormone data were linked with clinical data, including acute care mortality and Glasgow Outcome Scale (GOS) scores at 6 months. Hormone levels after TBI were compared to those in healthy controls (n=14). Group based trajectory analysis (TRAJ) was used to develop temporal hormone profiles that delineate distinct subpopulations in the cohort. Structural equations models were used to determine inter-relationships between hormones and outcomes within a multivariate model. Compared to controls, acute serum hormone levels were significantly altered after severe TBI. Changes in the post-TBI adrenal response and peripheral aromatization influenced hormone TRAJ profiles and contributed to the abnormalities, including increased estradiol in men and increased testosterone in women. In addition to older age and greater injury severity, increased estradiol and testosterone levels over time were associated with increased mortality and worse global outcome for both men and women. These findings represent a paradigm shift when thinking about the role of sex steroids in neuroprotection clinically after TBI.

5HT2A Receptor Binding is Increased in Borderline Personality Disorder

BACKGROUND Postmortem studies in suicide victims demonstrate an increase in the number of post-synaptic 5-HT(2A) receptor binding sites in ventral lateral and orbital frontal cortex. Diminished metabolic responses to serotonergic activation are noted in these areas in impulsive subjects with borderline personality disorder (BPD), a group at high risk for suicidal behaviors. We examined 5HT(2A) receptor binding potential (BP) in impulsive subjects with BPD, with positron emission tomography neuroimaging with [(18)F] altanserin. METHODS Fourteen female subjects with BPD were assessed for Axis I comorbidity, depressed mood, impulsivity, aggression, suicidality, childhood abuse, and compared with 11 healthy female control subjects. The 5HT(2A) receptor binding was evaluated in prefrontal cortex, anterior cingulate, hippocampus, temporal lobe, occipital cortex, and thalamus. Data were analyzed with Logan graphical analysis and a four-compartment (4C) model. RESULTS Hippocampal 5HT(2A) receptor binding was significantly increased in BPD subjects compared with control subjects in both Logan and 4C analyses, covarying for age. Hippocampal BP values were related to comorbid major depressive episode, with highest values found in non-depressed BPD subjects and lowest in healthy control subjects. The BP values were not related to depressed mood, impulsivity, aggression, suicidality, or childhood abuse. CONCLUSIONS 5HT(2A) receptor binding is increased in the hippocampus of BPD subjects independent of depressed mood, impulsivity, aggression, suicidality, or childhood abuse. Dysregulation of serotonergic function in hippocampus might contribute to affective and behavioral symptoms in BPD.

S100b as a Prognostic Biomarker in Outcome Prediction for Patients with Severe Traumatic Brain Injury

As an astrocytic protein specific to the central nervous system, S100b is a potentially useful marker in outcome prediction after traumatic brain injury (TBI). Some studies have questioned the validity of S100b, citing the extracerebral origins of the protein as reducing the specificity of the marker. This study evaluated S100b as a prognostic biomarker in adult subjects with severe TBI (sTBI) by comparing outcomes with S100b temporal profiles generated from both cerebrospinal fluid (CSF) (n = 138 subjects) and serum (n = 80 subjects) samples across a 6-day time course. Long-bone fracture, Injury Severity Score (ISS), and isolated head injury status were variables used to assess extracerebral sources of S100b in serum. After TBI, CSF and serum S100b levels were increased over healthy controls across the first 6 days post-TBI (p ≤ 0.005 and p ≤ 0.031). Though CSF and serum levels were highly correlated during early time points post-TBI, this association diminished over time. Bivariate analysis showed that subjects who had temporal CSF profiles with higher S100b concentrations had higher acute mortality (p < 0.001) and worse Glasgow Outcome Scale (GOS; p = 0.002) and Disability Rating Scale (DRS) scores (p = 0.039) 6 months post-injury. Possibly as a result of extracerebral sources of S100b in serum, as represented by high ISS scores (p = 0.032), temporal serum profiles were associated with acute mortality (p = 0.015). High CSF S100b levels were observed in women (p = 0.022) and older subjects (p = 0.004). Multivariate logistic regression confirmed CSF S100b profiles in predicting GOS and DRS and showed mean and peak serum S100b as acute mortality predictors after sTBI.

Risk factors for sleep disturbances in older adults: Evidence from prospective studies

No systematic review of epidemiological evidence has examined risk factors for sleep disturbances among older adults. We searched the PubMed database combining search terms targeting the following domains 1) prospective, 2) sleep, and 3) aging, and identified 21 relevant population-based studies with prospective sleep outcome data. Only two studies utilized objective measures of sleep disturbance, while six used the Pittsburgh sleep quality index (PSQI) and thirteen used insomnia symptoms or other sleep complaints as the outcome measure. Female gender, depressed mood, and physical illness were most consistently identified as risks for future sleep disturbances. Less robust evidence implicated the following as potentially relevant predictors: lower physical activity levels, African-American race, lower economic status, previous manual occupation, widowhood, marital quality, loneliness and perceived stress, preclinical dementia, long-term benzodiazepine and sedative use, low testosterone levels, and inflammatory markers. Chronological age was not identified as a consistent, independent predictor of future sleep disturbances. In conclusion, prospective studies have identified female gender, depressed mood, and physical illness as general risk factors for future sleep disturbances in later life, although specific physiological pathways have not yet been established. Research is needed to determine the precise mechanisms through which these factors influence sleep over time.

Trajectory Analysis of Serum Biomarker Concentrations Facilitates Outcome Prediction after Pediatric Traumatic and Hypoxemic Brain Injury

Traumatic brain injury (TBI) and hypoxic ischemic encephalopathy (HIE) are leading causes of morbidity and mortality in children. Several studies over the past several years have evaluated the use of serum biomarkers to predict outcome after pediatric brain injury. These studies have all used simple point estimates such as initial and peak biomarker concentrations to predict outcome. However, this approach does not recognize patterns of change over time. Trajectory analysis is a type of analysis which can capture variance in biomarker concentrations over time and has been used with success in the social sciences. We used trajectory analysis to evaluate the ability of the serum concentrations of 3 brain-specific biomarkers – S100B, neuron-specific enolase (NSE) and myelin basic protein (MBP) – to predict poor outcome (Glasgow Outcome Scale scores 3–5) after pediatric TBI and HIE. Clinical and biomarker data from 100 children with TBI or HIE were evaluated. For each biomarker, we validated 2-, 3- and 4-group models for outcome prediction, using sensitivity and specificity. For S100B, the 3-group model predicted poor outcome with a sensitivity of 59% and specificity of 100%. For NSE, the 3-group model predicted poor outcome with a sensitivity of 48% and specificity of 98%. For MBP, the 3-group model predicted poor outcome with a sensitivity of 73% and specificity of 61%. Thus, when the models predicted a poor outcome, there was a very high probability of a poor outcome. In contrast, 17% of subjects with a poor outcome were predicted to have a good outcome by all 3 biomarker trajectories. These data suggest that trajectory analysis of biomarker data may provide a useful approach for predicting outcome after pediatric brain injury.

Literature review of HPV vaccine delivery strategies: Considerations for school- and non-school based immunization program

School-based vaccination is becoming a more widely considered method of delivering HPV immunizations to an adolescent population; however, many countries do not have experience with delivering adolescent vaccines or school-based programs. This literature review will summarize the experiences from countries implementing non-health facility-based and health facility-based vaccination programs and assess HPV vaccine coverage. In October 2012, a systematic search in PubMed for studies related to the evaluation of national/regional, pilot, or demonstration HPV immunization programs that worked within existing health system yielded nine articles, representing seventeen countries. School-based programs achieved high HPV vaccination coverage rates in 9 to 13-year-old girls across the different studies and geographic locations, suggesting non-health facility-based programs are possible for HPV vaccine introduction. Grade-based, compared to age-based, eligibility criteria may be easier to implement in school settings. More studies are needed to explore the methods to standardize estimates for HPV vaccine coverage so that programs can be appropriately evaluated.

An Interactive Text Message Intervention to Reduce Binge Drinking in Young Adults: A Randomized Controlled Trial with 9-Month Outcomes

Background Binge drinking is associated with numerous negative consequences. The prevalence and intensity of binge drinking is highest among young adults. This randomized trial tested the efficacy of a 12-week interactive text message intervention to reduce binge drinking up to 6 months after intervention completion among young adults. Methods and Findings Young adult participants (18–25 y; n = 765) drinking above the low-risk limits (AUDIT-C score >3/4 women/men), but not seeking alcohol treatment, were enrolled from 4 Emergency Departments (EDs) in Pittsburgh, PA. Participants were randomized to one of three conditions in a 2:1:1 allocation ratio: SMS Assessments + Feedback (SA+F), SMS Assessments (SA), or control. For 12 weeks, SA+F participants received texts each Thursday querying weekend drinking plans and prompting drinking limit goal commitment and each Sunday querying weekend drinking quantity. SA+F participants received tailored feedback based on their text responses. To contrast the effects of SA+F with self-monitoring, SA participants received texts on Sundays querying drinking quantity, but did not receive alcohol-specific feedback. The control arm received standard care. Follow-up outcome data collected through web-based surveys were provided by 78% of participants at 3- months, 63% at 6-months and 55% at 9-months. Multiple imputation-derived, intent-to-treat models were used for primary analysis. At 9-months, participants in the SA+F group reported greater reductions in the number of binge drinking days than participants in the control group (incident rate ratio [IRR] 0.69; 95% CI .59 to.79), lower binge drinking prevalence (odds ratio [OR] 0.52; 95% CI 0.26 to 0.98]), less drinks per drinking day (beta -.62; 95% CI -1.10 to -0.15) and lower alcohol-related injury prevalence (OR 0.42; 95% CI 0.21 to 0.88). Participants in the SA group did not reduce drinking or alcohol-related injury relative to controls. Findings were similar using complete case analyses. Conclusions An interactive text-message intervention was more effective than self-monitoring or controls in reducing alcohol consumption and alcohol-related injury prevalence up to 6 months after intervention completion. These findings, if replicated, suggest a scalable approach to help achieve sustained reductions in binge drinking and accompanying injuries among young adults. Trial Registration ClinicalTrials.gov NCT01688245